Over the last 20 years, there have been concerns that too few women and minorities are enrolled in clinical trials to provide confidence about drug safety and effectiveness. Women’s advocacy groups, in particular, have called for more representation in trials of cardiovascular diseases. In 2012, the US Food and Drug Administration (FDA) Safety and Innovation Act (FDASIA 907) was enacted and required the FDA to report on the diversity of participants in clinical trials and the extent to which safety and effectiveness data are based on demographic factors such as sex, race, and age. In response, the FDA piloted a new transparency initiative called the Drug Trials Snapshots Program. Snapshots are data posted online in a standardized format after approval of a “new molecular entity” (NME). They show who participated in the pivotal clinical trials used to approve the drug by sex, race, and age subgroups. Snapshots also provide statements on observed demographic subgroup differences in safety and efficacy. The FDA releases a Snapshot for every NME approved after January 2015 within 30 days of the approval date.
Reviewing the first year of Snapshot data from January 1, 2015, through December 31, 2015, we documented the reported number of women in cardiovascular drug trials and whether any statements of subgroup difference were made. We compared the sex-specific safety and efficacy statements in Snapshots (http://www.fda.gov/Drugs/InformationOnDrugs/ucm412998.htm) with those made in the corresponding prescribing information (PI) accessed on Drugs@FDA: FDA Approved Drug Products (http://www.accessdata.fda.gov/scripts/cder/daf/) (and also linked on the Snapshots page).
In 2015, there were 9 NMEs with cardiovascular indications. Of these, the number of women enrolled in the trials was 22 621, accounting for 35% of the 64 611 total participants (Table 1).1-5 Inclusion of women ranged from 24 participants to 8006 (mean of 2262 and median of 1691). Nine Snapshot statements concluded that men and women responded similarly. Seven PI statements concluded that men and women responded similarly, and 2 did not provide efficacy statements on sex. Two Snapshot statements concluded that there were safety differences between men and women; 6 concluded that the risk of adverse effects appeared to be similar in men and women; and 1 concluded there were not enough participants to determine the difference. The PI did not include any statements on adverse effects differences between men and women (Table 2).
Previous investigations into the number of participants by sex were limited to aggregate data and broad therapeutic area.6 The FDA Drug Trials Snapshots Program represents the first time that pivotal trial demographic information and subgroup analysis statements for safety and efficacy of all newly approved NMEs are consistently reported and readily available in 1 place. Cardiovascular disease appears to be an area where enrollment of women is disproportionately low. The FDA plans to work with the cardiology community to address this issue.
A comparison of the statements made in Snapshots and PI statements shows more consistency in efficacy statements than safety statements. For the 2015 cardiovascular NMEs, Snapshots documented 2 safety statements related to increased bleeding risk and 1 statement where there were not enough participants to determine the difference, whereas the PI did not have any sex subgroup statements related to safety. These differences may be owing to the legal requirements imposed on the PI, for which sex demographic labeling is not a required subsection.
With only a year’s worth of Snapshot data, we are limited in understanding if these data are comparable to those of other years. Beyond the demographics of sex, variability in response to drugs may also be caused by a large number of factors including diet, concomitant medications, genetic traits, and other factors. As a transparency initiative, the Snapshots Program intends to catalyze a broader discussion on ways to improve our understanding of biologic variability in drug response, when it should be measured, and how best to design clinical trials to capture it.
Corresponding Author: John Whyte, MD, MPH, Professional Affairs and Stakeholder Engagement, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD 20993 (firstname.lastname@example.org).
Published Online: March 13, 2017. doi:10.1001/jamainternmed.2017.0033
Author Contributions: Dr Whyte had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: All authors.
Acquisition, analysis, or interpretation of data: Whyte, Wang.
Drafting of the manuscript: Whyte, Wang.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Whyte, Wang.
Administrative, technical, or material support: Whyte.
Supervision: Whyte, Woodcock.
Conflict of Interest Disclosures: None reported.
Additional Contributions: We are grateful to Robert Temple, MD, Center for Drug Evaluation and Research Deputy Center Director for Clinical Science and Acting Deputy Director of the Office of Drug Evaluation I, for his editorial advice. He is employed by FDA and has not received additional compensation for this work.
Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the views of the FDA.
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