Table 1 Sections of the National Institutes of Health (NIH) Policy document of relevance to the inclusion of pregnant women

The NIH is mandated by law (Public Health Service Act sec. 492B, 42 U.S.C. sec. 289a-2) to ensure the inclusion of women and minority groups in clinical research

Inclusion of women and minorities in NIH-sponsored research is mandated by law: “The [Director of NIH] will, subject to subsection (b) of this section, ensure that…women are included as subjects in each project of such research”…, unless the research “(1) is inappropriate with respect to the health of the subjects;(2) is inappropriate with respect to the purpose of the research; or (3) is inappropriate under such other circumstances as the [Director of NIH] may designate”

Section C: Design of clinical trials In the case of any clinical trial in which women or members of minority groups will under subsection (a) of this section be included as subjects, the [Director of NIH] shall ensure that the trial is designed and carried out in a manner sufficient to provide for a valid analysis of whether the variables being studied in the trial affect women or members of minority groups, as the case may be, differently than other subjects in the trial.

NIH Policy

A. Inclusion of Women and Minorities as Subjects in Clinical Research

It is the policy of NIH that women and members of minority groups and their subpopulations must be included in all NIH-funded clinical research, unless a clear and compelling rationale and justification establishes to the satisfaction of the relevant institute/center director that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. Exclusion under other circumstances may be made by the [Director of NIH] upon the recommendation of an institute/center director based on a compelling rationale and justification. Cost is not an acceptable reason for exclusion except when the study would duplicate data from other sources. Women of childbearing potential should not be routinely excluded from participation in clinical research. This policy applies to research subjects of all ages in all NIH-supported clinical research studies.

The inclusion of women and members of minority groups and their subpopulations must be addressed in developing a research design or contract proposal appropriate to the scientific objectives of the study/contract. The research plan/proposal should describe the composition of the proposed study population in terms of sex/gender and racial/ethnic group, and provide a rationale for selection of such subjects. Such a plan/proposal should contain a description of the proposed outreach programs for recruiting women and minorities as participants.

B. NIH-defined, Phase III Clinical Trials: Planning, Conducting, and Reporting of Analyses for Sex/Gender and Race/Ethnicity Differences

When an NIH-defined, phase III clinical trial is proposed, evidence must be reviewed to show whether or not clinically important sex/gender and race/ethnicity differences in the intervention effect are to be expected. This evidence may include, but is not limited to, data derived from prior animal studies, clinical observations, metabolic studies, genetic studies, pharmacology studies, and observational, natural history, epidemiology and other relevant studies Investigators must consider the following when planning, conducting, analyzing and reporting an NIH-defined, phase III clinical trial. Based on prior studies, one of the three situations below will apply:

1. Prior studies support the existence of significant differences

If the data from prior studies strongly support the existence of significant differences of clinical or public health importance in intervention effect based on sex/gender, racial/ethnic, and relevant subpopulation comparisons, the primary question(s) to be addressed by the proposed NIH-defined, phase III clinical trial and the design of that trial must specifically accommodate this. For example, if men and women are thought to respond differently to an intervention, then the phase III clinical trial must be designed to answer two separate primary questions, one for men and the other for women, with adequate sample size for each

2. Prior studies support no significant differences

If the data from prior studies strongly support no significant differences of clinical or public health importance in intervention effect based on sex/gender, racial/ethnic and/or relevant subpopulation comparisons, then sex/gender and race/ethnicity will not be required as subject selection criteria. However, the inclusion and analysis of sex/gender and/or racial/ethnic subgroups is still strongly encouraged

3. Prior studies neither support nor negate significant differences

If the data from prior studies neither strongly support nor strongly negate the existence of significant differences of clinical or public health importance in intervention effect based on sex/gender, racial/ethnic, and relevant subpopulation comparisons, then the NIH-defined, phase III clinical trial will be required to include sufficient and appropriate entry of sex/gender and racial/ethnic participants, so that valid analysis of the intervention effects can be performed. However, the trial will not be required to provide high statistical power for these comparisons