Wanted: Women in Clinical Trials

Abstract

M ost biomedical and clinical research has been based on the assumption that the male can serve as representative of the species. This has been true in spite of increasing awareness of significant biological and physiological differences between the sexes, beyond the reproductive ones. Women and men differ in their susceptibility to and risk for many medical conditions, and they respond differently to drugs and other interventions. The close of the previous decade saw 8 out of 10 prescription drugs withdrawn from the U.S. market because they caused statistically greater health risks for women than men. Thus, what is true and good for the gander does not seem to be necessarily good for the goose. After a long history of underrepresentation of women and minorities in clinical trials, federal mandates now require their inclusion in federally funded clinical research in "sufficient [numbers] to provide for a valid analysis of any differences. .. in response to drugs, therapies and treatments." The old paradigm of the "70-kg white male" has finally been replaced by a population sample that attempts to include women and minorities at rates proportional to disease incidence. This evolution of clinical trials has provided much new information about sex differences in healthy and diseased individuals. Sex is a basic biological variable and should be part of the clinical study design when relevant. Already, a few strategies to standardize methods for conducting such studies in animals and humans have been proposed. However, procedures to enhance the collection and analysis of sex-specific data need to be implemented. For instance, female-specific variables, including the stage of ovarian cycle and use of oral contraceptives or hormone replacement therapy, are factors that may influence intervention outcomes. Moreover, routine pharmacokinetic analysis during early phases of drug development (phases I and II) would be advantageous in determining potential sex differences in dosage recommendations and to prevent adverse responses. Critics of sex-specific analysis claim that conducting scientifically rigorous trials with enough statistical power to detect sex differences is prohibitive in terms of time as well as cost. Nevertheless, when prescription drugs are withdrawn from the U.S. market because they cause greater health risks for women than men, the cost of not doing such analyses becomes a greater liability for drug companies. It is not necessary that every large, double-blind, randomized, placebo-controlled clinical trial be sufficiently powered to include sex as a covariant, if appropriate preliminary studies are conducted. Small pilot trials can provide information about drug or treatment efficacy for specific populations. These studies can be useful in establishing procedures, protecting against undesirable outcomes, and determining the statistically significant sample size for subgroup analysis. To this end, common protocols are still needed to determine whether subgroup analysis to detect sex differences must be con...

Examining Sex and Gender Disparities in Total Joint Arthroplasty

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Knee osteoarthritis in women

“…Despite being a majority of the population, women's representation in scientific research on women still lags behind that of men's [42••, 51,52]. The reasons for this are varied: inequality in recruitment, women excluded because of pregnancy, and willingness to participate.…”

Beliefs of Women's Risk as Research Subjects: A Four-City Study Examining Differences by Sex and by Race/Ethnicity

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