Variability in Application of Regulatory Requirements

There are two principal sets of regulations governing human subjects protections in research.  The Food and Drug Administration (FDA) human subjects regulations are found in 21 CFR parts 50 and 56.  These regulations are similar to, but distinct from, the “Common Rule” implemented by Department of Health and Human Services (DHHS) and 17 other agencies.   The DHHS rules, found in 45 CFR part 46, are enforced by the DHHS Office for Human Research Protections (OHRP). 

The FDA and DHHS regulations differ slightly from one another with respect to certain definitions and concepts. Furthermore, both rules employ regulatory terminology that IRBs often having difficulty interpreting and applying.  Some of these terms and concepts are pivotal to discerning how to apply the regulations.  These terms and concepts include:

•          “Minimal risk” 
•          “Minor increase over minimal risk”
•          “Disorder”
•          “Condition”
•          “Human subject”
•          “Research”

The lack of consistent interpretation of regulatory language by IRBs creates unnecessary variability and uncertainty in the review of research.  Examples of research where applying the above terms and concepts can be difficult includes research:

•          Involving children
•          Using human specimens and data
•          Collecting data on third parties

Such uncertainty can result in a lack of clarity on the part of investigators and IRBs about how to comply appropriately with the regulations.  This in turn can led to gaps in human subjects protections and unnecessary barriers to research. 

On behalf of the NIH research community, the CRpac program is working to help clarify interpretation of federal regulations for human subjects research. CRpac serves as a centralized resource for the NIH community in several ways. First, CRpac collects and coordinates NIH comments on important policy processes at other agencies, such as FDA and OHRP. Second, CRpac staff serve as NIH representatives for interagency policy development activities. Third, CRpac is a resource for communication and sharing of best practices within the NIH community regarding ethical and scientific challenges in human subjects research.

Pertinent Resources, Policies, and Regulations

Department of Health and Human Services:

• Department of Health and Human Services (DHHS): Protection of Human Subjects. Code of Federal Regulations, 45 CFR 46

• Guidance for Clinical Investigators, Institutional Review Boards and Sponsors Process for Handling Referrals to FDA Under 21 CFR 50.54: Additional Safeguards for Children in Clinical Investigations 

• Office for Human Research Protections (OHRP): 1993 IRB Guidebook

• Secretary's Advisory Committee on Human Research Protections (SACHRP) OHRP, DHHS, Recommendations and Communications to the HHS Secretary

Food and Drug Administration:

• Protection of Human Subjects. Code of Federal Regulations, 21 CFR Parts 50 and 56
• Significant Differences in FDA and HHS Regulations for the Protection of Human Subjects"