NOTE: THIS GUIDANCE DOCUMENT HAS BEEN ARCHIVED BECAUSE THE LIST OF CATEGORIES HAS BEEN REVISED AND CAN BE FOUND AT http://grants.nih.gov/grants/funding/women_min/women_min.htm.
Human Subject Protections
April 25, 1994
Inclusion of Women and Minorities in Research
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).
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.
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
- 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
- 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.)
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.
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
Gary B. Ellis, Ph.D.
for Protection from Research Risks