Amendment: NIH Policy and Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research

Notice Number: NOT-OD-18-014

Key Dates
Release Date: November 28, 2017  

Related Announcements
NOT-OD-02-001
NOT-OD-01-053
NOT-OD-16-149

Issued by
National Institutes of Health (NIH)

Purpose

This Notice amends NOT-OD-02-001.  The purpose of this Notice is to inform the research community that NIH is amending its NIH Policy and Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research to include a requirement that recipients conducting applicable NIH-defined Phase III clinical trials ensure results of valid analyses by sex/gender, race, and/or ethnicity are submitted to Clinicaltrials.gov.  All other aspects of the NIH Policy and Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research remain unchanged.  

Background

The NIH Revitalization Act of 1993, PL 103-43 (Public Health Service Act sec. 492B, 42 U.S.C. sec. 289a-2), signed into law on June 10, 1993, directed the NIH to establish guidelines for inclusion of women and minorities in clinical research  The statute requires NIH to ensure that clinical trials are carried out in a manner sufficient to provide for a valid analysis of whether the variables being studied affect women or members of minority groups differently than other trial participants.  See the NIH Policy and Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research for more information.

The 21st Century Cures Act, PL 114-255, enacted December 13, 2016, requires entities conducting applicable clinical trials submit results of valid analyses by sex/gender, race, and ethnicity in Clinicaltrials.gov. The statute further requires that NIH consider, as appropriate, whether the entity has complied with this reporting requirement when awarding any future grant to that entity; and that NIH encourage the reporting of the results of valid analysis through any additional means determined appropriate.

Scope and Applicability

The requirement for submission of results of valid analyses by sex/gender and race/ethnicity to Clinicaltrials.gov applies to all NIH conducted or supported applicable NIH-defined Phase III clinical trials.  This requirement does not apply to NIH-defined Phase III trials not considered to be applicable clinical trials under 42 CFR Part 11. This requirement applies to applicable NIH-defined Phase III clinical trials involving research subjects of all ages, including foreign awards and domestic awards with a foreign component.

The requirement for submission of results of valid analyses by sex/gender and race/ethnicity to Clinicaltrials.gov applies to all new, competing grants and cooperative agreements awarded on or after December 13, 2017.  Ongoing, non-competing awards will not be expected to comply with the revised policy until the grantee submits a competing renewal application.  For R&D contracts, the policy will apply to all solicitations issued on or after this effective date.  For the intramural program, the policy applies to intramural studies initiated on or after December 13, 2017.

Guidelines for Reporting Results of Valid Analyses in Clinicaltrials.gov

When registering in Clincialtrials.gov, applicable NIH-defined Phase III clinical trials must specify outcomes on sex/gender and race/ethnicity, as required based on prior evidence, and as explained in the NIH Policy and Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research.  For applicable NIH-defined Phase III clinical trials, submissions of results to Clinicaltrials.gov must include results of valid analyses by sex/gender and race/ethnicity, as required based on prior evidence.

This policy is complementary to requirements in the Clinical Trial Registration and Results Information Submission regulation at 42 CFR Part 11.  Applicable clinical trials are required to be registered in ClinicalTrials.gov not later than 21 calendar days after the enrollment of the first participant.  Results information, including the results of valid analyses by sex/gender and race/ethnicity, from those trials generally must be submitted not later than one year after the trial's primary completion date.  Submission of results information can be delayed in certain circumstances for up to two additional years for trials of products regulated by the FDA that are unapproved, unlicensed, or uncleared or for trials of products for which approval, licensure, or clearance of a new use is being sought.

Definitions

Applicable Clinical Trial.  Applicable clinical trial is the term used in Title VIII of the Food and Drug Administration Amendments Act (FDAAA) of 2007 (P.L. 110-85) to designate the scope of clinical trials that may be subject to the registration and results reporting requirements in FDAAA.  Clinical trials that are subject to the regulation are, in general, clinical trials of drug, biological, and device products regulated by the Food and Drug Administration (FDA).  A pediatric post-market surveillance study of a device product required by the FDA is also subject to the regulation. 

NIH-defined Phase III Clinical Trial.  An NIH-defined Phase III clinical trial is a broadly based prospective Phase III clinical investigation, usually involving several hundred or more human subjects, for the purpose of evaluating an experimental intervention in comparison with a standard or controlled intervention or comparing two or more existing treatments. Often the aim of such investigation is to provide evidence leading to a scientific basis for consideration of a change in health policy or standard of care. The definition includes pharmacologic, non-pharmacologic, and behavioral interventions given for disease prevention, prophylaxis, diagnosis, or therapy. Community trials and other population-based intervention trials are also included.

Valid Analysis.  This term means an unbiased assessment. Such an assessment will, on average, yield the correct estimate of the difference in outcomes between two groups of subjects. Valid analysis can and should be conducted for both small and large studies. A valid analysis does not need to have a high statistical power for detecting a stated effect. The principal requirements for ensuring a valid analysis of the question of interest are: allocation of study participants of both sexes/genders (males and females) and from different racial and/or ethnic groups to the intervention and control groups by an unbiased process such as randomization; unbiased evaluation of the outcome(s) of study participants; and use of unbiased statistical analyses and proper methods of inference to estimate and compare the intervention effects by sex/gender, race, and/or ethnicity.

Resources

Further information regarding NIH expectations for the inclusion of women and minorities is available at the following website: https://grants.nih.gov/grants/funding/women_min/women_min.htm

Further information about Clinicaltrials.gov registration and results reporting is available at https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Inquiries

Please direct all inquiries to:

NIH Inclusion Policy Officer
Office of Extramural Research (OER)
Telephone: 301-435-0921
Email: inclusion@od.nih.gov