MSU HRPP Manual Section 4-3

4-3, Determination of Human Subject Research

Investigators should contact the Institutional Review Board (IRB) office with any questions regarding whether an activity constitutes research and/or a clinical investigation involving human subjects. The investigators will be asked to submit a “Determination of Whether an Activity Involves Human Subject Research” form. Based on the definitions below, HRPP staff will determine whether the activity meets the definition of human subject research based on federal regulatory definitions, 45 CFR 46.102(d), 21 CFR 50, or 21 CFR 56. The Compliance office will be consulted when there are questions about the applicability of 21 CFR 50 or 21 CFR 56.

For cases in which the determination is questionable, the HRPP staff will ask the HRPP manager to review the description of the activity submitted by the investigator. The HRPP manager or staff may consult with the IRB chair(s) or member(s) for their determination when needed (e.g. expertise in the field of study). The investigator will be contacted for additional information as needed. The HRPP manager, staff, chair(s), or member(s) will make the determination based on the definitions below. The IRB office will notify the investigator of the determination in writing (i.e., email, letter). The determination will include an explanation of whether the activity requires submission to the IRB. The determination should be made within one to three working days of receipt of the completed form. Determinations in cases where additional information is needed from the investigator may take additional time.

The HRPP staff, IRB chair, or designated reviewer will also utilize the procedure described above when processing applications submitted to the IRB to determine whether the activity requires IRB review, although the “Determination of Whether an Activity Involves Human Subject Research” form may not be needed if sufficient information is provided in the submitted IRB application.

In some instances, sponsors or other entities or individuals may require IRB review and approval, even when the activity does not meet the definition of human subject research. In those instances, IRB review and approval will be required and the activity will be subject to HRPP Manual Section 4-1, “Applicability.”

The records (e.g., form, correspondence, initial application, determinations) will be maintained for a minimum of three years. The correspondence should include the description of the activity provided by the investigator and the HRPP staff, the IRB chair, or IRB member’s written response.

Definitions and Evaluation Criteria: U.S. Department of Health and Human Services (DHHS)

When an activity meets the definition of “research” and involves “human subjects” as defined below, the DHHS regulations regarding the protection of human subjects apply, with limited exceptions outlined in Human Research Protection Program (HRPP) Manual 8-8 “Flexibility Initiative.”

1.  Does the activity involve research?

Research means 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.”  45 CFR 46.102(d)

To be considered a “systematic investigation,” the research study must:

  • Attempt to answer research questions (in some research, this would be a hypothesis)
  • Is methodologically driven (i.e., it collects data or information in an organized and consistent way)
  • Data or information is analyzed in some way, be it quantitative or qualitative data analysis
  • Conclusions are drawn from the results

To be considered “generalizable knowledge,” the activity would include the following concepts:

  • Knowledge contributes to a theoretical framework of an established body of knowledge
  • Results are expected to be generalized to a larger population beyond the site of data collection or population studied
  • Results are intended to be replicated in other settings

Presently, Michigan State University (MSU) masters’ theses and Ph.D. dissertations are considered to present generalizable knowledge.

2. If the activity is determined to be research, does the research involve “human subjects?”

Human subject is defined as a living individual(s) about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information.”  45 CFR 46.102(f)

Intervention includes 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.” 45 CFR 46.102(f)

Interaction includes communication or interpersonal contact between investigator and subject.” 45 CFR 46.102(f)

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.” 45 CFR 46.102(f)

Definitions: U.S. Food and Drug Administration (FDA)
When an activity meets the definitions of “clinical investigation” and “human subject” provided below, the FDA’s regulations regarding the protection of human subjects also apply (e.g. 21 CFR 50, 21 CFR 56, 21 CFR 312, 21 CFR 812).

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), 507(d), 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 56.102(c)

For an activity involving drugs: “Clinical investigation means any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects. For the purposes of this part, an experiment is any use of a drug except for the use of a marketed drug in the course of medical practice.” 21 CFR 312.3(b)

For an activity involving devices: “Investigation means a clinical investigation or research involving one or more subjects to determine the safety or effectiveness of a device.” 21 CFR 812.3(h)

Test article means any drug (including a 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 and 354-360F of the Public Health Service Act” (42 U.S.C. 262 and 263b-263n). 21 CFR 50.3(j)

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 a clinical investigation involving drugs: “Subject means a human who participates in an investigation, either as a recipient of the investigational new drug or as a control. A subject may be a healthy human or a patient with a disease.” 21 CFR 312(b)

For a clinical investigation involving devices: “(p) Subject means a human who participates in an investigation, either as an individual on whom or on whose specimen an investigational device is used or as a control. A subject may be in normal health or may have a medical condition or disease.

For clinical investigations of research involving devices, the definition of “subject” includes the use of specimens, even if the specimen is unidentified. While such research is not considered “human subjects” under the DHHS regulations, such research would be considered “subjects” under the FDA regulation for certain types of research.

Newborn Screening Research
Research on newborn dried blood spots shall be considered research carried out on human subjects meeting the definition of section 46.102(f)(2) of title 45, Code of Federal Regulations, for purposes of Federally funded research conducted pursuant to the Public Health Service Act until such time as updates to the Federal Policy for the Protection of Human Subjects (the Common Rule) are promulgated pursuant to subsection (c).  For purposes of this subsection, sections 46.116(c) and 46.116(d) of title 45, Code of Federal Regulations, shall not apply. Section 12 of the “Newborn Screening Saves Lives Reauthorization Act of 2014.

Additional Considerations
For research studies subject to agency specific requirements, see the following sections of the HRPP Manual:

2-2-A       U.S. Department of Defense
2-2-B       U.S. Environmental Protection Agency
2-2-C       U.S. Department of Justice
2-2-D       U.S. Department of Education
2-2-E       U.S. Department of Energy

For policies, procedures, and guidance on when specific activities are outside the scope of IRB review, see the following sections of the HRPP Manual:

4-3-A       Clinical Case Reports
6-9-A       Student Classroom Research
12-1        Quality Assurance, Quality Improvement, or Program Evaluation

This policy and procedure supersedes those previously drafted.

Approved By: Vice President of Research and Graduate Studies, 4-21-2005. Revision 1 approved by VP Research & Graduate Studies on 3-9-2008. Revision 2 approved by VP Research & Graduate Studies on 9-3-2009. Revision 3 approved by Assistant VP for Regulatory Affairs on 12-17- 2009. Revision 4 approved by VP Research & Graduate Studies on 7-21-2011. Revision 5 approved by Assistant VP Regulatory Affairs on 11-23-2015.

Related HRPP Manual Sections

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