Beginner’s Guide to Minimal Risk Research
When an institutional review board (IRB) determines research is “minimal risk” (as defined in Department of Health and Human Services [HHS] and Food and Drug Administration [FDA] regulations), the research is potentially eligible for several regulatory flexibilities. How can researchers know when research is minimal risk? This blog aims to provide a beginner’s overview to the regulatory concept of “minimal risk,” and which regulatory flexibilities research might be eligible for.
When is Research Minimal Risk, and What Regulatory Flexibilities Might Apply?
First, let’s define “minimal risk” and understand how a minimal risk determination might affect an activity. The FDA and HHS regulations state, “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” (21 CFR 56.102(i), 45 CFR 46.102(j)).
If an IRB determines an activity is minimal risk, the research might be eligible for review through expedited procedures. An IRB can follow expedited review procedures if the IRB determines the research is minimal risk and the research fits into one of the categories on the 1998 List of Categories of Research That May be Reviewed Through an Expedited Review Procedure (“1998 List”). Additionally, minor changes to previously approved research during the period for which approval is granted may also be reviewed through expedited procedures (21 CFR 56.110, 45 CFR 46.110). (Also, for research subject to the revised Common Rule, if limited IRB review is required as a condition of an exemption, that review may also be done through expedited procedures.)
It’s important to note in this case, “expedited” is a regulatory term and does not mean “fast.” “Expedited” only refers to how the review is performed. Expedited reviews can be conducted by just the IRB chairperson or their designee(s), rather than by the full board at a convened meeting. In some cases, expedited review may be completed more quickly than a full board review, but not always.
During expedited review, the IRB reviewer examines the study and supporting documentation, just as would happen during a full board review. The criteria for approval of research reviewed through expedited procedures is the same as it is for research reviewed by the full board. In other words, researchers can still expect the same thorough review regardless of how the study is reviewed.
Qualifying for Expedited Review
Expedited review cannot simply be requested like you might request “rush” review; a protocol must first meet certain qualifications. FDA and OHRP provide a list of categories of research that may be reviewed through an expedited review procedure.
If you are unsure about whether your study qualifies for expedited review, talk with your IRB; they should be able to help guide you and your team. Remember: The IRB must determine the proposed research is minimal risk and meets one of the categories on the 1998 List. Thus, not all minimal risk research may be reviewed through expedited procedures. For example, consider a research activity involving blood draws from healthy, non-pregnant adults who weigh over 110 pounds. If the total volume of blood to be drawn exceeds 550 ml in an 8-week period, an initial review of this study could not occur through the expedited pathway, even if the research is also minimal risk.
Additionally, the IRB may decide a study should receive full board review board even if it is minimal risk and fits into one of the categories on the 1998 Expedited Review Categories list. For example, an IRB might make this determination if the research involves a population potentially vulnerable to coercion or undue influence (e.g., students, employees, decisionally impaired adults). An IRB might also decide to take this approach if an activity satisfies one of the expedited review categories but does not clearly satisfy the definition of minimal risk. As another example, an IRB could send a study qualifying for expedited review to the full board if the researcher overseeing the study has a substantial financial conflict of interest.
Finally, even if research is not reviewed under expedited procedures for initial review, the IRB can determine future reviews of the study may be conducted via the expedited pathway. Consider again the blood draw example above. As long as the IRB determines that the research is minimal risk, the IRB may also determine that future reviews (e.g., continuing review) may be done through expedited procedures.
Preparations for IRB Submission
Even when research is reviewed through expedited procedures, researchers must ensure proper documentation before IRB submission. The regulatory requirements for IRB review do not change simply because an individual conducts the review rather than the full board. Researchers should make sure to provide a detailed and thorough protocol, paying special attention to the inclusion and exclusion criteria, description of the data/biospecimens to be collected and protected, and measures the team will go to protect participant confidentiality. Additionally, in order for the IRB to consider expedited review, research teams will need to specify the procedures they will perform in enough detail, so the IRB can determine whether the study is minimal risk and satisfies one of the expedited review categories.
Seeking and Obtaining Informed Consent
When seeking and obtaining informed consent from participants involved in minimal risk research, the content requirements for the informed consent form (ICF) are the same as for any other type of research. This includes a discussion of the reasonably foreseeable risks related to the research. In minimal risk research, these risks often include things like loss of confidentiality or accidental disclosure of data. In minimal risk research where it isn’t feasible to seek informed consent, researchers may request that an IRB waive the requirement that informed consent be sought and obtained. For minimal risk research, researchers may also request that an IRB waive the requirement for informed consent to be documented (i.e., the requirement for the subject to sign the consent form).
Revised Common Rule
The revised Common Rule states continuing review is not required in:
- Research eligible for expedited review
- Exempt research that requires limited IRB review
- Research that has reached the point where only data analysis is being performed and/or where investigators are only accessing follow-up clinical data from procedures that subjects would undergo as part of clinical care
Under these updated regulations, the IRB may choose to still require continuing review in the above circumstances, provided the IRB determines and documents its rationale. Other reporting requirements, such as alerting the IRB of serious or continuing noncompliance, remain.
While some minimal risk research might be eligible for certain regulatory flexibilities, that does not mean the IRB’s responsibility to ensure human subjects’ protection is diminished. A lot goes into determining whether a study qualifies as minimal risk. If you are unsure if your study meets the definition of minimal risk and might be eligible for expedited review, a waiver of informed consent, or a waiver of documentation of consent, reach out to your IRB, as they will be able to provide guidance on whether or not these flexibilities are available for your study.