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Part 46 of Title 45 of the U.S. Code of Federal Regulations (45 CFR 46) provides the regulatory framework for Protection of Human Subjects within the broader topic of Public Welfare. Importantly, 46.111(a)(1)(i) states that:

“Risks to subjects are minimized by using procedures that are consistent with sound research design and that do not unnecessarily expose subjects to riskā€¦”

and, in 46.111(a)(2), that:

“Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result.”

Interpretation of these regulations requires that no scientific research experiment using one or more human subjects may be conducted without consideration of risk or in the absence of valid scientific design to benefit subjects and/or the larger society. Proposed scientific research that does not adhere to these principles is unethical and antithetical to Federal and University standards. The University of North Carolina at Chapel Hill (UNC-CH) has designated a Scientific Review Committee (SRC) to assess initial clinical research studies for scientific merit and integrity as a precursor to IRB review.

The SRC is comprised of senior clinical and translational research investigators and professional biostatisticians who, as a group, evaluate targeted research projects, which include those:

  • That meet the regulatory and/or institutional greater than minimal risk criteria (Generally, a study that requires Full Board review at a convened IRB Committee Meeting meets the threshold for greater than minimal risk and review by the SRC)ā€¦

    — AND —

  • That have not previously undergone rigorous scientific review by a panel of experts assembled specifically to evaluate the project using criteria similar to the SRC. FDA or NIH Study Section review is not synonymous with SRC review and cannot be substituted as suchā€¦

    — AND —

  • That do not have a focus on cancer research nor recruit research subjects from UNC oncology clinics. Such studies are to be submitted for review by the UNC Protocol Review Committeeā€¦

    — AND —

  • Whose role is NOT SOLELY that of a participating study site in a multi-center, industry-sponsored study.

Scientific review at UNC-CH requires submission of a comprehensive protocol written to accepted industry standards and incorporating all the elements that the SRC considers when reviewing proposed research for scientific merit (the value to be gained, e.g., how the new information will advance understanding in a particular line of scientific inquiry) and scientific integrity (the yielding of useful information, e.g., alignment between study design, sample size calculation, aim(s), recruitment method(s), outcome measures, study procedures, data collection/quality assurance, safety monitoring, and statistical analysis plan(s)). Please refer to “What is a Protocol” to better understand the differences between a protocol and a grant proposal.

If a protocol meeting SRC standards was developed as part of a grant or funding application, it may be possible to submit it for scientific review. Consult the templates library. If the existing protocol does not contain each of the template elements, it must either be amended to include them or a new protocol using the appropriate template must be created and submitted.

Note: The UNC SRC is not alone in requiring a protocol for scientific review; other agencies/entities are increasingly mandating submission of a standardized, comprehensive protocol as part of their application/registration/review processes:

  • FDA IND or IDE submission
  • NIH clinical trial grant submission
  • External (single) IRB review
  • registration
  • Scientific journals (per ICMJE: “As part of peer review, editors are encouraged to review research protocols, plans for statistical analysis if separate from the protocolā€¦”)

While the specific responsibility for insuring human research subject protection rests with the UNC Office of Human Research Ethics (the IRB), the SRC has a complementary role as a gatekeeper that proactively identifies research proposals that do not demonstrate the required degree of thoughtful, well-founded, sufficiently-detailed description that is critical to the successful implementation and execution of clinical research.

IRB reviewers have access to SRC correspondence to and from investigators and may consider its final determination as part of their deliberations, which includes whether a study makes an adequate case for participation by human subjects. In this way, the SRC helps to insure that the effort, resources and reputations of researchers and the University are safeguarded and that the voluntary burden placed upon research participants is warranted. For more detail regarding the SRC → IRB relationship, see SRC → IRB Relationship and Interface.