Oregon State University (OSU) fosters a research environment that promotes the respect for the rights and welfare of individuals recruited for, or participating in, research conducted by or under the auspices of OSU. In the review and conduct of research, actions by OSU will be guided by the principles (i.e., respect for persons, beneficence, and justice) set forth in Ethical Principles and Guidelines for the Protection of Human Subjects of Research, issued by the Office of the Secretary of the US Department of Health and Human Services (often referred to as the “Belmont Report”). The actions of OSU will also conform to all applicable federal, state, and local laws and regulations.

In order to fulfill this mission, OSU has established an Institutional Review Board (IRB). OSU has designated an Institutional Official (IO) who has overall responsibility for OSU’s IRB. The IO is responsible for ensuring that the IRB has the resources and support necessary to comply with all federal regulations and guidelines that govern research involving human subjects. The IO is legally authorized to represent the Institution, is the signatory official for all Assurances, and assumes the obligations of the Institution’s Assurance. It is through the Federal Wide Assurance that an Institution commits to the U.S. Department of Health and Human Services (DHHS) that, for all federally funded research, it will comply with the requirements in the HHS Protection of Human Subjects regulations at 45 CFR 46, also referred to as the “Common Rule.”

While the policies and procedures set forth in this document are primarily informed by the Common Rule, additional regulations, laws, or policies may apply, depending on the funding source, state laws, or the type or site of research. Similarly, for research that is not funded by DHHS, the policies and procedures may differ from those set forth in the Common Rule.

To conduct its responsibility effectively, OSU maintains one or more IRBs to review research protocols involving human subjects. The IRB is an autonomous administrative body established to protect the rights and welfare of human research subjects participating in research activities conducted under the auspices of OSU.

The OSU IRB(s) will review all research involving human subjects regardless of funding source or status, or performance site.

Research under the auspices of the Institution includes research:

· Conducted at this Institution

· Conducted by or under the direction of any employee or agent of this Institution (including students) in connection with his or her Institutional responsibilities

· Conducted by or under the direction of any employee or agent (including students) of this Institution using any property or facility of this Institution, and/or

· Involving the use of this Institution's non-public information to identify or contact human subjects

Agents include all individuals performing institutionally designated activities or exercising Institutionally delegated authority or responsibility. Determinations of whether or not an employee is acting as an agent of the Institution will be made in accordance with the OSU Conflict of Commitment Policy.

No research involving human subjects may commence until all required Institutional approvals (including IRB) are obtained. The results from studies conducted without obtaining IRB review and approval may not be published or distributed outside of OSU, nor can such data be used to satisfy honors theses, master's theses or doctoral dissertation requirements.

Representatives from the OSU administration may choose to review and disapprove the implementation of a research protocol that has been approved by the IRB. Those representatives may include the President and his or her designees, the Provost and his or her designees, the Senior Vice Provost for Academic Affairs, the Institutional Official, the Vice President for Research and his or her designees. However, no one at OSU shall approve or permit the implementation of any research protocol that has not been approved by the IRB.

All Institutional and non-Institutional performance sites for OSU, domestic or foreign, will be obligated by this policy to conform to ethical principles which are at least equivalent to those of this Institution or as may be determined by the DHHS Secretary.

The purpose of this document is to implement this policy.

This document is based on a template provided by The HRP Consulting Group and borrows extensively from the best practices of a variety of academic Institutions national-wide. Further, the information contained herein reflects advice received from federal regulators as well as leaders in ethics and responsible conduct of research.

(top) 1.2 Institutional Authority

The policies and operating procedures in this document serve as the governing procedures for the conduct and review of all human subjects research conducted under the auspices of OSU. The authority to carry out these procedures as described comes from the President of the University via the Institutional Official.

Oregon State University faculty, staff and students engage in activities associated with innovative and high impact research, instruction and outreach/engagement, and are at the forefront of many new discoveries. The activities bear with them certain ethical and legal responsibilities. The University Administration is committed to the highest standards of integrity and resolves that such activities undertaken by OSU faculty, staff, and students should be conducted in accordance with strict ethical principles and in compliance with Institutional policies, federal and state laws and regulations, and other applicable requirements.

Adherence to high standards provides a framework for (i) achieving full compliance with applicable ethical, regulatory and University requirements and (ii) promoting an organizational culture that encourages ethical conduct and a commitment to compliance. Areas in which integrity is critical to success include, but are not limited to: human subject research; animal care and use; biosafety; chemical safety; radiation safety; occupational safety; export controls; conflicts of interest; diving safety; small boat safety; handling of hazardous, controlled or regulated substances; material transfers; environmental protection; and research misconduct.

The University, through its compliance committees and authorized officials, will issue and promulgate Institutional policies and procedures to ensure the appropriate and responsible conduct of all applicable activities at Oregon State University.

-Oregon State University President Edward J. Ray (May 2011)

These policies and operating procedures are made available to all OSU investigators and research staff and are posted on the IRB website http://oregonstate.edu/research/irb/.

1.3 Mission

The mission of the IRB is to:

· Safeguard the health and welfare of human research subjects by ensuring that their rights, safety and well-being are protected;

Provide guidance and support to the research community in the conduct of research with human subjects
Assist the research community in ensuring compliance with the standards set forth in the Code of Federal Regulations by the U.S. Department of Health and Human Services

· Facilitate ethical research with human subjects

· Review and monitor research involving human subjects; and

The IRB includes formal and informal mechanisms to:

· Monitor, evaluate, and continually improve the protection of human research participants.

· Educate investigators, student researchers, and other study team members about their ethical responsibility to protect research participants.

· When appropriate, intervene in research and respond directly to concerns of research participants.

· Dedicate resources sufficient to carryout the above listed actions.

(top) 1.4 Ethical Principles

OSU is committed to conducting research with the highest regard for the welfare of human subjects. It upholds and adheres to the principles of The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects in Research by the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research (1979). These principles are:

a) Respect for Persons, which is ensured by obtaining informed consent, consideration of privacy, confidentiality, and additional protections for vulnerable populations.

b) Beneficence, which is assured by ensuring that possible benefits are maximized and possible risks are minimized to all human subjects.

c) Justice, the equitable selection of subjects.

OSU’s IRB, in partnership with its research community, is responsible for ensuring the ethical and equitable treatment of all human subjects in research conducted under its auspices.

1.5 Regulatory Compliance

The IRB is responsible for ensuring compliance with federal regulations, state law and Institutional policies. All human subjects research at OSU that is funded by a federal agency must be conducted in accordance with this policy and the regulations found in the 45 CFR 46 (the “Common Rule”) and 21 CFR 50 and 56 when applicable.

Unregulated research is conducted in accordance with these policies and procedures.

1.6 Federalwide Assurance (FWA)

The IRB operates under the authority of its current Federalwide Assurance (00003920) and has designated two IRBs (registered as 00000122 and 00009613).

In its FWA, OSU has opted to limit the application of the Assurance to research funded by DHHS or federal agencies that have adopted the Common Rule.

1.7 Research Covered by the IRB

The OSU IRB covers all research involving human subjects that is under the auspices of the Institution, whether or not that research is externally funded or conducted without direct funding.

Research. The Common Rule defines research as a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalized knowledge.

For the purposes of this policy, a systematic investigation is an activity that involves a prospective study plan that incorporates data collection, either quantitative or qualitative, and data analysis to answer a study question.

Designed to develop or contribute means that the investigator intends to disseminate results to those outside of the University via the web, social networks or other electronic media, poster presentations, conferences, library placement, or publications. Examples that would not be seen as dissemination outside of the University include: presentation to a department in fulfillment of a university requirement; sharing results with the sponsor or a collaborator; or student presentations to a class or campus organization.

Investigations designed to develop or contribute to generalizable knowledge are those designed to draw general conclusions. Knowledge gained may be applied to populations outside of the specific study population, it may be used to inform policy, or be analyzed for predictive value.

Research subject to FDA regulations. Research, as defined by FDA regulations, means any experiment that involves a test article and one or more human subjects, and that either must meet the requirements for prior submission to the Food and Drug Administration under section 505(i) or 520(g) of the Federal Food, Drug, and Cosmetic Act, or need not meet the requirements for prior submission to the Food and Drug Administration under these sections of the Federal Food, Drug, and Cosmetic Act, but the results of which are intended to be later submitted to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit. The terms research, clinical research, clinical study, study, and clinical investigation are synonymous for purposes of FDA regulations. [21 CFR 50.3(c), 21 CFR 56.102(c)]

Experiments that must meet the requirements for prior submission to the Food and Drug Administration under section 505(i) of the Federal Food, Drug, and Cosmetic Act means any use of a drug other than the use of an approved drug in the course of medical practice. [21 CFR 312.3(b)]

Experiments that must meet the requirements for prior submission to the Food and Drug Administration under section 520(g) of the Federal Food, Drug, and Cosmetic Act means any activity that evaluates the safety or effectiveness of a device. [21 CFR 812.2(a)]

Any activity in which results are being submitted to or held for inspection by FDA as part of an application for a research or marketing permit is considered to be FDA-regulated research. [21 CFR 50.3(c), 21 CFR 56.102(c)]

Human Subject. A human subject as defined by the Common Rule is a living individual about whom an investigator conducting research obtains data through intervention or interaction with the individual or through identifiable private information (45 CFR 46.102(f)).

· Intervention means both physical procedures by which data are gathered (for example, venipuncture) and manipulations of the subject or the subject’s environment that are performed for research purposes.

· Interaction means communication or interpersonal contact between investigator and subject.

· Private information means information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record).

· Information is considered to be individually identifiable if the identity of the subject is or may readily be ascertained by the investigator or associated with the information.

For research covered by FDA regulations (21 CFR 50 and 56), a human subject means an individual who is or becomes a participant in a clinical investigation, either as a recipient of the test article or as a control. A subject may be in normal health or may have a medical condition or disease. In the case of a medical device, a human subject/participant also includes any individual on whose tissue specimen an investigational device is used or tested. If tissue is used to test an investigational device, the tissue donor is a human subject.

Test Article. A test article is a drug, device, or other article including a biological product that is the object of a clinical investigation involving human subjects or their specimens.

(top) 1.8 Written policies and procedures

This document details the policies and regulations governing all research with human subjects, regardless of funding source, and the requirements for submitting research proposals for review by the OSU IRB. This is not a static document. The policies and procedures are annually reviewed and revised by the Director of the Office of Research Integrity (ORI), the IRB Administrator, and designated members of the Institutional Review Board. These individuals will also make policy recommendations to the IO. Votes on these recommendations may occur at the discretion of the Chair, but will not be required. The IO will review and approve revisions to this manual on an annual basis and will review and approve new or revised policies as needed.

This manual will be available on the IRB website and this will serve as the mechanism for keeping the Institution’s research community apprised of new information that may affect the IRB, including laws, regulations, policies, procedures, and emerging ethical and scientific issues.

1.9 Organization of the IRB

The IRB consists of various individuals, boards, and committees. The IRB Office is a unit of the Office of Research Integrity. The officials, administrative units and individuals outlined below have primary responsibilities for implementing the IRB.

1.9.1 Institutional Official

The ultimate responsibility of the IRB resides with the Institutional Official (IO) of the program. The IO is responsible for ensuring that OSU’s IRB has the resources and support necessary to comply with all Institutional policies and with federal regulations and guidelines that govern human subjects research. The IO is legally authorized to represent OSU. He/she is the signatory of the FWA and assumes the obligations of the FWA.

The IO also holds ultimate responsibility for:

Oversight of the Institutional Review Board (IRB);
Oversight over the conduct of research conducted by all OSU investigators;
Assuring the IRB members are appropriately knowledgeable to review research in accordance with ethical standards and applicable regulations;
Assuring that all investigators are appropriately knowledgeable to conduct research in accordance with ethical standards and applicable regulations;
Facilitating the development and implementation of an educational plan for IRB members, staff and investigators.

(top) 1.9.2 IRB Administrator

The IRB Administrator is selected by and reports to the Institutional Official (IO). The Administrator is responsible for:

· Developing, managing and evaluating policies and procedures that ensure compliance with all state and federal regulations governing research. This includes monitoring changes in regulations and policies that relate to human research protection and overseeing all aspects of the IRB program.

· Advising the IO on key matters regarding research at OSU.

· Implementing the Institution’s IRB policy.

· Submitting, implementing and maintaining an approved FWA through the IO and the Department of Health and Human Services (DHHS) Office of Human Research Protection (OHRP).

· Assisting investigators in their efforts to carry out the Institution’s research mission.

· Developing and implementing needed improvements and ensuring follow-up of actions, as appropriate, for the purpose of managing risk in the research program.

· Developing training requirements as required and as appropriate for investigators, subcommittee members and research staff, and ensuring that training is completed on a timely basis.

· Serving as the primary contact at OSU for OHRP and other federal regulatory agencies.

· Day-to-day responsibility for the operation of the IRB office, including supervision of IRB staff.

· Responding to faculty, student and staff questions.

· Working closely with the Chair of the IRB and on the development of policy and procedures, as well as organizing and documenting the review process.

1.9.3 Institutional Review Board (IRB)

OSU has two IRBs, appointed by the Institutional Official (IO). These IRBs prospectively review and make decisions concerning all human research conducted at OSU facilities, by its employees or agents, or under its auspices. Both Boards are responsible for the protection of rights and welfare of human research subjects at OSU. They discharge this duty by complying with the requirements of the Common Rule, state laws, the FWA, and Institutional policies.

Throughout this document, there will be references to “the IRB” and “IRB Chair” singular rather plural, as the number of registered Boards and Chairs may change, but all Boards and Chairs share a single charge.

1.9.4 IRB Chairs and Vice Chairs

Each Board will have a Chair and a Vice Chair who will work closely with the Administrator to carry out the mission of the IRB. Details of their role appear in section 4.

1.9.5 IRB Coordinators and Support Staff

IRB Coordinators are responsible for all aspects processing proposals involving human subjects. This responsibility includes the initial review of documents and screening of research proposals prior to its review by the IRB, as well as serving as liaisons between the investigators and the IRB. IRB Coordinators review the IRB minutes for accuracy and ensures proper documentation of discussions, including controverted issues and actions taken by the IRB during its convened meetings.

IRB Coordinators and support staff are responsible for providing administrative and clerical support to the IRB Chair and IRB Administrator as well as scheduling and coordinating all IRB functions. IRB Coordinators are also responsible for IRB record retention. IRB Coordinators are responsible for maintaining complete IRB files, records of all research protocols, IRB correspondence (including e-mails), as well as Research Credentialing records of investigators and research staff.

IRB Coordinators must be Certified IRB Professionals (CIP) within 24 months of hire.

The IRB Staff are required to complete the relevant CITI courses in the Protection of Human Research Subjects. Staff members will be provided with sufficient training opportunities to maintain their required certification (CIP). This training will include attendance at national or regional conferences at least annually, and periodic webinars.

(top) 1.9.6 Unit Heads

Department Heads, Department Chairs, and Directors of Centers and Institutes (“Unit Heads”) are responsible for ensuring that the Principal Investigator (PI) is qualified by training and experience to conduct the proposed research.

Unit Heads are responsible for assuring that investigators have the resources required to conduct the research in a way that will protect the rights and welfare of participants. Such resources include but are not necessarily limited to adequate personnel, space, equipment and time to minimize risk and result in valid data.

(top) 1.9.7 Investigators

The investigator is the ultimate protector of the human subjects who participate in research. The investigator is expected to abide by the highest ethical standards in the conduct and oversight of research and for developing a protocol that incorporates the principles of the Belmont Report. Investigators are expected to conduct research in accordance with the approved research protocol and to oversee all aspects of the research by providing supervision of all study team members, including oversight of the informed consent process. Unless consent is waived by the IRB, all subjects must give informed consent and the investigator must provide all research subjects within his/her responsibility with direct contact information to use in the event that they wish to contact the PI with questions or concerns.

In addition to complying with all the policies and standards of the governing regulatory bodies, the investigator must comply with Institutional and administrative requirements for conducting research. The investigator is responsible for ensuring that all research staff complete appropriate training and must obtain all required approvals prior to initiating research. When investigational drugs or devices are used, the investigator is responsible for providing written procedures for their storage, security, dispensing and disposal.

1.9.8 Other Related Units

1.9.8.1 Committee on Conflict of Interest

The OSU policy for Conflict of Interest promotes objectivity in research by establishing expectations and disclosure requirements to ensure that the design, conduct and reporting of research will not be biased by a Significant Financial Interest of an individual. Communication between the IRB and CCOI is facilitated through four mechanisms:

· Applications that are received by the IRB which include a disclosure of a conflict of interest are forwarded to the COI Administrator for review. The study file is accessible to CCOI while under review and after it has been approved. IRB approval may be issued prior to a determination from the CCOI if the IRB has reviewed the relevant details and finds that the matter is appropriately managed within the protocol and, if applicable, the consent process.

· The IRB Administrator is alerted to disclosures made in the COI system when they involve, or appear to involve, research with human subjects. Any resulting management plan is accessible to the IRB.

· At the discretion of the Vice President for Research, a representative from the IRB will serve as a non-voting member of the CCOI.

· A representative from the CCOI will serve as a non-voting member of the IRB.

1.9.8.2 Institutional Animal Care and Use Committee

In the event that a research protocol involves both human and animal subjects, the Administrators for the IRB and the Institutional Animal Care and Use Committee (IACUC) will work together to ensure that information regarding the reviews is shared between committees.

1.9.8.3 Diving Safety and Small Boats: Pending information from DSO

In the event that a research protocol involves human subjects and scientific diving operations or small boat use, the IRB Administrator and the Diving Safety Officer will work together to ensure that information regarding reviews is shared between committees.

1.9.8.4 Office for Commercialization & Corporate Development

The Office for Commercialization & Corporate Development (OCCD) supports research development and commercialization of University intellectual property. Applications that are received by the IRB which include the transfer of biological materials to or from OSU are referred to the OCCD for consultation regarding the potential need for a Material Transfer Agreement (MTA). Similarly, researchers will be referred to the IRB if they indicate to OCCD that they plan to conduct research involving human subjects.

1.9.8.5 Office of Sponsored Programs

The Office of Sponsored Programs staff review and approve all research proposals and agreements with external sponsors. This Institutional review ensures that all terms of the award are in compliance with Institutional policies.

When the grant or contract agreement includes human research activities that will be conducted by investigators who are not employees or agents of OSU, a subcontract is executed between OSU and the collaborating Institution. The subcontract includes the requirement for the collaborating Institution to assure compliance with federal regulations for the protection of human subjects in research and to provide certification and documentation of current and ongoing IRB approval upon execution of the subcontract, and annual certification thereafter, during the life of the sub-award. The collaborating Institution must also ensure that key personnel involved in human subjects research are in compliance with the NIH policy on education in the protection of human research subjects and provide documentation of education of key personnel to OSU.

For all externally funded research, the IRB Office will include OSP on notices of exemption, approval, suspension, or termination sent to Investigators.

(top) 1.9.8.6 Office of Post Award Administration

The Office of Post Award Administration (OPAA) provides post award administration, reporting, and accounting for OSU researchers. For all externally funded research, the IRB Office will include the Office of Post Award Administration (OPAA) on notices of exemption, approval, suspension, or termination sent to Investigators.

1.9.8.7 Radiation Safety Committee

All research and teaching activities at OSU that require the possession and/or use of radioisotopes or radiation-emitting machines are governed by the provisions of a license and/or regulations issued by the State of Oregon. The Radiation Safety Program provides for these uses under the applicable laws and regulations of federal, state, and local agencies. Furthermore, the Program ensures that no risk from ionizing radiation shall be incurred except where justified by benefits from the activity and that radiation exposure shall be as low as reasonably achievable. The Radiation Safety Committee (RSC) must specifically authorize all uses of ionizing radiation and the authorized user has primary responsibility for all safety aspects of work under the program. This includes familiarity with and adherence to all regulations, personnel training, and the conduct of safe operations with the assistance of Radiation Safety.

Applications that are received by the IRB which include the use of radiation are forwarded to the RSC for simultaneous review. Once the IRB approves the application, the approval documents will be forwarded to the RSC so that they may be passed on to the State of Oregon. When State approval is obtained, the RSC will send a Radiation Use Authorization to the IRB Administrator for signature. At this point, the IRB will release the IRB approved documents to the PI.

(top) 1.9.8.8 Biological Safety Committee

In recognition of the necessity for conducting research utilizing potentially hazardous biological materials in a safe and secure manner, the Institutional Biosafety Committee (IBC) reviews biohazardous work conducted for any purpose by OSU personnel or in any OSU facility. The IBC has full authority to impose containment requirements or procedural safeguards, audit programs, and inspect facilities to ensure that biohazards are handled, used, and disposed of in a safe and compliant manner.

Applications that are received by the IRB which include the collection and/or use of biological samples are forwarded to the Biosafety Officer for review. IRB approval of a study will not be issued until and unless it is first approved by the Biosafety Officer.

1.9.8.9 Chemical Safety Committee

Applications that are received by the IRB which include the use of chemicals are forwarded to the Chemical Safety Officer (CSO) for simultaneous review. In turn, the CSO will send the IRB the approval documentation issued by that committee and indicate whether or not the protocol submitted for IRB review is consistent with the application materials reviewed and approved by the Chemical Safety Committee.

1.9.8.10 General (top) Counsel’s Office

The OSU IRB relies on the Institution’s Office of General Counsel for the interpretations and applications of Oregon State law, and the laws of any other jurisdiction where research is conducted, as they apply to human subjects research.

1.9.9 Relationship Between Components

The IRB functions independently of, but in coordination with, other Institutional compliance committees. The IRB, however, makes independent determinations about whether to approve or disapprove a protocol based upon whether or not human subjects are adequately protected. The IRB has review jurisdiction over all research involving human subjects conducted under the auspices of OSU.

1.9.9.1 Office of Research Integrity

Under the direction of the Associate Vice President for Research, and in accordance with University policies, procedures, and guidelines, the Director of ORI provides advice to senior management, staff, and employees to maximize compliance with statutory and regulatory requirements; regularly reviews compliance programs to identify areas of risk and works with senior administration to secure solutions that will manage or eliminate threats to research integrity; works with administrative units across campus to harmonize policies between ORI and other areas impacting the OSU research community; and collaborates with senior management and campus compliance areas to organize and provide a coordinated education and outreach program to promote the responsible conduct of research.

The Director of ORI provides leadership and coordination for the administration, support, monitoring, and assessment of a range of research compliance functions, including: the Institutional Review Board, Animal Care and Use Committee, Conflict of Interest Committee, Scientific Diving and Small Boat use for research, and the Biosafety Committee.

This position also provides the Research Office interface and linkage to the Environmental Health and Safety programs. The Director provides leadership to ORI by establishing and maintaining research compliance systems; embracing the vision and goals for research integrity and assuring those are aligned with those of the University; communicating the vision and goals to staff; developing a highly cohesive compliance work team; and enabling staff to perform effectively.

While the Director has a critical role for overseeing the compliance programs and for coordinating activities of the compliance groups broadly across campus, administrators and officers for each of the compliance units will have direct and unimpeded access to the Institutional Official (IO) at their discretion.

1.9.9.2 Research Integrity and Environmental Health and Safety

Administrators and Safety Officers from each of the ORI and EH&S units meet regularly. The group focuses on policy harmonization across units and works to identify areas of risk and vulnerability related to the conduct of research at OSU.

1.9.9.3 Institutional Compliance Office

The Institutional Compliance Office coordinates the network of compliance functions across the OSU campus, through the Compliance Partners Network. The Director of this office develops and coordinates the compliance program by obtaining periodic reports from the decentralized compliance units, conducting risk analyses to prioritize senior leadership focus for improvements, developing compliance policies and a central University-wide compliance calendar, and communicating with senior leadership, campus and compliance units.

The Director acts in an advisory capacity only. The IRB’s authority, autonomy, and reporting structure are not impacted by this office; however, the IRB Administrator provides the Director with information related to the IRB’s compliance functions as requested and participates in the network of compliance functions and offices across OSU.

(top) 1.10 IRB Resources

In accordance with 45 CFR 46.103, the IO will ensure that the IRB has adequate meeting space and sufficient staff to support the IRB’s review and record keeping duties. The resources provided for the IRB and IRB office will be reviewed during the annual budget review process.

2. Investigator Responsibilities

2.1 Policy

Principal Investigators are ultimately responsible for the conduct of research. Principal Investigators may delegate research responsibility. However, investigators must maintain oversight and retain ultimate responsibility for the conduct of those to whom they delegate responsibility.

The following procedures describe the investigator responsibilities in the conduct of research involving human participants.

2.2 Investigators

Principal Investigators

OSU unclassified employees with the following appointments may serve as a Principal Investigator (PI), if they are otherwise sufficiently qualified to conduct and oversee the research:

· Academic Teaching and Research Faculty: Assistant, Associate, Professor (includes Clinical, Extension, Practice, Senior Research, Endowed Chair); Faculty Research Assistant; Instructor (includes ALS, ELS, PAC); Lecturer; Research Associate; Research Associate (Post Doc); Senior Faculty Research Assistant I or II; Senior Instructor I or II; paid Visiting Faculty.

· Non-teaching Administrative and Professional Faculty

· Federal

OSU unclassified employees with the following appointments are not permitted to serve as the PI on a study involving human subjects:

· Unclassified hourly

· Academic wage appointment

The following additional classifications are not permitted to serve as the PI on a study involving human subjects:

· Classified employees

· Temporary Support Staff

· Student Appointments: Student, Graduate Assistant, Postdoctoral Scholar, Clinical Fellow

· Unpaid: Affiliate, Courtesy, Emeritus, Postdoctoral Fellow, Graduate Fellow, unpaid Visiting Faculty

The IRB recognizes one Principal Investigator (PI) for each study. The PI is ultimately responsible for the conduct of the entire study and all study team members.

Protocols that require skills beyond those held by the PI must be modified to meet the investigator's skills or have one or more additional qualified faculty as Co-investigator(s).

Research Team

Any individuals who will interact with subjects or have access to individually identifiable data should be listed as study team members. When this is not a reasonable requirement for enhancing the protection of human subjects, or the individuals are not considered to be key personnel, the PI must follow the procedures below.

Procedures for Certifying Research Team Members

There are circumstances under which listing individual study team members on an IRB application is not a reasonable requirement for enhancing the protection of human subjects. Examples of such circumstances can include:

· Individual researchers will be identified in the field;

· The study involves community based participatory research and data collection is conducted by lay individuals and/or study participants;

· Individuals obtaining consent or conducting data collection are not considered to be key personnel because they will not contribute to the scientific development of the project or assist with data analysis.

While these individuals need not be listed on the application to the IRB, the PI is required to train, oversee, and certify these individuals as qualified members of the team. The protocol must include the following:

· A description of who these individuals will be (e.g., community members, regional high school teachers, Extension Agents, etc.)

· A description of the responsibilities and activities that these individuals will perform

· A detailed plan for training, oversight, and procedures for ensuring protocol adherence

· A copy of the certification document

At a minimum, certification documents must include a list of responsibilities, an acknowledgement of training, a commitment to protocol adherence and the protection of the rights and welfare of human subjects, and signature lines for the PI and study team member. A comprehensive list of these individuals and a copy of each certificate should be included at the time of each continuing review. A template for this certification is available on the IRB website.

Certification should be submitted to the IRB Office at the time of Continuing Review for non-exempt studies and with the Final Report for exempt studies.

2.3 Responsibilities

In order to satisfy the requirements of this policy, investigators who conduct research involving human subjects must attest:

a) That the information contained in the application is accurate and complete;

b) That research involving humans, including recruitment, will not begin until IRB approval has been granted;

c) To the scientific merit and importance of this study;

d) To the competency and availability of the study team member(s) to conduct the project;

e) That facilities, equipment, and personnel are adequate to conduct the research.

Furthermore, investigators must agree to:

a) Comply with all IRB policies, decisions, conditions, and requirements;

b) Accept responsibility for every aspect of the conduct of this study;

c) Obtain prior approval from the IRB before amending or altering the study and/or study documents;

d) Report to the IRB in accord with current policy, any adverse event(s) and/or unanticipated problem(s);

e) Complete and submit continuing review documentation or a final report prior to the expiration date;

f) Notify the IRB immediately of the development of any potential conflict of interest not already disclosed.

2.4 Training for Investigators

The OSU IRB is committed to providing training and an on-going educational process for investigators and members of their research team related to ethical concerns and regulatory and Institutional requirements for the protection of human subjects.

(top) 2.4.1 Initial Education

The research community has a responsibility to ensure that the treatment of human subjects in research meets the highest ethical standards. Recognizing this responsibility, the National Institutes of Health (NIH) requires NIH funding recipients to certify training in the ethical use of humans in research. Endorsing the goals of such training, the OSU Institutional Review Board (IRB) requires education in the protection of human research participants for all researchers conducting research involving human subjects, not just those receiving NIH funding.

OSU study team members have two training options:

a) CITI Course

b) NIH Course

Non-OSU study team members have three training options:

a) CITI Course

b) NIH Course

c) Provide an electronic copy of the certificate of education found acceptable by the IRB at their home Institution.

If a non-OSU study team member is unable to complete, or provide proof of completion, of the above described training (for reasons such as illiteracy, inability to use or access the internet, or CITI training is not offered in the individual’s native language), they may contact the IRB Administrator for additional options.

Approval of research projects will not be issued until documentation of training has been received by the IRB for all study team members. Such documentation need only be submitted once. Study team members for whom the IRB has already recorded training completion will not be required to provide additional documentation of training.

2.5 Investigator Concerns

Investigators who have concerns or suggestions regarding OSU’s Institutional Review Board (IRB) should convey them to the Institutional Official or other responsible parties (e.g. Director of ORI, college dean, departmental chair) regarding the issue, when appropriate. The Institutional Official or their designee will investigate the issue. When deemed necessary, the IO may convene the parties involved to form a response for the investigator or make necessary procedural or policy modifications, as warranted. In addition, the Chair of the IRB or the IRB Administrator will be available to address investigators’ questions, concerns, and suggestions.

3. Quality Assurance/Quality Improvement Activities

The objective of the IRB Quality Assurance / Quality Improvement Activities are to maintain and improve the effectiveness of human research protections, and compliance with Institutional policies and procedures as well as applicable federal, state, and local laws.

3.1 Investigator Audits and Compliance Reviews

Directed (“for cause”) audits and periodic (not “for cause”) compliance reviews will be conducted, as resources allow, to assess investigator compliance with federal, state, and local law, and Institutional policies, and to identify areas for improvement, and suggest recommendations based on existing policies and procedures. Directed audits of IRB-approved research studies are in response to identified concerns. Periodic compliance reviews will be conducted using a systematic method to review IRB-approved research. The results will be reported to the Administrator and the IRB Chair.

Activities of auditors during directed audits and periodic compliance reviews may include:

a) Requesting progress reports from researchers;

b) Examining investigator-held research records;

c) Contacting research subjects;

d) Observing research sites where research involving human research subjects and/or the informed consent process is being conducted;

e) Auditing advertisements and other recruiting materials as deemed appropriate by the IRB;

f) Reviewing projects to verify from sources other than the researcher that no unapproved changes have occurred since previous review;

g) Monitoring conflict of interest concerns to assure the consent documents include the appropriate information and disclosures;

h) Conducting other monitoring or auditing activities as deemed appropriate by the IRB.

3.1.1 Independent Verification That No Material Changes Have Occurred

The IRB recognizes that protecting the rights and welfare of subjects sometimes requires that the IRB verify independently, utilizing sources other than the investigator, that no material changes occurred during the IRB-designated approval period. Independent verification from sources other than the investigator may be necessary at times, for example, in cooperative studies, or other multi-center research.

The IRB will determine the need for verification from outside sources on a case-by-case basis and according to the following criteria:

a) Protocols where concerns about possible material changes occurring without IRB approval have been raised, based on information provided in continuing review reports or from other sources

b) Protocols conducted by Principal Investigators who have previously failed to comply with federal regulations and/or the requirements or determinations of the IRB

c) Protocols subject to internal audit

d) Whenever else the IRB deems verification from outside sources is relevant

The following factors will also be considered when determining which studies require independent verification:

a) The probability and magnitude of anticipated risks to subjects.

b) The likely medical condition of the proposed subjects.

c) The probable nature and frequency of changes that may ordinarily be expected in the type of research proposed.

In making determinations about independent verification, the IRB may prospectively require that such verification take place at predetermined intervals during the approval period, or may retrospectively require such verification at the time of continuing review, review of amendments and/or unanticipated problems.

If any material changes have occurred without IRB review and approval, the IRB will decide the corrective action to be taken.

3.1.2 Consent Monitoring

In reviewing the adequacy of informed consent procedures for proposed research, the IRB may on occasion determine that special monitoring of the consent process by an impartial observer (consent monitor) is required in order to reduce the possibility of coercion and undue influence.

Such monitoring may be particularly warranted where the research presents significant risks to subjects, or if subjects are likely to have difficulty understanding the information to be provided. Monitoring may also be appropriate as a corrective action where the IRB has identified problems associated with a particular investigator or a research project.

If the IRB determines that consent monitoring is required, the IRB Chair and the Administrator will develop a monitoring plan and submit it to the Board for approval. The consent monitoring may be conducted by IRB staff, IRB members or another party, either affiliated or not with the Institution. The PI will be notified of the IRB’s determination and the reasons for the determination. Arrangements will be made with the PI for the monitoring of the consent process for a specified number of subjects. When observing the consent process, the monitor will determine:

· Whether the informed consent process was appropriately completed and documented,

· Whether the participant had sufficient time to consider study participation,

· Whether the consent process involved coercion or undue influence,

· Whether the information was accurate and conveyed in understandable language, and

· Whether the subject appeared to understand the information and gave their voluntary consent.

Following the monitoring, a report of the findings will be submitted to the IRB, which will determine whether and what action will be taken.

3.2 External Site Audits and Compliance Reviews

External directed audits and periodic compliance reviews may be conducted at external sites, where the Institution’s IRB serves as the “IRB of Record,” to assess compliance with federal, state, and local law, research subject safety, and IRB policies and procedures.

3.3 Reporting and Disposition

The results of all quality assurance activities are reported to the Administrator, the IRB Chair, and the Director of ORI. Non-compliance will be handled according the procedures articulated in later sections.

If an audit or review finds that subjects in a research project have been exposed to unexpected harm, the reviewer will promptly report such findings to the Administrator, the IRB Chair, and the Director of ORI for immediate action. The Director of ORI will report such incidents to the Institutional Compliance Office.

In the event that evidence of scientific or scholarly misconduct is found during an audit or investigation, that information will be reported in accordance with the OSU Policy on Scientific and Scholarly Misconduct.

3.4 IRB Internal Compliance Reviews

A periodic review of the IRB may be conducted by parties internal or external to OSU, but not affiliated with the IRB through membership, reporting lines, or appointment authority. The results of the review will be reported to the IO, the IRB Administrator, the IRB Chair(s), and the Director of ORI. The reviewer(s) will be sufficiently knowledgeable of IRB processes and procedures to carry out the following activities:

a) Review of the IRB minutes to determine that adequate documentation of meeting discussions has occurred. This review will include assessing the documentation surrounding the discussion for protections of vulnerable populations as well as other risk/benefit ratio and consent issues that are included in the criteria for approval;

b) Assess the IRB minutes to assure that quorum was met and maintained;

c) Assess the current adverse event reporting process;

d) Assess if privacy provisions have been adequately reviewed, discussed and documented in the IRB minutes;

e) Evaluate the continuing review discussions to assure they are substantive and meaningful and that no lapse has occurred since the previous IRB review;

f) Observe IRB meetings or other related activities;

g) Review IRB files to assure retention of appropriate documentation and consistent organization of the IRB file according to current policies and procedures;

h) Review the IRB database or electronic system to assure all fields are completed accurately;

i) Review of evaluations by the IRB members;

j) Verify IRB approvals for collaborating Institutions or external performance sites;

k) Verify that IRB and institutional policies and procedures have been followed;

l) Review other activities deemed appropriate by the IO.

The Administrator will review the results of internal compliance reviews with the IRB Chair, the Director of ORI, and the Institutional Official. If any deficiencies are noted in the review, a corrective action plan will be developed by the Administrator and approved by the Director of ORI, and by the Institutional Official. The Administrator will have responsibility for implementing the corrective action plan, the results of which will be evaluated by the Institutional Official.

3.5 Quality Improvement

All quality assurance reports, both research-related and IRB-related, will be reviewed by the Administrator, the Director of ORI, the IRB Chair, and the IO in order to determine if systemic changes are required in the IRB to prevent re-occurrence. If so, a corrective action plan will be developed, implemented and evaluated by the Administrator and IO.

4. Institutional Review Board

4.1 Policy

OSU has established an Institutional Review Board (IRB) to ensure the protection of human subjects involved in research conducted under the auspices of the Institution. All human subjects research conducted under the auspices of the Institution must be reviewed and approved (or acknowledged if exempt) by the IRB prior to the initiation of the research. The IRB will review proposed research involving human subjects for ethical considerations, scientific merit, and adherence to applicable federal regulations and IRB policies. The results from studies conducted without obtaining IRB approval may not be represented as having IRB approval and should not be published or used to satisfy the requirements for an undergraduate thesis, master's thesis or doctoral dissertation.

4.2 IRB Authority

The IRB derives its authority from the Federal Regulations and from OSU Institutional policy. Under the Federal Regulations, the IRB has the authority to:

a) Approve, require modifications to secure approval, or disapprove all research activities overseen and conducted under the auspices of the IRB;

b) Suspend or terminate approval of research not being conducted in accordance with the IRB’s requirements or that has been associated with unexpected serious harm to participants;

c) Observe, or have a third party observe, the consent process; and

d) Observe, or have a third party observe, the conduct of the research.

Research that has been reviewed and approved by the IRB may be subject to review and disapproval by officials of the Institution. However, those officials may NOT approve research if it has not been approved by the IRB. Institution officials may strengthen requirements and/or conditions, or add other modifications to secure Institutional approval or approval by another committee, or may disallow continuation of the research project, or of components of the project involving human subjects research. If the Institution requires changes to previously approved research proposals and/or consent forms, these documents must be re-reviewed and approved by the IRB before initiating those changes or modifications.

4.3 Number of Boards

OSU currently has two Boards. The IRB Administrator and the IRB Chairs will review the activity of the IRBs on at least an annual basis and make recommendations to the Director of ORI and the IO regarding any changes in the number of boards needed for the Institution.

4.4 Board (top) Composition

Each IRB shall have at least five members, with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the Institution.

The IRB shall be sufficiently qualified through the experience and expertise of its members, and the diversity of the members, including consideration of race, gender, and cultural backgrounds and sensitivity to such issues as community attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects.

In addition to possessing the professional competence necessary to review specific research activities, the IRB shall be able to ascertain the acceptability of proposed research in terms of Institutional commitments and regulations, applicable law, and standards of professional conduct and practice. The IRB shall therefore include persons knowledgeable in these areas.

If an IRB regularly reviews research that involves a vulnerable category of subjects, such as children, prisoners, pregnant women, or handicapped or mentally disabled persons, consideration shall be given to the inclusion of one or more individuals who are knowledgeable about and experienced in working with these subjects.

Every nondiscriminatory effort will be made to ensure that no IRB consists entirely of men or entirely of women, including the Institution's consideration of qualified persons of both sexes, so long as no selection is made to the IRB on the basis of gender. No IRB may consist entirely of members of one profession.

Each IRB shall include at least one member whose primary concerns are in scientific areas and at least one member whose primary concerns are in nonscientific[1] areas.

Each IRB shall include at least one member who is not otherwise affiliated[2] with the Institution and who is not part of the immediate family of a person who is affiliated with the Institution.

No IRB may have a member participate in the IRB's initial or continuing review of any project in which the member has a conflicting interest, except to provide information requested by the IRB.

An IRB may, in its discretion, invite individuals with competence in special areas to assist in the review of issues that require expertise beyond or in addition to that available on the IRB. These individuals may not vote with the IRB.

One member may satisfy more than one membership category.

On an annual basis, the IRB Chair and the Administrator shall review the membership and composition of the IRB to determine if they continue to meet regulatory and Institutional requirements. Required changes in IRB membership will be reported to the OHRP.

Members from one board may serve as expedited reviewers for another board, as needed.

4.5 Board Membership

The structure and composition of the IRB must be appropriate to the amount and nature of the research that is reviewed. Every effort is made to have member representation that has an understanding of the areas of specialty that encompasses most of the research performed at OSU.

In addition, the IRB will include members who are knowledgeable about and experienced working with vulnerable populations that typically participate in OSU research.

4.5.1 Appointment of Members to the IRB

The IRB Chair, Vice Chair and/or the Administrator of the IRB office, may identify a need for a new, replacement, or alternate member. Any Board or staff member may nominate candidates and provide the Administrator with the names of the nominees. Department Chairs may also forward nominations to the Institutional Official, the Administrator, or the IRB Chair. OSU faculty may also indicate their interest in serving on the Board by contacting the IRB Administrator or by selecting the IRB as one of their top choices in the faculty committee survey. Individuals selecting the IRB as one of their top three choices for Board service may be contacted by the IRB Administrator.

The final decision in selecting a new member is made by the Institutional Official, in consultation with the Director of ORI, the IRB Chair and the Administrator of the IRB office.

Appointments are made for a renewable three-year period of service. Any change in appointment, including reappointment or removal, requires written notification. Members may resign by written notification to the Chair or may be removed at the discretion of the IO.

4.5.2 Chair of the (top) IRB

The Institutional Official (IO) appoints the Chair and Vice Chair of the IRB to serve for renewable three-year terms. Any change in appointment, including reappointment or removal, requires written notification.

The IRB Chair should be a highly respected individual, from within the Institution, fully capable of managing an IRB, and the matters brought before it with fairness and impartiality. The task of making the IRB a respected part of the Institutional community will fall primarily on the shoulders of the Chair. The IRB must be perceived to be fair, impartial and immune to pressure by the Institution's administration, the investigators whose protocols are brought before it, and other professional and nonprofessional sources.

The IRB Chair is responsible for conducting the meetings and they are signatories for correspondence generated by the IRB. The IRB Chair may designate the Administrator or other IRB members to perform duties, as appropriate, for review, signature authority, and other IRB functions.

The IRB Chair advises the Institutional Official and the Administrator of the IRB office about IRB member performance and competence.

The performance of the IRB Chair will be reviewed on an annual basis by the Administrator of the IRB office in consultation with the Institutional Official. Feedback from this evaluation will be provided to the Chair. If a Chair is not acting in accordance with the IRB’s mission, policies or procedures, has an undue number of absences, or not fulfilling the responsibilities of the Chair, he/she may be removed by and at the discretion of the IO.

4.5.3 Vice Chair of the IRB

The Vice Chair serves as the Chair of an IRB in the absence of the Chair and has the same qualifications, authority, and duties as Chair. In addition, the Vice Chair is responsible for the organization and presentation of continuing education offered to IRB members at full board meetings.

4.5.4 Alternate members

The appointment and function of alternate members is the same as that for primary IRB members, and the alternate's expertise and perspective are comparable to those of the primary member. The role of the alternate member is to serve as a voting member of the IRB when the regular member is unavailable to attend a convened meeting or may attend according to a pre-arranged schedule (e.g., every other meeting). When an alternate member substitutes for a primary member, the alternate member will receive and review the same materials prior to the IRB meeting that the primary member received or would have received.

The IRB roster identifies the primary member(s) for whom each alternate member may substitute. The alternate member will not be counted as a voting member unless the primary member is absent. The IRB minutes will document when an alternate member replaces a primary member.

4.5.5 Subcommittees of the IRB

The IRB Chair, in consultation with the Administrator, may designate one or more IRB subcommittees to perform duties, as appropriate, to review and undertake IRB functions, and to make recommendations to the IRB. The number and composition of the IRB Subcommittee members shall depend on the authority delegated by the IRB Chair to such IRB Subcommittee (e.g., limited to making recommendations versus decision-making authority).

4.6 IRB Member Conflict of Interest[3]

Relevant regulation(s): §46.107(e) No IRB may have a member participate in the IRB's initial or continuing review of any project in which the member has a conflicting interest, except to provide information requested by the IRB.

No regular, alternate, or ex officio member may participate in the review of any research project in which the member has a conflict of interest (COI), except to provide information as requested by the Chair or other members present. It is the responsibility of each IRB voting and non-voting member to disclose any COI in a study submitted for review and recuse him/herself from the deliberations and vote.

OSU IRB members and consultants are responsible for disclosing to the Board any actual, potential, or perceived conflicts of interest (COI) concerning protocols reviewed by the IRB.

The Chair will ask the Board if any member present has a potential conflict of interest with any investigator or protocol that is under consideration on the day's agenda. This COI query by the Chair will be recorded in the minutes, along with any declarations of COI made by the members/consultants.

In the event that a member believes that she or he cannot provide an independent review, that member will leave the meeting room prior to final deliberation on that protocol. They will not vote on the outcome of the review, nor will they comment on the protocol unless relevant information is requested by a Board member. Members and consultants with conflicts of interest will leave the meeting room prior to the Board’s final deliberation and vote. If quorum is lost as a result, the protocol will be tabled until the next convened meeting of the Board. Their exit and re-entrance will be recorded in the minutes as a recusal.

If any member discloses a conflicting interest but indicates that they are able to provide an independent review, Board members will discuss the conflict and make a determination regarding the need for recusal. If there is disagreement on the need for recusal, the issue will be put to a vote. All members, including the member with the potential conflict may participate in the vote.

An IRB member or consultant may be considered to have a conflicting interest requiring recusal when they, or member of their family (top) [4], has any of the following:

a) Substantive involvement in the design, conduct, or reporting of the research

b) Direct supervisory line or mentorship of member of the study team

c) Ownership interest, stock options, or other financial interest related to the research

d) Agreement to receive compensation related to the research

e) Proprietary interest related to the research including, but not limited to, a patent, trademark, copyright or licensing agreement

f) Board or executive relationship related to the research

g) Any other reason for which the member/consultant believes that he or she cannot provide an independent review or which may lend itself to the perception of a conflicted interest. Reasons may include personal or professional relationships, minor consultation on study design.

IRB members are responsible for self-identifying any conflicting interests to the IRB Office before conducting review using the expedited procedure, so as to remove themselves’ from involvement in the review of the research.

(top) 4.7 Duties of IRB Members

Members of the IRB and their designated alternates are expected to:

Attend and participate in the majority of the convened IRB meetings;
Review all materials provided in each meeting packet in advance of the convened meetings they attend;
Review all materials relevant to study proposals assigned to them for an expedited review;
Review and promptly inform the IRB staff of corrections or additions to convened board meeting minutes;
Treat the research proposals, protocols, and supporting data confidentially

(top) 4.8 Attendance Requirements

Members should attend all meetings for which they are scheduled. If a member is unable to attend a scheduled meeting, they should inform the IRB office. If the inability to attend will be prolonged, a request for an alternate to be assigned may be submitted to the Chair or the Administrator.

If an IRB member is to be absent for an extended period of time, such as for a sabbatical, he or she must notify the IRB at least 30 days in advance so that an appropriate replacement can be obtained. The replacement can be temporary, for the period of absence, or permanent if the member is not returning to the IRB. If the member has a designated alternate, the alternate can serve during the primary member’s absence, provided the IRB has been notified in advance.

(top) 4.9 Education for IRB Members

A vital component of a comprehensive human research protection program is an education program for IRB members. OSU is committed to providing training and an on-going educational process for IRB members and the staff of the IRB office, related to ethical concerns and regulatory and Institutional requirements for the protection of human subjects.

4.9.1 Orientation

New IRB members, including alternate members will meet with the IRB Chair and/or the Administrator for an informal orientation session. At the session, the new member will be given a binder that includes:

· Belmont Report and Nuremberg Code;

· OSU Policies and Procedures for the Protection of Human Subjects;

· Federal regulations relevant to the IRB

· Guidance documents relevant to the IRB

New members are required to complete the Initial Education requirement for IRB members before they may serve as a primary reviewer.

4.9.2 Initial Education

IRB members will complete the relevant modules in the CITI Course.

4.9.3 Continuing Education

To ensure that oversight of human research is ethically grounded and the decisions made by the IRB are consistent with current regulatory and policy requirements, training is continuous for IRB members throughout their service on the IRB. Educational activities include, but are not limited to:

· In-service training at IRB meetings;

· Annual retreats;

· Copies of appropriate publications;

· New information that might impact the IRB, including laws, regulations, policies, procedures, and emerging ethical and scientific issues;

· Unlimited access to the IRB office resource library.

Other training opportunities will be considered by the IO on a case-by-case basis, including attendance at the annual PRIM&R conference or regional conferences on human research protections.

4.10 Review of IRB Member Performance

The IRB Members’ performance will be reviewed on an annual basis. IRB members will receive formal feedback on the results of this review, and exemplary service will be recognized by the IO in writing. The quality of service will be measured by engaged attendance and timeliness of reviews. Performance evaluations will be conducted by the Chair and Administrators and submitted to the IO for consideration. Members who are not acting in accordance with the IRB’s mission or policies and procedures or who have an undue number of absences may be removed at the discretion of the IO.

(top) 4.11 Liability Coverage for IRB Members

The Institution’s insurance coverage applies to employees and any other person authorized to act on behalf of the Institution or acts or omissions within the scope of their employment or authorized activity.

4.12 Use of Consultants

When necessary, the IRB Chair or the Administrator of the IRB office may solicit individuals from the Institution or elsewhere with competence in special areas to assist in the review of issues or protocols, which require appropriate scientific or scholarly expertise beyond or in addition to that available on the IRB. The need for an outside reviewer is determined in advance of the meeting by the Administrator or the Chair by reviewing the protocols scheduled to be reviewed at the convened meeting. The IRB office will ensure that all relevant materials are provided to the outside reviewer prior to the convened meeting.

Written statements of consultants will be kept in IRB records. Key information provided by consultants at meetings will be documented in the minutes. Written reviews provided by the outside reviewer will be filed with the protocol.

The Administrator of the IRB office reviews the conflicting interest policy for IRB members with consultants.

The consultant’s findings will be presented to the full board for consideration either in person or in writing. If in attendance, these individuals will provide consultation but may not participate in the vote.

Ad hoc or informal consultations requested by individual members (rather than the full board) will be requested in a manner that protects the researcher’s confidentiality and is in compliance with the IRB conflict of interest policy (unless the question raised is generic enough to protect the identity of the particular PI and research protocol).

4.13 Reporting and Investigation of Allegations of Undue Influence

If an IRB Chair, member, or staff person feels that the IRB has been unduly influenced by any party, they may work with the Administrator to make a confidential report to the Institutional Official (IO). In the event that the Administrator is conflicted, the complainant may work with the Director of ORI to make the report to the IO. If both the Administrator and Director are conflicted, the complainant may make the report directly to the IO. If the IO is conflicted, the complainant may make the report directly to the University President. In any event, the report will follow the chain of IRB authority (i.e., Administrator and/or Chair, then Director of ORI, then IO, then the University President), rather than supervisory reporting lines.

The official receiving the report will conduct a thorough investigation and, when necessary, take corrective action to prevent additional occurrences.

5. Records and Documentation

5.1 Policy

IRB shall prepare and maintain adequate documentation of the IRB’s activities. All records must be accessible for inspection and copying by authorized representatives of the FDA, OHRP, sponsors, and other authorized entities at reasonable times and in a reasonable manner.

OSU IRB documents are not signed by the Chairperson or designee. Federal regulations do not require signatures on approval documents (see FDA Factsheet FAQ 1998). Therefore, the OSU IRB documents meet the regulatory requirements for notifications.

5.1.1 IRB Records

IRB records include, but are not limited to:

a) Written operating procedures

b) IRB membership rosters

c) Records of research investigators, IRB members, and IRB staff that have fulfilled the Institution’s ethics/compliance training requirements

d) IRB correspondence (other than protocol related)

e) IRB Study Files

f) Documentation of Emergency Exemption from Prospective IRB Approval (21 CFR 56.104(c))

g) Documentation of Exceptions from Informed Consent Requirements for Emergency Use of a Test Article (21 CFR 50.23)

h) Documentation of exemptions

i) Documentation of convened IRB meetings minutes

j) Documentation of review by another Institution’s IRB when appropriate

k) Documentation of cooperative review agreements, e.g. Memoranda of Understanding (MOUs)

l) Federal Wide Assurances

m) Protocol violations submitted to the IRB

n) Quality assurance reviews

5.2 IRB Study Files

The IRB will maintain a separate IRB study file for each research application (protocol) that it receives for review. Protocols will be assigned a unique identification number by the IRB Administrative Staff and entered into the IRB tracking system.

The IRB maintains a separate file for each research protocol that includes (when applicable), but is not limited to:

a) Protocol and all other documents submitted as part of a new protocol application

b) Protocol and all other documents submitted as part of a request for continuing review/termination of research application. This also includes progress reports, statements of significant new findings provided to participants, reports of injuries to subjects

c) Documents submitted and reviewed after the study has been approved, including reports of modifications to research/amendments and adverse event reports

d) Copy of IRB-approved Consent Form

e) DHHS-approved sample consent form document and protocol, when they exist

f) Review forms from IRB members (if exempt or expedited), scientific reviews, and consultants. Review forms are to be used as a guide for full board studies and not a reflection of final determinations.

g) Documentation of type of IRB review

h) Documentation of any determinations required by the regulations and protocol-specific findings supporting those determinations, including: waiver or alteration of the consent process, research involving pregnant women, fetuses, and neonates, research involving prisoners, and research involving children

i) Documentation of all IRB review actions

j) Notification of expiration of IRB approval to the PI and instructions for submitting relevant continuing review materials

k) Notification of suspension of research

l) Correspondence pertaining to appeals

m) Copies of approval letters and forms that describe what Principal Investigator must have before beginning the study

n) IRB correspondence to and from research investigators

o) All other IRB correspondence related to the research

p) For devices, a report of prior investigations

q) Reports of unanticipated problems involving risk to subjects or others and adverse events

r) Documentation of audits, investigations, reports of external site visits

5.3 The IRB Minutes

It is the responsibility of the IRB Coordinator present to record the proceedings and take minutes of the meeting. The audio recording of the each meeting is destroyed after the minutes for that meeting are approved.

Proceedings must be written and available for review by the next regularly scheduled IRB meeting date. Once approved by the members at a subsequent IRB meeting, the minutes must not be altered by anyone, including a higher Institutional authority.

A copy of the minutes for each IRB meeting will be distributed to the IO via the meeting agenda packet.

Minutes of IRB meetings must contain sufficient detail to show each of the items below, as applicable:

a) Attendance

i. Names of members present

ii. Names of members or alternate members who are participating through videoconference or teleconference and documentation that those attending through videoconferencing or teleconferencing received all pertinent material prior to the meeting and were able to actively and equally participate in all discussions

iii. Names of alternates attending in lieu of specified (named) absent members. (Alternates may substitute for specific absent members only as designated on the official IRB membership roster)

iv. Names of consultants present

v. Name of investigators present

vi. Names of guests present

Note: The initial attendance list shall include those members present at the beginning of the meeting. The minutes will indicate, by name, those members who enter or leave the meeting. The vote on each action will reflect those members present for the vote on that item. Members who recuse themselves because of conflict of interest are listed by name and the reason documented.

b) The presence of a quorum throughout the meeting, including the presence of one member whose primary concern is in a non-scientific area

c) Business Items discussed

d) Continuing Education

e) Actions taken, including separate deliberations, actions, and votes for each protocol undergoing initial review, continuing review, or review of modifications by the convened IRB

f) Votes on these actions (Total Number Voting; Number voting for; Number voting against; Number abstaining; Number of those excused, Number of those recused)

g) Basis or justification for these actions including required changes in research

h) Summary of controverted issues and their resolution

i) Approval period for initial and continuing approved protocols, including identification of research that warrants review more often than annually and the basis for that determination

j) Risk level of initial and continuing approved protocols

k) Review of interim reports, e.g. unanticipated problems or safety reports; amendments; report of violation/deviations; serious or continuing non-compliance; suspensions/terminations, etc.

l) Review of Data and Safety Monitoring Board (DSMB) summary

m) Review of Plans for Data and Safety Monitoring

n) Justification of deletion or substantive modification of information concerning risks or alternative procedures contained in the DHHS-approved sample consent document.

o) Protocol-specific documentation that the research meets the required criteria [45 CFR 46.116(d)] when approving a consent procedure that does not include or that alters some or all of the required elements of informed consent, or when waiving the requirement to obtain an informed consent

p) Protocol-specific documentation that the research meets the required criteria [45 CFR 46.117(c)] when the requirements for documentation of consent are waived

q) When approving research that involves populations covered by Subparts B, C, or D of 45 CFR 46, the Minutes will document the IRB’s justifications and findings regarding the determinations stated in the Subparts or the IRB’s agreement with the findings and justifications as presented by the investigator on IRB forms.

r) Special protections warranted for other groups of subjects who are likely to be vulnerable to coercion or undue influence, such as mentally disabled persons, or economically or educationally disadvantaged persons, regardless of source of support for the research.

s) The rationale for significant risk/non-significant risk device determinations.

t) Determinations of conflict of interest.

u) Identification of any research for which there is need for verification from sources other than the investigator that no material changes are made in the research.

v) A list of research approved since the last meeting utilizing expedited review procedures.

w) An indication that, when an IRB member has a conflicting interest with the research under review, the IRB member was not present during the deliberations or voting on the proposal, and that the quorum was maintained.

x) Key information provided by consultants will be documented in the minutes or in a report provided by the consultant

5.4 IRB Minutes and Public Records Requests

IRB meeting minutes are subject to the Oregon Public Records Rule. Rules regarding public records requests made to OSU are available in OSU’s Oregon Administrative Rules, at 576-004-0000 through 576-004-00020. All requests should be made directly to the Office of General Counsel. The procedures are available on the OSU website and Requests for OSU public records may be made by e-mail to this address: [email protected].

5.5 IRB Membership Roster

A membership list of IRB members must be maintained; it must identify members sufficiently to describe each member's chief anticipated contributions to IRB deliberations. The list must contain the following information about members:

a) Name

b) Gender

c) Earned degrees

d) Affiliated or non-affiliated status (neither the member nor an immediate family member of the member may be affiliated with the Institution)

e) Status as scientist (physician-scientist, other scientist, non-scientist or social behavioral scientist).

f) Representative capacities of each IRB member; which IRB member is a prisoner representative (as required by Subpart C), and which IRB members are knowledgeable about or experienced in working with children, pregnant women, cognitively impaired individuals, and other vulnerable populations locally involved in research.

g) Role on the IRB (Chair, Co-Chair, etc.)

h) Voting status (Any ex officio members are non-voting members)

i) For alternate members, the primary member or class of members for whom the member could substitute

The IRB office must keep IRB membership list current. The Administrator of the IRB office must promptly report changes in IRB membership to the Office for Human Research Protections, Departments of Health and Human Services.

5.6 Documentation of Exemptions

Documentation of verified exemptions consists of the reviewer’s citation of a specific exemption category and written concurrence that the activity described in the investigator’s request for satisfies the conditions of the cited exemption category. The exempt determination is reported at the next convened IRB meeting and documented in the Minutes.

5.7 Documentation of Expedited Reviews

IRB records for initial and continuing review by the expedited procedure must include: the specific permissible category; that the activity described by the investigator satisfies all of the criteria for approval under expedited review; the approval period and any determinations required by the regulations including protocol-specific findings supporting those determinations.

5.8 Access to IRB Records

The IRB has policies and procedures to protect the confidentiality of research information:

a) When unattended, all paper IRB records are kept secure in locked cabinets or locked storage rooms.

b) Ordinarily, access to all IRB records is limited to the Director of ORI, IRB Chair, IRB members, IRB Administrator, IRB staff, authorized Institutional official, and officials of Federal and state regulatory agencies (OHRP, FDA). Research investigators are provided reasonable access to files related to their research. Appropriate accreditation bodies are provided access and may recommend additional procedures for maintaining security of IRB records. All other access to IRB records is limited to those who have legitimate need for them, as determined by the IO and Director.

c) Records are accessible for inspection and copying by authorized representatives of Federal regulatory agencies during regular business hours.

d) IRB staff will provide copies of records for authorized personnel if requested.

e) All other access to IRB study files is prohibited.

5.9 Record Retention

OSU’s IRB has adopted a consistent and conservative approach to the retention of human subjects research review records. A list of relevant references appears at the end of this section. All research-related records, regardless of funding source and review level, will be retained for a minimum of seven years post-study termination.

All records described in this policy shall be accessible for inspection and copying by authorized representatives of the IRB, by authorized representatives of the federal funding agency, if any, and any federal oversight body with relevant authority.

Records retained by the IRB. Records document the review of research proposals that involve the use of human subjects. Reviews may be made by the entire review board (IRB), by selected members, the board’s chair, or by IRB staff. Records will be retained for seven years post-study termination and may include, but are not limited to; approved protocols and consent forms; samples and/or approved test instruments; copies of grant proposals; review summaries; and related memoranda and correspondence.

IRB minutes are retained permanently. The electronic (born-digital) version is considered the record copy.

In accordance with 45 CFR 46.115 and 21 CFR 56.115, the IRB shall also prepare and maintain adequate documentation of IRB activities, including the following:

· Copies of all research proposals reviewed, scientific evaluations, if any, that accompany the proposals, approved sample consent documents, progress reports submitted by investigators, and reports of injuries to subjects.

· Minutes of IRB meetings.

· Records of continuing review activities.

· Copies of all correspondence between the IRB and the investigators.

· A list of IRB members in the same detail as described in 45 CFR 46.103(b)(3).

· Written procedures for the IRB in the same detail as described in 45 CFR 46.103(b)(4) and 45 CFR 46.103(b)(5), 21 CFR 56.108(a) and (b).

· Statements of significant new findings provided to subjects, as required by 45 CFR 46.116(b)(5) and 21 CFR 50.25.

Records retained by the Principal Investigator. The principal investigator shall have primary responsibility for curating their research records for a minimum of seven years post-study termination, including signed consent forms and completed surveys, research notebooks, as well as digital records or other media form.

For FDA-regulated research. In accordance with 21 CFR 312, an investigator or sponsor shall retain the records and reports for 2 years after a marketing application is approved for the drug; or, if an application is not approved for the drug, until 2 years after shipment and delivery of the drug for investigational use is discontinued and FDA has been so notified.

In accordance with 21 CFR 812, An investigator or sponsor shall maintain the records required by this subpart during the investigation and for a period of 2 years after the latter of the following two dates: The date on which the investigation is terminated or completed, or the date that the records are no longer required for purposes of supporting a premarket approval application or a notice of completion of a product development protocol.

Departing faculty. In the event of exigent circumstances where the investigator cannot retain research records, or if the investigator intends to leave their position at the university, the investigator and their Department Head or Dean (not the IRB) should identify the successor responsible for maintaining those Institutional records, and for determining whether the original records or verified copies shall be retained by the university. In the event a researcher leaving their position at the university removes the original research data from the university, they must leave a verified copy and agree to provide access to the university to the original data, as well as to other individuals or entities having a legitimate need for access.

Relevant references:

· 45 CFR 46.115 IRB Records

· 21 CFR 56.115 IRB Records

· 21 CFR 312 Investigational New Drug Application

· 21 CFR 812 Investigational Device Exemptions

· 42 CFR 93.317 Retention and custody of the research misconduct proceeding record

· OMB Circular A-110 Uniform Administrative Requirements for Grants and Agreements With Institutions of Higher Education, Hospitals, and Other Non-Profit Organizations (part 50, Reports and Records)

· US Department of Health and Human Services, Office of Research Integrity, on Responsible Conduct of Research – Lab Management/Notebook and Data Management

6. IRB Review Process

6.1 Sponsored Research

6.1.1 Policy

It is OSU’s policy that any sponsored research conducted under the auspices of the Institution is conducted in accordance with federal guidelines and ethical standards.

The following describe the procedures required to ensure that all sponsored research meets this requirement.

6.1.2 Definitions

Sponsor. Sponsor means the company, Institution, individual donor, or organization responsible for the initiation, management, or financing of a research study.

Sponsored research. Sponsored research means research funded by external entities through a grant or contract that involves a specified statement of work (e.g., the research proposal) with a related transfer of value to the sponsor, including clinical trials involving investigational drugs, devices or biologics.

6.1.3 Responsibility (top)

1) Grants and contracts will be reviewed by the IRB staff for the following:

a) Indication that the information in the grant or contract is consistent with the protocol and consent form.

b) Indication that the investigator will follow the protocol, applicable regulations and its ethical standards.

c) Identification of entity responsible for research related injuries.

d) Indication that, if monitored and the study monitor uncovers information that could affect the safety of participants or their willingness to continue participation, influence the conduct of the study, or alter the IRB’s approval to continue the study, the sponsor will make sure that the information is communicated to the IRB.

e) Indication that if the sponsor discovers results that could affect the safety or care of subjects, the sponsor will make sure the IRB is notified.

f) Conflicts of interest, including those related to recruitment incentives (see “finders fees” and “bonus payments”).

2) The IRB will forward a copy of the approval letter to the Office of Sponsored Programs and the Office of Post Award Administration for any sponsored research, regardless of funding source.

6.2 Conflict of Interest in Research

6.2.1 Policy

It is the IRB’s policy to preserve public trust in the integrity and quality of research at the Institution by minimizing actual or perceived conflict of interest in the conduct of research.

The following describe the procedures by which this responsibility is carried out.

(top) 6.2.2 Definitions

Conflict of Interest. A financial or other business interest in the source(s) of funding, materials, or equipment related to a research study. These interests are exclusive of the costs of conducting the research.

Examples of potential conflicts of interest in research involving human subjects may include, but are not limited to:

An investigator or family member participates in research on a technology, process or product owned by a business in which the faculty member holds a financial interest. Any interest should be disclosed to the IRB, regardless of whether it meets the threshold of a “significant financial interest,” as defined by the Public Health Service (PHS).
An investigator or family member has a financial or other business interest in an entity that is supplying funding, materials, products, or equipment for the current research project.
An investigator or family member serves on the Board of Directors of a business that is supplying funding, materials, products, or equipment for the current research project.
An investigator receives consulting income from an entity that is funding the current research project.
An investigator participates in research on a technology, process or product developed for which the investigator has intellectual property rights (e.g., copyrights, trademarks, patents, or trade secrets) or receives royalties.

Non-financial Conflict of Interest. Non-financial conflict of interest may exist when an individual serves dual roles, such as health care provider and investigator. Other interests such as publication, promotion or tenure, can also become conflicts of interest that may affect an individual's judgment. Membership in oversight committees, such as the IRB, as well as positions of authority may pose potential conflicts of interest. Any position that includes responsibilities for the review and approval of research projects or contracts other than his/her own may potentially affect the design of, decisions made and/or action taken surrounding a specific study.

Investigator. For the purposes of this policy, “investigator” refers to any member of the study team or a member of their immediate family.

Equity Interest. Stock, stock options or ownership interest as determined through reference to public prices or other reasonable measures of fair market value during the time the investigator is carrying out the study and for 1 year following completion of the study.

Immediate Family Member. Immediate family member is defined as anyone having a relationship to a person as a spouse or domestic partner; the parent, child, or sibling of the individual or domestic partner; or any person for whom the individual has a legal support obligation.

6.2.3 Investigator Conflicts of Interest

These procedures apply to both financial and non-financial conflicts of interest and promote objectivity in research to ensure conflict of interests do not adversely affect the protection of participants.

For clinical studies involving the use of new human drugs and biological products or medical devices, certifications and disclosure requirements are defined in Food and Drug Administration (FDA) regulations, Title 21 CFR Part 54.

Conflicts of interest should be eliminated when possible and effectively disclosed and managed when they cannot be eliminated.

The research application asks protocol-specific questions regarding conflict of interest for all study team members and their immediate family members. Applications that are received by the IRB which include a disclosure of a conflict of interest are forwarded to the COI Administrator for review. The study file is accessible to COI Committee while under review and after it has been approved. IRB approval may be issued prior to a determination from the COI Committee if the IRB has reviewed the relevant details and finds that the matter is appropriately managed within the protocol and, if applicable, the consent process.

6.2.3.1 Evaluation of COI

At initial review of the research protocol and COI disclosure, the IRB also determines whether the financial or non-financial interest affects the protections of research participants.

6.2.3.2 Management of COI

The IRB will determine if the rights and welfare of human research participants will be better protected by one or more of the following:

1. Disclosure to subjects through the consent process

2. Modification of the research protocol or safety monitoring plan

3. Monitoring of research by independent reviewers

4. Disqualification of the conflicted party from participation in all or a portion of the research

5. Appointment of a non-conflicted Principal Investigator

6. Prohibition of the conduct of the research at OSU

6.2.4 Recruitment Incentives

Payment arrangements among sponsors, organizations, investigators, and those referring research participants may place participants at risk of coercion or undue influence or cause inequitable selection. Payment in exchange for referrals of prospective participants from researchers (physicians) (“finder’s fees”) is not permitted. Similarly payments designed to accelerate recruitment that is tied to the rate or timing of enrollment (“bonus payments”) is also not permitted.

(top) 6.2.5 Institutional Conflict Of Interest

The policy of the IRB is to ensure that the welfare of human subjects and the integrity of research will not be compromised, or appear to be compromised, by competing Institutional interests or obligations.

Although the IRB policy has separated OSU Foundation functions from the University functions, circumstances may exist in which separation of function is not sufficient to avoid the appearance of Institutional conflict of interest.

6.2.6 Identification of Institutional Conflict of Interest

The Conflict of Interest Committee will make all disclosures and management plans accessible to the IRB Administrator and Chair. If the Administrator and Chair determine that the I-COI is related to the research, information about the I-COI will be disclosed to all IRB members for consideration regarding the impact on new or ongoing studies.

6.2.7 Management of Conflict of Interest

6.2.7.1 Decision making

A key aspect in decision-making is to analyze when it would be appropriate and in the public interest to accept and manage a COI, rather than require that the COI be eliminated prior to the initiation of research. In some cases, the benefits of conducting a proposed research activity at the Institution will be potentially high, and the risks will be low. In other cases, the scientific advantages of conducting the research may be speculative and the risks may be great. In these latter instances, the conflict should be avoided by disapproving the research application.

6.2.7.2 Evaluation of risk

Each case should be evaluated based upon the following:

a) The nature of the science;

b) The nature of the interest;

c) How closely the interest is related to the research;

d) The degree of risk that the research poses to human participants; and

e) The degree to which the interest may be affected by the research.

6.2.7.3 Potential actions

Potential actions to be considered to better protect subjects are any (or a combination) of the following:

a) Public disclosure of the financial interest;

b) Not conducting proposed research at that Institution, or halting it if it has commenced;

c) Reducing or otherwise modifying the financial (equity or royalty) stake involved;

d) Increasing the segregation between the decision-making regarding the financial and the research activities;

e) Requiring an independent data and safety monitoring committee or similar monitoring body; or

f) Establishing a research monitoring process, so that the research can be closely scrutinized to ensure that potential conflicts do not undermine the integrity of the work and of the Institution.

6.3 Levels of Review

All human subjects research conducted under the auspices of OSU must meet the criteria for one of the following methods for review:

· Exempt

· Expedited Review

· Full Committee Review

The IRB will ensure that the research meets all required ethical and regulatory criteria for initial and continuing review and any modifications of approved research.

The following describe the procedures required for the review of research by the IRB.

(top) 6.4 Exempt Studies

Studies determined to be “exempt” are acknowledged rather than approved by the IRB. Before they will be acknowledged, exempt studies must be found to be ethical and in compliance with the policies articulated in this manual. Although exempt research is not covered by the federal regulations, the ethical principles articulated in the Belmont Report continue to apply. The individual making the determination of exemption will determine whether to require additional protections for subjects in keeping with the Belmont Report.

Exempt determinations are made by the Chair of the IRB or his/her designee. The designee may be a voting member of the board or an IRB staff member (regardless of voting status). Identification of the designee will be made in writing.

In order to be deemed exempt, all research activities must fit into one or more of the exempt categories.

6.4.1 Limitations on Exemptions

Children: Exemption for research involving survey or interview procedures or observations of public behavior does NOT apply to research in children, except for research involving observations of public behavior when the investigator does not participate in the activities being observed.

Prisoners: Exemptions do NOT apply. Full board review is required. Expedited categories 8 and 9 may apply to continuing reviews.

Risk: If the study presents a risk not articulated in the categories of exemption, such as the risk of causing distress to the subject, the IRB may review the study by an expedited or full board procedure.

6.4.2 Categories of Exempt Research

With the above exceptions, research activities not regulated by the FDA in which the only involvement of human subjects will be in one or more of the following categories are exempt from full board review:

1. Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as:

a) Research on regular and special education instructional strategies, or

b) Research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.

2. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless:

a) Information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and

b) Any disclosure of the human subjects' responses outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subject’s financial standing, employability, or reputation.

Note: At the discretion of the IRB, non-federally funded studies qualifying for an exemption in this category may include activities that supplement or help to inform procedures in this category. Additional activities must be without risk and physically passive in nature. The inclusion of additional activities that are physically active in nature, such as performing a task, will generally result in the study being reviewed by an expedited procedure.

Examples of passive tasks include: watching a video, looking at pictures, listening to an audio file or lecture, free listing, mapping activities, and computer programming or software testing as long as these activities supplement or inform the tests, surveys, or interviews.

Examples of active tasks: engaging in a physical activity such as walking, riding, driving, or exercise.

3. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior that is not exempt under paragraph (2), if:

a) The human subjects are elected or appointed public officials or candidates for public office; or

b) Federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.

The “note” in exempt category 2 above applies here as well.

4. Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.

Note: In order to be eligible for this exemption, all of the materials have to exist at the time the research is proposed.

5. Research and demonstration projects which are conducted by or subject to the approval of federal department or agency heads, and which are designed to study, evaluate, or otherwise examine:

a) Public benefit or service programs;

b) Procedures for obtaining benefits or services under those programs;

c) Possible changes in or alternatives to those programs or procedures; or

d) Possible changes in methods or levels of payment for benefits or services under those programs.

e) The program under study must deliver a public benefit (e.g., financial or medical benefits as provided under the Social Security Act) or service (e.g., social, supportive, or nutrition services as provided under the Older American Act).

f) The research demonstration project must be conducted pursuant to specific federal statutory authority, there must be no statutory requirements of IRB review, the research must not involve significant physical invasions or intrusions upon the privacy of subjects’, and the exemption must be invoked only with authorization or concurrence by the funding agency.

6. Taste and food quality evaluation and consumer acceptance studies,

a) If wholesome foods without additives are consumed; or

b) If a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.

6.4.3 FDA Exemptions

The following categories of clinical investigations are exempt from the requirements of IRB review:

a) Emergency use of a test article, provided that such emergency use is reported to the IRB within 5 working days. Any subsequent use of the test article at the Institution is subject to IRB review. [21 CFR 56.104(c)]

b) Taste and food quality evaluations and consumer acceptance studies, if wholesome foods without additives are consumed or if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural, chemical, or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture. [21 CFR 56.104(d)]

(top) 6.4.4 Procedures for Exemption Determination

Exempt determinations may take place during a meeting between the IRB Chair (or designee) and the Principal Investigator, or they can take place via electronic submission. Regardless of the setting for the review, investigators must submit:

a) The appropriate IRB application;

b) All recruitment materials (e.g., letter of invitation, recruitment script, flyer),

c) Consent form (when appropriate),

d) All surveys, questionnaires, instruments, etc.,

e) Letter(s) of support from each non-OSU site of performance (when appropriate)

f) If sponsored, one copy of the grant application(s) and/or contract

All members of the research team must have completed the required ethics training.

The IRB Chair (or designee) reviews all requests for exemptions and determines whether the request meets the criteria for exempt research.

To document the IRB reviewer’s determination of exempt status, he/she completes the appropriate reviewer worksheet. The IRB reviewer verifies whether the submission meets the definition for both research and human subject. The reviewer indicates whether the project is exempt. If the project is determined to be exempt, the reviewer will also note the rationale for the determination by identifying the category under which it was permitted.

Any issues related to the project will be communicated to investigators in writing, in person, or over the phone. Depending upon the nature of the issues, the IRB could designate any of the following individuals or groups of individuals to determine that the issues have been resolved:

The IRB Chairperson or designee for exempt reviews;
Another IRB member or group of IRB members with particular subject matter expertise or experience;
A consultant with particular subject matter expertise who is not an IRB member; and/or
The IRB Administrator or other qualified IRB administrative staff person, who need not be an IRB member.

This designation must be appropriate to the type and nature of the issues. Once determined to be resolved, the IRB staff may issue a Notification of Exemption to the investigator. In the event that the resolution of issues was to be verified by the Administrator or IRB staff, the notification may be issued without further review by the Chair or designee.

Annual renewal applications are not required for exempt research. The exemption is valid for five years[5]. If the research extends beyond that date then the researcher must submit new application materials and request another exempt determination. Investigators should submit a final report on or before the expiration date.

The Chair or designee will review all new exempt applications and project revisions by the above procedure. Final reports will be reviewed and acknowledged by the Administrator or IRB staff. Reportable events, such as deviations and unanticipated events, will be reviewed by the procedure described for review of those events regardless of review level.

Decisions related to exempt studies will be communicated in writing to the investigator and the IRB. Documentation must include the specific categories justifying the exemption.

All members of the IRB will be apprised of all exempt determinations via written monthly reports. Any IRB member can request to review the full protocol by contacting the IRB Office.

6.5 Expedited Review

An IRB may use the expedited review procedure to review either or both of the following:

1. Some or all of the research appearing on the list of categories of research eligible for expedited review and found by the reviewer(s) to involve no more than minimal risk,

2. Minor changes in previously approved research during the period (of one year or less) for which approval is authorized

Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.

6.5.1 Categories of Research Eligible for Expedited Review

[63 FR 60364-60367, November 9, 1998]

The activities listed below should not be deemed to be of minimal risk simply because they are included on this list. Inclusion on this list merely means that the activity is eligible for review through the expedited review procedure when the specific circumstances of the proposed research involve no more than minimal risk to human subjects.

The categories in this list apply regardless of the age of subjects, except as noted.

The expedited review procedure may not be used where identification of the subjects and/or their responses would reasonably place them at risk of criminal or civil liability or be damaging to the subjects financial standing, employability, insurability, reputation, or be stigmatizing, unless reasonable and appropriate protections will be implemented so that risks related to invasion of privacy and breach of confidentiality are no greater than minimal.

The expedited review procedure may not be used for classified research involving human subjects.

The standard requirements for informed consent (or its waiver, alteration, or exception) apply regardless of the type of review--expedited or convened--utilized by the IRB.

Research Categories one (1) through seven (7) pertain to both initial and continuing IRB review:

1. Clinical studies of drugs and medical devices only when condition (a) or (b) is met.

a) Research on drugs for which an investigational new drug application (21 CFR Part 312) is not required. (Note: Research on marketed drugs that significantly increases the risks or decreases the acceptability of the risks associated with the use of the product is not eligible for expedited review.)

b) Research on medical devices for which (i) an investigational device exemption application (21 CFR Part 812) is not required; or (ii) the medical device is cleared/approved for marketing and the medical device is being used in accordance with its cleared/approved labeling.

Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:

a) From healthy, nonpregnant adults who weigh at least 110 pounds. For these subjects, the amounts drawn may not exceed 550 ml in an 8 week period and collection may not occur more frequently than 2 times per week; or

b) From other adults and children, considering the age, weight, and health of the subjects, the collection procedure, the amount of blood to be collected, and the frequency with which it will be collected. For these subjects, the amount drawn may not exceed the lesser of 50 ml or 3 ml per kg in an 8 week period and collection may not occur more frequently than 2 times per week. [Children are defined in the DHHS regulations as "persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted."][45 CFR 46.402(a)]

3. Prospective collection of biological specimens for research purposes by noninvasive means.

Examples: (a) hair and nail clippings in a nondisfiguring manner; (b) deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction; (c) permanent teeth if routine patient care indicates a need for extraction; (d) excreta and external secretions (including sweat); (e) uncannulated saliva collected either in an unstimulated fashion or stimulated by chewing gum base or wax or by applying a dilute citric solution to the tongue; (f) placenta removed at delivery; (g) amniotic fluid obtained at the time of rupture of the membrane prior to or during labor; (h) supra- and subgingival dental plaque and calculus, provided the collection procedure is not more invasive than routine prophylactic scaling of the teeth and the process is accomplished in accordance with accepted prophylactic techniques; (i) mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings; (j) sputum collected after saline mist nebulization.

4. Collection of data through noninvasive procedures (not involving general anesthesia or sedation) routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. Where medical devices are employed, they must be cleared/approved for marketing. (Studies intended to evaluate the safety and effectiveness of the medical device are not generally eligible for expedited review, including studies of cleared medical devices for new indications.)

Examples: (a) physical sensors that are applied either to the surface of the body or at a distance and do not involve input of significant amounts of energy into the subject or an invasion of the subject’s privacy; (b) weighing or testing sensory acuity; (c) magnetic resonance imaging; (d) electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow, and echocardiography; (e) moderate exercise, muscular strength testing, body composition assessment, and flexibility testing where appropriate given the age, weight, and health of the individual.

5. Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected solely for nonresearch purposes (such as medical treatment or diagnosis). [NOTE: Some research in this category may be exempt from the DHHS regulations for the protection of human subjects. See Exempt Categories and 45 CFR 46 101(b)(4). This listing refers only to research that is not exempt.]

6. Collection of data from voice, video, digital, or image recordings made for research purposes.

7. Research on individual or group characteristics or behavior (including, but not limited to, research on perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and social behavior) or research employing survey, interview, oral history, focus group, program evaluation, human factors evaluation, or quality assurance methodologies. [NOTE: Some research in this category may be exempt from the DHHS regulations for the protection of human subjects. See Exempt Categories and 45 CFR 46.101(b)(2) and (b)(3). This listing refers only to research that is not exempt.]

8. Continuing review of research previously approved by the convened IRB as follows:

a) Where (i) the research is permanently closed to the enrollment of new subjects; (ii) all subjects have completed all research-related interventions; and (iii) the research remains active only for long-term follow-up of subjects; or

b) Where no subjects have been enrolled and no additional risks have been identified; or

c) Where the remaining research activities are limited to data analysis.

Note: Category (8) identifies three situations in which research that is greater than minimal risk and has been initially reviewed by a convened IRB may undergo subsequent continuing review by the expedited review procedure.

For a multi-center protocol, an expedited review procedure may be used by the IRB at a particular site whenever the conditions of category (8)(a), (b), or (c) are satisfied for that site. However, with respect to category 8(b), while the criterion that "no subjects have been enrolled" is interpreted to mean that no subjects have ever been enrolled at a particular site, the criterion that "no additional risks have been identified" is interpreted to mean that neither the investigator nor the IRB at a particular site has identified any additional risks from any site or other relevant source.

9. Continuing review of research, not conducted under an investigational new drug application or investigational device exemption where categories two (2) through eight (8) do not apply but the IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk and no additional risks have been identified.

Note: The determination that "no additional risks have been identified" does not need to be made by the convened IRB.

6.5.2 Expedited Review Procedures

Under an expedited review procedure, the review may be carried out by the IRB Chair or by one or more reviewers designated by the Chair from among members of the IRB. IRB members who serve as designees to the IRB Chair for expedited review will be matched as closely as possible with their field of expertise to the study.

All trained, voting members of the IRB are eligible to conduct expedited reviews. The IRB Staff will select expedited reviewers from the roster who have the qualifications, experience and knowledge in the content of the protocol to be reviewed, as well as knowledge of the requirements to approve research under expedited review. IRB members with a conflict of interest in the research disclose the COI to the IRB staff upon receipt of the assignment and the study will be re-assigned to a non-conflicted member.

When reviewing research under an expedited review procedure, the IRB Chair, or designated IRB member(s), should receive and review all documentation submitted by the PI. The reviewer will also receive and complete the appropriate reviewer worksheet(s) which will serve as documentation of the expedited category or categories as well as whether the research meets the regulatory criteria for approval. If the research does not meet the criteria for expedited review, then the reviewer will indicate that the research requires full review by the IRB and the protocol will be placed on the next agenda for an IRB meeting.

In reviewing the research, the reviewers will follow the review procedures described later in this section and may exercise all of the authorities of the IRB except that the reviewers may not disapprove the research. A research activity may be disapproved only after review in accordance with the non-expedited procedure set forth below.

Reviewers will indicate approval, required modifications, or requirement for convened board review on reviewer worksheet and return the worksheet to the IRB Office. If modifications are required the IRB staff will inform the investigator in writing.

In the event that expedited review is carried out by more than one IRB member and the expedited reviewers disagree, the IRB Administrator and/or IRB Chair may make a final determination. Upon the discretion of the IRB Administrator or IRB Chair the protocol will be submitted to the full board for review.

6.5.3 Informing the IRB

All members of the IRB will be apprised of all expedited review approvals via written monthly reports. Any IRB member can request to review the full protocol by contacting the IRB Office.

6.6 Convened IRB Meetings

All human subjects research involving greater than minimal risk will be reviewed at a convened meeting of the full board, except when an expedited review procedure is permitted by regulation.

6.6.1 IRB Meeting Schedule

The schedule for IRB meetings may be found on the IRB website. Special meetings may be called at anytime by the Chair or the Administrator.

6.6.2 Preliminary Review

An IRB Coordinator will perform a preliminary review of all protocol materials submitted to the IRB office for determination of completeness and accuracy. Initial pre-review sent from staff to the PI (prior to review by an IRB member) will include clarifying questions; requests for missing documents, or letters of support or permission; discrepancies and inconsistencies; missing sections or elements in sections of the documents; missing training; and clear regulatory or policy issues. Only complete submissions will be placed on the IRB agenda for review. The investigator will be informed in writing of missing materials. IRB Coordinators will also conduct a preliminary review of each submission for compliance with federal regulations and IRB policies. Any issues identified during this preliminary review will be noted for the reviewers on the worksheet.

6.6.3 Primary and Secondary Reviewers

After it has been determined that the protocol submission is complete, an IRB Coordinator, in consultation with the IRB Administrator, will assign protocols for review paying close attention to the scientific content of the protocol, the potential reviewer’s area of expertise and representation for vulnerable populations involved in the research. At least one reviewer will be assigned to each protocol and a reviewer may be assigned several protocols or other research items for review. Reviewers are assigned to all protocols requiring initial review, continuing review, and review of modifications. Initial protocols requiring full board review will reviewed by a primary and secondary reviewer, with a consultant on an as-needed basis. All other submissions will be reviewed by a primary reviewer, with a secondary reviewer or consultant on an as needed basis. When the IRB is presented with a protocol that may be outside of the knowledge base or representative capacity of the IRB members, a consultant will be sought. Protocols for which appropriate expertise cannot be obtained for a given meeting will be deferred to another meeting when appropriate expertise can be achieved.

Primary reviewers are responsible for:

1. Having a thorough knowledge of all of the details of the proposed research.

2. Performing an in-depth review of the proposed research.

3. Leading the discussion of the proposed research at the convened meeting and leading the IRB through the regulatory criteria for approval.

4. Making suggestions for changes to the proposed research, where applicable.

5. Completing all applicable IRB reviewer forms.

Secondary reviewers are responsible for:

1. Having a thorough knowledge of all of the details of the proposed research.

2. Performing an in-depth review of the proposed research with a particular focus on the documents and methods related to consent and recruitment.

3. Making suggestions for changes to the proposed research that differ from, or were not identified by, the primary reviewer.

4. Completing all applicable IRB reviewer forms.

An absent reviewer can submit their written comments for presentation at the convened meeting, as long as there is another reviewer present at the convened meeting, who has read the materials and can serve as the reviewer.

All of the IRB members receive and are expected to review all studies, not just the ones they are responsible for reviewing.

6.6.4 Pre-Meeting Distribution of Documents

All required materials need to be submitted two weeks prior to the convened meeting for inclusion on the following IRB agenda. The meeting agenda will be prepared by an IRB Coordinator under the supervision of the IRB Administrator and distributed to the IRB members and the IO prior to the meeting. IRB members receive the agenda and materials for review one week prior to the scheduled meeting. At a minimum, agenda packets include the agenda, minutes from the previous meeting, and any study submissions for review.

6.6.5 Materials received by the IRB

Each IRB member receives and reviews the following documentation, as applicable, for all protocols on the agenda:

· Complete application form

· Internal or external protocol

· Proposed Consent / Parental Permission / Assent Form(s) or Guides

· Recruitment materials

· Data collection instruments

· Grant proposal or contract

· Approval documents from external IRB

· Investigator’s brochure

· Scientific review from sponsor or review committee

· Letters of support or permission from external sites

If an IRB member requires additional information to complete their review they may contact the investigator directly or may ask the IRB Office to make the request of the investigator.

6.6.6 Quorum

A quorum consists of a simple majority (more than half) of the voting membership, including at least one member whose primary concern is in a non-scientific area. If research involving an FDA-regulated article is involved, a licensed physician must be included in the quorum. The IRB Chair, with the assistance of the IRB staff, will confirm that an appropriate quorum is present before calling the meeting to order. The IRB Chair will be responsible for ensuring that the meetings remain appropriately convened.

At meetings of the IRB, a quorum must be established and maintained for the deliberation and vote on all matters requiring a vote. The IRB Chair, with the assistance of the IRB staff, will confirm that an appropriate quorum is present before calling the meeting to order and that quorum is maintained until the meeting is adjourned. If a quorum is not maintained, the pending action item(s) must be deferred until quorum is established or until the next meeting. The IRB Staff will document, in the minutes, the time of arrival and departure for all IRB members and notify the IRB Chair if a quorum is lost.

IRB members are considered present and participating at a duly convened IRB meeting when either physically present or participating through electronic means (e.g., teleconferencing or video conferencing) that permits them to listen to and speak during IRB deliberations and voting. When not physically present, the IRB member must have received all pertinent materials prior to the meeting and must be able to participate actively and equally in all discussions.

Opinions of absent members that are transmitted by mail, telephone, facsimile or e-mail may be considered by the attending IRB members but may not be counted as votes or to satisfy the quorum for convened meetings.

In some cases, primary members may not count towards quorum for every meeting. For example, the Prisoner Representative only counts towards quorum when his/her presence is required for the review of a protocol involving incarcerated subjects. Other members may serve similar roles and their impact on quorum will be noted in the roster filed with OHRP.

6.6.7 Meeting Procedures

The IRB Chair, or Vice-Chair in the event that the IRB Chair is absent, will call the meeting to order, once it has been determined that a quorum is in place. The IRB will review and discuss the IRB minutes from the prior meeting and determine if there are any revisions or corrections to be made. If there are no changes to be made, the minutes will be accepted as presented and considered final. If it is determined that revisions or corrections are necessary, the minutes will be amended. If the amendments are considered to be minor (e.g., typographical errors, revised language provided by members present), then the minutes will be considered approved after the IRB Staff makes the changes. If the amendments are considered to be major, they will be presented again at the following IRB meeting for a second vote.

The Chair or Vice-Chair will query the members about any conflicts of interest with the items appearing on the agenda and will remind members to recuse themselves from the discussion and vote by leaving the room when that agenda items is being reviewed.

The IRB reviews all submissions for initial and continuing review, as well as requests for modifications. The Primary and Secondary Reviewer present an overview of the research and lead the IRB through the regulatory criteria for approval. All voting members present at a convened meeting have full rights, except in the case of a conflict of interest. In order for the research to be approved, it must receive the approval of a majority of those voting members present at the meeting and meet all of the criteria for approval.

6.6.8 Guests

At the discretion of the IRB, the Principal Investigator may be invited to the IRB meeting to answer questions about their proposed or ongoing research. The Principal Investigator will be asked to leave for the discussion and subsequent vote on their research proposal.

In accordance with the Oregon’s Public Meetings Law, the public may attend IRB meetings and will be given notice of the time and place of these meetings. The meetings will be accessible to everyone, including persons with disabilities. The Public Meetings Law guarantees the public the right to view government meetings, but not to participate in them. While guests are permitted to attend IRB meetings, they may not participate unless requested by the IRB Chair or Administrator to do so and must sign a Non-member Confidentiality Agreement and Conflict of Interest Disclosure form prior to the meeting.

Executive sessions, which exclude the public, may be called during any regular, special, or emergency meeting. Such sessions will be convened and conducted in accordance with Oregon’s Public Meetings Law.

6.7 Collaborative Research Projects

In the conduct of cooperative research projects, OSU acknowledges that each Institution is responsible for safeguarding the rights and welfare of human subjects and for complying with applicable federal regulations. When a cooperative agreement exists, OSU may enter into a joint review arrangement, rely on the review of another qualified IRB, or make similar arrangements for avoiding duplication of effort. A formal relationship must be established between OSU and the other Institution through either a Cooperative Agreement or a Memorandum of Understanding. This relationship must be formalized before OSU will accept any human research proposals from the other Institution or rely on the review of the other Institution.

It is the policy of OSU to assure that all facilities participating in a human subjects study receive adequate documentation about the study in order to protect the interests of study participants. Before a study can begin, it must be approved by the IRB of record for each participating facility and, where appropriate, the IRB of record for the coordinating facility.

For collaborative research, the PI must identify all Institutions participating in the research, the responsible IRB(s), and the procedures for dissemination of protocol information (IRB initial and continuing approvals, relevant reports of unanticipated problems, protocol modifications, and interim reports) between all participating Institutions.

When OSU relies on another IRB, the Administrator of the IRB office will review the policies and procedures of the IRB to ensure that they meet OSU standards.

When OSU reviews research conducted at another Institution, the particular characteristics of each Institution’s local research context must be considered, either (i) through knowledge of its local research context by the OSU IRB or (ii) through subsequent review by appropriate designated Institutional officials, such as the Chairperson and/or other IRB members.

If OSU is the coordinating facility, the Principal Investigator must document how the important human subject protection information will be communicated to the other participating facilities engaged in the research study. The investigator is responsible for serving as the single liaison with outside regulatory agencies, with other participating facilities, and for all aspects of internal review and oversight procedures. The investigator is responsible for ensuring that all participating facilities obtain review and approval from their IRB of record and adopt all protocol modifications in a timely fashion. The investigator is responsible for ensuring that the research study is reviewed and approved by any other appropriate committees at the coordinating facility and at the participating facilities (e.g. VA Research and Development Committee approval) prior to enrollment of participants.

The PI must follow these procedures when OSU is the coordinating facility:

· During the initial IRB submission of the multi-site study, the investigator indicates in writing on the application form or in an application letter that OSU is the coordinating facility of a multi-site study.

· The investigator submits the following information in their IRB application materials:

o Whether research activities at participating Institutions are defined as engagement

o Name of each participating facility

o Confirmation that each participating facility has an FWA (including FWA number)

o Contact name and information for investigator at each participating facility

o Contact name and information for IRB of record at each participating facility

o Method for assuring all participating facilities have the most current version of the protocol

o Method for confirming that all amendments and modifications in the protocol have been communicated to participating sites

o Method for communicating to participating facilities any serious adverse events and unanticipated problems involving risks to subjects or others

o Method of communicating regularly with participating sites about study events

· The investigator submits approval letters from all the IRB of record for all participating sites.

· The investigator maintains documentation of all correspondence between participating sites and their IRBs of record.

7. FDA-Regulated Research

7.1 Policy

FDA regulations apply to any research that involves a test article in a clinical investigation involving human subjects as defined by the FDA regulations. For FDA regulated research, the IRB must apply the FDA regulations at 21 CFR 50 and 21 CFR 56, as well as, where appropriate, 45 CFR 46. (See Guidance Document “Comparison between FDA and HHS Regulations”)

Use of investigational drugs must be conducted according to FDA IND regulations, 21 CFR Part 312, and other applicable FDA regulations. Use of an investigational device in a clinical trial to obtain safety and effectiveness data must be conducted according to FDA’s IDE regulations, 21 CFR Part 812, and other applicable FDA regulations.

If there is any ambiguity about whether an IND is needed, the IRB may request that the PI provide a determination from the FDA. The PI may choose to request such a determination pre-emptively by taking the following steps:

a) Complete FDA forms 1571 and 1572. These forms are available on the FDA website.

b) Submit completed forms to FDA, along with a copy of the protocol to be submitted to the IRB.

c) Include cover letter specifically requesting a written determination regarding the need for an IND.

d) FDA will respond within 30 days. The response may then be submitted to the IRB.

The following procedures describe the use of investigational drugs and devices in research under the auspices of the IRB.

7.2 Definitions

Clinical Investigation. Clinical investigation means any experiment that involves a test article and one or more human subjects, and that either must meet the requirements for prior submission to the Food and Drug Administration under section 505(i) or 520(g) of the act, or need not meet the requirements for prior submission to the Food and Drug Administration under these sections of the act, but the results of which are intended to be later submitted to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit. The term does not include experiments that must meet the provisions of part 58, regarding nonclinical laboratory studies. The terms research, clinical research, clinical study, study, and clinical investigation are deemed to be synonymous for purposes of this part.

Dietary Supplement. A dietary supplement is a product taken by mouth that is intended to supplement the diet and that contains a dietary ingredient. The dietary ingredients in these products can include vitamins, minerals, herbs and other botanicals, amino acids, other dietary substances intended to supplement the diet, and concentrates, metabolites, constituents, extracts, or combinations of the preceding types of ingredients. Dietary supplements can be found in many forms such as tablets, capsules, softgels, liquids, or powders. See section 201(ff) of the FD&C Act (21 U.S.C. 321(ff)).

Investigational Drug. An investigational drug for clinical research use is one for which the PI or a sponsor has filed an IND application (21 CFR Part 312) or an approved drug that is being studied for an unapproved or approved use in a controlled, randomized, or blinded clinical trial.

Investigational Device. A medical device that is the subject of a clinical study designed to evaluate the effectiveness and/or safety of the device. As further stated, a device is any healthcare product that does not achieve its primary intended purpose by chemical action or by being metabolized.

IND. IND means an investigational new drug in accordance with 21 CFR Part 312.

IDE. IDE means an investigational device exemption in accordance with 21 CFR 812.

Significant Risk (SR). Significant risk device means an investigational device that:

(1) Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject; or

(2) Is purported or represented to be for a use in supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject; or

(3) Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject; or

(4) Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.

Non-Significant Risk (NSR). A non-significant risk device is an investigational device other than a significant risk device.

Sponsor. Sponsor means a person who takes responsibility for and initiates a clinical investigation. The sponsor may be an individual or pharmaceutical company, governmental agency, academic Institution, private organization, or other organization. The sponsor does not actually conduct the investigation unless the sponsor is a sponsor-investigator. A person other than an individual that uses one or more of its own employees to conduct an investigation that it has initiated is a sponsor, not a sponsor-investigator, and the employees are investigators.

Sponsor-Investigator. Sponsor-Investigator means an individual who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. The term does not include any person other than an individual. The requirements applicable to a sponsor-investigator under this part include both those applicable to an investigator and a sponsor.

Test Article. Test article means any drug for human use, biological product for human use, medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under the act or under sections 351 or 354-360F of the Public Health Service Act.

7.3 FDA Exemptions

The following categories of clinical investigations are exempt from the requirements of FDA regulations for IRB review:

Emergency use of a test article, provided that such emergency use is reported to the IRB within 5 working days. Any subsequent use of the test article at the Institution is subject to IRB review. [21 CFR §56.104(c)]

1. Taste and food quality evaluations and consumer acceptance studies, if wholesome foods without additives are consumed or if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural, chemical, or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture. [21 CFR §56.104(d)]

7.4 Procedures

1. At initial submission, the PI must indicate on the application form whether the research involves a test article and is a clinical investigation involving human subjects.

2. During the pre-review process, the IRB Administrator will confirm whether and which FDA regulations are applicable.

7.5 Dietary Supplements

Research involving dietary supplements may or may not fall under FDA regulations. Under the Dietary Supplement Health and Education Act (DSHEA) of 1994, a dietary supplement is not considered a drug and is not subject to the premarket approval requirements for drugs if the intended use for which it is marketed is only to affect the structure or any function of the body (i.e., not intended to be used for a therapeutic purpose). Whether a study falls under FDA oversight is determined by the intent of the clinical investigation. If the clinical investigation is intended only to evaluate the dietary supplement’s effect on the structure or function of the body, FDA regulations do not apply. However, disease claims (claims to diagnose, cure, mitigate, treat, or prevent a disease) require FDA approval. Studies involving the ingestion of dietary supplements that are not subject to FDA oversight are still covered by the regulations at 45 CFR 46 and will be reviewed at a convened meeting of the IRB.

Whether an IND is needed for a study evaluating a dietary supplement is determined by the intent of the study. If the study is intended only to evaluate the dietary supplement’s effect on the structure or function of the body, an IND is not required. However, if the intention is to make disease claims, an IND is required under part 312.

The examples below are provided to illustrate the difference between a structure and function claim and a disease claim. For additional guidance see Guidance for Industry: Structure/Function Claims, Small Entity Compliance Guide, January 9, 2002 (http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/DietarySupplements/ucm103340).

a) A statement is a disease claim if it mentions a specific disease or class of diseases. For example, a claim that a product is "protective against the development of cancer" or "reduces the pain and stiffness associated with arthritis" would be a disease claim.

b) Some claims imply disease treatment or prevention because they are so intimately tied to a disease. For example, "inhibits platelet aggregation" or "reduces cholesterol" are such characteristic signs or symptoms associated with stroke and cardiovascular disease and interventions to treat those diseases that any claim about them would be an implied disease claim.

7.5.1 Researcher Responsibilities

The researcher must submit all of the following with their application to the IRB:

List all dietary supplements or foods to be used in this study. Include the following:

a) Name

b) Chemical formula

c) Dosage strength(s)

d) Method/route of administration

e) Mechanism of action

f) Known drug interactions

g) Manufacturer/Sponsor

h) Name of supplier

i) IND number if applicable and letter from the FDA or industry sponsor setting forth the IND number

j) Documentation of approval for use in humans

k) Documentation or certification of quality or purity

The rationale for choosing the supplement and dose.
Justification and safety information if over-the-counter supplements will be administered for non-approved indications or if doses or routes of administration or subject populations are changed.
Explain whether the use of the supplement involves a route of administration or dosage level, use in a subject population, or other factor that increases the risks (or decreases the acceptability of the risks) associated with its use.
Provide a plan for the storage, dispensing, handling, inventory control, and disposal of supplements.
If there is no IND, confirmation that the study will be limited to evaluation of the dietary supplement’s effect on the structure or function of the body
For IND studies, a summary of preclinical and early human studies. All of the requirements for an IND study described below apply.

7.6 IND/IDE Requirements

The PI must indicate in the protocol whether the research involves investigational drugs or devices. If it does, the PI must provide documented assurance from the sponsor that the manufacture and formulation of investigational or unlicensed test articles conform to federal regulations and provide the letter from the FDA.

For investigational devices, Non-Significant Risk (NSR) device studies follow abbreviated IDE requirements and do not have to have an IDE application approved by the FDA. If the FDA or a sponsor has identified a study as NSR, then the investigator must provide an explanation and documentation of that determination.

If the research involves drugs or devices and there is no IND/IDE, the PI must provide a rationale why it is not required.

The IRB will review the application and determine:

1. Whether there is, or should be, an IND/IDE and if so, whether there is appropriate supporting documentation.

2. If the research involves drugs or devices with no IND/IDE, and whether the research meets the exemption criteria below.

7.6.1 IND Exemption

For drugs, an IND is not necessary if the research falls in one of the following categories:

1. The drug being used in the research is lawfully marketed in the United States and all of the following requirements are met:

a. The research is not intended to be reported to FDA in support of a new indication for use or to support any other significant change in the labeling for the drug

b. The research is not intended to support a significant change in the advertising for the product;

c. The research does not involve a route of administration or dosage level, use in a subject population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product

d. The research is conducted in compliance with the requirements for IRB review and informed consent [21 CFR parts 56 and 50, respectively]

e. The research is conducted in compliance with the requirements concerning the promotion and sale of drugs [21 CFR 312.7]

f. The research does not intend to invoke FDA regulations for planned emergency research [21 CFR 50.24].

2. The research only involves one or more of the following: (a) Blood grouping serum, (b) Reagent red blood cells or (c) Anti-human globulin;

3. For clinical investigations involving an in vitro diagnostic biological product, an IND is not necessary if a) it is intended to be used in a diagnostic procedure that confirms the diagnosis made by another, medically established, diagnostic product or procedure; and b) it is shipped in compliance with 312.160

(top) 7.6.2 Exempted IDE Investigations

For devices, an IDE is not necessary if:

1. The research involves a device, other than a transitional device, in commercial distribution immediately before May 28, 1976, when used or investigated in accordance with the indications in labeling in effect at that time;

2. The research involves a device other than a transitional device, introduced into commercial distribution on or after May 28, 1976, that FDA has determined to be substantially equivalent to a device in commercial distribution immediately before May 28, 1976, and that is used or investigated in accordance with the indications in the labeling FDA reviewed under subpart E of 21 CFR 807 in determining substantial equivalence;

3. The research involves a diagnostic device, if the sponsor complies with applicable requirements in 21 CFR 809.10(c) and if the testing:

a. Is noninvasive,

b. Does not require an invasive sampling procedure that presents significant risk,

c. Does not by design or intention introduce energy into a subject, and

d. Is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically established diagnostic product or procedure;

4. The research involves a device undergoing consumer preference testing, testing of a modification, or testing of a combination of two or more devices in commercial distribution, if the testing is not for the purpose of determining safety or effectiveness and does not put subjects at risk;

5. The research involves a device intended solely for veterinary use;

6. The research involves a device shipped solely for research on/or with laboratory animals and labeled in accordance with 21 CFR 812.5(c);

7. The research involves a custom device as defined in 21 CFR 812.3(b), unless the device is being used to determine safety or effectiveness for commercial distribution.

7.7 Responsibilities

7.7.1 PI

1. The PI is responsible for ensuring that the research is conducted according to all regulatory guidelines and the IRB policies and procedures

2. The PI must obtain approval from the IRB before initiating any research activities.

3. The PI proposing the drug/device research will be required to provide a plan – to be evaluated by the IRB - that includes storage, security, and dispensing of the drug/biologics/device.

a. The PI is responsible for the investigational drug/device accountability that includes storage, security, dispensing, administration, return, disposition, and records of accountability.

b. The PI is responsible for all record keeping related to drug/biologic/supplement accountability. Such record keeping must be done in accordance with the FDA regulations (21 CFR 312 (d)).

c. All devices received for a study must be stored in a locked environment under secure control with limited access. The area must be within an area of PI’s control. Proper instructions on the use of the device must be provided to the subjects. A log must be kept regarding the receipt, use, and/or dispensing of the device and the disposition of remaining devices at the conclusion of the investigation.

4. The PI shall report all unanticipated problems involving risk to subjects or others to the IRB according to the procedures outlined in Section 8.

5. For research involving investigational new drugs:

a. The PI must inform the IRB when a study involving investigational drugs has been terminated by the sponsor.

b. The PI will report to the sponsor any adverse effect that may reasonably be regarded as caused by, or probably caused by, the drug (21 CFR 312 (b)) according to the procedures in the protocol.

c. The PI will maintain the following:

i. Current curriculum vitae (CV)

ii. Protocol

iii. Records of receipt and disposition of drugs

iv. List of any co-investigators with their curriculum vitae

v. Certification that all physicians, dentists, and/or nurses responsible in the study have appropriate valid licenses for the duration of the investigation, and

vi. Case histories with particular documentation on evidence of drug effects. Emphasis is on toxicity and possible untoward happenings. All unexpected adverse effects are reportable; even if the investigator considers that the event is not related to the drug. All unexpected adverse effects shall be reported immediately to the IRB in the manner defined by the protocol.

vii. IRB letters of approval.

viii. Other documents as outlined in the Human Subject Protection Program Standard Operating Procedures.

1. For research involving investigational devices:

a) If a device is considered NSR by the PI or sponsor, but after review the IRB determines the device to have significant risk, upon receipt of written notice the PI is responsible for notifying the sponsor of the IRB’s determination. The PI must provide the IRB with confirmation of this action.

b) If the PI is storing the devices, he/she must maintain a log indicating the identification/serial number of the device, name of subject, date dispensed, by whom it was dispensed, and amount remaining.

c) The PI will maintain the following:

i. Current curriculum vitae (CV)

ii. Protocol of the study

iii. Records of animal study reports

iv. Records of receipt and disposition of devices

v. List of any co‑investigators with their curriculum vitae

vi. Certification that all physicians, dentists, and/or nurses responsible in the study have appropriate valid licenses for the duration of the investigation

vii. Case histories with particular documentation on evidence of effects. Emphasis is on safety and possible untoward happenings. All adverse device effects are reportable

viii. IRB letters of approval

ix. Device training

x. Other documents as outlined in the Human Subject Protection Program Standard Operating Procedures

d) Following completion of the study the termination procedure for investigational devices must be applied. If the devices are kept by the investigator, he/she must maintain a log regarding the receipt, use and/or re-dispensing of the device and the disposition of remaining devices at the conclusion of the investigation.

e) The PI will submit to the sponsor and to the IRB a report of any unanticipated adverse device effect occurring during an investigation as soon as possible, but in no event later than 3 working days[6] after the investigator first learns of the effect.

2. When a PI files an IND or IDE, the PI is considered the sponsor and as such is accountable for all of the FDA regulatory responsibilities and reporting obligations of both the PI and the sponsor, as described in the FDA regulations. The Research Plan asks the PI if he/she also acts as the sponsor of the research and, if so, asks him/her to affirm that he/she has reviewed the Guidance Document on Requirements of the Sponsor and the Investigator as a Sponsor and will comply with the regulatory responsibilities of a sponsor. The IRB will conduct education programs for investigators holding an IND or IDE on the sponsor regulations and periodically conduct random audits of PIs holding an IND or IDE as per the Research Quality Improvement Program.

7.7.2 IRB

1. The IRB will review the research in accordance with the following requirements and the same criteria it would use in considering approval of any research involving an FDA-regulated product (21 CFR 56.111).

2. The IRB will review the control plan for all test articles and determine whether it is adequate. If the Chair determines that the IRB does not have the necessary expertise to evaluate the plan, outside consultation will be used.

3. For research involving investigational devices:

a. Unless the FDA has already made a risk determination for the study, the IRB will review NSR studies and determine if the device represents significant or non-significant risk and report the findings to the PI in writing. The IRB will consider the risks and benefits of the medical device compared to the risks and benefits of alternative devices or procedures. Non-significant risk device studies do not require submission of an IDE application but must be conducted in accordance with the abbreviated requirements of IDE regulations. If the study that has been submitted as NSR is considered SR, the IRB may approve the study, but the study cannot begin until an IDE is obtained.

b. Determination of NSR/SR must be made at a convened meeting of the board.

c. The IRB will document in the minutes and provide written documentation to the PI of the rationale for determining whether a device is classified as NSR/SR.

d. Studies involving a Significant Risk Device will only be reviewed by the full board. If the full board determines that the device is NSR and the study is minimal risk, the board may further determine that the study may be reviewed by an expedited procedure.

e. If the FDA has already made the SR or NSR determination for the study, the agency’s determination is final and the IRB does not need to make a risk determination.

8. Submission Types

8.1 Determination of Human Subjects Research

The responsibility for initial determination as to whether an activity constitutes human subjects research (HSR) rests with the investigator. Since the Institution will hold them responsible if the determination is not correct, investigators are urged to request a confirmation that an activity does not constitute human subjects research from the IRB office. Requests for determinations must include sufficient information about the activity to support the determination.

Investigators who think that their project may not meet the definition of HSR should complete and submit a Determination Form to the IRB for review.

8.2 Determination of Engagement

OSU is considered engaged in a research project when the involvement of OSU employees or agents in that project includes any of the following:

a) Intervention for research purposes with any human subjects of the research by performing invasive or noninvasive procedures.

b) Intervention for research purposes with any human subject of the research by manipulating the environment.

c) Interaction for research purposes with any human subject of the research.

d) Obtaining the informed consent of human subjects for the research.

e) Obtaining for research purposes identifiable private information or identifiable biological specimens from any source for the research. In general, obtaining identifiable private information or identifiable specimens includes, but is not limited to:

· Observing or recording private behavior;

· Using, studying, or analyzing for research purposes identifiable private information or identifiable specimens provided by another Institution; and

· Using, studying, or analyzing for research purposes identifiable private information or identifiable specimens already in the possession of the investigators.

The criteria for this determination will be applied to both exempt and non-exempt studies.

8.3 Approval in Principle

Certain types of applications for grants, cooperative agreements, or contracts are submitted to departments or agencies with the knowledge that subjects may be involved within the period of support, but definite plans would not normally be set forth in the application or proposal. These include activities such as Institutional type grants when selection of specific projects is the Institution's responsibility; research training grants in which the activities involving subjects remain to be selected; and projects in which human subjects' involvement will depend upon completion of instruments, prior animal studies, or purification of compounds.

Under the federal regulations (§46.118) and in accordance with the OSU IRB’s policies and procedures, these applications need not be reviewed by an IRB before an award may be made. However, no human subjects may be involved in any project supported by these awards until the project has been reviewed and approved by the IRB.

Approval in Principle is granted to satisfy sponsoring agency requirements or to allow investigators to have access to funding to begin aspects of the project that do not involve human subjects. Funds may not be used to conduct research with human subjects until a study-specific protocol has been reviewed and approved.

Investigators seeking an Approval in Principle must complete and submit an Application for Approval in Principle.

8.4 Initial Application

All OSU researchers proposing to initiate research involving human subjects must submit an initial application to the IRB. Feasibility and pilot testing is considered research and requires IRB review. Testing of questionnaires and survey instruments on non-study subjects does not constitute “research” with “human subjects” and does not require prior IRB approval so long as the resulting data will only be used to improve the instruments.

Use of the IRB’s template documents are strongly recommended. A Coordinator will evaluate the submission for completeness and confirm the appropriate review level.

8.5 Continuing Review

The IRB will conduct a continuing review of ongoing research at intervals that are appropriate to the level of risk for each research protocol, but not less than once per year. Continuing review must occur as long as the research remains active for long-term follow-up of participants, even when the research is permanently closed to the enrollment of new participants and all participants have completed all research-related interventions. Continuing review of research must occur even when the remaining research activities are limited to the analysis of private identifiable information.

8.5.1 Approval Period

At OSU, determination of the approval period and the need for additional supervision and/or participation is made by the IRB on a protocol-by-protocol basis. For example, for an investigator who is performing particularly risky research, or for an investigator who has recently had a protocol suspended by the IRB due to regulatory concerns, an on-site review by a subcommittee of the IRB might occur or approval might be subject to an audit of study performance after a few months of enrollment, or after enrollment of the first several subjects.

For each initial or continuing approval the IRB will indicate an approval period with an approval expiration date specified. IRB approval is considered to have lapsed at midnight on the expiration date of the approval. For a study approved by the convened IRB, the approval period starts on the date that the IRB conducts its final review of the study; that is, the date that the convened IRB approved the research or the date the convened IRB deferred the research for non-substantive issues. For a study approved under expedited review, the approval period begins on the date the IRB Chair or IRB member(s) designated by the Chair gives final approval to the protocol.

The approval date and approval expiration date are clearly noted on all IRB certifications sent to the PI and must be strictly adhered to. Investigators should allow sufficient time for development and review of renewal submissions.

Review of a change in a protocol does not alter the date by which continuing review must occur.

The regulations make no provision for any grace period extending the conduct of research beyond the expiration date of IRB approval. Therefore, continuing review and re-approval of research must occur by midnight of the date when IRB approval expires. If the IRB performs continuing review within 30 days before the IRB approval period expires, the IRB may retain the anniversary date as the date by which the continuing review must occur.

8.5.2 Continuing Review Process

Continuing review provides the IRB with an opportunity to reassess the totality of the project and assure that, among other things, risks to subjects are being minimized and are still reasonable in relation to anticipated benefits, if any, to the subjects and the knowledge that is expected to result.

To assist investigators the IRB Office staff will send out renewal notices to investigators two months and one month in advance of the expiration date; however, it is the investigator’s responsibility to ensure that the continuing review of ongoing research is approved prior to the expiration date. By federal regulation, no extension to that date can be granted.

Investigators must submit the following for continuing review:

a) Continuing review application

b) A copy of the last signed consent form with the subject’s name blacked out, if a consent form is approved for the study;

In conducting continuing review of non-exempt research not eligible for expedited review, all IRB members are provided with and review the above material, and the currently approved consent form. The Primary Reviewer will review the complete protocol, including any modifications previously approved by the IRB. At the meeting, the Reviewer leads the IRB through the regulatory criteria for approval.

At the convened meeting, IRB office staff ensures that the entire study file is available to members (via paper or electronic files).

In the case of expedited review, the IRB members may request that the IRB office staff provide them with any additional materials required for the review.

Continuing review applications and amendments may be submitted simultaneously.

8.5.3 Expedited Review of Continuing Review

In conducting continuing review under expedited review, the reviewers receive all of the above material. The reviewer(s) complete the appropriate worksheet(s) to determine whether the research meets the criteria allowing continuing review using the expedited procedure, and if so, whether the research continues to meet the regulatory criteria for approval.

Generally, if research did not qualify for expedited review at the time of initial review, it does not qualify for expedited review at the time of continuing review, except in limited circumstances described by expedited review categories (8) and (9) at 63 FR 60364-60367 (see Expedited Review Categories). It is also possible that research activities that previously qualified for expedited review in accordance with 45 CFR 46.110, have changed or will change, such that expedited IRB review would no longer be permitted for continuing review.

8.5.4 Lapse in IRB Approval

If approval by the IRB lapses, all research activity must stop. The investigator can petition the IRB to continue an individual participant’s research intervention/interaction during a period of lapsed IRB approval if the investigator believes there is a safety concern or ethical issue such that it is in the best interests of the individual participant to do so.

The regulations permit no grace period or approval extension after approval expiration. Research that continues after the approval period has expired is research conducted without IRB approval. If the continuing review and subsequent approval does not occur within the timeframe set by the IRB, all research activities must stop, including recruitment, enrollment, consent, interventions, interactions, data collection, unless the IRB finds that it is in the best interests of individual subjects to continue participating in the research interventions or interactions. This will occur even if the investigator has provided the continuing information before the expiration date. Therefore, investigators must allow sufficient time for IRB review before the expiration date.

The IRB Office is responsible for notifying the investigator of the expiration of approval and that all research activities must stop. Such notifications will be sent within 10 business days of expiration.

Failure to submit continuing review information on time is non-compliance and will be handled according to the non-compliance policy.

Once approval has expired outside of review (i.e., no continuing review information was submitted prior to the expiration date), the file is administratively closed. Decisions of this kind must be made in a manner that ensures that closure will not harm any participants previously enrolled who may require ongoing treatment as part of the research study. A new application must be submitted to the IRB for review and approval prior to re-initiation of the research. Data previously collected under an approved protocol may be referenced in the new application and used in data analysis.

8.6 Project Revisions

Investigators may wish to modify or amend their approved applications. Investigators must seek IRB approval before making any changes in approved research - even though the changes are planned for the period for which IRB approval has already been given - unless the change is necessary to eliminate an immediate hazard to the subject (in which case the IRB must then be notified immediately).

Modifications may be approved if they are within the scope of what the IRB originally authorized. For example, if a researcher wishes to add a population to an existing study, but not alter the study procedures or purpose, a modification request is usually appropriate. Likewise, modifying a procedure without changing the study's purpose or study population may also be appropriate. If, however, the researcher wishes to add a population and revise study procedures, he or she may need to submit a new application for human subjects approval.

Investigators must submit documentation to inform the IRB about the changes in the status of the study, including, but not necessarily limited to:

· Completed “Project Revision” form;

· Revised protocol (if applicable)

· Revised approved consent or assent documents (if applicable) or other documentation that would be provided to subjects when such information might relate to their willingness to continue to participate in the study

· Revised or additional recruitment materials

· Any other relevant documents

IRB Office staff will determine whether the proposed changes require a reclassification of the review level, may be approved through an expedited review process (if the changes are minor), or whether the modification warrants full board review. The reviewer(s) using the expedited procedure has the ultimate responsibility to determine that the proposed changes may be approved through the expedited review procedure and, if not, must refer the protocol for full board review.

8.6.1 Expedited review of Project Revisions

An IRB may use expedited review procedures to review minor changes in ongoing previously approved research during the period for which approval is authorized. An expedited review may be carried out by the IRB Chair and/or designee(s) among the IRB members.

The reviewer(s) completes the appropriate worksheet to determine whether the modifications meet the criteria allowing review of the amendment using the expedited procedure, and if so, whether the research with the proposed modifications continues to meet the regulatory criteria for approval.

The reviewer will also consider whether information about those modifications might relate to participants’ willingness to continue to take part in the research and if so, whether to provide that information to participants.

8.6.1.1 Minor Change

A minor change is one that, in the judgment of the IRB reviewer, makes no substantial alteration in:

a) The level of risks to subjects

b) The research design or methodology (adding procedures that are not eligible for expedited review would not be considered a minor change)

c) The number of subjects enrolled in the research (no greater than 10% of the total requested)

d) The qualifications of the research team (change in PI is not considered to be minor)

e) The facilities available to support safe conduct of the research, or

f) Any other factor which would warrant review of the proposed changes by the convened IRB or was used to initially to evaluate the risk:benefit ratio or any other criteria for approval

8.6.2 Full Board Review of Project Revisions

When a proposed change in a research study is not minor (e.g., procedures involving increased risk or discomfort are to be added), then the IRB must review and approve the proposed change at a convened meeting before the change can be implemented. The only exception is a change necessary to eliminate apparent immediate hazards to the research subjects. In such a case, the IRB should be promptly informed of the change following its implementation and should review the change to determine that it is consistent with ensuring the subjects' continued welfare.

All IRB members are provided and review all documents provided by the investigator.

At the meeting, the Primary Reviewer presents an overview of the modifications and leads the IRB through the completion of the regulatory criteria for approval. The IRB will determine whether the research with the proposed modifications continues to meet the regulatory criteria for approval.

When the IRB reviews modifications to previously approved research, they consider whether information about those modifications might relate to participants’ willingness to continue to take part in the research and if so, whether to provide that information to participants.

8.7 Reportable Events

Investigators are required to submit reports of deviations, adverse events, and unanticipated problems in accordance with the requirements outlined in later sections of this policy.

8.8 Significant New Findings

During the course of research, significant new knowledge or findings about the medication or test article and/or the condition under study may develop. The PI must report any significant new findings to the IRB and the IRB will review them with regard to the impact on the subjects’ rights and welfare. These reports may be submitted to the IRB as part of the continuing review process or as an unanticipated problem – whichever is appropriate to the findings. Since the new knowledge or findings may affect the risks or benefits to subjects or subjects' willingness to continue in the research, the IRB may require, during the ongoing review process, that the PI contact the currently enrolled subjects to inform them of the new information. The IRB will communicate this to the PI. The consent document may need to be revised and the IRB may require that the PI obtain written consent again from currently enrolled subjects, acknowledging receipt of this new information and affirming their continued participation.

8.9 Final Reports

The completion of the study, whether premature or not, is a change in activity and must be reported to the IRB. Although subjects will no longer be "at risk" under the study, a final report to the IRB allows it to close its files and assess information that may be used by the IRB in the evaluation and approval of related studies. Any qualified staff member may review final reports. If the final report contains errors or describes complaints, problems, or other reportable events, the report will be forwarded to the IRB Chair for review.

9. Review of Research

9.1 Criteria for IRB Approval of Research

In order for the IRB to approve non-exempt human subjects research, it must determine that the following requirements are satisfied:

a) Risks to subjects are minimized: (i) by using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.

b) Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.

c) Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disable persons, or economically or educationally disadvantaged persons.

d) Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with, and to the extent required by the Federal Regulations.

e) Informed consent will be appropriately documented, in accordance with, and to the extent required by the Federal Regulations.

f) When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.

g) When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.

h) When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects.

The above criteria must be satisfied for each review (initial, continuing, and project revisions).

9.1.1 Risk/Benefit Assessment

The goal of the risk/benefit assessment is to ensure that the risks to research subjects posed by participation in the research are justified by the anticipated benefits to the subjects and/or society. To that end, the IRB must:

· Judge whether the anticipated benefit, either of new knowledge or of improved health for the research subjects, justifies asking any person to undertake the risks, and

· Disapprove research in which the risks are judged unreasonable in relation to the anticipated benefits.

The assessment of the risks and benefits of proposed research involves a series of steps:

Identify and evaluate the risks associated with the research, as distinguished from the risks of non-research activities or therapies;
Determine whether the risks will be minimized to the extent possible;
Identify the probable benefits to be derived from the research;
Determine whether the risks are reasonable in relation to the benefits to subjects, if any, and assess the importance of the knowledge to be gained;
Ensure that potential subjects will be provided with an accurate and fair description of the risks or discomforts and the anticipated benefits;

Risks to subjects are reasonable in relation to anticipated benefits, if any, and to the importance of the knowledge that may reasonably be expected to result.

The IRB should not consider possible long-range effects of applying knowledge gained in the research (e.g., the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.

9.1.1.1 Determination of Risk

At the time of initial and continuing review, the IRB will make a determination regarding the risks associated with the research protocols. Risks associated with the research will be classified as either “minimal” or “greater than minimal”. The meeting minutes will reflect the Committee’s determination regarding risk levels.

9.1.2 Scientific Merit

IRB review of scientific merit and the methodology of a proposed research protocol is a basic expectation of the IRB and refers to the overall evaluation of ethics, risks, and benefits. In order to approve research involving human subjects, the IRB shall determine that risks to subjects are minimized by using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk.

To put subjects in harm’s way, add risk, or simply inconvenience subjects is not considered ethical if the research has no merit. The extent of scientific review by the IRB takes into consideration other scientific peer reviews undergone by the study before it comes to the IRB. In making this determination, the IRB may draw on its own knowledge and disciplinary expertise, and/or the IRB may draw on the knowledge and disciplinary expertise of others, such as reviews by a funding or regulatory agency. Documented interdepartmental and intradepartmental review also adds validity to the research proposed. All such reviews provide assurance that experts have evaluated the study and found it to be meritorious.

(top) 9.1.3 E quitable Selection of Subjects

In order to approve research involving human subjects, the IRB must determine that selection of subjects is equitable. In making this assessment the IRB will take into account the purpose of the research and the setting in which the research will be conducted. The IRB will be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons.

The IRB will not approve a study that fails to provide adequate scientific and ethical justification for excluding persons who might benefit from the research, nor will the IRB approve a study that fails to provide scientific and ethical justification for targeting vulnerable populations.

(top) 9.1.4 Recruitment of Subject s

The investigator will provide the IRB with information about recruitment methods, including how participants will be identified and all materials to be used to recruit them (e.g., fliers, advertisements, listserv postings, planned correspondence).

9.1.4.1 Advertisements

The IRB must approve the final content of any and all advertisements and recruitment materials prior to posting and/or distribution for studies that are conducted under the purview of the IRB.

This information should be submitted to the IRB with the initial application or as an amendment to the protocol.

The IRB reviews the material to assure that it is accurate, not coercive or unduly optimistic, and not creating undue influence on the subject to participate, which includes but is not limited to:

a) Statements implying a certainty of favorable outcome or other benefits beyond what is outlined in the consent document and protocol

b) Claims, either explicit or implicit, that the activity, intervention, drug, biologic or device is safe or effective for the purposes under investigation

c) Claims, either explicit or implicit, that the activity, intervention, or test article is known to be equivalent or superior to any other drug, biologic or device

d) Use of terms like “new test,” “new treatment,” “new method,” or “new drug” without explaining that it is investigational

e) Promise of “free tests,” or “free treatment” when, in actuality, the participants will just not be charged for taking part in the investigation

f) Emphasis on compensation (e.g., bold type, larger font, etc.) [only relevant to non-exempt studies]

g) Inclusion of exculpatory language

Recruitment materials should be limited to the information the prospective subjects need to determine their eligibility and interest. Recruitment materials must include:

a) Title of the study

b) Name of the PI

c) Clear statement that this is research

d) Contact information for interested individuals

When appropriately worded, the following items may be included:

a) Condition being studied and/or the purpose of the research

b) Primary criteria that will be used to determine eligibility for the study

c) Time or other commitment required of the subjects

d) Location of the research

e) Potential direct or societal benefits

f) Recruitment material and compensation plan cannot include coupons or discounts on the purchase price of the study product, if marketed

Once approved by the IRB, recruitment material cannot be altered or manipulated in any way without prior IRB approval.

9.1.5 Compensation for Research Subjects

Payment to research subjects may be an incentive for participation or a way to reimburse a subject for travel and other experiences incurred due to participation. However, payment for participation is not considered a research benefit. Regardless of the form of remuneration, investigators must take care to avoid unduly influencing subjects. Compensation should reflect the degree of risk, effort, inconvenience, or discomfort associated with participation.

Research subjects should not be disadvantaged by their participation in research. Payments should reflect the degree of risk, inconvenience, or discomfort associated with participation. Appropriate compensation to all subjects for time and expenses is acceptable.

Participants in a single study may receive unequal compensation under two circumstances:

· The investigator demonstrates that not all subjects are experiencing the same degree of risk, inconvenience or discomfort. For example, subjects participating in only one component of a study may be compensated less than subjects who consent to participating in multiple components of a study. Similarly, subjects traveling longer distances may be compensated at a higher rate to reflect greater travel expenses. However, subjects who are higher wage earners should not receive greater compensation than lower wage earners in the same study for participating in the same study activities.

· OSU students who enroll in the study will be compensated with extra credit and another (non-OSU student) cohort will be uncompensated or minimally compensated.

Investigators who wish to pay research subjects must provide the details of the compensation plan in the protocol and consent documents. The IRB will review both the amount of compensation (e.g., dollars, number of extra credit points, etc.) and the proposed method of disbursement (e.g., cash, gift cards, etc.). Compensation involving extra credit must include an alternative non-research activities requiring equal or lesser effort for which students may be given extra credit.

When the study involves multiple activities or multiple visits, the entire payment should not be contingent upon completion of the entire study. Completion bonuses, if offered, should not be so great that it unduly influences participants to remain in the study if they wish to withdraw.

The consent form must describe the terms and type of compensation, as well as the conditions under which subjects would receive partial payment or no payment.

Compensation offered in the form of checks and compensation greater than or equal to $600 paid within one calendar year, requires the collection of identifying information for the purposes of tax reporting. In these cases, the consent document must inform subjects that they will be asked to provide their Social Security Number or Individual Tax Identification Number to receive payment. In the event that the target population is known not to possess such identification, a flat tax may be withheld from payments large enough to require reporting to the Internal Revenue Service (IRS). If this is the approach to be taken by the PI, the consent document should include a brief statement indicating that taxes will be withheld from the study payment and an estimate of the net amount subjects should anticipate.

9.1.5.1 Raffles and Lotteries

The use of lotteries and raffles in non-exempt research studies may be permitted if all of the following conditions are met:

· All subjects are at least 18 years of age

· Study participation is not required for entry into the drawing

· Limit 1 drawing per study

· Limit 1 entry per drawing

· Baseline compensation will be provided to all enrolled participants

· Compensation plan does not create the potential for undue inducement

Raffles and lotteries may be used to compensate subjects enrolled in exempt studies without meeting the above listed conditions.

Policy originally approved March 16, 2010. Revisions approved May 21, 2013. Revisions approved by the IO on April 9, 2014.

9.1.6 Informed Consent

The IRB will ensure that informed consent will be sought from each prospective subject or the subject’s legally authorized representative, in accordance with, and to the extent required by 45 CFR 46.116 and 21 CFR 50.20 (when applicable). In addition, the Committee will ensure that consent process will be appropriately documented in accordance with, and to the extent required by 45 CFR 46.117 and 21 CFR 50.27 (when applicable). Informed consent is addressed in detail in a later section.

9.1.7 Data and Safety Monitoring

For all research that is more than minimal risk, the investigator must submit a Data and Safety Monitoring Plan (DSMP). The plan may stand alone or be incorporated into other sections of the protocol and should describe the procedures for safety monitoring, reporting of unanticipated problems involving risks to subjects or others, descriptions of interim safety reviews and the procedures planned for transmitting the results to the IRB. This description should include information regarding an independent Data and Safety Monitoring Board (DSMB), if one exists, or an explanation why an independent data safety monitor is not necessary.

The IRB determines that the monitoring plan makes adequate provision for monitoring the reactions of subjects and the collection of data to ensure the safety of subjects and address problems that may arise over the course of the study. The overall elements of the monitoring plan may vary depending on the potential risks, complexity, and nature of the research study. The method and degree of monitoring needed is related to the degree of risk involved. Monitoring may be conducted in various ways or by various individuals or groups, depending on the size and scope of the research effort. These exist on a continuum from monitoring by the principal investigator in a small, low risk study to the establishment of an independent data and safety monitoring board for a large phase III clinical trial.

The factors the IRB will consider in determining whether the DSMP is adequate for the research are as follows:

1. Monitoring is commensurate with the nature, complexity, size and risk involved.

2. Monitoring is timely. Frequency should be commensurate with risk. Conclusions are reported to the IRB.

3. For low risk studies, continuous, close monitoring by the study investigator or an independent individual may be an adequate and appropriate format for monitoring, with prompt reporting of problems to the IRB, sponsor and regulatory bodies as appropriate.

4. For an individual Safety Monitor the plan must include:

· Parameters to be assessed

· Mechanism to assess the critical efficacy endpoints at intervals in order to determine when to continue, modify, or stop a study.

· Frequency of monitoring

· Procedures for reporting to the IRB

5. For a Data and Safety Monitoring Board, the plan must include:

· The name of the Data Safety Monitoring Board

· Where appropriate, is independent from the sponsor

· Availability of written reports

· Composition of the monitoring group (if a group is to be used): experts in all scientific disciplines needed to interpret the data and ensure patient safety. Clinical trial experts, biostatisticians, bioethicists, and clinicians knowledgeable about the disease and treatment under study should be part of the monitoring group or be available if warranted.

· Frequency and content of meeting reports

· The frequency and character of monitoring meetings (e.g., open or closed, public or private)

In general, it is desirable for a Data and Safety Monitoring Board (DSMB) to be established by the study sponsor for research that is blinded, involves multiple sites, involves vulnerable subjects, or employs high-risk interventions. For some studies the National Institutes of Health (NIH) require a DSMB. The IRB has the authority to require a DSMB as a condition for approval of research where it determines that such monitoring is needed. When DSMBs are utilized, IRBs conducting continuing review of research may rely on a current statement from the DSMB indicating that it has and will continue to review study-wide adverse events, interim findings, and any recent literature that may be relevant to the research, in lieu of requiring that this information be submitted directly to the IRB.

9.1.8 Privacy and Confidentiality

The IRB will determine whether adequate procedures are in place to protect the privacy of subjects and to maintain the confidentiality of the data.

Privacy is a subject’s control over the extent, timing, and circumstances of sharing oneself (physically, behaviorally, or intellectually) and private information with others.

Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical or academic record). Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects.

Identifiable information is information that would allow a researcher to readily ascertain the identity of an individual, either through direct or indirect identifiers.

The IRB must determine whether the activities in the research constitute an invasion of privacy. In order to make that determination, the IRB must obtain information regarding how the investigators are getting access to subjects or subjects’ private, identifiable information and the subjects’ expectations of privacy in the situation. Investigators must have appropriate authorization to access the subjects or the subjects’ information.

In developing strategies for the protection of subjects’ privacy, consideration should be given to:

a) Methods used to identify and contact potential participants

b) Settings in which an individual will be interacting with an investigator

c) Appropriateness of all personnel present for research activities

d) Methods used to obtain information about participants and the nature of the requested information

e) Information that is obtained about individuals other than the “target participants,” and whether such individuals meet the regulatory definition of “human subject” (e.g., a subject provides information about a family member for a survey). See Botkin, JR JAMA 2001; 285:207-211 for Recommendation for Investigators and Institutional Review Boards Regarding Privacy of Family Members in Research.

f) How to access the minimum amount of information necessary to complete the study

Confidentiality involves the methods that an investigator uses to ensure that information obtained by researchers about their subjects is not inappropriately divulged.

If anyone, including the investigator, can readily ascertain the identity of the subjects from the data, then the IRB must determine if appropriate protections are in place to minimize the likelihood that the information could be inappropriately divulged. Safeguards designed to protect confidentiality should be commensurate with the potential degree of harm from inappropriate disclosure. The PI will provide the information regarding the privacy and confidentiality of research subjects at the time of initial review through the completion of the application, protocol, and/or other applicable materials. The IRB will review all information received from the PI and determine whether or not the privacy and confidentiality of research subjects is sufficiently protected.

At the time of initial review, the IRB assesses whether there are adequate provisions to protect subject privacy and maintain confidentiality. The IRB does this through the evaluation of the methods used to obtain information about:

a) Subjects

b) Individuals who may be recruited to participate in studies

c) The use of personally identifiable records

d) The methods used to protect the confidentiality of research data

The IRB shall evaluate the effectiveness of proposed de-identification techniques, coding systems, encryption methods, storage facilities, access limitations, external protections (e.g., Certificate of Confidentiality), and other proposed safeguards in determining the adequacy of confidentiality protections. In reviewing confidentiality protections, the IRB shall consider the nature, probability, and magnitude of harms that would be likely to result from a disclosure of collected information outside the research.

9.1.9 Vulnerable Populations

At the time of initial review the IRB will consider the scientific and ethical reasons for including vulnerable subjects in research. The IRB may determine and require that, when appropriate, additional safeguards be put into place for vulnerable subjects, such as those with compromised decision-making capacity. Additional information regarding vulnerable populations appears elsewhere in this policy.

9.1.10 Compliance with all Applicable State and Local Laws

The IRB follows and must adhere to all applicable state and local laws in the jurisdictions where the research is taking place. The IRB relies on the General Counsel’s office for the interpretation and application of Oregon State law and the laws of any other jurisdiction where research is conducted as they apply to human subjects research.

All consent forms must be consistent with applicable state and local laws.

9.2 Possible IRB Actions and Determinations

Possible IRB actions and determinations include:

a) Human Subjects Research Determination

b) Engagement Determination

c) Approval in Principle

d) Acknowledge

e) Approve

f) Defer for minor revisions

g) Defer for major revisions

h) Disapprove

i) Close

j) Suspend

k) Terminate

9.2.1 Human Subjects Research Determination

Studies are considered “Not Human Subjects Research” (NHSR) if they do not meet the regulatory definitions of human subjects and/or research defined in the Common Rule (§46.102).

In addition, research using de-identified or coded information or specimens that were not collected by the current investigator, nor collected for the currently proposed project do not need IRB review. To be considered NHSR, the study team members must not be able to link the coded data or specimens back to the individual subjects. If the provider of the data or specimens has access to the identities of the subjects, the provider and recipient investigators must enter into a written agreement that states that under no circumstances will the identities of the subjects be released to the investigator (see OHRP Guidance on Research Involving Coded Private Information or Biological Specimens).

Determination Forms will be reviewed by a Coordinator who will then make a recommendation to the Administrator or Chair for final determination. A determination will then be issued to the investigator.

9.2.2 Engagement Determination

Under some circumstances, the OSU IRB may determine that the conduct of non-exempt research activities involving human subjects research do not engage the Institution in research and those activities will not require IRB review. Engagement determinations are made in accordance with OHRP’s 2008 Guidance on Engagement of Institutions in Human Subjects Research and their 2011 Correspondence on “Non-engaged” Scenarios.

An Institution is automatically considered to be engaged in human subjects research whenever it receives a direct HHS award to support such research. In such cases the awardees Institution bears ultimate responsibility for protecting human subjects under the award.

Engagement determinations should be made by the IRB, not investigators. Investigators who think that their project may not engage the Institution in research should complete and submit a Determination Form to the IRB for review. Determination Forms will be reviewed by a Coordinator who will then make a recommendation to the Administrator or Chair for final determination. A determination will then be issued to the investigator.

9.2.3 Approval in Principle

A request for an Approval in Principle must be sponsor-driven, rather than in anticipation of a request from the funding source. Applications for an Approval in Principle will be reviewed by a Coordinator, who will then make a recommendation to the Administrator or Chair for final approval. A formal notice, either approving or denying the application, will then be issued to the investigator.

9.2.4 Acknowledge

Submissions that may be acknowledged rather than approved include applications and other materials related to exempt research, reportable events, and documentation of relevant new information (e.g., progress reports to funding agencies).

9.2.5 Approve

Per OHRP guidance (2010), when an IRB conducts the initial review of a research project at a convened meeting and approves the research for one year without requiring either (a) changes to the protocol or informed consent document(s), or (b) submission of clarifications or additional documents, the effective date of the initial approval is the date of that IRB meeting. In such circumstances, the expiration date of the initial approval period and the date by which the first continuing review must occur may be as late as one year after the date of the IRB meeting at which the research project initially was approved (45 CFR 46.109(e)).

9.2.5.1 Period of Approval

At the time of initial review and at continuing review, the IRB will make a determination regarding the frequency of review of the research protocols. All protocols will be reviewed by the IRB at intervals appropriate to the degree of risk but no less than once per year. In some circumstances, a shorter review interval (e.g. biannually, quarterly, or after accrual of a specific number of participants) may be required (see below). The meeting minutes will reflect the IRB’s determination regarding review frequency.

9.2.5.2 Review More Often Than Annually

Unless specifically waived by the IRB, research that meets any of the following criteria will require review more often than annually:

a) Significant risk to research subjects (e.g., death, permanent or long lasting disability or morbidity, severe toxicity) without the possibility of direct benefit to the subjects

b) The involvement of especially vulnerable populations likely to be subject to coercion (e.g., terminally ill)

c) A history of serious or continuing non-compliance on the part of the PI

The following factors will also be considered when determining which studies require review more frequently than on an annual basis:

a) The probability and magnitude of anticipated risks to subjects

b) The likely medical condition of the proposed subjects

c) The overall qualifications of the PI and other members of the research team

d) The specific experience of the Principal Investigator and other members of the research team in conducting similar research

e) The nature and frequency of adverse events observed in similar research at this and other Institutions

f) The novelty of the research making unanticipated adverse events more likely

g) Any other factors that the IRB deems relevant

In specifying an approval period of less than one year, the IRB may define the period with either a time interval or a maximum number of subjects either studied or enrolled. If a maximum number of subjects studied or enrolled is used to define the approval period, it is understood that the approval period in no case can exceed one year and that the number of subjects studied or enrolled determines the approval period only when that number of subjects is studied or enrolled in less than one year. If an approval period of less than one year is specified by the IRB the reason for more frequent review must be documented in the minutes.

(top) 9.2.6 Defer for minor revisions

Deferred for minor revisions[7]: The Board determines that the submission cannot be approved without minor revisions. Examples of such revisions may include:

Confirmation of specific assumptions or understandings on the part of the IRB regarding how the research will be conducted (e.g., confirmation that the research excludes children);
Submission of additional documentation (e.g., certificate of ethics training);
Precise language changes to protocol or informed consent documents; or
Substantive changes to protocol or informed consent documents along with clearly stated parameters that the changes must satisfy.

For protocols reviewed by the full board, the needed revisions are agreed upon at the IRB meeting. If the precise language for the pending items is not agreed upon during the meeting, a vote for major revisions may still occur but the vote(s) on the phrasing of the pending items will occur via email prior to sending the notice to the PI. For protocols reviewed under expedited review, the needed revisions are designated by the reviewer(s). None of the required modifications can be related to the regulatory criteria for approval. These revisions are presented to the PI for incorporation by simple concurrence. Revisions must be made exactly as designated by the IRB or reviewer(s).

In order to receive approval for a protocol deferred for minor revisions:

· Full Board: The investigator’s response, the revised documents and the previously submitted documents are given to the IRB Chair, Vice Chair, a subcommittee of the IRB for review, the primary reviewer, or a qualified member of the IRB office (voting or non-voting) [see OHRP Guidance on IRB Approval of Research with Conditions, 11/10/2010]. The reviewer(s) will be determined at the time of the convened meeting when a vote for minor revisions has occurred. The reviewer(s) may verify the adequacy of the revisions and issue approval documents or return the submission as inadequately revised, without further action by the IRB.

· Expedited: The investigator’s response, the revised documents and the previously submitted documents are given to the primary reviewer, or a qualified member of the IRB office as indicated by the reviewer. The reviewer(s) may verify the adequacy of the revisions and issue approval documents or return the submission as inadequately revised.

Approval of the study documents will not be granted and certification will not be issued until all deficiencies, if any, are corrected to the satisfaction of the IRB or the reviewer(s).

The outcome of the IRB's deliberations is once again communicated to the investigator in writing.

The IRB's determination concerning the subsequent amended submission will be documented in the minutes of the next IRB meeting or in the file for expedited review.

Determination of Approval and Expiration Dates: Per OHRP guidance (2010), the effective date of the initial approval in this case is the date on which the IRB chairperson (or other individual(s) designated by the IRB) has reviewed and accepted as satisfactory all changes to the protocol or consent documents, or any other responsive materials, required by the IRB from the investigator. In such circumstances, the expiration date of the initial approval period, which is the date by which the first continuing review must occur, may be as late as one year after that effective date of initial IRB approval (45 CFR 46.109(e)).

The IRB records must include documentation of the date when the IRB chairperson (or designee) determined that all conditions of IRB approval have been satisfied and the approval becomes effective, and the expiration date of the initial IRB approval (45 CFR 46.102(h) and 46.115(a)).

9.2.7 Defer for major revisions

Deferred for major revisions: This action is taken when substantial modification or clarification is required, or insufficient information is provided to adequately assess the risks, benefits, or other aspects of the study. IRB approval of the proposed research must not occur until subsequent review of the material the PI submitted has been reviewed by the convened IRB or the expedited reviewer(s).

In order to receive approval for a protocol deferred for major revisions:

· Full Board: The investigator’s response must be submitted for review at a subsequent, convened meeting of the same IRB. The IRB Office provides the IRB with the investigator’s response, the revised documents and the previously submitted documents. The item is placed on the agenda for re-review at the next meeting.

· Expedited: The investigator’s response, the revised documents and the previously submitted documents are given to the same reviewer(s) for re-review.

Approval of the study documents will not be granted and certification will not be issued until all deficiencies are corrected to the satisfaction of the IRB or the reviewer(s).

The outcome of the IRB's deliberation is communicated to the investigator in writing.

The IRB's determination concerning the amended submission will be documented in the minutes of the IRB meeting or in the file for expedited review.

Note: Failure to submit a response to IRB-stipulated changes or inquires related to deferred protocols within 60 days of the IRB date of determination will result in administrative closure of the IRB file. The PI will receive notification of the closure of the IRB file, including an explanation for this action. An extension beyond 60 days may be granted by the IRB if sufficient cause is provided by the PI.

Determination of Approval and Expiration Dates: The effective date of the initial approval in this case is the date on which the convened Board has reviewed and accepted as satisfactory all changes to the protocol or consent documents, or any other responsive materials, required by the IRB from the investigator. In such circumstances, the expiration date of the initial approval period, which is the date by which the first continuing review must occur, may be as late as one year after that effective date of initial IRB approval (45 CFR 46.109(e)).

The IRB records must include documentation of the date when the IRB voted that all conditions of IRB approval have been satisfied and the approval becomes effective, and the expiration date of the initial IRB approval (45 CFR 46.102(h) and 46.115(a)).

9.2.8 Disapprove

Disapproved. The IRB has determined that the research cannot be conducted at OSU or by employees or agents o OSU or otherwise under the auspices of OSU.

9.2.9 Close

A study may be closed by an investigator when data collection and analysis of any identifiable data are complete. A study may also be administratively closed by the IRB staff if it expires outside of review (prior to the submission of a continuing review application). In either case, the IRB shall notify the PI of the closure in writing.

9.2.10 Suspend or Terminate

IRB approval may be suspended or terminated if research is not being conducted in accordance with IRB or regulatory requirements or has been associated with unexpected problems or serious harm to subjects.

Suspension of IRB approval is a directive of the convened IRB or IRB Chair or the Administrator to temporarily stop some or all previously approved research activities. Suspension directives made by the IRB Chair or Administrator must be reported to a meeting of the convened IRB. Suspended protocols remain open and require continuing review.

Termination of IRB approval is a directive of the convened IRB to stop permanently all activities in a previously approved research protocol. Terminated protocols are considered closed and no longer require continuing review. Terminations of protocols approved under expedited review must be made by the convened IRB.

The IRB shall notify the PI in writing of such suspensions or terminations and shall include a statement of the reasons for the IRB's actions. The terms and conditions of the suspension must be explicit. The investigator shall be provided with an opportunity to respond in person or in writing.

When study approval is suspended or terminated by the convened IRB or an authorized individual, in addition to stopping all research activities, the convened IRB or individual ordering the suspension or termination will notify any subjects currently participating that the study has been suspended or terminated. The convened IRB or individual ordering the suspension or termination will consider whether procedures for withdrawal of enrolled subjects are necessary to protect their rights and welfare of subjects (see “Protection of Currently Enrolled Participants”).

If follow-up of subjects for safety reasons is permitted/required by the convened IRB or individual ordering the suspension or termination, the convened IRB or individual ordering the suspension or termination will require that the subjects should be so informed and that any adverse events/outcomes be reported to the IRB and the sponsor.

Investigator MUST continue to provide reports on adverse events and unanticipated problems to both the IRB and sponsor just as if there had never been a suspension (i.e., all events that need to be reported during a study need to continue to be reported during the suspension period.)

Note: Suspension or termination of protocols approved by the IRB can also be issued by Institutional officials acting outside of and unrelated to the IRB (i.e., not necessarily related to protecting the rights and welfare of study participants). Such Institutional actions can be made by the President, Vice Presidents, Provost, Senior Vice Provost, Vice Provosts, and Deans. Such Institutional actions may be made for any reason in furtherance of the Institution’s interest provided, however, that the aggrieved PI is entitled to all rights and procedures afforded to him/her under the OSU Grievance Policy.

(top) 9.2.11 Investigator Hold

An investigator may request an administrative hold on a protocol when the investigator wishes to temporarily or permanently stop some or all approved research activities. An administrative hold is initiated by an investigator. Administrative holds are not suspensions or terminations and may therefore be lifted at the discretion of the investigator.

Investigators must notify the IRB in writing that:

a) They are voluntarily placing a study on administrative hold

b) A description of the research activities that will be stopped

c) Proposed actions to be taken to protect current participants

d) Actions that will be taken prior to IRB approval of proposed changes in order to eliminate apparent immediate harm

Upon receipt of written notification of the investigator the IRB staff places the research on the agenda for review.

The IRB Chair and/or Administrator, in consultation with the investigators, determine whether any additional procedures need to be followed to protect the rights and welfare of current participants as described in “Protection of currently enrolled participants” below.

The IRB Chair and/or Administrator, in consultation with the investigators, determine how and when currently enrolled participants will be notified of the administrative hold.

Investigators may request a modification of the administrative hold by submitting a project revision. The revision may include ending the administrative hold.

9.2.12 Protection of Currently Enrolled Participants

Before an administrative hold, termination, or suspension, is put into effect the convened IRB or IRB designee considers whether any additional procedures need to be followed to protect the rights and welfare of current participants. Such procedures might include:

· Transferring participants to another investigator

· Making arrangements for clinical care outside the research

· Allowing continuation of some research activities under the supervision of an independent monitor

· Requiring or permitting follow-up of participants for safety reasons

· Requiring adverse events or outcomes to be reported to the IRB and the sponsor

· Notification of current participants

· Notification of former participants

9.3 Reporting IRB Actions

All IRB actions are communicated to the Principal Investigator (PI), or designated primary contact person for the protocol, in writing within ten (10) working days via a letter prepared by the IRB staff. For an approval, along with written notification of approval, a copy of the approved consent form containing the IRB footer with the dates of the approval and expiration on each sheet will be sent to the investigator. For a deferral, the notification will include the modifications required for approval along with the basis for requiring those modifications. For a disapproval, termination or suspension, the notification will include the basis for making that decision.

All letters to investigators must be filed in the protocol files maintained by the IRB.

The IRB reports its findings and actions to the Institution in the form of its minutes, which are distributed by IRB staff to the Institutional official and are stored permanently and securely in the IRB Office or electronically on a secure server.

9.4 Appeal of IRB Decisions

When an IRB protocol presented at a convened meeting is disapproved or deferred, the IRB will notify the PI in writing about the specific deficiencies and the modifications that are necessary for appropriate IRB approval. The IRB shall include in its written notification a statement of the reasons for its decision and give the investigator an opportunity to respond in person or in writing.

In cases where there is disagreement between the IRB and the PI regarding the nature and extent of the requested changes and these disagreements cannot be resolved, the PI and/or the IRB may make an appeal to the IO. The IO may organize a meeting to help facilitate discussion between the IRB and the PI. While the IO may provide input and make recommendations to the IRB for expeditious resolution of the matter, final determinations for approval remain under the purview of the IRB.

Since the IO is responsible for policies and procedures followed by the IRB, the IO may review IRB decisions to ensure that the decision-making process is appropriate. If the IO has concerns regarding the process that the IRB has followed in making a decision, he/she may require the IRB to reconsider the decision. However, the IO cannot overrule an IRB decision.

10. Obtaining Informed Consent from Research Subjects

10.1 Policy

No investigator conducting research under the auspices of OSU may involve a human being as a subject in research without obtaining the legally effective informed consent of the subject or the subject’s legally authorized representative unless a waiver of consent has been approved by the IRB in accordance with the federal regulations and these policies and procedures. Except as provided by these procedures, informed consent must be documented by the use of a written consent form approved by the IRB.

The IRB will evaluate both the consent process and the procedures for documenting informed consent to ensure that adequate informed consent is obtained from participants.

The following procedures describe the requirements for obtaining consent from participants in research conducted under the auspices of OSU.

10.2 Definitions

Legally Authorized Representative. A legally authorized representative is an individual or body authorized under applicable law to provide permission on behalf of a prospective subject to the subject's participation in the procedure(s) involved in the research.

Legal guardian. "Guardian" means an individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care. In Oregon, a “Guardian” of a minor means a person or agency having the powers and responsibilities of a parent to make binding decisions for a child.”

10.3 Basic Requirements

The requirement to obtain the legally effective informed consent of individuals before involving them in Research is one of the central protections provided for by the Federal regulations and the OSU IRB. Investigators are required to obtain legally effective informed consent from a subject or the subject’s Legally Authorized Representative. When informed consent is required, it must be sought prospectively, and properly documented.

The informed consent process involves three key features: (1) disclosing to the prospective human subject information needed to make an informed decision; (2) facilitating the understanding of what has been disclosed; and (3) promoting the voluntariness of the decision about whether or not to participate in the Research.

Informed consent is a process of information exchange that may include reading and signing the consent document. The informed consent process is the critical communication link between the prospective Human Subject and an Investigator, beginning with the initial approach of an Investigator and continuing through the completion of the study. Investigators must have received the appropriate training and be knowledgeable about the study protocol in order that they may answer questions to help provide understanding to the study participant or potential study participant. The following are some of the ways that the exchange of information between the Investigator and study participant may occur:

· Face to face contact

· Mail (paper or electronic)

· Telephone

· Fax

· Initial screen of an online form or first page of a paper form

Investigators must obtain consent prior to entering a subject into a study and/or conducting any study activities, unless consent is waived by the IRB.

If someone other than the investigator obtains consent from a subject, the investigator needs to formally delegate this responsibility, and the person so delegated must have received appropriate training to perform this activity. The person so delegated must be knowledgeable enough about both the research to be conducted and the consent process, to be able to answer questions about the study and to assess whether or not the subject is able to comprehend the information provided.

Sample or draft consent documents may be developed by a Sponsor or cooperative study group. However, the IRB-of-record is the final authority on the content of the consent documents that are presented to the prospective study subjects.

These informed consent requirements are not intended to preempt any applicable federal, state, or local laws that require additional information to be disclosed for informed consent to be legally effective.

10.4 Informed Consent Process

Informed consent must be obtained under the following circumstances:

a) Informed consent may only be obtained from subjects who have the legal and mental capacity to give consent. For subjects without that capacity, consent must be obtained from a legal guardian or a legally authorized representative.

b) The informed consent process shall be sought under circumstances that provide the subject (or legally authorized representative) with sufficient opportunity to consider whether or not to participate.

c) The informed consent process shall be sought under circumstances that minimize the possibility of coercion or undue influence.

d) The informed consent information must be presented in language that is understandable to the subject (or legally authorized representative).

For subjects who are not fluent in English, informed consent must be obtained in a language that is understandable to the subject (or the subject’s legally authorized representative). In accordance with this policy, the IRB requires that the informed consent process include an appropriate and qualified translator when the prospective subject does not understand the language of the person who is obtaining consent. A qualified translator is one who is either a professional translator, an individual with a master’s degree in languages, or a native speaker of the relevant language(s).

The informed consent documents must be in a language understandable to the proposed participants. Therefore, the IRB will review the document and a back translation of the exact content contained in the foreign language informed consent document which must be provided by the Investigator, with the credentials of the translator detailed in the IRB application or amendment form. The IRB cannot verify the accuracy of translated documents. Therefore, verification of the back translation must be made available before the IRB may approve the translated documents.

The requirement for back translation will be waived if the translation is certified by a qualified translator. Translated documents will be processed (stamped) in a manner consistent with documents presented in English.

e) The informed consent process may not include any exculpatory language through which the subject is made to waive, or appear to waive any of the subject’s legal rights or through which the investigator, the sponsor, OSU employees or agents are released from liability for negligence, or appear to be so released.

f) The PI is responsible for insuring that each prospective subject is adequately informed about all aspects of the research and understands the information provided.

10.5 Basic Elements of Informed Consent

To be valid, the consent process must provide the following basic elements of information to potential subjects:

1. A statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures which are experimental; a description of any reasonably foreseeable risks or discomforts to the subject;

2. A description of any benefits to the subject or to others which may reasonably be expected from the research;

3. A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject;

4. A statement describing the extent, if any, to which confidentiality of records identifying the subject must be maintained;

5. For research involving more than minimal risk, an explanation as to the availability of medical treatment in the case of research-related injury, including who will pay for the treatment and whether other financial compensation is available;

6. An explanation of whom to contact on the research team for answers to pertinent questions about the research or to voice concerns or complaints about the research, and whom to contact in the event of a research-related injury to the subject;

7. Contact information for the IRB to obtain answers to questions about the research; to voice concerns or complaints about the research; to obtain answers to questions about their rights as a research participant; in the event the research staff could not be reached; and in the event the subject wishes to talk to someone other than the research staff.

8. A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled;

9. For FDA-regulated studies, the possibility that the Food and Drug Administration may inspect the records needs to be included in the statement regarding subject confidentiality.

10. For applicable FDA-regulated clinical trials, informed consent documents must include a specific statement that refers to the trial’s description on www.ClinicalTrials.gov.

Additional elements of informed consent to be applied, as appropriate:

1. A statement that the particular treatment or procedure may involve risks to the subject, which are currently unforeseeable. (For example: Include when the research involves investigational test articles or other procedures in which the risks to subjects is not well known.)

2. A statement that if the subject is or becomes pregnant, the particular treatment or procedure may involve risks to the embryo or fetus, which are currently unforeseeable. (For example: Include when the research involves pregnant women or women of childbearing potential and the risk to fetuses of the drugs, devices, or other procedures involved in the research is not well known.)

3. Anticipated circumstances under which the subject’s participation may be terminated by the investigator without regard to the subject’s consent.

4. Any additional costs to the subject that may result from participation in the research.

5. The consequences of a subject’s decision to withdraw from the research. (For example: Include when withdrawal from the research is associated with adverse consequences.

6. Procedures for orderly termination of participation by the subject. (For example: Include when the protocol describes such procedures.)

7. A statement that significant new findings developed during the course of the research which may relate to the subject’s willingness to continue participation will be provided to the subject. (For example: Include when the research is long term and interim information is likely to be developed during the conduct of the research.)

8. The approximate number of subjects involved in the study. (For example: Include when the research involves more than minimal risk.)

10.6 Documentation of Informed Consent

Unless waived by the IRB, informed consent must be documented by the use of a written consent form approved by the IRB.

1. Informed consent is documented by the use of a written consent form approved by the IRB and signed and dated by the subject or the subject's legally authorized representative at the time of consent.

2. A copy of the signed and dated consent form must be given to the person signing the form.

3. The consent form may be either of the following:

a. A written consent document that embodies the basic and required additional elements of informed consent. The consent form may be read to the subject or the subject's legally authorized representative, but the subject or representative must be given adequate opportunity to read it before it is signed; or

b. A short form written consent document stating that the elements of informed consent have been presented orally to the subject or the subject's legally authorized representative.

When this method is used:

i. There must be a witness to the oral presentation; and

ii. The IRB must approve a written summary of what is to be signed by the subject or representative; and

iii. The witness must sign both the short form and a copy of the summary; and

iv. The person actually obtaining consent must sign a copy of the summary; and

v. A copy of the summary must be given to the subject or representative, in addition to a copy of the short form.

When this procedure is used with subjects who do not speak English, (i) the oral presentation and the short form written document should be in a language understandable to the subject; (ii) the IRB-approved English language informed consent document may serve as the summary; and (iii) the witness should be fluent in both English and the language of the subject. When the person obtaining consent is assisted by a translator, the translator may serve as the witness.

The IRB must receive all foreign language versions of the short form document as a condition of approval, but not necessarily at the time of initial submission. If the study is to be reviewed by the full board, expedited review of these versions is acceptable after initial approval if the protocol, the full English language informed consent document, and the English version of the short form document have already been approved by the convened IRB.

10.7 Waiver of Informed Consent

An IRB may approve a consent procedure that does not include, or that alters, some or all of the elements of informed consent set forth above; or waive the requirements to obtain informed consent, provided the IRB finds and documents that:

a) The research involves no more than minimal tangible or intangible risk to the subjects;

b) The waiver or alteration will not adversely affect the rights and welfare of the subjects;

c) The research could not practicably be carried out without the waiver or alteration; and

d) Whenever appropriate, the subjects must be provided with additional pertinent information after participation.

In addition, an IRB may approve a consent procedure that does not include, or that alters, some or all of the elements of informed consent; or waive the requirements to obtain informed consent, provided the IRB finds and documents that:

a) The research or demonstration project is to be conducted by or subject to the approval of state or local government officials and is designed to study, evaluate, or otherwise examine:

i. Public benefit or service programs

ii. Procedures for obtaining benefits or services under those programs

iii. Possible changes in or alternatives to those programs or procedures; or

iv. Possible changes in methods or levels of payment for benefits or services under those programs.

b) The research could not practicably be carried out without the waiver or alteration.

FDA regulations do not provide for waivers of informed consent except in emergency situations.

10.8 Waiver of Documentation of Informed Consent

The IRB may waive the requirement for the investigator to obtain a signed consent form for some or all subjects if it finds either that the:

a) Only record linking the subject and the research would be the consent document and the principle risk would be potential harm resulting from a breach of confidentiality; or
Note 1: Subjects must be asked whether they want documentation linking them with the research, and their wishes must govern. (Example: domestic violence research where the primary risk is discovery by the abuser that the subject is talking to researchers.)
Note 2: In order to waive written documentation of consent where the only record linking the participant and the research would be the consent document, the IRB has to determine that the research was not FDA-regulated.

b) The research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context. Procedures such as non-sensitive surveys, questionnaires and interviews generally do not require written consent when conducted by non-researchers.

In cases in which the documentation requirement is waived, the IRB requires the investigator to provide in the application materials a written summary of the information to be communicated to the subject, and the IRB will consider whether to require the investigator to provide subjects with a written statement regarding the research.

(top) 10.9 Deception in Research[8]

Definition: Deception occurs as the result of investigators providing false or incomplete information to participants for the purpose of misleading research subjects.

The IRB accepts the need for certain types of studies to employ strategies that include deception. However, employment of such strategies must be justified. In general, deception is not acceptable if, in the judgment of the IRB, the participant may have declined to participate had they been informed of the true purpose of the research.

In the event that a study includes the use of deception, the investigator must provide:

• Confirmation that the study design meets all of the criteria for a waiver of consent [§46.116(d)][9]

• Justification for the deception

• A description of the manner of deception and how the deception will take place

• An explanation as to why deception is necessary to this protocol

• A description of whether the deception results in any increased risk to participants

• A indication of whether the deception may affect a subject’s willingness to participate in research

• A description of the post-study debriefing that includes offering the participant the option to withdraw their data from the study

o If an exception to the requirement for a debriefing is requested, the study must be reviewed by the full board

• A description of any previous use of deception in similar research and a summary of any actual harms or reactions from participants to the use of deception

• A description of alternatives to deception that were considered and an explanation as to why these alternatives were rejected

11. Vulnerable Subjects in Research

11.1 Policy

When some or all of the participants in research conducted under the auspices of OSU are likely to be vulnerable to coercion or undue influence or have diminished decision-making capacity, the research must include additional safeguards to protect the rights and welfare of these participants. Examples of vulnerable populations include children, prisoners, pregnant women, mentally disable persons, and economically or educationally disadvantaged persons. The IRB must ensure that all of the regulatory requirements for the protection of vulnerable subjects are met and that appropriate additional protections for vulnerable subjects are in place.

The following procedures describe the requirements for involving vulnerable participants in research.

11.2 Definitions (top)

Children are persons who have not attained the legal age for consent, under the applicable law of the jurisdiction in which the research will be conducted. According to Oregon law, minors are persons under the age of eighteen. The general rule in Oregon, however, is that a person may consent for his or her own medical care at the age of fifteen (15). Other statutes provide minors with the right to consent to certain types of medical care. For example: emancipated minors, certain minors seeking care for drug addiction, sexually transmitted diseases, birth control, emotional disorders, or mental health treatment. Because Oregon law does not specifically address consent of children with majority status to research, the OSU IRB will review issues of consent related to enrollment of these children in research on a case-by-case basis.

NOTE: For research conducted in jurisdictions other than Oregon, the research must comply with the laws regarding the legal age of consent in all relevant jurisdictions. OSU’s Office of General Counsel will be consulted with regard to the laws in other jurisdictions.

Guardian means an individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care. In Oregon, a “Guardian” of a minor means a person or agency having the powers and responsibilities of a parent to make binding decisions for a child.”

NOTE: For research conducted in jurisdictions other than Oregon, the research must comply with the laws regarding guardianship in all relevant jurisdictions. OSU’s Office of General Counsel will be consulted with regard to the laws in other jurisdictions.

Fetus means the product of conception from implantation until delivery.

Dead fetus means a fetus that exhibits neither heartbeat, spontaneous respiratory activity, spontaneous movement of voluntary muscles, nor pulsation of the umbilical cord.

Delivery means complete separation of the fetus from the woman by expulsion or extraction or any other means.

Neonate means a newborn.

Viable, as it pertains to the neonate, means being able, after delivery, to survive (given the benefit of available medical therapy) to the point of independently maintaining heartbeat and respiration.

Nonviable neonate means a neonate after delivery that, although living, is not viable.

Pregnancy encompasses the period of time from implantation until delivery. A woman shall be assumed to be pregnant if she exhibits any of the pertinent presumptive signs of pregnancy, such as missed menses, until the results of a pregnancy test are negative or until delivery.

Prisoner is any individual involuntarily confined or detained in a penal Institution. The term is intended to encompass individuals sentenced to such an Institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures that provide alternatives to criminal prosecution or incarceration in a penal Institution, and individuals detained pending arraignment, trial, or sentencing.

Surrogate Consent is consent obtained from a legally authorized representative on behalf of a participant determined to lack decision-making capacity.

(top) 11.3 Involvement of Vulnerable Populations

If the IRB reviews research that involves categories of participants vulnerable to coercion or undue influence, the review process will include one or more individuals who are knowledgeable about or experienced in working with these participants. For example, the IRB will include one or more individuals who are knowledgeable about or experienced in working with children, prisoners, or adults with limited decision-making capacity, when reviewing research that involves individuals from these populations.

45 CFR 46 has additional subparts designed to provide extra protections for vulnerable populations that also have additional requirements for IRBs.

Subpart B - Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research

Subpart C - Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects

Subpart D - Additional Protections for Children Involved as Subjects in Research

DHHS-funded research that involves any of these populations must comply with the requirements of the relevant subparts. Research funded by other federal agencies may or may not be covered by the subparts.

OSU limits the application of the FWA to federally funded research. Consequently, under OSU’s FWA the subparts only apply to DHHS-funded research and research funded by other federal agencies that require compliance with the subparts (FDA regulations include Subpart D, which applies to all FDA-regulated research). The following policies and procedures, which are based on the subparts, apply to all research regardless of funding. The individual sections describe how the subparts apply to DHHS-funded research.

(top) 11.4 Responsibilities

The PI is responsible for identifying the potential for enrolling vulnerable subjects in the research proposal. The PI is responsible for identifying subjects who are at risk for impaired decisional capacity.

The IRB shall include representation, either as members or ad hoc consultants, individual(s) who have experience with the vulnerable populations involved in a given research proposal.

The IRB reviews the PI’s justifications for including vulnerable populations in the research to assess appropriateness of the research proposal.

The IRB must ensure that additional safeguards have been included in each study to protect the rights and welfare of vulnerable subjects as needed at the time of initial review of the research proposal.

Information reviewed as part of the continuing review process should include the number of participants considered as members of specific vulnerable populations and how many, if any, required independent monitoring (see below regarding monitoring).

For studies that do not have or are not required to have a Data and Safety Monitoring Board (DSMB) or a Data Monitoring Committee and have entered vulnerable subjects, the IRB needs to carefully review the safety monitoring plan, if one was required as part of the initial submission.

(top) 11.5 Procedures

Initial Review of Research Proposal:

a) The PI identifies the potential to enroll vulnerable subjects in the proposed research and provides the justification for their inclusion in the study.

b) The IRB evaluates the proposed plan for consent of the specific vulnerable populations involved. If the research involves adults unable to consent, the IRB evaluates the proposed plan for obtaining permission from legally authorized representatives.

c) The IRB evaluates and approves the proposed plan for the assent of participants.

d) The IRB evaluates the research to determine the need for additional protections and consideration of the use of a data and safety monitoring board, committee, or plan as appropriate.

e) The PI provides appropriate safeguards to protect the subject’s rights and welfare, which may include the addition of an independent monitor. The independent monitor is a qualified individual not involved in the research study who will determine the subject’s capacity to provide voluntary informed consent.

f) The IRB assesses the adequacy of additional protections for vulnerable populations provided by the PI.

11.6 Research Involving Pregnant Women, Human Fetuses and Neonates

11.6.1 Research Involving Pregnant Women or Fetuses (top)

For research not funded by DHHS, and where the risk to the fetus is no more than minimal, no additional safeguards are required and there are no restrictions on the involvement of pregnant women in research.

Research not funded by DHHS: Pregnant women or fetuses may be involved in research involving more than minimal risk to fetuses if all of the conditions below are met.

DHHS-funded research: 45 CFR Subpart B applies to all research involving pregnant women. Under 45 CFR Subpart B, pregnant women or fetuses may be involved in research (minimal risk or greater) if all of the conditions below are met.

Conditions:

1. Where scientifically appropriate, pre-clinical studies, including studies on pregnant animals, and clinical studies, including studies on non-pregnant women, have been conducted and provide data for assessing potential risks to pregnant women and fetuses;

2. The risk to the fetus is caused solely by interventions or procedures that hold out the prospect of direct benefit for the woman or the fetus;

3. Any risk is the least possible for achieving the objectives of the research;

4. If the research holds out the prospect of direct benefit to the pregnant woman, the prospect of a direct benefit both to the pregnant woman and the fetus, then the consent of the pregnant woman is obtained in accord with the provisions for informed consent;

5. If the research holds out the prospect of direct benefit solely to the fetus then the consent of the pregnant woman and the father is obtained in accord with the provisions for informed consent, except that the father's consent need not be obtained if he is unable to consent because of unavailability, incompetence, or temporary incapacity or the pregnancy resulted from rape or incest.

6. Each individual providing consent under paragraph 4 or 5 of this section is fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate;

7. For children who are pregnant, assent and permission are obtained in accord with the provisions of permission and assent;

8. No inducements, monetary or otherwise, will be offered to terminate a pregnancy;

9. Individuals engaged in the research will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy; and

10. Individuals engaged in the research will have no part in determining the viability of a neonate.

(top) 11.6.2 Research involving neonates

Neonates of uncertain viability and nonviable neonates may be involved in research if all of the following conditions are met:

1. Where scientifically appropriate, preclinical and clinical studies have been conducted and provide data for assessing potential risks to neonates.

2. Each individual providing consent is fully informed regarding the reasonably foreseeable impact of the research on the neonate.

3. Individuals engaged in the research will have no part in determining the viability of a neonate.

4. The requirements of Neonates of Uncertain Viability or Nonviable Neonates (see below in this section) have been met as applicable.

Neonates of Uncertain Viability. Until it has been ascertained whether or not a neonate is viable, a neonate may not be involved in research covered by this subpart unless the following additional conditions have been met:

The IRB determines that:

1. The research holds out the prospect of enhancing the probability of survival of the neonate to the point of viability, and any risk is the least possible for achieving that objective, or

2. The purpose of the research is the development of important biomedical knowledge which cannot be obtained by other means and there will be no added risk to the neonate resulting from the research; and

3. The legally effective informed consent of either parent of the neonate or, if neither parent is able to consent because of unavailability, incompetence, or temporary incapacity, the legally effective informed consent of either parent's legally authorized representative is obtained in accord with the provisions of permission and assent, except that the consent of the father or his legally authorized representative need not be obtained if the pregnancy resulted from rape or incest.

Nonviable Neonates. After delivery, nonviable neonates may not be involved in research covered by this subpart unless all of the following additional conditions are met:

1. Vital functions of the neonate will not be artificially maintained;

2. The research will not terminate the heartbeat or respiration of the neonate;

3. There will be no added risk to the neonate resulting from the research;

4. The purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means; and

5. The legally effective informed consent of both parents of the neonate is obtained in accord with the provisions of permission and assent, except that the waiver and alteration of the provisions of permission and assent do not apply.

6. However, if either parent is unable to consent because of unavailability, incompetence, or temporary incapacity, the informed consent of one parent of a nonviable neonate will suffice to meet the requirements of this paragraph, except that the consent of the father need not be obtained if the pregnancy resulted from rape or incest. The consent of a legally authorized representative of either or both of the parents of a nonviable neonate will not suffice to meet the requirements of this paragraph.

Viable Neonates. A neonate, after delivery, that has been determined to be viable may be included in research only to the extent permitted by and in accord with the requirements of IRB Review Process and Research Involving Children.

11.6.3 Research Involving, After Delivery, the Placenta, the Dead Fetus or Fetal Material

Research involving, after delivery, the placenta; the dead fetus; macerated fetal material; or cells, tissue, or organs excised from a dead fetus, must be conducted only in accord with any applicable Federal, State, or local laws and regulations regarding such activities.

If information associated with material described above in this section is recorded for research purposes in a manner that living individuals can be identified, directly or through identifiers linked to those individuals, those individuals are research subjects and all pertinent sections of this manual are applicable.

11.6.4 Research Not Otherwise Approvable

11.6.4.1 Research Not Funded by DHHS

If the IRB finds that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of pregnant women, fetuses or neonates; and the research is not approvable under the above provisions, then the IRB will consult with a panel of experts in pertinent disciplines (for example: science, medicine, ethics, law). Based on the recommendation of the panel, the IRB may approve the research based on either:

1. That the research in fact satisfies the conditions of detailed above, as applicable; or

2. The following:

a. The research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of pregnant women, fetuses or neonates;

b. The research will be conducted in accord with sound ethical principles; and

c. Informed consent will be obtained in accord with the provisions for informed consent and other applicable sections of this manual.

11.6.4.2 Research Funded by DHHS

DHHS-funded research that falls in this category must be approved by the Secretary of Health and Human Services. If the IRB finds that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of pregnant women, fetuses or neonates; and the research is not approvable under the above provisions, then the research will be sent to OHRP for DHHS review.

11.7 Research Involving Prisoners

The following applies to all research involving prisoners, regardless of funding source. The requirements in this section are consistent with Subpart C of 45 CFR 46.

11.7.1 Applicability

This policy applies to all biomedical and behavioral research conducted under the auspices of OSU involving prisoners as subjects. Even though the IRB may approve a research protocol involving prisoners as subjects according to this policy, investigators are still subject to the Administrative Regulations of the Oregon Department of Corrections and any other applicable State or local law. [45 CFR 46.301]

11.7.2 Purpose

Inasmuch as prisoners may be under constraints because of their incarceration which could affect their ability to make a truly voluntary and uncoerced decision whether or not to participate as subjects in research, it is the purpose of this section to provide additional safeguards for the protection of prisoners involved in activities to which this section is applicable.

11.7.3 Composition of the IRB

In addition to satisfying the general requirements detailed in the IRB section of this manual, when reviewing research involving prisoners, the IRB must also meet the following requirements:

· A majority of the IRB (exclusive of prisoner members) must have no association with the prison(s) involved, apart from their membership on the IRB.

· At least one member of the IRB must be a prisoner, or a prisoner representative with appropriate background and experience to serve in that capacity, except that where a particular research project is reviewed by more than one IRB, only one IRB need satisfy this requirement. This must be a full voting member – not a consultant. A note may be included on the FWA that this member does not count towards quorum because the member in this role will only be present in the event that a protocol involving prisoners is under review.

11.7.4 Review of Research Involving Prisoners

1. At the recommendation of the Office for Human Research Protections (OHRP), OSU’s IRB has elected to have all research involving prisoners reviewed by the convened Board (full Board review). However, expedited categories 8 and 9 may apply to continuing review of research involving prisoners.

2. The prisoner representative must review research involving prisoners, focusing on the requirements in Subpart C.

3. The prisoner representative must receive all review materials pertaining to the research (same as primary reviewer)

4. The prisoner representative must be present at a convened meeting when the research involving prisoners is reviewed. If the prisoner representative is not present, research involving prisoners cannot be reviewed or approved. The prisoner representative may attend the meeting by phone, video-conference, or webinar, as long as the representative is able to participate in the meeting as if they were present in person at the meeting.

5. The prisoner representative must present his/her review either orally or in writing at the convened meeting of the IRB when the research involving prisoners is reviewed.

6. Modifications.

a. Minor modifications to research may be reviewed using the expedited procedure described below, using either of the two procedures described based on the type of modification.

b. Modifications involving more than a minor change reviewed by the convened IRB must use the same procedures for initial review including the responsibility of the prisoner representative to review the modification and participate in the meeting (as described above).

7. Continuing review. Continuing review must use the same procedures as the initial review including the responsibility of the prisoner representative to review the continuing review materials. Expedited categories 8 and 9 may apply.

8. Expedited Review

a. Research involving individuals who are incarcerated may be reviewed by an expedited procedure under any of the following three circumstances:

i. Minor changes in previously approved research during the period (of one year of less) for which approval is authorized

ii. Continuing review of research previously approved by the convened IRB as follows:

1. 1. 1. Where (i) the research is permanently closed to the enrollment of new subjects; (ii) all subjects have completed all research-related interventions; and (iii) the research remains active only for long-term follow-up of subjects; or
    2. Where no subjects have been enrolled and no additional risks have been identified; or
    3. Where the remaining research activities are limited to data analysis.
  2. Continuing review of research, not conducted under an investigational new drug application or investigational device exemption where categories two (2) through eight (8) do not apply but the IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk and no additional risks have been identified.
2. In each of the circumstances in paragraph (a) of this section, the expedited review must be completed by the prisoner representative.

11.7.5 Incarceration of an Enrolled Subject

If a participant becomes a prisoner while enrolled in a research study that was not reviewed according to Subpart C and Subpart C applies, the IRB must:

1. Confirm that the participant meets the definition of a prisoner.

2. Terminate enrollment or review the research study under Subpart C if it is feasible for the participant to remain in the study.

3. Before terminating the enrollment of the incarcerated participant the IRB should consider the risks associated with terminating participation in the study. If the participant cannot be terminated for health or safety reasons, one of two options are available:

a. Keep the participant enrolled in the study and review the research under Subpart C. If some the requirements of Subpart C cannot be met, but it is in the best interests of the participant to remain in the study, keep the participant enrolled and inform OHRP of the decision along with the justification.

b. Remove the participant from the study and keep the participant on the study intervention under an alternate mechanism such as compassionate use, off label use, etc.

4. If a participant is incarcerated temporarily while enrolled in a study.

a. Keep the participant enrolled if the temporary incarceration has no effect on the study

b. Handle according to the above guidance, if the temporary incarceration has an effect on the study

(top) 11.7.6 Additional Duties of the IRB

In addition to all other responsibilities prescribed for IRB in other sections of this manual, the IRB will review research involving prisoners and approve such research only if it finds that:

· The research falls into one of the following permitted categories [45 CFR 46.306]:

o Study of the possible causes, effects, and processes of incarceration, and of criminal behavior, provided that the study presents no more than minimal risk and no more than inconvenience to the subjects;

o Study of prisons as Institutional structures or of prisoners as incarcerated persons, provided that the study presents no more than minimal risk and no more than inconvenience to the subjects;

o Research on conditions particularly affecting prisoners as a class (for example, research on social and psychological problems such as alcoholism, drug addiction, and sexual assaults);

o Research on practices, both innovative and accepted, which have the intent and reasonable probability of improving the health or well-being of the subject.

· Any possible advantages accruing to the prisoner through his or her participation in the research, when compared to the general living conditions, medical care, quality of food, amenities and opportunity for earnings in the prison, are not of such a magnitude that his or her ability to weigh the risks of the research against the value of such advantages in the limited choice environment of the prison is impaired;

· The risks involved in the research are commensurate with risks that would be accepted by non-prisoner volunteers;

· Procedures for the selection of subjects within the prison are fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners. Unless the principal investigator provides to the IRB justification in writing for following some other procedures, control subjects must be selected randomly from the group of available prisoners who meet the characteristics needed for that particular research project;

· The information is presented in language which is understandable to the subject population;

· Adequate assurance exists that the Parole Board will not take into account a prisoner's participation in the research in making decisions regarding parole, and each prisoner is clearly informed in advance that participation in the research will have no effect on his or her parole; and

· Where the IRB finds there may be a need for follow-up examination or care of subjects after the end of their participation, adequate provision has been made for such examination or care, taking into account the varying lengths of individual prisoners' sentences, and for informing subjects of this fact.

11.7.7 Certification to HHS

This section only applies to research that is conducted or funded by DHHS.

Under 45 CFR 46.305(c), the Institution responsible for conducting research involving prisoners that is supported by HHS shall certify to the Secretary (through OHRP) that the IRB has made the seven findings required under 45 CFR 46.305(a). For all HHS conducted or supported research OSU’s IRB will send to OHRP a certification letter to this effect, which will also include the name and address of the Institution and specifically identify the research protocol in question and any relevant HHS grant application or protocol. HHS conducted or supported research involving prisoners as subjects may not proceed until OHRP issues its approval in writing to OSU on behalf of the Secretary under 45 CFR 46.306(a)(2).

Under its authority at 45 CFR 46.115(b), OHRP requires that the Institution responsible for the conduct of the proposed research also submit to OHRP a copy of the research proposal so that OHRP can determine whether the proposed research involves one of the categories of research permissible under 45 CFR 46.306(a)(2), and if so, which one. The term "research proposal" includes the IRB-approved protocol, any relevant HHS grant application or proposal, any IRB application forms required by the IRB, and any other information requested or required by the IRB to be considered during initial IRB review.

11.7.8 Waiver for Epidemiology Research (top) with Prisoners

The Secretary of DHHS has waived the applicability of 45 CFR 46.305(a)(l) and 46.306(a)(2) for certain research conducted or supported by DHHS that involves epidemiologic studies that meet the following criteria:

1. In which the sole purposes are

a. To describe the prevalence or incidence of a disease by identifying all cases, or

b. To study potential risk factor associations for a disease, and

2. Where the IRB has approved the research and fulfilled its duties under 45 CFR 46.305(a)(2)–(7) and determined and documented that

a. The research presents no more than minimal risk and no more than inconvenience to the prisoner-subjects, and

b. Prisoners are not a particular focus of the research.

3. The specific type of epidemiological research subject to the waiver involves no more than minimal risk and no more than inconvenience to the human subject participants. The waiver would allow the conduct of minimal risk research that does not now fall within the categories set out in 45 CFR 46.306(a)(2).

4. The range of studies to which the waiver would apply includes epidemiological research related to chronic diseases, injuries, and environmental health. This type of research uses epidemiologic methods (such as interviews and collection of biologic specimens) that generally entail no more than minimal risk to the subjects.

5. In order for a study to be approved under this waiver, the IRB would need to ensure that, among other things, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of the data.

11.8 Research Involving Children

The following applies to all research involving children, regardless of funding source. The requirements in this section are consistent with Subpart D of 45 CFR 46 and Subpart D of 21 CFR 50.

11.8.1 Allowable Categories

Research on children must be reviewed and categorized by the IRB into one of the following groups:

1. Research not involving physical or emotional risk greater than that ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests (i.e., minimal risk).

· Adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians as set forth in Section 6.8.2

2. Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subject.

· The risk is justified by the anticipated benefit to the subjects;

· Adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians.

3. Research involving greater than minimal risk and no reasonable prospect of direct benefit to the individual subject, but likely to yield generalizable knowledge about the subject's disorder or condition.

· The risk represents a minor increase over minimal risk;

· The intervention or procedure presents experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations;

· Adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians.

4. Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate serious problems affecting the health or welfare of children.

· Federally-funded research in this category must be approved by the Secretary of Health and Human Services,

· FDA-regulated research in this category must be approved by the Commissioner of Food and Drugs.

· For non-federally-funded, non-FDA research, the IRB will consult with one or more experts in pertinent disciplines. The IRB will strongly consider the recommendation of the expert(s) and may approve the research based on either:

o That the research in fact satisfies the conditions of the previous categories, as applicable; or

o The following:

§ The research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children;

§ The research will be conducted in accord with sound ethical principles; and

§ Informed consent will be obtained in accord with the provisions for informed consent and other applicable sections of this manual.

· Adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians as set forth in 46.408.

11.8.2 Parental Permission and Assent

11.8.2.1 Parental Permission

The IRB must determine that adequate provisions have been made for soliciting the permission of each child’s parent(s) or guardian(s). Parents or guardians must be provided with the basic elements of consent and any additional elements the IRB deems necessary.

The IRB may find that the permission of one parent is sufficient for research to be conducted under Categories 1 & 2 above (46.404 and 46.405). The IRB’s determination of whether consent must be obtained from one or both parents will be documented in the reviewer worksheet when a protocol receives expedited review, and in meeting minutes when reviewed by the convened committee.

Consent from both parents is required for research to be conducted under Categories 3 & 4 (46.406 and 46.407) above unless:

· One parent is deceased, unknown, incompetent, or not reasonably available; or

· When only one parent has legal responsibility for the care and custody of the child.

For research not covered by the FDA regulation, the IRB may waive the requirement for obtaining consent from a parent or legal guardian if:

· The research meets the provisions for waiver of informed consent, or

· If the IRB determines that the research protocol is designed for conditions or a subject population for which parental or guardian permission is not a reasonable requirements to protect the subjects (for example, neglected or abused children), provided an appropriate mechanism for protecting the children who will participate as subjects in the research is substituted, and that the waiver is not inconsistent with Federal, State, or local law. The choice of an appropriate mechanism would depend upon the nature and purpose of the activities described in the protocol, the risk and anticipated benefit to the research subjects, and their age, maturity, status, and condition.

Parental permission may not be waived for research covered by the FDA regulations.

Permission from parents or legal guardians must be documented in accordance with and to the extent required by earlier sections regarding documentation of consent.

11.8.2.2 Assent from Children

Because “assent” means a child’s affirmative agreement to participate in research, the child must actively show his or her willingness to participate in the research, rather than just complying with directions to participate and not resisting in any way. When judging whether children are capable of assent, the IRB is charged with taking into account the ages, maturity, and psychological state of the children involved. The IRB has the discretion to judge children’s capacity to assent for all of the children to be involved in a proposed research activity, or on an individual basis

The IRB should take into account the nature of the proposed research activity and the ages, maturity, and psychological state of the children involved when reviewing the proposed assent procedure and the content of the information conveyed to the prospective subjects. The assent procedure should reflect a reasonable effort to enable the child to understand, to the degree they are capable, what their participation in the research activities would involve.

In most cases, a verbal assent process is appropriate for children up to 7 years of age. When appropriate, the assent process may be supplemented with a written form for children 8 to 17. Regardless of which approach is chosen for soliciting assent, a summary of the proposed conversation and documents must be submitted to the IRB for review.

Parents and children will not always agree on whether the child should participate in research. Dissent from the child overrides consent from a parent except in the case when the intervention or procedure involved in the research holds out a prospect of direct benefit that is important to the health or well-being of the children and is available only in the context of the research. Similarly, a child typically cannot decide to be in research over the objections of a parent. There are individual exceptions to these guidelines but in general, children should not be forced to be research subjects, even when consent has been given by their parents.

If the IRB determines that the capability of some or all of the children is so limited that they cannot reasonably be consulted or that the intervention or procedure involved in the research holds out a prospect of direct benefit that is important to the health or well-being of the children and is available only in the context of the research, the assent of the children is not a necessary condition for proceeding with the research.

Even when the IRB determines that the subjects are capable of assenting, the IRB may still waive the assent requirement under circumstances detailed in the Waiver of Informed Consent section of this manual.

The Assent Form

When the IRB determines that assent is required, it shall also determine whether and how assent must be documented.

Researchers should propose a process and form that is age appropriate and study specific, taking into account the typical child's experience and level of understanding, and composing a document that treats the child respectfully and conveys the essential information about the study. The assent form should:

1. Explain why the research is being conducted;

2. Describe what will happen and for how long or how often;

3. State that it is up to the child to participate and that it is okay to say no;

4. Explain whether it will hurt and if so for how long and how often;

5. Indicate what the child's other choices are;

6. Describe any good things that might happen;

7. State whether there is any compensation for participating; and

8. Encourage questions.

Whenever possible, an assent document should be limited to one page. Illustrations, larger type, and other age appropriate improvements are encouraged when they have the potential to enhance comprehension.

(top) 11.8.2.3 Children Who are Wards

Children who are wards of the State or any other agency, Institution, or entity can be included in research involving greater than minimal risk and no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subject's disorder or condition, only if such research is:

1. Related to their status as wards; or

2. Conducted in schools, camps, hospitals, Institutions, or similar settings in which the majority of children involved as subjects are not wards.

If the research meets the condition(s) above, an advocate must be appointed for each child who is a ward (one individual may serve as advocate for more than one child), in addition to any other individual acting on behalf of the child as legal guardian or in loco parentis.

The advocate must be an individual who has the background and experience to act in, and agrees to act in, the best interests of the child for the duration of the child's participation in the research and who is not associated in any way (except in the role as advocate or member of the IRB) with the research, the investigator(s), or the guardian organization.

11.9 Persons with Impaired Decision-Making Capacity

The requirements in this section apply to all research involving persons with mental disabilities or persons with impaired decision-making capacity.

Decisional capacity in the research context has been interpreted by the American Psychiatric Association as requiring:

1. Ability to evidence a choice,

2. Ability to understand relevant information,

3. Ability to appreciate the situation and its likely consequences, and

4. Ability to manipulate information rationally.

Research involving persons with impaired decision-making capability may only be approved when each of the following conditions is met:

1. The investigator must demonstrate to the IRB that there is a compelling reason to include incompetent individuals or persons with impaired decision-making capacity as subjects.

2. Any risk to subjects is outweighed by the probability of direct benefit to the individual subject.

3. Procedures have been devised to ensure that each participant’s legally authorized representative (LAR) is well informed regarding their role and obligation to protect the subject.

4. The proposal includes a plan to provide the LAR with a description of the proposed study and to explain to them that their obligation is to try to determine what the subject would do if competent, or if the subject's wishes cannot be determined, what they think is in the incompetent person's best interest.

11.9.1 IRB composition

The IRB membership must include at least one member who is an expert in the area of the research. Consideration may be given to adding another member who is a member of the vulnerable population, a family member of such a person or a representative of an advocacy group for that population. The IRB may utilize ad hoc members as necessary to ensure appropriate expertise.

(top) 11.9.2 Additional Safeguards

For research protocols that involve subjects with diminished or fluctuating decision-making capacity, the IRB may require investigators to include one or more of the following safeguards:

· Use of formal or informal capacity assessments;

· Use of independent and qualified professionals to assess whether potential subjects have the capacity to give voluntary, informed consent;

· Initial and/or ongoing communication with involved caregivers;

· Periodic repetition of the consent process with the subject and/or caregiver(s);

· Third party consent monitors used during the recruitment and consent process;

· Waiting periods to allow more time for the subject and/or caregivers to consider the information that has been presented;

· Use of multiple measures to inform the subject and assess comprehension (e.g., follow-up questions, multiple visits, audio or video recording and play back of consent-related conversations, use of an interpreter for hearing-impaired subjects, involvement of a trusted family member or friend).

11.9.2.1 Procedures for Determining Capacity to Consent

The decision-making capacity of a potential research subject should be evaluated when there are reasons to believe that the subject may not be capable of making voluntary and informed decisions about research participation.

The investigator and research staff must have adequate procedures in place for assessing and ensuring subjects’ capacity, understanding, and informed consent or assent. The IRB will evaluate whether the proposed plan to assess capacity to consent is adequate.

The IRB will consider the qualifications of the assessor(s) and, when necessary, whether he or she is sufficiently independent of the research team and/or Institution. A range of professionals and methods may be utilized to assess capacity. In general the assessor should be a researcher or consultant familiar with the conditions(s) resulting in the potential subject’s lack of capacity to consent. The assessor should be qualified and available to conduct an initial assessment and, when appropriate, to monitor the subject for capacity over the course of the study.

In the event that a research participant becomes incompetent or impaired in decision-making capacity after enrollment, the PI is responsible for notifying the IRB.

11.9.3 Informed Consent and Assent

Whenever the participants have the capacity to give consent (as determined by qualified professionals), informed consent should be obtained and documented. When participants lack the capacity to give consent, investigators may obtain consent from a subject’s legally authorized representative (LAR).

A person who lacks the capacity to consent to participate in research should be informed about the study to the extent compatible with their ability to comprehend information and, if possible, the subject should give their assent to participate, sign and date the written consent or assent form. If the subject expresses resistance or dissent to participation, or to the use of surrogate consent by word or gesture, the subject shall be excluded from the research study. Under no circumstances may a researcher or caregiver override a subject’s dissent. If no resistance or dissent is expressed by the potential subject, the investigator shall document this fact and that the description of the research project was communicated to the subject.

12. Unanticipated Problems

12.1 Policy

The IRB complies with DHHS and FDA regulations which state that Institutions must have written policies on reporting unanticipated problems involving risks to subjects or others to the IRB, Institutional officials and relevant federal agencies and departments.

The following procedures describe how unanticipated problems involving risk to subjects or others are handled in research under the auspices of the IRB.

12.2 Definitions

Unanticipated problems (UPs) include any incident, experience, or outcome that meets all of the following criteria:

Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied;

Related or possibly related to participation in the research (in this guidance document, possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); and

Suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized. For example, breach of confidentiality is considered to place subjects at risk, but is only unanticipated if it was not described as a risk in the consent form.

An adverse event is any untoward or unfavorable occurrence in a human subject, temporally associated with the subject’s participation in the research. Adverse events encompass both physical and psychological harms.

Anticipated adverse events are adverse events that were expected and therefore articulated in the approved protocol, consent document, data and safety monitoring plan, and/or Investigator Brochure.

Attribution: Adverse event attribution will fall into one of the following categories:

Related or possibly related to participation in the research (in this guidance document, possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); or

Unrelated events are those that could in no way be attributed to study participation. These events are not reportable.

Severity: Adverse event severity will fall into one of the following categories:

Mild: Event results in transient discomfort; does not influence performance or functioning; does not require intervention or treatment; does not limit or interfere with daily activities; expected to resolve quickly with no physical, psychological, social, or economic consequences.

Moderate: Of sufficient severity to make the patient uncomfortable; may include worsening of conditions present at the onset of the study; treatment of symptom(s) may be needed; expected to resolve but short term physical, psychological, social, or economic consequences are possible.

Severe: Event results in significant symptoms that prevents normal daily activities; may require hospitalization or invasive intervention. Long term physical, psychological, social, or economic consequences are possible.

12.3 Procedures

12.3.1 Reporting

Anticipated adverse events must be reported to the IRB within 30 business days if they are related or possibly related to the research and moderate to severe in nature.

Unanticipated problems must be reported to the IRB within three (3) business days.

NOTED EXCEPTION: An unanticipated death must be reported to the IRB within 24 hours of the discovery of the occurrence.

Additional exceptions noted below.

Investigators must promptly report the following problems to the IRB:

1. Adverse events which are related or possibly related to the research and are moderate to severe in nature.

2. Unanticipated events which are related or possibly related to the research and which places subjects or others (e.g., investigators, students, the public, subjects’ family members) at a greater risk of harm than was previously recognized.

3. Information that indicates a change to the risks or potential benefits of the research. For example:

a. An interim analysis or safety monitoring report indicates that frequency or magnitude of harms or benefits may be different than initially presented to the IRB.

b. A paper is published from another study that shows that the risks or potential benefits of your research may be different than initially presented to the IRB.

4. A breach of confidentiality. This includes reporting to the Office of Equity of Inclusion triggered by Title IX; reporting to state or federal authorities triggered by a mandatory reporting law; disclosures required by subpoena; and other similar disclosures. Other breaches include loss of a field notebook; theft of a research computer; or a security violation in a locked space or restricted drive.

5. Incarceration of a participant in a protocol not approved to enroll prisoners.

6. Change to the protocol taken without prior IRB review to eliminate an apparent immediate hazard to a research participant.

7. Complaint of a participant when the complaint indicates unanticipated risks or cannot be resolved by the research team.

8. Protocol deviations (reporting exception: report within 10 business days; see additional information regarding deviations in a later section).

9. Sponsor imposed suspension.

10. Any other event that indicates participant or others might be at risk of serious, unanticipated harms that are reasonably related to the research.

12.3.2 Submission of Reports

IRB_chart

The Principal Investigator must report possible unanticipated problems to the IRB office in writing using the appropriate form (available on the IRB website).

If the IRB office staff believes that immediate intervention may be required to protect participants or others from serious harm, the report of a possible unanticipated problem involving risks to participants or others will be immediately forwarded by the IRB staff to one or more of the following, in this order of priority: IRB Administrator, Chair, IO, or Risk Management.

Upon receipt of a report of a possible unanticipated problem from someone other than the PI, the IRB Administrator will notify the PI on the study when appropriate.

(top) 12.3.3 IRB Procedures for Handling Reports of Possible Unanticipated Problems

12.3.3.1 Reporting a Death, Serious Injury, or Significant Breach of Sensitive Information

In the event of a death, serious injury, or significant breach of sensitive information, the IRB Administrator will, upon discovery, notify the following individuals within 24 hours of discovery:

1. Institutional Official

2. IRB Chair(s)

3. Director of ORI

4. Dean of the PI’s College

5. PI’s Department Head or equivalent

6. University Relations and Marketing

7. General Counsel

8. Risk Management Office

12.3.3.2 Report Review by IRB Staff and Chair

1. Upon receipt of a report of a possible unanticipated problem, the IRB staff checks the report for completeness. If any applicable sections of the form are incomplete or have been answered unsatisfactorily, the IRB staff will contact the investigator or the designated contact person to obtain additional information. Corrections are documented in the IRB file, indicating the date, the person spoken with, and the IRB staff making the correction. The completed form is sent to the IRB Chair or other designated member.

2. The IRB Chair and/or other experienced member(s) designated by the IRB Chair receives and reviews the report of the event(s) considered to be an unanticipated problem. The IRB Chair (or designee) will make the final determination as to whether the event is to be regarded as an unanticipated problem.

3. Based on the information received from the investigator, the IRB Chair may suspend research to ensure protection of the rights and welfare of participants. Suspension directives made by the IRB Chair or designee must be reported to a meeting of the convened IRB.

4. The IRB, IRB Chair, or designee has authority to require submission of more detailed contextual information by the PI, the sponsor, the study coordinating center, or DSMB/DMC about any event occurring in a research protocol as a condition of the continuation of the IRB’s approval of the research.

5. If the Chair or designee determines that the report does NOT constitute an unanticipated problem, serious or continuing non-compliance, or warrant suspension or termination, the report will be forwarded to the full board as a non-actionable item.

6. If the Chair or designee determines that the report constitutes an unanticipated problem, serious or continuing non-compliance, or warrant suspension or termination, but the study is exempt and the risks to subjects or others is not greater than minimal, the report will be forwarded to the full board as a non-actionable item.

7. If the Chair or designee determines that the report constitutes an unanticipated problem, serious or continuing non-compliance, or warrant suspension or termination, and the study is non-exempt, the report will be forwarded to the full board as an actionable item and to OHRP if HHS funded. At the discretion of the Chair, suspension or termination may occur prior to review by the full board.

8. If the Chair or designee determines that the report constitutes an unanticipated problem, serious or continuing non-compliance, or warrant suspension or termination, the study is exempt but the risks to subjects or others is greater than minimal, the report will be forwarded to the full board as an actionable item. At the discretion of the Chair, suspension or termination may occur prior to review by the full board.

12.3.3.3 IRB Review

The Chair or designee will serve as the primary reviewer for all unanticipated problems and adverse events. The Chair or designee will be given the protocol file, the currently approved consent document, previous reports of unanticipated problems involving risks to participants or others, the investigator’s brochure (if one exists), and the event report. All IRB members will receive the event report.

After review of the protocol and event report, the full IRB will make findings and recommendations based on the following considerations:

a. Whether the reported event is an unanticipated problem involving risks to participants or others according to the definition in this policy.

b. What action is appropriate in response to the report.

c. Whether suspension or termination of IRB approval is warranted.

d. Whether further reporting to Institutional and/or federal officials is required.

If the IRB finds that the event is not an unanticipated problem involving risks to participants or others, according to the definition in the policy, the IRB may recommend any of the following actions:

a. No action

b. Modifications to the protocol

c. Revisions to the continuing review timetable

d. Modifications to the consent process

e. Modifications to the consent document

f. Modifications requiring that additional information be given to current participants (e.g. whenever the information may relate to the participant’s willingness to continue participation)

g. Modifications requiring that additional information be given to past participants

h. Additional training or oversight of the investigator and/or study staff

i. Other actions appropriate for the local context or the nature of the event

If the IRB finds that the event is an unanticipated problem involving risks to participants or others, according to the definition in the policy, the IRB may recommend any of the following actions:

a. Modifications to the protocol

b. Revisions to the continuing review timetable

c. Modifications to the consent process

d. Modifications to the consent document

e. Modifications requiring that additional information be given to current participants (e.g. whenever the information may relate to the participant’s willingness to continue participation)

f. Modifications requiring that additional information be given to past participants

g. Additional training or oversight of the investigator and/or study staff

h. Reconsideration of IRB approval

i. Requirement that current participants re-consent to participation

j. Monitoring of the research

k. Monitoring of the consent process

l. Referral to other Institutional area (e.g., legal counsel, risk management, Institutional official)

m. Study suspension

n. Study termination

o. Other actions appropriate for the local context or the nature of the event

If a report suggests that participant safety is at risk, the IRB may immediately suspend or terminate the research. Any suspension or termination of research by the IRB must be promptly reported, in writing, to the IO, and OHRP (if HHS funded), and FDA (if FDA-regulated research).

If, after reviewing a report, the IRB finds that the event is an unanticipated problem involving risks to participants or others and that such risk is greater than minimal, or that suspension or termination of approval is warranted, the IRB will:

a. Notify the investigator in writing of its findings, with copies to the investigator’s Department Head and/or Dean, and

b. Report its findings and recommendations to the IO.

13. Protocol Exceptions or Deviations

13.1 Policy

The following procedures describe how protocol exceptions and deviations are reported to the IRB.

13.2 Definitions

Exceptions. A protocol exception is defined as a circumstance in which the specific procedures called for in a protocol are not in the best interests of a specific subject.

Deviations. A protocol deviation is defined as a violation that is unanticipated and happens without prior IRB approval. The IRB will review these reports for frequency and may audit any protocol reporting frequent deviations.

13.3 Exceptions

It is the responsibility of the Investigator to request permission from the IRB for planned exceptions to the approved protocol. Exceptions must be approved by the IRB before being implemented.

Exceptions may not increase risk or decrease benefit, affect the participant’s rights, safety, welfare, or affect the integrity of the resultant data.

13.4 Deviations

It is the responsibility of the Investigator not to deviate from the protocol approved by the IRB, except to avoid an immediate hazard to the participant. The Investigator must submit an amendment request to the IRB and receive written approval prior to implementation of any change to the protocol. However, in the event that an unexpected deviation occurs, it must be reported to the IRB.

Deviations that increase risk, have the potential to recur, or undertaken to eliminate an immediate hazard, would be considered an Unanticipated Problem.

Repetitive deviations may be ruled by the IRB to constitute non-compliance resulting in suspension of IRB approval.

13.5 Reporting & Review

Deviations must be reported to the IRB within 10 business days after the PI becomes aware that the deviation has occurred. Forms for Deviations and Requests for Exceptions are to be completed and filed with the IRB Office. The IRB Office will forward the report to the IRB Chair or designee for review.

All deviations and exceptions will appear on the Board’s next meeting agenda. The full committee will be provided with a copy of the deviation form or request for exception and a description of any actions taken by the IRB Chair, Administrator, and/or Principal Investigator. However, they will only be discussed if there is an actionable item.

If the deviation is non-actionable or the exception is acceptable, the notice of Acknowledgement may be sent to the PI prior to the event’s appearance on the next agenda.

14. Complaints and Non-compliance

14.1 Policy (top)

As part of its commitment to protecting the rights and welfare of human subjects in research, the IRB reviews all complaints and allegations of non-compliance and takes any necessary action to ensure the ethical conduct of research.

All Investigators and other study personnel involved in human subjects research are required to comply with all laws and regulations governing their research activities, as well as with requirements and determinations of the IRB. Study personnel include the principal Investigator and any staff member directly involved with participants or the informed consent process.

The following procedures describe how complaints and allegations of non-compliance are handled by the IRB. This section does not pertain to allegations of misconduct.

14.2 Definitions

Non-compliance. Non-compliance is defined as failure to comply with any of the regulations and policies described in this document and/or failure to follow the determinations of the IRB. Non-compliance may be minor or sporadic, or it may be serious or continuing.

Serious non-compliance. Serious non-compliance is defined as failure to follow any of the regulations and policies described in this document or failure to follow the determinations of the IRB and which, in the judgment of either the IRB Chair or the convened IRB, increases risks to participants, decreases potential benefits, or compromises the integrity of the human research protection program. Examples of serious non-compliance include, but are not limited to, (a) research being conducted without prior IRB approval, and (b) participation of subjects in research activities without their prior consent (in studies where consent was not specifically waived by the IRB) is considered serious non-compliance.

Continuing non-compliance. Continuing non-compliance is defined as a pattern of non-compliance that, in the judgment of the IRB Chair or convened IRB, suggests a likelihood that instances of non-compliance will continue without intervention. Continuing non-compliance also includes failure to respond to a request to resolve an episode of non-compliance.

Allegation of Non-Compliance. Allegation of Non-Compliance is defined as an unproved assertion of non-compliance.

Finding of Non-Compliance. Finding of Non-Compliance is defined as an allegation of non-compliance that is proven true or a report of non-compliance that is clearly true. A finding on an audit of an unsigned consent document, or an admission of an investigator that the protocol was willfully not followed would represent reports of non-compliance that would require no further action to determine their truth and would therefore represent findings of non-compliance. Once a finding of non-compliance is proven, it must be categorized as serious, non-serious, or continuing.

14.3 Complaints

The IRB Chair or Administrator will promptly handle and, if necessary, investigate all complaints, concerns, and appeals received by the IRB. This includes complaints, concerns, and appeals from investigators, research participants and others.

All complaints, written or verbal, and regardless of point of origin, are recorded on a complaint form and forwarded to the IRB Chair.

Upon receipt of the complaint, the Chair will make a preliminary assessment of whether and what action(s) should be taken. A determination will be made as to whether the complaint warrants immediate suspension of the research project; is an allegation of non-compliance; or meets the definition of an unanticipated problem involving risk to subjects or others. The appropriate, related procedure will be followed.

All complaints will appear on the Board’s next meeting agenda. The full committee will be provided with a copy of the complaint form and a description of any actions taken by the IRB Chair, Administrator, and/or Principal Investigator. However, they will only be discussed if there is an actionable item.

If the complaint is non-actionable, the notice of Acknowledgement may be sent to the PI prior to the event’s appearance on the next agenda.

14.4 Non-compliance

Investigators and their study staff are required to report instances of possible non-compliance to the IRB. The Principal Investigator is responsible for reporting any possible non-compliance by study personnel to the IRB. Common reports to the IRB that are not serious or continuing are typically protocol deviations that should be reported on the appropriate Deviation Form. However, any individual or employee may report observed or apparent instances of non-compliance to the IRB. In such cases, the reporting party is responsible for making these reports in good faith, maintaining confidentiality and cooperating with any IRB and/or Institutional review of these reports.

If an individual, whether investigator, study staff or other, is uncertain whether there is cause to report non-compliance, he or she may contact the IRB Chair or Administrator directly to discuss the situation informally.

Complainants may choose to remain anonymous.

14.4.1 Review of Allegations of Non-compliance

All allegations of non-compliance will be reviewed by the IRB Chair and Administrator, who will review:

1. All documents relevant to the allegation;

2. The last approval letter from the IRB;

3. The last approved IRB application and protocol;

4. The last approved consent document;

5. The grant or contract, if applicable; and

6. Any other pertinent information (e.g., questionnaires, DSMB reports, publications, etc.).

The IRB Chair and/or the Administrator may interview the complainant and/or the respondent and any other relevant parties.

The IRB Chair and Administrator will review the allegation and make a determination as to the truthfulness of the allegation. They may request additional information or an audit of the research in question. In addition, the Chair or Administrator may choose to interview the investigator(s), other study team members, the individual(s) making the allegation or complaint, and any other individual(s) who may have relevant information.

In the event that the IRB Chair and Administrator find that there is reason to suspect that the allegation involves research misconduct, they will report that information in accordance with the OSU Policy on Scientific and Scholarly Misconduct. The IRB Chair and Administrator will determine whether it is appropriate to suspend the IRB investigation and/or the research protocol until the conclusion of the misconduct investigation.

If, in the judgment of the Chair, non-compliance did not occur because the incident was within the limits of an approved protocol for the research involved, the determination is reported in writing to the PI and if applicable the reporting party. The determination letter will be copied to the Institutional Official in cases where the Institutional Official and any other parties had been notified at the outset.

If in the judgment of the IRB Chair, the reported allegation of non-compliance is true, the non-compliance will be processed according to the section on Review of Findings of Non-compliance.

If in the judgment of the IRB Chair, any allegation or findings of non-compliance warrants suspension of the research before completion of any review or investigation to ensure protection of the rights and welfare of participants, the IRB Chair may suspend the research with subsequent review by the IRB.

The Chair may determine that additional expertise or assistance is required to make these determinations and may form an ad hoc committee to assist with the review and fact gathering process. When an ad hoc committee assists in the review process, the Chair is responsible for appointing the members and assuring that minutes of the meeting are generated and kept to help support any determinations or findings made by the ad hoc committee.

14.4.2 Review of Findings of Non-compliance

Non-compliance is not serious or continuing:

When the Chair determines that the non-compliance occurred, but the non-compliance does not meet definition of serious or continuing non-compliance, the determination is reported in writing to the PI and if applicable the reporting party. The Chair will work with the PI to develop a corrective action plan to prevent future non-compliance. The report of non-compliance and corrective action is reported to the IRB through the “expedited review report”. If however, the PI refuses to cooperate with the corrective action plan, the matter is referred to a convened meeting of the IRB with notification to the IO.

Serious or Continuing Non-compliance

When the Chair determines that non-compliance has occurred and that the non-compliance meets the definition of serious or continuing non-compliance, the report of non-compliance is referred for review by the IRB at the next convened available meeting. However, the Chair may use discretion and call an emergency IRB meeting should the circumstances warrant such an urgent meeting.

All findings of serious or continuing non-compliance referred to the IRB will be reviewed at a convened meeting. All IRB members will receive all documents relevant to the allegation.

At this stage, the IRB may request additional information and/or VOTE on one of the a specific findings below:

1. Finding that there is no issue of non-compliance;

2. Finding that there is non-compliance that is neither serious nor continuing and an adequate corrective action plan is in place;

3. Finding that there is serious or continuing non-compliance and approve any changes proposed by the Chair and/or ad hoc committee;

4. Finding that there may be serious or continuing non-compliance and direct that a formal inquiry (described below) be held.

Regardless of the determination, the PI and the reporting party/complainant (if appropriate) will be notified in writing. If the determination is that there is, or may be serious or continuing non-compliance, the IRB will also notify the IO, Dean, Associate Dean for Research, Unit Head, and the Institutional Compliance Office.

14.4.3 Inquiry Procedures

The IRB may, at its discretion, convene an inquiry. Examples of matters that may warrant an inquiry include:

1. Subjects' complaint(s) that rights were violated;

2. Report(s) that investigator is not following the protocol as approved by the IRB;

3. Unusual and/or unexplained adverse events in a study;

4. Repeated failure of investigator to report required information to the IRB.

The inquiry will be lead by either the full board or a subcommittee appointed by the Chair. The inquiry can include any or all of the following:

1. Review of protocol(s) in question;

2. Review of sponsor audit report of the investigator;

3. Review of any relevant documentation, including consent documents, case report forms, subject's investigational and/or medical files etc., as they relate to the investigator's execution of her/his study involving human subjects;

4. Interview of appropriate personnel;

5. Preparation of a written report of the findings, which is presented to the full IRB at its next meeting;

6. Recommend actions, if appropriate.

14.4.4 Final Review

The results of the inquiry will be reviewed at a convened IRB meeting. If the results of the inquiry substantiate the finding of serious or continuing non-compliance, the IRB’s additional actions must include:

1. Notification to the PI, all co-investigators (including student researchers), Unit Head, Associate Dean for Research and Dean (or equivalent), the IO, and the Institutional Compliance Office

2. If funded, notification to the sponsor, OSP, and OPAA

The IRB’s additional actions may also include:

1. Request for a corrective action plan from the investigator

2. Verification that participant selection is appropriate and observation of the actual informed consent

3. Request for an increase in data and safety monitoring of the research activity

4. Directed audit of targeted areas of concern

5. Request for a status report after each participant receives intervention

6. Modification of the continuing review cycle

7. Request for additional Investigator and staff education

8. Notification to current subjects, if the information about the non-compliance might affect their willingness to continue participation

9. Require modification of the protocol

10. Require modification of the information disclosed during the consent process

11. Require PI to approach current participants about consenting to continued participation

12. Suspend the study

13. Terminate the study

14. Notification to the journal Editor

15. Notification to other compliance areas within the Research Office

16. Notification to General Counsel

17. Notification to others at the discretion of the IRB Chair

In cases where the IRB determines that the event of non-compliance also meets the definition of unanticipated problems involving risks to subjects or others, the policy and procedure for review of such events will also be followed.

The investigator is informed of the IRB determination and the basis for the determination in writing and is given a chance to respond. However, there is no formal appeals process. If the IRB determines that the non-compliance was serious or continuing, the results of the final review will be reported as described below.

15. Reporting to Regulatory Agencies and Institutional Officials

15.1 Policy

Federal regulations require prompt reporting to appropriate Institutional officials, and the [DHHS] department or agency head of (i) any unanticipated problems involving risks to subjects or others or any serious or continuing non-compliance with this policy or the requirements or determinations of the IRB; and (ii) any suspension or termination of IRB approval. The OSU IRB will comply with this requirement and the following procedures describe how these reports are handled.

15.2 Procedures

1. IRB staff will initiate these procedures as soon as the IRB takes any of the following actions:

a. Determines that an event may be considered an unanticipated problem involving risks to participants or others

b. Determines that non-compliance was serious or continuing

c. Suspends or terminates approval of research

2. The Administrator or designee is responsible for preparing reports or letters that include the following information:

a. The nature of the event (Unanticipated problem involving risks to participants or others, serious or continuing non-compliance, suspension or termination of approval of research)

b. Name of the Institution conducting the research

c. Title of the research project and/or grant proposal in which the problem occurred

d. Name of the principal investigator on the protocol

e. Number of the research project assigned by the IRB and the number of any applicable federal award(s) (grant, contract, or cooperative agreement)

f. A detailed description of the problem including the findings of the organization and the reasons for the IRB’s decision

g. Actions the Institution is taking or plans to take to address the problem (e.g., revise the protocol, suspend subject enrollment, terminate the research, revise the informed consent document, inform enrolled subjects, increase monitoring of subjects, etc.)

h. Plans, if any, to send a follow-up or final report by the earlier of

1. A specific date

2. When an investigation has been completed or a corrective action plan has been implemented

3. The IRB Chair and the IO review the letter and modify the letter/report as needed.

4. The IO is the signatory for all correspondence from the Institution to Federal Agencies.

5. The Administrator or designee sends a copy of the report to:

a. The IRB by including the letter in the next agenda packet as an information item

b. The Institutional Official

c. The following federal agencies:

· OHRP, if the study is subject to DHHS regulations or subject to a DHHS Federalwide assurance (non-exempt studies with federal funding)

· FDA, if the study is subject to FDA regulations.

· Reporting to a regulatory agency is not required if the event occurred at a site that was not subject to the direct oversight of OSU, and the agency has been notified of the event by the investigator, sponsor, another organization, or other mechanisms.

d. Principal Investigator

e. Sponsor, if the study is sponsored

f. Contract research organization, if the study is overseen by a CRO

g. Principal Investigator’s Unit Head, Associate Dean for Research and Dean (or equivalent)

h. The Information Security Officer, if the event involved violations of information security requirements

i. General Counsel, if appropriate

j. Director of ORI

k. Institutional Compliance Office

l. Others as deemed appropriate by the IRB Chair or the Institutional Official

The Administrator ensures that all steps of this policy are completed within 10 working days of the determination. For more serious actions, the Administrator may expedite reporting.

16. Special Topics

16.1 Certificate of Confidentiality (CoC)

Certificates of Confidentiality are issued by the National Institutes of Health (NIH) to protect identifiable research information from forced disclosure. They allow the investigator and others who have access to research records to refuse to disclose identifying information on research participants in any civil, criminal, administrative, legislative, or other proceeding, whether at the federal, state, or local level. By protecting researchers and Institutions from being compelled to disclose information that would identify research subjects, Certificates of Confidentiality help achieve the research objectives and promote participation in studies by helping assure confidentiality and privacy to participants.

16.1.1 Statutory Basis for Protection

Protection against compelled disclosure of identifying information about subjects of biomedical, behavioral, clinical, and other research is provided by the Public Health Service Act §301(d), 42 U.S.C. §241(d):

"The Secretary may authorize persons engaged in biomedical, behavioral, clinical, or other research (including research on mental health, including research on the use and effect of alcohol and other psychoactive drugs) to protect the privacy of individuals who are the subject of such research by withholding from all persons not connected with the conduct of such research the names or other identifying characteristics of such individuals. Persons so authorized to protect the privacy of such individuals may not be compelled in any Federal, State or local civil, criminal, administrative, legislative, or other proceedings to identify such individuals."

16.1.2 Eligibility and Usage

Any person engaged in research in which sensitive information is gathered from human research participants (or any person who intends to engage in such research) may apply for a Certificate of Confidentiality.

Generally, any research project that collects personally identifiable, sensitive information and that has been approved by an IRB operating under either an approved Federal-Wide Assurance issued by the Office of Human Research Protections or the approval of the Food and Drug Administration is eligible for a Certificate. Federal funding is not a prerequisite for an NIH-issued Certificate, but the subject matter of the study must fall within a mission area of the National Institutes of Health, including its Institutes, Centers and the National Library of Medicine.

When a researcher obtains a Certificate of Confidentiality, the subjects must be told about protections afforded by the Certificate and any exceptions to those protections - i.e., the circumstances in which the investigators plan to disclose, voluntarily, identifying information about research participants (e.g., child abuse, harm to self or others, etc.). This information should be included in the informed consent form unless a research subject is no longer actively participating in the project so amendment of the informed consent would be impractical. The researchers should eliminate provisions in consent form templates that may be inconsistent with the Certificate protections (such as references to disclosures required by law, since the Certificate enables researchers to resist disclosures that would otherwise be compelled by law). In addition, researchers may not represent the Certificate as an endorsement of the research project by the DHHS or use it in a coercive manner when recruiting subjects.

16.1.3 Limitations

The protection offered by a Certificate of Confidentiality is not absolute. A Certificate protects research subjects only from legally compelled disclosure of their identity. It does not restrict voluntary disclosures.

For example, a Certificate does not prevent researchers from voluntarily disclosing to appropriate authorities such matters as child abuse, a subject's threatened violence to self or others, or from reporting a communicable disease. However, if researchers intend to make such disclosures, this should be clearly stated in the informed consent form which research subjects are asked to sign.

In addition, a Certificate of Confidentiality does not authorize the person to whom it is issued to refuse to reveal the name or other identifying characteristics of a research subject if:

1. The subject (or, if he or she is legally incompetent, his or her legal guardian) consents, in writing, to the disclosure of such information;

2. Authorized personnel of the Department of Health and Human Services (DHHS) request such information for audit or program evaluation, or for investigation of DHHS grantees or contractors and their employees; or

3. Release of such information is required by the Federal Food, Drug, and Cosmetic Act or regulations implementing that Act.

(top) 16.1.4 Application Procedures

Any person engaged in research collecting sensitive information from human research subjects may apply for a Certificate of Confidentiality. For most research, Certificates are obtained from NIH. If NIH funds the research project, the investigator may apply through the funding Institute. However, even if the research is not supported with NIH funding, the investigator may apply for a Certificate through the NIH Institute or Center (IC) funding research in a scientific area similar to the project.

If the research is a sensitive project that is covered by the AHRQ confidentiality statute (42 U.S.C. section299a-1(c) entitled “limitation on use of certain information”) or the Department of Justice confidentiality statute (42USC section 3789g), then a CoC is not required. See the National Institute of Justice for additional guidance: http://www.nij.gov/funding/humansubjects/privacy-certificate-guidance.htm

If there is an Investigational New Drug Application (IND) or an Investigational Drug Exemption (IDE), the sponsor can request a CoC from the FDA.

For more information, see the NIH Certificates of Confidentiality Kiosk (http://grants.nih.gov/grants/policy/coc/).

16.2 Mandatory Reporting

While any person may make a report if they have reasonable cause to believe that a child or elder person was abused or neglected, Oregon State law mandates that certain persons who suspect child or elder abuse or neglect report this to the appropriate authorities. Under the current state law, all OSU employees are considered to be mandatory reporters.

The IRB’s policy requires the solicitation of informed consent from all adult research subjects and assent from children involved as research subjects, in addition to the consent of their parents. In situations where conditions of abuse or neglect might be revealed, mandated reporters should make themselves known as such to parents of children under age 18, to subjects who are children, and to subjects who are potential victims of abuse or neglect.

16.3 Title IX Sexual Harassment and Sexual Violence

All OSU employees are required to consult with the University Title IX Coordinator, or his designee, in the Office of Equity and Inclusion if they receive information about sexual harassment or sexual violence that meets one or more of the following criteria:

Is alleged to have been perpetrated by an OSU student, staff, or faculty member, OR
Has occurred on OSU property or during an OSU activity, OR
Has created continuing effects in the educational setting

The requirement to consult with the Office of Equity and Inclusion is specific to OSU employees. Student researchers who learn of reportable events should discuss this information with the Principal Investigator (PI) on the study. It is then the responsibility of the PI to contact the Title IX Coordinator.

If the research topic is sexual harassment or sexual violence:

If there is a reasonable expectation that the target population will disclose information triggering the need for consultation with the Office of Equity and Inclusion, a plan for this circumstance must be included in the research protocol and the consent form.

In the event that individually identifying information about the research participant is disclosed to the Office of Equity and Inclusion or other non-study team members, this would constitute an anticipated adverse event and the corresponding form must be submitted to the IRB within 30 days of this disclosure.

If the research topic is not sexual harassment or sexual violence:

If a research participant discloses information triggering the need for consultation with the Office of Equity and Inclusion, this will constitute a reportable event to the IRB since it could not have been anticipated. The Principal Investigator must complete and submit the “Unanticipated Problem” form within three days of learning of the issue.

Relevant References

University Policy Prohibiting Sexual Harassment: http://oregonstate.edu/oei/sexual-harassment-and-violence-policy

Additional resources: http://studenthealth.oregonstate.edu/sexual-violence-resources

(top) 16.4 Recruitment of(top) Students and Employees as Subjects (top) [10]

Students and employees recruited as research subjects are more vulnerable to coercion because of the possibility that they may perceive grades, employment or other benefits as dependent upon their participation in research. Students and employees are at greater risk of experiencing negative ramifications related to an inability to maintain strict confidentiality and because more information is known about these individuals than is collected during the course of the study.

The IRB considers these individuals to be more vulnerable to coercion (real or perceived) and to issues related to confidentiality than individuals not affiliated with OSU and, therefore, will apply additional safeguards to protect their rights and welfare.

Recruitment of Students

Justification for Targeting Students: Researchers who plan to exclude individuals who are not students must be able to provide a rationale, other than convenience, for restricting the study population to students and must show that the recruitment method does not lead potential subjects to think they will be compromised by not participating. Examples of such rationale include: a) participation as a valuable educational experience demonstrated by a substantive plan for debriefing, b) the need for an alternative mechanism for study compensation (e.g. extra credit) due to lack of monetary resources, c) the existence of a formal student subject pool and related departmental policy. Note that investigators and instructors may not impose penalties on students who fail to show up for scheduled research-related appointments.
Direct Recruitment: Investigators may make study-related announcements (such as study title and investigator contact information) or provide recruitment materials (such as fliers) to students in OSU classrooms, so long as the investigator is not also the class instructor. Exceptions may be granted if the purpose of the research is directly connected to students in a particular class. For example, if the research is intended to examine teaching methods in a particular course taught by the investigator. Recruitment methods should permit students to self-identify outside of the classroom so as to maintain confidentiality and minimize the potential for peer pressure. For example, students should be provided with contact information for a study team member who they may contact for more information after class, rather than be asked to express interest at the time of the announcement.
Indirect Recruitment: IRB-approved recruitment materials may be posted anywhere on the OSU campus with the appropriate departmental permission (e.g. unit office sign-off if necessary).
Mass email from Registrar: Investigators seeking approval from the Registrar’s Office to email recruitment materials or study announcements to students must explain this recruitment method in the protocol and provide the Registrar with a copy of the IRB approval letter before such an email may be sent. The Registrar may or may not grant such a request, regardless of IRB approval.
Consent: A student may not be compelled to participate in research as part of a course requirement. Investigators will ensure that students know that they may choose not to participate in the research and that their decision will not affect their grade, class standing, or relationship with any instructor.
Extra Credit: If extra credit is offered in exchange for participation, an alternate means of earning equivalent extra credit for an equivalent commitment of time and effort should be made available for those who cannot, or choose not to participate in a study.
Use of Class Time: Submissions proposing the use of class time for research should include an explanation of the benefit of the research to the students. Specifically, the investigator should explain how participation in the research would be a learning experience for the students and how the research is relevant to the course of study being taught in that class.
Use of Class Assignments in Research: Instructors should not use their students' class assignments (e.g., journals, term papers, etc.) in research without the prior permission from the Registrar and the consent of the students.

Recruitment of Employees

Justification for Targeting Employees: Researchers who plan to exclude individuals who are not employees must be able to provide a rationale, other than convenience, for restricting the study population to employees and must show that the recruitment method does not lead potential subjects to think they will be compromised by not participating.
Consent: An employee may not be required to participate in research as a condition of employment. Investigators will ensure that employees know that they may choose not to participate in the research and that their decision will not affect their employment or benefits at OSU.
Direct Recruitment: Investigators may make study-related announcements or provide recruitment materials to employees at regular meetings. However, recruitment methods should permit employees to self-identify as interested in participation in a way that maintains confidentiality. For example, employees should be provided with contact information for a study team member who they may contact for more information.
Indirect Recruitment: IRB-approved recruitment materials may be posted anywhere on the OSU campus with the appropriate departmental permission (e.g. unit office sign-off if necessary).

16.5 Student Research

16.5.1 Human Subjects Research and Course Projects

Research activities involving human subjects that are designed as part of a course requirement for purposes of learning experience only and are not designed to develop or contribute to generalizable knowledge do not require IRB review and approval if:

Results of the research are viewed only by the course instructor for teaching purposes and discussed within the classroom for teaching and learning purposes; and
Results of the research are not made public through presentation (outside of the classroom) and are not published in paper or electronic format (e.g., cannot be made available on the internet, cannot be published in a journal, etc.).

16.5.1.1 (top) Responsibility of the Course Instructor

The course instructor is responsible for working with the IRB to determine whether or not a project requires IRB review. The instructor is also responsible for communicating to the students the ethics of human subjects research, for ensuring the protection of human subjects (including a process is in place for obtaining voluntary informed consent from research subjects when appropriate), and for monitoring the students’ adherence to an approved protocol.

When designing a project, students should be instructed on the ethical conduct of research and on the preparation of the IRB application when such is required. In particular, instructors and students should:

· Understand the elements of informed consent

· Develop appropriate consent documents

· Plan appropriate strategies for recruiting subjects

· Identify and minimize potential risks to subjects

· Assess the risk-benefit ratio for the project

· Establish and maintain strict guidelines for protecting confidentiality

· Allow sufficient time for IRB review (if necessary) and completion of the project

16.5.2 Theses and Dissertations

Human subjects research activities that will contribute to part or all of a thesis, dissertation, or other type of publication or presentation must go through the IRB review process prior to enrolling subjects and collecting data. These research activities are considered to meet the federal definition of human subjects research and must be submitted to the IRB. When students conduct research as part of a course of study, a faculty member ultimately is responsible for the protection of the subjects, even if the student directs the project.

Students may not serve as Principal Investigators. They must have a faculty sponsor who fulfills the principal investigator eligibility criteria and who will serve as PI and faculty advisor on the study. The PI must be qualified and available to provide the appropriate training and oversight, and to ensure both protocol adherence and the responsible conduct of research from initiation of the study through reporting of results.

16.6 Oral History

A decision regarding whether oral history (or similar activities) are subject to IRB oversight is based on the prospective intent of the investigator and the definition of "research" under HHS regulations at 45 CFR 46.102(d): "a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge."

General principles for evaluating Oral History type activities:

1. Oral history activities that only document a specific historical event or the experiences of individuals without intent to draw conclusions or generalize findings would not constitute "research" as defined by HHS regulations 45 CFR part 46.

Example: The creation of a video of interviews with holocaust survivors is created for viewing in the Holocaust Museum. The sole purpose is to create a historical record of personal events and experiences related to the Holocaust. There is no intent to inform policy, draw conclusions, or generalize the experiences of these individuals to a larger population. Therefore, this activity does not meet the definition of research and does not require IRB review.

2. Systematic investigations involving open-ended interviews that are designed to develop or contribute to generalizable knowledge (e.g., designed to draw conclusions, inform policy, or generalize findings) would constitute "research" as defined by HHS regulations at 45 CFR part 46.

Example: Qualitative interviews of Gulf War veterans to document their experiences and to demonstrate the need for additional research and facilities for the treatment of traumatic brain injuries. The intent here is to draw conclusions, inform policy, and/or generalize findings.

3. Oral historians and qualitative investigators may want to create archives for the purpose of providing a resource for others to do research. Such a repository of information meets the definition of “research” because it includes “research development.”

Example: Qualitative interviews are conducted with Negro League Baseball players in order to create an archive for future researchers. The creation of such an archive would constitute research under 45 CFR 46 because the intent is to collect data for future research.

Investigators are advised submit a Determination Form to the IRB Office prior to initiating an oral history project.

16.7 Genetic Studies

According to the National Institutes of Health, Genetic Home Reference, genetic testing is:

“…a type of medical test that identifies changes in chromosomes, genes, or proteins. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder. More than 1,000 genetic tests are currently in use, and more are being developed.

Several methods can be used for genetic testing:

· Molecular genetic tests (or gene tests) study single genes or short lengths of DNA to identify variations or mutations that lead to a genetic disorder.

· Chromosomal genetic tests analyze whole chromosomes or long lengths of DNA to see if there are large genetic changes, such as an extra copy of a chromosome, that cause a genetic condition.

· Biochemical genetic tests study the amount or activity level of proteins; abnormalities in either can indicate changes to the DNA that result in a genetic disorder.”

Not all studies involving genetic material include genetic testing. However, those that do may create special risks to human subjects and their relatives. These involve medical, psychosocial, and economic risks, such as the possible loss of privacy, insurability, and employability, change in immigration status and limits on education options, and may create a social stigma. Knowledge of one's genetic make-up may also affect one's knowledge of the disease risk status of family members.

If the study involves genetic testing, address the following questions:

· Will test results be disclosed to the subject or their physician?

· Will disease risk be quantified, including the limits on certainty of the testing?

· Will a change in a family relationship be disclosed, such as mistaken paternity?

· Does the subject or family member have the option not to know the results? How will this decision be recorded?

· Could other clinically relevant information be uncovered by the study? How will disclosure of this added information occur?

· Do any practical limitations exist on the subject's right to withdraw from the research, withdraw data, and/or withdraw DNA?

· Is the subject permitted to participate in the study if they decline to participate in the genetic testing?

For DNA banking studies, address the following questions:

· Will DNA be stored or shared? If shared, will the subject's identity be known by any new recipient investigators?

· Will the subject be contacted in the future by the investigator to obtain updated clinical information?

How can the subject opt out of any distribution or subsequent use of his/her genetic material?

16.8 Research Involving Coded Private Information or Biological Specimens

The IRB policy is based on the OHRP guidance document entitled, “Guidance on Research Involving Coded Private Information or Biological Specimens” (October 16, 2008 http://www.hhs.gov/ohrp/policy/cdebiol.html). This document:

1. Provides guidance as to when research involving coded private information or specimens is or is not research involving human subjects, as defined under HHS regulations for the protection of human research subjects (45 CFR part 46).

2. Reaffirms OHRP policy that, under certain limited conditions, research involving only coded private information or specimens is not human subjects research.

3. Provides guidance on who should determine whether human subjects are involved in research.

For purposes of this policy, coded means that: (1) identifying information (such as name or social security number) that would enable the investigator to readily ascertain the identity of the individual to whom the private information or specimens pertain has been replaced with a number, letter, symbol, or combination thereof (i.e., the code); and (2) a key to decipher the code exists, enabling linkage of the identifying information to the private information or specimens.

Under the definition of “human subject,” obtaining identifiable private information or identifiable specimens for research purposes constitutes human subjects research. Obtaining means receiving or accessing identifiable private information or identifiable specimens for research purposes. This includes an investigator’s use, study, or analysis for research purposes of identifiable private information or identifiable specimens already in the possession of the investigator.

In general, private information or specimens are considered to be individually identifiable when they can be linked to specific individuals by the investigator(s) either directly or indirectly through coding systems.

Research involving only coded private information or specimens do not involve human subjects if the following conditions are both met:

1. the private information or specimens were not collected specifically for the currently proposed research project through an interaction or intervention with living individuals;

and

2. the investigator(s) cannot readily ascertain the identity of the individual(s) to whom the coded private information or specimens pertain because, for example:

a. the key to decipher the code is destroyed before the research begins;

b. the investigators and the holder of the key enter into an agreement prohibiting the release of the key to the investigators under any circumstances, until the individuals are deceased (note that the HHS regulations do not require the IRB to review and approve this agreement);

c. there are IRB-approved written policies and operating procedures for a repository or data management center that prohibit the release of the key to the investigators under any circumstances, until the individuals are deceased; or

d. there are other legal requirements prohibiting the release of the key to the investigators, until the individuals are deceased.

In some cases an investigator who obtains coded private information or specimens about living individuals under one of the conditions cited in 2(a)-(d) above may (1) unexpectedly learn the identity of one or more living individuals, or (2) for previously unforeseen reasons now believe that it is important to identify the individual(s). If, as a result, the investigator knows, or may be able to readily ascertain, the identity of the individuals to whom the previously obtained private information or specimens pertain, then the research activity now would involve human subjects. IRB review of the research would be required. Informed consent of the subjects also would be required unless the IRB approved a waiver of informed consent.

Investigators are advised to submit a Determination Form to the IRB Office prior to initiating work with coded or de-identified samples.

16.9 Case Reports Requiring IRB Review

In general, an anecdotal report of a single individual and a comparison of this individual to existing reports in the literature is not research and would not require IRB approval. A case series will be considered systematic and require IRB review.

16.9.1 Definitions

Case Study: External reporting (e.g., publication or poster/verbal presentation) about a single case or individual. Case reports normally contain detailed information about an individual and may include demographic information, as well as a discussion of existing relevant literature. The individual’s information used in the report must have been originally collected solely for non-research purposes.

Case Series: External reporting (e.g., publication or poster/verbal presentation) about a series of individuals (i.e., more than one person). Case series usually contain detailed information about each person and may include demographic information, as well as a discussion of existing relevant literature. The information used in the report must have been originally collected solely for non-research purposes as the result of a clinical experience.

16.10 International Research

The IRB will review all international research utilizing human participants to assure adequate provisions are in place to protect the rights and welfare of the participants.

Approval of research is permitted if the procedures prescribed by the foreign Institution afford protections that are at least equivalent to those provided in 45 CFR 46.

The IRB must receive and review the foreign Institution or site’s IRB review and approval of each study prior to the commencement of the research at the foreign Institution or site.

For Federally funded research, approval of research for foreign Institutions or sites “engaged” in research is only permitted if the foreign Institution or site holds an Assurance with OHRP and local IRB review and approval is obtained.

Approval of research for foreign Institutions or sites “not engaged” in research is only permitted if one or more of the following circumstances exist:

· When the foreign Institution or site has an established IRB/IEC (institutional ethics committee), the Investigator must obtain approval to conduct the research at the "not engaged" site from the site’s IRB/IEC or provide documentation that the site’s IRB/IEC has determined that approval is not necessary for the Investigator to conduct the proposed research at the site.

· When the foreign Institution or site does not have an established IRB/IEC, a letter of cooperation must be obtained demonstrating that the appropriate Institutional or oversight officials are permitting the research to be conducted at the performance site.

· IRB approval to conduct research at the foreign Institution or site is contingent upon receiving documentation of the performance site’s IRB/IEC determination, or letter of cooperation, as applicable.

· It is the responsibility of the OSU Investigator and the foreign Institution or site to assure that the resources and facilities are appropriate for the nature of the research.

· It is the responsibility of the OSU Investigator and the foreign Institution or site to notify the IRB promptly if a change in research activities alters the performance site’s engagement in the research (e.g., performance site “not engaged” begins consenting research participants, etc.).

· The IRB will consider local research context when reviewing international studies to assure protections are in place that are appropriate to the setting in which the research will be conducted.

· In the case where there is no local ethics review the IRB may require a letter of support or a review from a consultant. In either case, the individual must have expertise or knowledge required to adequately evaluate the risk and the cultural appropriateness of the proposed research

· The informed consent documents must be in a language understandable to the proposed participants. Therefore, the IRB will review the document and a back translation of the exact content contained in the foreign language informed consent document which must be provided by the Investigator, with the credentials of the translator detailed in the IRB application or amendment form. The IRB cannot verify the accuracy of translated documents. Therefore, verification of the back translation must be made available before the IRB may approve the translated documents. The requirement for back translation will be waived if the translation is certified by a professional translator, an individual with a master’s degree in languages, or a native speaker of the relevant language(s). Translated documents will be processed (stamped) in a manner consistent with documents presented in English.

16.10.1 Monitoring of Approved International Research

The IRB is responsible for the ongoing review of international research conducted under its jurisdiction through the continuing review process in accordance with all applicable federal regulations.

(top) 16.10.2 Conducting Chart Reviews (top) [11]

16.10.2.1 Retrospective vs. prospective chart review

A Retrospective Chart Review evaluates patient data that is existing at the time the project is submitted to the IRB for initial review.

A Prospective Chart Review evaluates patient data that does not yet exist at the time the project is submitted to the IRB for initial review.

16.10.2.2 Authorization to conduct chart reviews

Only individuals with existing legal access to the charts may conduct reviews. Depending on the circumstances, written permission from the Institution holding the records, and/or external IRB approval, may be necessary.

16.10.2.3 Determining review level

Exempt: Exempt review should only be requested if the information to be collected already exists and is publicly available or data will be recorded in such a manner that subjects cannot be identified, either directly or indirectly (Exempt Category #4). As data must exist at the time the project is submitted to the IRB, this limits exempt review to retrospective chart reviews. In the majority of cases, chart reviews do not qualify for exempt status because most investigators need to retain identifiers at least through the data collection process. Even if an investigator plans to eventually discard all identifiers once data collection is complete, this is not sufficient for the project to qualify for exempt review.

Expedited: Expedited review can be granted for retrospective and prospective chart reviews under expedited category #5 which is defined as: Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected solely for non-research purposes (such as medical treatment or diagnosis). Most chart reviews fall into this category.

Full Board: While rare, full board review may be required for both retrospective and prospective chart reviews. Some circumstances under which this occurs is if the investigator plans to collect sensitive data, or if the chart review results in a change in care for the patients whose data is being collected.

16.10.2.4 Non-exempt Chart review and consent

Waiver of Consent: Waiver of consent is the most frequently requested type of consent for both retrospective and prospective chart reviews. In order for the IRB to approve a waiver of consent, the IRB must be satisfied that the following criteria are met:

The research involves no more than minimal risk to the subjects;
The waiver or alteration will not adversely affect the rights and welfare of the subjects;
The research could not practicably be carried out without the waiver or alteration; and
Whenever appropriate, the subjects will be provided with additional pertinent information after participation.

Waiver of Documentation of Consent: This type of consent is not usually requested for a chart review. Under a waiver of documentation of consent, an investigator must still obtain consent from the subject. However, the investigator does not need to obtain a signed consent form from subjects if the IRB agrees that the following criteria are met:

That the only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality. Each subject will be asked whether the subject wants documentation linking the subject with the research, and the subject's wishes will govern; or
That the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context.

Written Consent: In certain instances the IRB may determine that written consent is required if the investigator is unable to justify why it’s impracticable to conduct the research without a waiver. This is more often the case for prospective chart review studies, but sometimes occurs in retrospective chart review studies. For example, an investigator wants to conduct a study that would include the review of the charts of all of her clinic patients who have a history of mental illness. The IRB may determine that the investigator should obtain prior written consent from each patient.

17. Participant Outreach

17.1 Policy

The IRB is committed to ensuring that educational opportunities are offered to research participants, prospective research participants, and community members, which will enhance their understanding of research involving human participants at OSU.

The following procedures describe how the IRB fulfils that responsibility.

17.2 Responsibility

It is the responsibility of the IRB Administrator to implement the procedures outlined below.

17.3 Outreach Resources and Educational Materials

The FAQ section of the IRB website contains the question, “What do I need to know before enrolling in a research study?” This question links directly to the OHRP brochure for potential research participants.

18. Relevant References

Food and Drug Administration (FDA)

http://www.fda.gov

Federal Food, Drug, and Cosmetic Act 505(i) and 520(g)

http://www.fda.gov/regulatoryinformation/legislation/federalfooddrugandcosmeticactFDCAct/default.htm

21 CFR 50 Protection of Human Subject

http://www.ecfr.gov/cgi-bin/text-idx?SID=7245f9aabb60e500d335d28b0430daa6&node=21:1.0.1.1.20&rgn=div5

21 CFR 54 Financial Disclosure by Clinical Investigators

http://www.ecfr.gov/cgi-bin/text-idx?SID=7245f9aabb60e500d335d28b0430daa6&node=21:1.0.1.1.21&rgn=div5

21 CFR 56 Institutional Review Boards

http://www.ecfr.gov/cgi-bin/text-idx?SID=7245f9aabb60e500d335d28b0430daa6&node=21:1.0.1.1.22&rgn=div5

21 CFR 312 Investigational New Drug Application

http://www.ecfr.gov/cgi-bin/text-idx?SID=7245f9aabb60e500d335d28b0430daa6&node=21:5.0.1.1.3&rgn=div5

21 CFR 807 Establishment Registration And Device Listing For Manufacturers And Initial Importers Of Devices

http://www.ecfr.gov/cgi-bin/text-idx?SID=7245f9aabb60e500d335d28b0430daa6&node=21:8.0.1.1.5&rgn=div5

21 CFR 809 In Vitro Diagnostic Products For Human Use

http://www.ecfr.gov/cgi-bin/text-idx?SID=7245f9aabb60e500d335d28b0430daa6&node=21:8.0.1.1.7&rgn=div5

21 CFR 812 Investigational Device Exemptions

http://www.ecfr.gov/cgi-bin/text-idx?SID=7245f9aabb60e500d335d28b0430daa6&node=21:8.0.1.1.9&rgn=div5

45 CFR 46 Protection of Human Subjects

http://www.ecfr.gov/cgi-bin/text-idx?SID=7245f9aabb60e500d335d28b0430daa6&node=45:1.0.1.1.25&rgn=div5

[1] Scientist/Non-scientist: Members whose training, background, and occupation would incline them to view scientific activities from the standpoint of someone within a behavioral or biomedical research discipline should be considered a scientist, while members whose training, background, and occupation would incline them to view research activities from a standpoint outside of any biomedical or behavioral scientific discipline should be considered a nonscientist. In addition, the IRB must have members with sufficient knowledge of the specific scientific discipline(s) relevant to the research that it reviews.

[2] Affiliated: An employee or agent of the organization registering the IRB (or a member of that person’s immediate family) is considered affiliated. Affiliated members include, but are not limited to, individuals who are: part-time employees; current students; members of any governing panel or board of the Institution; paid or unpaid consultants; healthcare providers holding credentials to practice at the Institution; and volunteers working at the Institution on business unrelated to the IRB. An individual that has no affiliation with the organization registering the IRB, other than as an IRB member, is considered unaffiliated with the entity operating the IRB. Unaffiliated members may include people whose only association with the Institution is that of a patient, subject, or former student at that Institution. Paying unaffiliated members for their services would not make the member “otherwise affiliated” as stated in the regulations, or cause the member to have a conflicting interest.

[3] Policy approved by the IRB March 2, 2010.

[4] “Family member” is defined as anyone having a relationship to a person as a spouse or domestic partner; the parent, child, or sibling of the individual or domestic partner; or any person for whom the individual has a legal support obligation.

[5] IRB policy effective 07/01/2010

[6] FDA requires 10 days. This has been shortened to three days to be consistent with the unanticipated problem reporting requirements set forth in other areas of this document.

[7] OHRP refers to this category as “approved with conditions”.

[8] Policy approved by IRB in 09/2011

[9] 46.116(d) An IRB may approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent set forth in this section, or waive the requirements to obtain informed consent provided the IRB finds and documents that:

1) The research involves no more than minimal risk to the subjects;

2) The waiver or alteration will not adversely affect the rights and welfare of the subjects;

3) The research could not practicably be carried out without the waiver or alteration; and

4) Whenever appropriate, the subjects will be provided with additional pertinent information after participation.

[10] Policy approved by IRB on 02/02/2010

[11] Guidance adapted, in part, from the Chart Review Protocol Instructions from Northwestern University Office for Research (2009).