NOTE: THIS GUIDANCE DOCUMENT HAS BEEN ARCHIVED BECAUSE THE LIST OF CATEGORIES HAS BEEN REVISED AND CAN BE FOUND AT http://grants.nih.gov/grants/funding/women_min/women_min.htm.

  Number 94-01 
  Human Subject Protections 

OPRR Reports
NIH PHS HHS 

April 25, 1994

Subject:  Inclusion of Women and Minorities in Research 

Dear Colleague:

This letter is being forwarded to Institutional Officials and Institutional Review Board (IRB) Chairs throughout the country. It transmits new National Institutes of Health (NIH) Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research (Federal Register, 59FR14508, March 28, 1994; also published in the NIH Guide for Grants and Contracts, Vol. 23, Number 11, March 18, 1994) and offers points to consider based on these guidelines and responsibilities under the Department of Health and Human Services (DHHS) regulations for protection of human subjects (45 CFR 46).

IRBs have long had as part of their responsibilities examining issues of justice and determining equitable selection of subjects in accordance with the Belmont Report and the regulations for protection of human subjects (45 CFR 46.111(a)(3)). The inclusion of both women and men and of minorities in research is important, both to ensure that they receive an appropriate share of the benefits of research and that they do not bear a disproportionate burden. To the extent that participation in research offers direct benefits to the participants, underrepresentation of men, women or minorities denies them the opportunity to benefit. Moreover, for purposes of generalizing research results, investigators must include the widest possible range of population groups.

Institutions have a responsibility to create an environment in which equitable selection of research participants is fostered. In so doing, they must support their IRBs and investigators in goals of increasing participation of women and minorities in research trials. Institutions must empower IRBs to fulfill the mandates of the NIH Guidelines and their regulatory responsibilities. They are called upon to promote and support effective recruitment strategies and communication mechanisms to ensure policy implementation.

Institutions have a responsibility to create an environment in which equitable selection of research participants is fostered. In so doing, they must support their IRBs and investigators in goals of increasing participation of women and minorities in research trials. Institutions must empower IRBs to fulfill the mandates of the NIH Guidelines and their regulatory responsibilities. They are called upon to promote and support effective recruitment strategies and communication mechanisms to ensure policy implementation.

Seven points to consider in deliberations about appropriate selection of research participants are offered. Institutions and IRBs have responsibilities, as follows:
   
  •  To help ensure that investigators understand the importance of inclusion of both genders and minorities in research and clearly delineate the expectations for the design and conduct of such research. They should assist in providing investigators with written guidance and educational opportunities for clarification.

  • To specify that, when scientifically appropriate, investigators cite evidence or lack of evidence if a health situation or intervention in the proposed research may affect one gender or minority group differently and describe how the proposed research addresses that evidence. Investigators should be prepared to describe the extent to which both genders and persons of various ethnic and racial backgrounds are or have been involved in similar research.

  • To help create guidelines for investigators to facilitate recruitment and retention of participants to ensure
    representation and sufficient involvement of targeted populations. The extent to which investigators are collaborating with those at other institutions that can involve increased numbers of men or women or populations from different minority groups must be a part of the information the IRB reviews, particularly with regard to Phase 3 clinical trials.

  • To ensure that any special vulnerabilities of participants (e.g., educational level, socioeconomic status) are
    accounted for and handled appropriately. The IRB should carefully consider if reimbursements (cash or material
    provisions) are appropriate to the context of the proposed research, with special attention that these reimbursements do not promote coercion or undue influence to participate or to remain in a study.

  • To safeguard the consent process and to promote open and free communication between the researcher and the participants. Investigators and IRBs must seek to understand cultural nuances and types of foreign languages
    inherent in the populations to be enrolled. The possibility of illiteracy of a potential research participant must also be considered and assurances given that adequate provision has been made for appropriate translations of the consent documents or the availability of translators.

  • To arrange for inclusion of women and members of minority groups on the IRB, especially if the nature and volume of the research to be conducted at the institution routinely includes these populations. IRBs should also consider consulting ad hoc advisors who could help with understanding the perspectives of various groups. Also, institutions and IRBs can encourage investigators to seek out such perspectives during planning of research protocols.

  • To specify that NIH-supported investigators provide details of the proposed involvement of humans in the research, including the characteristics of the subject population, anticipated numbers, age ranges, and health statuses. The proposed research should specify the gender and racial/ethnic composition of the subject population, as well as criteria for inclusion or exclusion of any subpopulation. If ethnic, racial, and gender estimates and continuing review numbers are not included in the background data for a protocol, the investigators must provide a clear rationale for exclusion of this information.

The enclosed Federal Register notice includes the NIH Guidelines, based on provisions in the NIH Revitalization Act of 1993 (Public Law 103-43), on the inclusion of women and minorities and their subpopulations in clinical research conducted or supported by NIH. Some of the other Federal Departments and Agencies that conduct or support research involving humans currently have mandates in their statutes or congressional committee reports similar to those given by the Congress to NIH. Institutions must determine the extent to which they will apply the specific requirements of the enclosed Federal Register notice to research other than that conducted or supported by NIH. 

The definition of "clinical research" in the NIH Guidelines includes all research involving humans, even that which is exempt from IRB review in accordance with 45 CFR 46. The Guidelines do not require IRBs to review research which is exempt under 45 CFR 46, however. 

The NIH Guidelines indicate the circumstances under which various populations must be included in clinical investigations, with special criteria for Phase 3 clinical trials. The Guidelines refer to a "clinical trial" as a broadly-based prospective Phase 3 clinical investigation for the purpose of evaluating an experimental intervention that is to provide evidence leading to a scientific basis for consideration of a change in health policy or standard of care. (See Section V.A of the enclosed NIH Guidelines.) If data from prior studies indicate that there are differences between the genders or among racial/ethnic groups in the proposed research, or if there are no data to support or to negate differences, Phase 3 clinical trials will be required to include sufficient and appropriate entry of gender and racial/ethnic subgroups, so that analysis of detected trends in the affected subgroups can be performed. If prior evidence indicates that the results will not show gender or racial differences, researchers are not required to use gender or race/ethnicity as selection criteria for study subjects. They are, however, encouraged to include these groups. (See Section III.B of the enclosed NIH Guidelines.

CLEAR="ALL" />IRBs are empowered by 45 CFR 46, the DHHS assurances to comply with 45 CFR 46 under which they operate, and the NIH Guidelines, to approve, request modification of, or disapprove research based on their review and assessment of the extent to which the analysis criteria specified in the NIH Guidelines will be met in the proposed research. 

OPRR encourages you to direct questions and comments about the new NIH Guidelines to the NIH Office of Research on Women's Health (301-402-1770) or the NIH Office of Research on Minority Health (301-402-1366) and to the contact points listed in the enclosed Federal Register notice. 

  Gary B. Ellis, Ph.D.
Director
Office for Protection from Research Risks 

Enclosure