Next Gen Innovators
Next Gen Innovators
May 01, 2018
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FDA analysis: Women underrepresented in HF, CAD, ACS trials

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Women are underrepresented in pivotal clinical trials of drugs for patients with HF, CAD and ACS, according to an FDA analysis published in the Journal of the American College of Cardiology.

Representation of women was appropriate in trials of drugs for hypertension and atrial fibrillation, and women may have been overrepresented in trials of drugs for pulmonary artery hypertension, Janet Woodcock, MD, director of the Center for Drug Evaluation and Research at the FDA, and colleagues wrote.

“As we move into the era of precision medicine, that is assessing the impact of a wide range of patient and disease characteristics on drug effects, it is imperative that clinical trial participants represent the full spectrum of patients for whom the drug will be prescribed,” Woodcock said in a press release. “This will move us closer to our goal of providing the best information possible about the use of drugs for every patient.”

Enrollment of women

Woodcock and colleagues assessed the enrollment of women in trials supporting the approvals of 36 CV drugs between 2005 and 2015. They calculated prevalence-corrected estimates of participation by women according to disease area. This figure was determined by the percentage of women in a trial divided by the percentage of women in the disease population. The resulting prevalence-to-participation ratio was considered appropriate if it fell between 0.8 and 1.2.

The researchers also analyzed whether there were any clinically meaningful differences by sex in trial results.

Among the trials analyzed, the enrollment percentage of women ranged from 22% to 81% (mean, 46%), Woodcock and colleagues wrote.

The prevalence-to-participation ratio was less than 0.8, signifying underrepresentation of women, in trials for drugs to treat HF (0.5 to 0.6), CAD (0.6) and ACS or MI (0.6), according to the researchers.

The ratio was in the acceptable range for trials for drugs to treat AF (0.8 to 1.1) and hypertension (0.9) and was high in trials for drugs to treat PAH (1.4), Woodcock and colleagues wrote.

“Based on this work, future research is needed to identify factors leading to under-participation of women in cardiovascular clinical trials, particularly those occurring before screening,” Pamela Scott, PhD, director of research in the Office of Women’s Health at the FDA, said in the release. “Research is needed to better define barriers that limit participation of diverse populations, not only of women but of minority and older populations.”

Results of most trials did not differ by sex. The trial for the angina drug ranolazine (Ranexa, Gilead Sciences) showed women had fewer reductions in angina frequency and nitroglycerin use compared with men, and trials for three hypertension drugs showed clinically significant sex differences in safety, the researchers wrote, noting that in all four cases, the differences are described in the product labeling.

Possible consequences

In a related editorial, Louise Pilote, MD, MPH, PhD, from the divisions of general internal medicine and clinical epidemiology at McGill University Health Centre in Montreal, and Valeria Raparelli, MD, PhD, from the department of experimental medicine at Sapienza University of Rome, wrote: “The inadequate participation of women in clinical trials could result in several significant issues, including male-patterned inclusion criteria, sex-biased outcomes measurements, inadequate data analysis, and the missed opportunity to transfer results in clinical practice.” – by Erik Swain

Disclosures: The authors, Pilote and Raparelli report no relevant financial disclosures.