The Common Rule (subpart A of 45 CFR part 46) requires that each institution engaged in nonexempt human subjects research that is conducted or supported by a Common Rule department or agency “provide written assurance satisfactory to the department or agency head that it will comply with the requirements of [the Common Rule]” (45 CFR 46.103(a)). Currently, the Office for Human Research Protections (OHRP) administers one type of assurance: the Federalwide Assurance (FWA). All other Common Rule departments and agencies recognize and accept the FWA.
Under the “Applicability” section of the FWA, an institution can voluntarily elect to apply the Common Rule to all of its nonexempt human subjects research regardless of the source of support. This voluntary election is often referred to as “the box.” If the box is checked on an institution’s FWA, it means that all research conducted at the institution must comply with the Common Rule. It also means that OHRP has compliance oversight authority over the research that follows the Common Rule solely because the box has been checked (also referred to as “check the box research”).
Historically, OHRP has said that the Common Rule reporting requirements apply to all nonexempt human subjects research covered by an FWA, regardless of funding source. In other words, institutions must follow the Common Rule reporting requirements for activities supported by a Common Rule department or agency, or for check the box research. The terms of the assurance require institutions to abide by whatever commitments have been made in that document. If the box is selected on the FWA, it is up to the assurance-holding institution to ensure that all of the institution’s nonexempt research complies with the Common Rule, regardless of whether the institution relies on internal or external IRBs.
This means that a study not supported by a Common Rule department or agency might still be required to follow the Common Rule. Consider a hospital evaluating whether to implement a new pre-surgical checklist within that institution. If the hospital has checked the box on the FWA, a determination will need to be made about whether the study is nonexempt human subjects research, even though federal funding is not being received. Also consider studies not supported by a Common Rule department or agency that are under FDA’s jurisdiction. If an institution has checked the box on its FWA, this type of research must also comply with the Common Rule. While the FDA regulations at 21 CFR parts 50 and 56 are similar to the Common Rule, they are not identical (especially when considering the revised Common Rule). Thus, it is critical for FWA-holding institutions to know whether the box is checked on their FWA and to understand what that means for research at their institution.
Revised Common Rule Changes?
During the process to revise the Common Rule, OHRP announced its intention to eliminate the box. However, the FWA form approved by OMB for use through 2023 still includes this option. In other documents, OHRP has noted that no changes have been made to the assurance process in consideration of the revised Common Rule. OHRP has indicated that it will give the regulated community the opportunity to comment on any proposed changes before they are implemented.
Institutions should note that there are several revised Common Rule requirements where it is unclear if they apply to check the box research. The two provisions that would have the most impact on check the box research are the clinical trial informed consent posting requirement at 45 CFR 46.116(h) and the single IRB requirement at 45 CFR 46.114(b). The language of these provisions suggest that they only apply to research that is federally supported or conducted; thus, arguably, even if check the box research needs to comply with other provisions of the revised Common Rule, these activities do not need to comply with the two provisions cited above.
Without clarity from OHRP, these outstanding questions may cause institutions significant confusion. We recommend institutions carefully consider whether it makes sense to check the box on the FWA at this time.
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