In Part 1 of this series, we discussed the basic summary of FDA’s two proposed rules involving human subject protections and IRBs, as well as the extension FDA made to allow for commenters to have more time to develop thoughtful responses to the proposed rules. Part 2 will focus on breaking down the first proposed rule, “Protection of Human Subjects and Institutional Review Boards.”
The first section of FDA’s proposed rule is intended to enhance human subject protections by adding and simplifying requirements to the informed consent process so that subjects fully understand whether they want to participate in the research.
In alignment with the Common Rule, FDA proposes to require that informed consent start with a short presentation of the important information that will help a subject understand whether they want to participate in the research. FDA intends to require 1) a statement that the subject’s biospecimens may be used for commercial profit and whether the subject will share in this profit; 2) a statement on whether clinically relevant research will be disclosed to subjects; 3) that subjects be informed whether research involving biospecimens will include whole genome sequencing.
FDA also proposes to require informed consent forms (ICFs) to include a description of how information or biospecimens obtained during the clinical investigation may be used or distributed for future research—a slight deviation from the Common Rule. The revised Common Rule necessitates that subjects be provided with one of two statements in the ICF: 1) private information or biospecimens might be used or distributed for future research without obtaining additional informed consent; or 2) private information or biospecimens will not be used or distributed for future research. FDA considers its proposed approach to offer flexibility in requiring a description of future use and distribution, rather than a binary choice. FDA seeks comments on whether this proposed addendum would adequately inform subjects about the possible future use of their information and biospecimens, and whether the research community anticipates challenges in implementing this proposal.
The second part of FDA’s proposed rule suggests modifications to some provisions in an effort to update and clarify the IRB review process and streamline some differences between FDA regulations and the revised Common Rule.
FDA proposes to eliminate the requirement for IRBs to conduct continuing review of research under certain circumstances. The elimination would only apply to 1) data analysis (including analysis of identifiable private information or identifiable biospecimens) and 2) accessing follow-up clinical data from procedures that subjects would undergo as part of their clinical care. This proposed change would align with the Common Rule.
FDA is not planning on adopting two other Common Rule provisions that identify circumstances where continuing review is not required:
- FDA is not eliminating the requirement for an IRB to conduct continuing review of research that is eligible for expedited review. FDA suggests that keeping this requirement would “provide meaningful protections for human subjects participating in such investigations.”
- FDA is not eliminating the continuing review requirement for research evaluated under the limited IRB review procedures because FDA has not implemented the Common Rule’s limited IRB review process. However, FDA notes that it “may take additional steps to harmonize with such provisions at a later time.”
FDA intends to maintain its language on expedited IRB review procedures, despite revisions to the corresponding provision in the Common Rule. Under current FDA regulations, an IRB may use the expedited review procedure to review research appearing on FDA’s expedited review list “and found by the reviewer(s) to involve no more than minimal risk.” The revised Common Rule now states that an IRB may use the expedited review procedure to review research appearing on the expedited review list of the Department of Health and Human Services (HHS) “unless the reviewer determines that the study involves more than minimal risk.” FDA considers its existing regulations to be consistent with the revised Common Rule because it still must be determined that research involves no more than minimal risk in order for research to qualify for expedited review. IRBs will therefore still be able to use the same procedures to review research that may be reviewed via expedited review under the Common Rule and FDA’s regulations.
In addition to the proposals mentioned above, FDA also requests comments on the following issues:
- Not adopting the Common Rule provision that allows an IRB to approve a research proposal in which information or biospecimens will be obtained without the subject’s informed consent. Certain preliminary activities to a clinical investigation do not require IRB review or informed consent under FDA’s regulations.
- Not including the Common Rule’s exception to the requirement for documentation of informed consent in certain situations. These situations include 1) when the only record linking the subject and the research is the ICF; and 2) when the principal risk would be potential harm resulting from a breach of confidentiality.
- The proposed effective date and approach to implementation. FDA proposes that the effective date of the final rule would be 180 days from the date of publication. FDA also proposes that research initially approved by an IRB before the effective date would not be required to comply with the new informed consent requirements.
FDA is accepting comments on this proposal until December 28, 2022, which can be submitted electronically at www.regulations.gov.
Two commenters have already suggested adjusting some of the definitions in this proposal. The first suggested that the definition of “Human Subject” here be consistent with the definition as written here—they advised to replace “human” in the former with “individual” to match the latter and differentiate from the Common Rule’s definitions of “Human.” The second commenter, AdvaMed, suggested to align the definition of “Subject” here to the definition of “Human Subject” here. Changing “specimen” to “identifiable biospecimen” will keep FDA’s definitions consistent, providing clarity within FDA’s and the Common Rule’s definitions.
AdvaMed also countered FDA’s plan to not adopt the Common Rule’s provision on expedited IRB review procedures. They argued that because clinical trials are design validation studies, “product and trial risk indicators and potential clinical trial safety signals are part of the continuum of product and clinical risk management.” Therefore, any new risks to human subjects identified during the study would be included into the trial design and would result in either an update of the clinical trial protocol, suspension, or termination of the study. The IRB would be informed to guarantee appropriate subject protections, and a revised trial protocol would undergo IRB review. Because of this continual monitoring of clinical trial risk indicators, AdvaMed contends that the adoption of the Common Rule’s provision would still guarantee continued protection of human subjects.
For more information on this proposal, review the published proposal in the Federal Register here: Protection of Human Subjects and Institutional Review Boards.
Have questions or want to learn more? Visit www.medicept.com or email us at email@example.com. And make sure to stay tuned for Part 3 of the series, which will break down the proposed rule on “Institutional Review Boards; Cooperative Research.”