National Heart, Lung, and Blood Institute
National Institutes of Health
Revised: March 2011
The National Heart, Lung, and Blood Institute (NHLBI) has a continuing commitment to health problems related to minorities and women. Research (grants, cooperative agreements, and contracts) to be supported by the Institute must comply with the NIH Inclusion of Minorities and Women policy that was mandated by law. Women and members of minority groups must be included in all clinical research studies unless the nature of the research makes it inappropriate to do so.
(See the NIH Guidelines On The Inclusion Of Women And Minorities As Subjects In Clinical Research.)
Phase III clinical trials are held to a higher standard:
- When designing and developing a phase III trial, the investigator must evaluate all relevant data to assess whether or not the trial should include adequate numbers of subgroups of participants to allow for separate and adequately powered analyses.
- Even if no such evidence is available, the trial must include sufficient numbers of women and minorities to conduct valid analyses (that is, unbiased assessment) of subgroup effects.
- During the peer review of the trial, this aspect will be considered in the evaluation.
- Before any phase III trial is funded, this aspect will be considered by NHLBI staff.
- During the conduct of the trial, and indeed any clinical study, success in enrolling appropriate numbers of women and minorities will be monitored by NHLBI staff.
- Finally, it is expected that the investigators will perform the necessary analyses and include the results in submitted publications.
The following series of questions and answers are intended to assist you in preparation of research applications in accordance with the NIH Guidelines. If you have any questions about this policy, please contact the appropriate NHLBI Division representative listed at the end of this document.
Question: What is the definition of clinical research?
Answer: The NIH definition of clinical research includes all NIH supported biomedical and behavioral research involving human subjects. Applications for support of clinical research studies should address the policy by providing a description and justification of the study population.
Research is a continuum of studies from basic laboratory to observational to clinical. Assessment of differential effects of an intervention or therapy on women, men, or members of minority groups and their subpopulations requires fundamental information on such groups. Therefore, at the earliest stages of research, investigators are expected to include individuals (or tissues) of both genders and diverse racial and ethnic groups in order to generate information necessary for the rational design of appropriate Phase III clinical trials. Investigators are expected to report results on all participating gender and minority groups, as appropriate.
(See Section VB. and VI A. in the NIH Guidelines)
Question: What is the definition of a clinical trial?
Answer: In October 2014, NIH revised its definition of “clinical trial” in order to make the distinction between clinical trials and clinical research studies clearer and to enhance the precision of the information NIH collects, tracks, and reports on clinical trials. The change is not intended to expand the scope of the category of clinical trials. No changes have been made to the NIH definition of a “Phase III clinical trial.”
In addition, because clinical trials are subject to additional oversight, a clearer definition will help investigators ensure that they are meeting all of their obligations, and it will help NIH ensure that the additional oversight is occurring when it is needed. For example, NIH policy requires clinical trials to be monitored, and applicants and offerors seeking NIH support are expected to describe their plans for data and safety monitoring in their applications and proposals. Final data and safety monitoring plans must be approved by the NIH prior to award. In addition, throughout the life of the award, NIH staff monitors the clinical trial’s progress to ensure that milestones are met and that any safety concerns are addressed.
The revised definition will replace the current clinical trial definition in relevant extramural and intramural NIH policies, guidance, and instructional materials. It will apply to competing grant applications that are submitted to NIH for the January 25, 2015, receipt date and subsequent receipt dates and to contract proposals that are submitted to NIH on or after January 25, 2015. If you have questions or comments about the definition, decision tree, case studies, or the Q&A document, please email them to Valery Gordon, Ph.D., Office of Science Policy, at firstname.lastname@example.org.
Question: What is sufficient and appropriate representation of women and minorities?
Answer: Ideally, women and minorities in the study population are in the same proportions as in the U.S. population having the disease entity being studied. If prevalence is unknown, the NHLBI standard for evaluation of the proposed study population is the composition of the population of the United States which, according to the 2010 census, is 51% women and 30% minorities. However, there are acceptable justifications for a study population that does not meet these criteria. (See answers to questions 4-6 below and Section II [subsection on exclusions] in the NIH Guidelines).
Question: Does the policy permit a study population that contains only one gender or minority group or subpopulation?
Answer: If a study of only one gender or minority group or subpopulation is proposed, there must be a scientific justification for limiting the diversity of the study population, such as high prevalence of the condition, unique disease characteristics, or gaps in knowledge in the select population. The review committee will include the adequacy and scientific appropriateness of a justification in its determination of the priority score. Women of childbearing potential should not be routinely excluded from participation in clinical research.
(See Section VI.C. and VI.D. in the NIH Guidelines)
Question: Can study populations in other related studies (research portfolio) be used to justify a study population that does not comply with the policy?
Answer: In cases where the proposed study population is limited in diversity, it may be possible to justify this situation if the combination of the study population in the application and related past or ongoing studies provides the diversity required by the policy. Applicants should use published reports and discussions with NHLBI staff concerning ongoing research to identify studies that provide the diversity. A list of such studies, the study population composition, and a discussion of the basis of the research portfolio justification should be incorporated, as appropriate, into the application. NHLBI will determine if the research portfolio justification is adequate to allow support of the project.
(See Section V.G. in the NIH Guidelines)
Question: What should applicants do if they are in a geographic area that does not offer a study population with the diversity required by the policy?
Answer: Applicants must address this issue in terms of the purpose of the research, the relevant characteristics of the disease, disorder, or condition, and the feasibility of developing a collaboration, consortium, or other arrangements to include minority groups. A justification is required if there is limited representation. Peer reviewers and NHLBI staff will consider the justification in their evaluations of the project.
(See Section VI.D. in the NIH Guidelines)
Question: Is it acceptable to use existing cohorts that are deficient in women or minority participants?
Answer: Use of an existing cohort that lacks the diversity required by the policy must be justified. The nature of the scientific question, a requirement for data provided by the cohort, or research portfolio balance may provide the basis of a justification.
(See Section IV.C.1., VB., and VI.A. in the NIH Guidelines)
Question: Is increased cost an acceptable justification for not including women, minorities, and minority subpopulations?
Answer: No. The policy states that the cost associated with increasing the diversity of a study population composition to include women, minorities, and minority subpopulations is not an acceptable justification for excluding them.
(See Section I., II., III.A., and III.B. in the NIH Guidelines)
Question: What is the definition of minority groups and minority subpopulations?
Answer: There are four minority racial groups: American Indian/Alaska Native; Asian; Native Hawaiian/Pacific Islander; and Black. Individuals of Hispanic origin are an ethnic minority and may be of any race. Caucasians, not of Hispanic origin, are considered the majority group for the purpose of this policy.
Each minority group contains subpopulations that may be defined by geographic origin, national origin, cultural differences, or mixed racial and/or ethnic parentage. The minority group or subpopulation to which an individual belongs is determined by self-reporting.
( See Section V.E.1. through V.E.3. in the NIH Guidelines)
Question: Do all minority groups and subpopulations have to be included in a study population?
Answer: It is not expected that every minority group and subpopulation will be included in each study. However, broad representation and diversity are strongly encouraged, even if multiple clinics and sites are needed to accomplish it. When determining the composition of the study population, health of the subjects, scientific issues, e.g., high prevalence of a condition, different disease characteristics, or gap(s) in knowledge in a minority subpopulation, should be considered. If the prevalence of the disease, disorder, or condition is not known or if normal volunteers are used in the study, the proportion of minority group and subpopulation participants in the study population should reflect their population in the United States.
(See Section II [subsection on exclusions] and IV.C.1. in the NIH Guidelines)
Question: What is meant by outreach efforts to recruit women, minorities, and members of minority subpopulations?
Answer: Outreach efforts are attempts by investigators and their staff to recruit and retain women and minority populations. Such efforts could include involvement of organizations and persons relevant to the populations and communities of interest, e.g., religious organizations, community leaders, and public and private institutions. The research plan should contain a description of the institutions. The research plan should contain a description of the proposed outreach programs for recruiting women and minorities as participants. The NIH Office of Research on Women’s Health has developed an online resource, NIH Outreach Toolkit: How to Engage, Recruit, and Retain Women in Clinical Research, that contains information to assist investigators develop outreach programs.
(See Section IV.C.7. and V.F. in the NIH Guidelines)
NHLBI Representatives for Inclusion of Minorities and Women in Study Populations
Office of Clinical Research
Katie Kavounis, MPH
Clinical Trials Specialist
Last Updated October 2016