Research Involving Human Subjects

Federal Definition of Research1: A systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Activities which meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program which is considered research for other purposes. For example, some demonstration and service programs may include research activities.

Systematic Investigation2,3: Typically predetermined method for studying a specific topic, answering a specific question(s), testing a specific hypothesis(es), or developing theory. A scientific or scholarly activity involving qualitative or quantitative data collection and/or data analysis that sets forth an objective(s) and a set of procedures intended to reach the objective(s), i.e., to acquire knowledge, develop a theory, or to answer a question.

  • Includes: observational studies, interview or survey studies, group comparison studies, test development and interventional research
  • Not systematic investigations: oral histories, journalism, phenomenological activities
  • Gray Area: Program Evaluation – need to assess design and intent

Designed to Develop or Contribute: Intent to disseminate results to those outside of the University via the web, poster presentations, conferences, library placement, or publication. 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.

Generalizable Knowledge4: The intent or purpose of the systematic investigation is dissemination of findings (publication or presentation) outside of OSU. Designed to draw conclusions from the data; results are analyzed for predictive value; results can be applied to a larger population (i.e., applicability is not limited to the participants) or inform policy.

  • Intended to have an impact (theoretical or practical) on others within one’s discipline.
  • Dissemination with the intent to influence behavior, practice, theory, future research designs, etc. are contributing to generalizable knowledge.5
  • Consider: Would this project be conducted as proposed if the PI knew that he or she would never receive any form of academic recognition for the project, including publication of results or presentation of the project at an academic meeting? If the activity would remain exactly the same, the project is likely NOT research.

Evaluation6:  Form of inquiry that seeks to address critical questions concerning how well a program, process, product system, or organization is working. It is typically undertaken for decision-making purposes, and should lead to a use of findings by a variety of stakeholders, who may be internal or external to OSU. Some evaluations will be classified as research and some will not. Please see the ‘scenarios and examples’ document for additional information.

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. [21 CFR §50.3 (c)]

Human Subject7: A living individual about whom an investigator conducting research obtains:

  • Data through intervention or interaction with the individual, OR
  • Identifiable private information

About an individual: Information is about an individual whenever the answer involves demographic information (e.g., age, gender, etc.) or requests that the individual provides information based in their opinions, attitudes, behaviors, or perceptions.

Intervention includes both physical procedures by which data are gathered and manipulations of the subject or the subject's environment that are performed for research purposes.

Interaction includes communication or interpersonal contact between investigator and subject. The interaction may be as remote as an anonymous online survey.

Identifiable 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 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 individuals may include third parties.

Examples of identifiable information: Name; Address, including city and zip code; Telephone number; Fax number; Email address; Social Security Number; Date of birth; Medical record number; Health plan ID number; Dates of treatment; Account number; Certificate/license number; Device identifiers and serial number; Vehicle identifiers and serial number; URL; IP address; Biometric identifiers, including fingerprints; Full face photo and other comparable image8

Human Subject: means an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy human or a patient. [21 CFR §50.3(g)] For medical devices, an individual on whose specimen an investigational device is used.

 

Drugs, Biologics, Devices, and Food

Biological Specimens8A sample, as of human tissue, blood or urine, used for diagnostic or pathological analyses.

Bioavailability: Bioavailability means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.  [21 CFR §320.1(a)]

Bioequivalence: Bioequivalence means the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study. Where there is an intentional difference in rate (e.g., in certain extended release dosage forms), certain pharmaceutical equivalents or alternatives may be considered bioequivalent if there is no significant difference in the extent to which the active ingredient or moiety from each product becomes available at the site of drug action. This applies only if the difference in the rate at which the active ingredient or moiety becomes available at the site of drug action is intentional and is reflected in the proposed labeling, is not essential to the attainment of effective body drug concentrations on chronic use, and is considered medically insignificant for the drug. [21 CFR §320.1(e)]

Biological Product: A biological product is a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein (except any chemically synthesized polypeptide), or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings. [42 U.S.C. 262(i)]

Custom Device: means a device that:

  1. Necessarily deviates from devices generally available or from an applicable performance standard or premarket approval requirement in order to comply with the order of an individual physician or dentist;
  2. Is not generally available to, or generally used by, other physicians or dentists;
  3. Is not generally available in finished form for purchase or for dispensing upon prescription;
  4. Is not offered for commercial distribution through labeling or advertising; and
  5. Is intended for use by an individual patient named in the order of a physician or dentist, and is to be made in a specific form for that patient, or is intended to meet the special needs of the physician or dentist in the course of professional practice. [21 CFR §812.3 (b)]

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)].

Drug: The term "drug" means

  1. articles recognized in the official United States Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them; and
  2. articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and
  3. articles (other than food) intended to affect the structure or any function of the body of man or other animals; and
  4. articles intended for use as a component of any article specified in (1), (2) or (3). Section 201(g)(1) of the FD&C Act [21 U.S.C. 321(g)(1)]

Food: Section 201(f) of the FD&C Act [21 U.S.C. 321(f)] defines a food as “(1) articles used for food or drink for man or other animals, (2) chewing gum, and (3) articles used for components of any such article.”

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 device, including a transitional device, which is the object of a clinical investigation or research involving one or more subjects to determine the safety or effectiveness of a device. [21 CFR §812.3 (g), (h)]

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.

Medical Device: A medical device is "an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is:

  • recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them,
  • intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or
  • intended to affect the structure or any function of the body of man or other animals, and which does not achieve any of its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes." Section 201(h) of the FD&C Act [21 U.S.C. 321(h)]

To assist with making a determination, please see the "Is it a Medical Device?" decision tree.

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. [21 CFR §812.3(m)]

To assist with making a determination, please see the "Is it a significant risk or nonsignificant risk" decision tree.

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 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. [21 CFR §50.3(j)]

 

Privacy, Confidentiality, and Identifiers

Anonymous: Subjects’ identities are unknown to the investigator, not requested, and not given. Data collected do not contain any information that would permit identification of the individual subjects.

Note: Subjects cannot be described as anonymous if the research involves audio/video recordings or in-person interviews.

Confidentiality: Subjects’ identities are known to the researchers and/or data contain information that would permit identification of the individual(s) about whom the data were collected. The data are transmitted and stored in a manner that protects the information from release to unauthorized individuals.  Information will not be divulged to others without permission in ways that are inconsistent with the understanding of the original disclosure.

Individually identifiable: The identity of the subject is or may readily be ascertained by the investigator or associated with the information. Individually identifiable information is not limited to name, date of birth, or contact information.

According to Sweeney (2000)9, it was found that 87% (216 million of 248 million) of the population in the United States had reported characteristics that likely made them unique based only on {5-digit ZIP, gender, date of birth}. About half of the U.S. population (132 million of 248 million or 53%) are likely to be uniquely identified by only {place, gender, date of birth}, where place is basically the city, town, or municipality in which the person resides. And even at the county level, {county, gender, date of birth} are likely to uniquely identify 18% of the U.S. population. In general, few characteristics are needed to uniquely identify a person.

Coded: 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 a key to decipher the code exists, enabling linkage of the identifying information to the private information or specimens.

Note: Private information or specimens are considered not to be individually identifiable when they cannot be linked to specific individuals by the investigator(s) either directly or indirectly through coding systems. For example, OHRP does not consider research involving only coded private information or specimens to 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
  1. the investigator(s) cannot readily ascertain the identity of the individual(s) to whom the coded private information or specimens pertain because, for example:
    1. 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);
    2. 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
    3. there are other legal requirements prohibiting the release of the key to the investigators, until the individuals are deceased10.

This guidance applies to existing private information and specimens, as well as to private information and specimens to be collected in the future for purposes other than the currently proposed research.

Examples of private information or specimens that will be collected in the future for purposes other than the currently proposed research include: (1) medical records; and (2) ongoing collection of specimens for a tissue repository.

De-identified: When collected, data contained identifiers or information that would permit identification of the individual(s) about whom the data were collected, but the identifiers or other links to identity do not exist anywhere in any form.

Exception: When coded data are shared between researchers and a written agreement is in place that no identifiers will be shared, this data are considered de-identified.  This exception does not apply when the holder of the key is involved in the research.  For example, a PI sharing coded data with a student researcher is conducting research with identifiable data because it is their responsibility to oversee all aspects of the study.

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 record).

Note: 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.  In the absence of private information, studies will still meet the definition of “research with human subjects” if there is an interaction or intervention taking place.

Privacy: Privacy means, in the context of a research protocol, respecting an individual’s, or group’s, right to be free from unauthorized or unreasonable intrusion, including control over the extent, timing, and circumstances of obtaining personal information from or about them.

 

General

Engagement in Research: An institution becomes "engaged" in human subjects research when its employees or agents1 (i) intervene or interact with living individuals for research purposes; or (ii) obtain individually identifiable private information for research purposes [45 CFR 46.102(d),(f)].

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 awardee institution bears ultimate responsibility for protecting human subjects under the award.

For more details, including examples of situations where an institution may or may not be considered engaged, please refer to the guidance provided by OHRP on this topic and to the OSU Engagement in Research Decision Tree.

Minimal Risk: A risk is minimal where the probability and magnitude of harm or discomfort anticipated in the proposed 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.

 

References

1Definition from http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#46.102

2University of Minnesota Institutional Review Board website.  “Does My Research Need IRB Review” http://www.research.umn.edu/irb/research.html#.UqjE3nfe71o

3The Ohio State University Policy and Procedures Manual http://orrp.osu.edu/irb/osuirbpolicies/hrpppolicies/ accessed 12/11/2013.

4University of Minnesota Institutional Review Board website.  “Does My Research Need IRB Review” http://www.research.umn.edu/irb/research.html#.UqjE3nfe71o

5Colorado State University. http://ricro.colostate.edu/IRB/Documents/GeneralizableData.pdf. Accessed 01/06/2014.

6Definition from Russ-Eft, D. “Evaluation in Organizations”

7Definition from http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#46.102

8Definition from https://www.irb.cornell.edu/glossary/

9L. Sweeney, Simple Demographics Often Identify People Uniquely. Carnegie Mellon University, Data

Privacy Working Paper 3. Pittsburgh 2000.

10Guidance from http://www.hhs.gov/ohrp/policy/cdebiol.html