HRPP Manual Section 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 new study submission including the HRP-512 - Template - Determination of Human Subject Research through the MSU IRB online system. See Human Research Protection Program (HRPP) Manual 3-1 “MSU Human Research Protection Program Plan” for a description of the MSU IRB online system.

HRPP staff will determine whether the activity meets the definition of human subject research based on federal regulatory definitions, 45 CFR 46.102, 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.

Ancillary reviewers are assigned to studies that may require additional MSU or other institutional reviews (e.g. hospital partners, biosafety review, raffle or drawings), that may utilize MSU resources (e.g. MSU Radiology), or that may be subject to additional federal requirements (e.g. Compliance office for U.S. Food and Drug Administration requirements, protected health information). The ancillary reviewer(s) is assigned to the study by the IRB coordinator. Depending on the ancillary review type and need, a response may be needed from the ancillary reviewer before a determination letter can be released.

The HRPP staff, IRB chair, or designated reviewer will also utilize the procedure described above when processing submissions to the IRB to determine whether the activity requires IRB review, although HRP-512 - Template - Determination of Human Subject Research form may not be needed if sufficient information is provided in the submitted IRB submission.

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 submission, 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: Common Rule
When an activity meets the definition of “research” and involves “human subjects” as defined below, the Common Rule regulations regarding the protection of human subjects apply, with limited exceptions outlined in HRPP Manual 8-8 “Flexibility Initiative.”

  1. Does the activity involve research?

Revised Common Rule

“Research means a systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge. Activities that meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program that is considered research for other purposes. For example, some demonstration and service programs may include research activities. For purposes of this part, the following activities are deemed not to be research:

(1) Scholarly and journalistic activities (e.g., oral history, journalism, biography, literary criticism, legal research, and historical scholarship), including the collection and use of information, that focus directly on the specific individuals about whom the information is collected.

(2) Public health surveillance activities, including the collection and testing of information or biospecimens, conducted, supported, requested, ordered, required, or authorized by a public health authority. Such activities are limited to those necessary to allow a public health authority to identify, monitor, assess, or investigate potential public health signals, onsets of disease outbreaks, or conditions of public health importance (including trends, signals, risk factors, patterns in diseases, or increases in injuries from using consumer products). Such activities include those associated with providing timely situational awareness and priority setting during the course of an event or crisis that threatens public health (including natural or man-made disasters).

(3) Collection and analysis of information, biospecimens, or records by or for a criminal justice agency for activities authorized by law or court order solely for criminal justice or criminal investigative purposes.

(4) Authorized operational activities (as determined by each agency) in support of intelligence, homeland security, defense, or other national security missions.” 45 CFR 46.102(l)(2018 Requirements)

Pre-2018 Common Rule Requirements

“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)(Pre-2018 Requirements)

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.

  1. If the activity is determined to be research, does the research involve “human subjects?”
Revised Common Rule (2018 Requirements)
“(1) Human subject means a living individual about whom an investigator (whether professional or student) conducting research:
 
(i) Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or
 
(ii) Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.
 
(2) Intervention includes both physical procedures by which information or biospecimens are gathered (e.g., venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes.
 
(3) Interaction includes communication or interpersonal contact between investigator and subject.
 
(4) 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 that has been provided for specific purposes by an individual and that the individual can reasonably expect will not be made public (e.g., a medical record).
 
(5) Identifiable private information is private information for which the identity of the subject is or may readily be ascertained by the investigator or associated with the information.
 
(6) An identifiable biospecimen is a biospecimen for which the identity of the subject is or may readily be ascertained by the investigator or associated with the biospecimen.” 45 CFR 46.102(e)(2018 Requirements)
 
Pre-2018 Common Rule Requirements
“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)(Pre-2018 Requirements)
 
“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)(Pre-2018 Requirements)
 
“Interaction includes communication or interpersonal contact between investigator and subject.” 45 CFR 46.102(f) (Pre-2018 Requirements)
 

“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) (Pre-2018 Requirements)

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.

Applicability of the Revised Common Rule (2018 Requirements)
See HRPP Manual Section 4-11 “Applicability of the Revised Common Rule (2018 Requirements)” for a description of whether the Revised Common Rule (2018 Requirements) or the Pre-2018 Common Rule Requirements apply.

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. Revision 6 approved by Assistant VP Regulatory Affairs on 6-27-2018. Revision 7 approved by Senior VP for Research and Innovation on 1-18-2019.

Related HRPP Manual Sections