Sex-specific analysis and reporting are not just “women’s health” issues. Better data on women would be better data for everyone, Clancy said. Sex-specific data could allow guidelines to be more specific and allow clinicians to better tailor care to individuals.
Speakers also presented examples of the importance of sex-specific differences. One example of critical differences between males and females is drug-induced electrocardiographic changes. Parekh explained that several drugs withdrawn from the market were associated with prolongation of the QT interval (a measure of cardiac repolarization) and torsades de pointes (a potentially fatal form of polymorphic ventricular tachycardia). Women have a longer baseline QT interval and a higher propensity for drug-induced QT prolongation, and they are two to three times more likely to develop torsades than men. The effects of drugs being studied for cardiotoxicity, Parekh said, need to be looked at and understood in both men and women.
A more recent example of the importance of sex-based data is A Diabetes Outcome Progression Trial (ADOPT), a randomized controlled trial (RCT) that compared rosiglitazone with metformin and glyburide over several years. The overall fracture rate associated with rosiglitazone use was higher than that associated with glyburide and metformin, but analysis by sex showed that women had a rate of fractures twice that of men (Kahn et al., 2008). As a result, the label for rosiglitazone includes data on the increased fracture risk for women.
A 1992 GAO review of FDA policies and pharmaceutical-industry practices found that women were not adequately included in clinical studies and that data were not analyzed for sex differences with any consistency, and that consequently there was a lack of understanding of sex differences (GAO, 1992). As a result, Parekh said, FDA issued several new guidance documents and regulations. The 1977 policy that mentioned exclusion of women of childbearing potential was reversed through the 1993 guideline Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs, which recommended collection and analysis of data on sex differences in effectiveness, adverse effects, pharmacokinetics, and pharmacodynamics.
The 1998 investigational new drug (IND) application and new drug application (NDA) regulation, also called the demographic rule, requires NDA submissions to provide safety and effectiveness data and IND submissions to tabulate numbers of participants according to age,