Once the PI determines whether the FDA regulations or the Common Rule apply, then the PI is primarily obligated to determine whether the activity is human research, as regulated by the Common Rule, or a clinical investigation as regulated by the FDA regulations. When there are questions about whether the PI’s activities are non-research/non-clinical investigation activities, the PI is encouraged to do the following:
- Consult with his/her peers and IRB members;
- Review federal regulations (see 45 CFR Part 6, FDA Regulations);
- Review OHRP and FDA interpretation documents and educational materials (see OHRP Education and Outreach, OHRP Policy and Guidance, and FDA Guidance Documents);
- Review these Written Procedures; and
- Use educational materials such as the Collaborative Institutional Training Initiative (CITI) Program human research modules (see CITI Program Homepage).
The IRB will not require the IRB to review non-research/non-clinical investigation activities.
The PI should make the determination that activities subject to Common Rule are research if they fall within the definition of research found at 45 CFR § 46.102(l). This definition under the Revised Common Rule states:
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.
In the Revised Common Rule definition, the drafting agencies removed four categories of activities from the definition of research including:
- Scholarly journalistic activities;
- Public health surveillance;
- Criminal justice activities; and
- Authorized operational activities in support of national security missions.
Any PI involved in these activities is not required to receive IRB review.
Other than the removed categories, the definition of research has remained unmodified. This is despite the drafting agencies’ acknowledgment in the Federal Register that critics of definition argue that it is not “sufficiently clear and precise . . . in a way that ma[kes] it immediately obvious which activities f[a]ll under the definition and which d[o] not” (see Federal Register).
Despite the ambiguity in the regulation, OHRP focuses on the terms “systematic investigation” and “generalizable knowledge” to interpret the definition of the term research. OHRP describes systematic investigation to involve a hypothesis and a plan to test the hypothesis. OHRP describes generalizable knowledge to be knowledge applicable to a larger source and generalized to enable additional research. While publication is a way to distribute generalizable knowledge, OHRP notes that publication is not determinative of whether an activity contributes to generalizable knowledge because research may occur which is not published for various reasons.
22.214.171.124 Classroom Activities
Classroom activities may or may not fall within the definition of research under the Revised Common Rule. The University recognizes the need to facilitate classroom research. Accordingly, it has created a system to facilitate the review of exempt research associated with classroom activities. Section 2.2 will outline this exempt review for classroom activities.
The University does not consider classroom activities ipso facto to not be research. This is not within the plain reading of the regulation. OHRP interpretations of the definition do not justify this interpretation. Based on the regulations, the test to determine whether an activity falls within the definition of research involves the following two steps:
- Whether the activity is a “systematic investigation”; and
- Whether this investigation may contribute to “generalizable knowledge.”
Classroom activities may involve a “systematic investigation” including a hypothesis and a plan to test the hypothesis. Further classroom activities may contribute to “generalizable knowledge” that can be applied to a larger source and generalized to result in additional research. To determine whether the classroom activities are research, it does not matter whether these activities are actually published or distributed outside of a classroom.
Based on the cannon of construction for statutes “expressio unius est exclusio alterius,” it is unlikely that classroom activities are categorically excluded from the definition of research. When participating federal agencies revised the definition of research for the Revised Common Rule, these agencies did not explicitly exclude classroom activities from its definition as it did with the four categories outlined above.
The Supreme Court has recognized the doctrine “expressio unius est exclusio alterius,” which translated from Latin into English means "the express mention of one thing excludes all others.” In Barnhart v. Peabody Coal Co., the Supreme Court held this doctrine “has force only when the items expressed are members of an "associated group or series," justifying the inference that items not mentioned were excluded by deliberate choice, not inadvertence” (see Barnhart v. Peabody Coal). In this instance, the courts would likely hold that the excluded categories of research are an “associated group or series.” According to legal precedent, the inference is then justified that classroom activities were “excluded by deliberate choice”; and consequently, classroom activities are not ipso facto excluded from research.
1.2.2 Clinical Investigation
The PI should make the determination of whether the activities are clinical investigation as defined by 21 CFR § 50.103 that reads:
Clinical investigation means any experiment that involves a test article and one or more human subjects and that either is subject to requirements for prior submission to the Food and Drug Administration under section 505(i) or 520(g) of the act, or is not subject to 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 submitted later 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 are subject to the provisions of part 58 of this chapter, regarding nonclinical laboratory studies.
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