We know the risks and benefits of many drugs and devices differ in men and women. The US Food and Drug Administration (FDA) notes that both extrinsic factors (such as socioeconomic and cultural influences) and intrinsic biological factors (such as genetics, hormones, and metabolism) may vary by sex.1 Unfortunately, women have been underrepresented in cardiovascular clinical trials for several decades, resulting in suboptimal understanding of the risks and benefits of many cardiovascular drugs and devices in women.2
The 2012 FDA Safety and Innovation Act3 directed the FDA to assess the inclusion, analysis, and public reporting of demographic subgroups—including by sex—in new drug, biologic, and device applications and to formulate an action plan to improve trial participation and data quality and transparency. As part of its response, the FDA has implemented Drug Trials Snapshots (DTS) for drugs approved beginning January 2015. The DTS program is a substantial step forward because the demographic characteristics of clinical trial participants are posted along with notes as to whether there were any differences in safety or efficacy by group, including sex.
In this issue, Whyte and his FDA colleagues4 review all 9 cardiovascular drugs approved during the first year of DTS, and found that women accounted for slightly more than one-third of study participants. All DTS noted similar efficacy by sex, but only 6 (67%) concluded similar safety profiles by sex.
The increased transparency offered by DTS is a great step forward, and it would be even more helpful to include drugs approved prior to 2015 as well as medical devices. Drug prescribing information is available on labels, but this information is more limited than DTS and can be hard to access for patients and physicians.
How can we continue this FDA effort to improve availability of information on sex-specific risks and benefits for drugs and devices? There should be transparent tracking of demographics in premarket clinical trials of drugs and devices; such data should be examined at regular intervals to ensure that a representative patient population is being enrolled prior to application for FDA approval. New drug or device applications submitted for FDA approval with insufficient or nonrepresentative numbers of women should be returned until the drug or device sponsor has adequate safety and effectiveness data in both sexes. As documented by DTS, progress in the last 30 years has been slow, and meaningful changes will require FDA action and consequences for noncompliance; such steps are urgently needed to ensure that the benefits outweigh risks for approved drugs and devices in both women and men.
Conflict of Interest Disclosures: None reported.
RF. Evaluating sex differences in medical device clinical trials: time for action. JAMA
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112th Congress (2011-2012). Food and Drug Administration Safety and Innovation Act. Public Law 112-144 (07/09/2012).
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