CONSORT statement 2010 flow diagram
11.6 Modifying Selection Criteria
Under certain circumstances, it may be necessary to modify the original study eligibility criteria after recruitment has been initiated. Although the post hoc modification of study eligibility criteria may increase recruitment, such alterations can result in challenges of interpretation of the study results, as there might be significant differences in the study cohort prior and after the change in the study protocol. For this reason, the modification of study selection criteria should be regarded only as a last resort, as it carries the risk of compromising the integrity and the safety of the clinical trial .
11.7 Ethical Considerations
In addition to being appropriately tailored to the individual study, selection criteria must meet certain baseline ethical criteria. The safety of the participants must be considered with respect to both their baseline level of health and the possibility of experiencing adverse events as part of their participation in the study. In addition, all subjects must have the capacity to understand the nature of the study in order to provide truly informed consent. Several national standards are in place to guide researchers on the ethical inclusion of special populations in research.
11.7.1 The Belmont Report
The Belmont Report, issued by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research in 1977, protects vulnerable populations from systematic inclusion in research and also protects vulnerable groups such as women and minorities from systematic exclusion from research. This report provides the basic ethical principles and guidelines for the conduct of research with human subjects, including clarification about the distinctions between medical practice and research. The Belmont Report put forth three basic ethical principles: first, respect for persons (individuals should be treated as autonomous agents, and persons with diminished autonomy are entitled to protection); second, beneficence (persons are to be treated in an ethical manner not only by respecting their decisions and protecting them from harm but also by making efforts to secure their well-being); and third, justice (who should receive the benefits of research and bear its burdens?). The principles of the Belmont Report have been incorporated into every aspect of human research and serve as the basis for ethical regulations in clinical trials today .
11.7.2 Women and Minorities
The NIH Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research encourage the inclusion of women and racial and ethnic minorities as subjects in clinical trials. The intent of the NIH guidelines is to ensure that both the burden and the benefits of clinical trials are evenly distributed throughout society and require that all NIH-funded clinical trials determine the effect of the study intervention on both men and women and study subjects from diverse racial and ethnic backgrounds. Research plans must therefore address (1) the targeted/planned distribution of the study subjects by sex/gender and racial/ethnic groups, (2) the selection criteria of the study subjects and the rationale for the selection of sex/gender and racial/ethnic study subjects for the proposed study design in relation to the scientific objectives, (3) a compelling rationale if the exclusion of any sex/gender or racial/ethnic group is proposed, and (4) a description of the proposed outreach programs for recruiting study subjects of both sex/gender and racial/ethnic groups. In some situations, it may be acceptable to exclude study subjects based on gender or race. Examples of acceptable justifications include (1) inappropriate burden to the participants’ health, (2) research questions that are only relevant to one sex/gender or racial/ethnic group, (3) if sufficient data already exist for one sex/gender or race/ethnicity, and (4) if preliminary evidence strongly suggests no difference between sex/gender and racial/ethnic groups .