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Women underrepresented in clinical trials for CV drugs, devices
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Sex disparities are evident, especially in the enrollment of clinical trials and the development of medical innovations for conditions that affect women disproportionately, according to a debate organized by the FDA.
“We recognize that there are meaningful differences between men and women when it comes to disease and the role that sex plays in the onset of illness and in the maintenance of health,” Scott Gottlieb, MD, commissioner of the FDA, said during the debate. “This wasn’t always the case, and years of neglect of these issues, and at times ignorance of them, have left us with disparities when it comes to the delivery of health care.”
Improvements in clinical trials
Although progress has been made throughout the years, there is still more work to be done to improve the representation of women, according to the debate.
“Women are half our population, looking at cardiology,” Rita F. Redberg, MD, MSc, FACC, cardiologist, professor of medicine at University of California, San Francisco, and Cardiology Today Editorial Board Member, said during the debate. “Women are half the population with heart disease, yet I’m still seeing new drugs and devices come on the market today that I cannot look at my women patients in the eye and say, ‘I know that this drug or device is safe and effective for you.’”
Many CV trials only include about 25% women, according to the debate. If bigger enrollment is an issue for a trial, only including women may be the best option to ensure that women are represented, especially since a drug or device may not work the same in women as it does in men, Redberg said.
The underrepresentation of women in clinical trials may be due to women not knowing that CVD is the biggest health issue that they face, Ellis F. Unger, MD, cardiologist and director of the Office of Drug Evaluation-I, Office of New Drugs at the Center for Drug Evaluation Research of the FDA, said during the debate.
Enrolling a balance of men and women is important for achieving statistical power for safety and efficacy in a clinical trial. Although this is critical, companies that sponsor clinical trials do not focus on exactly how many women are needed to determine the efficacy of a drug or device, as it may make a trial either undoable or too costly to complete. Trials are not designed to look at safety differences between the sexes, according to the debate.
Many drug withdrawals are due to negative effects on women, which can cost Medicare, insurers and taxpayers money and take a toll on patients’ lives, participants said.
Most drugs do not have weight-based dosing because of the relationship between exposure and response, according to the participants.
In contrast, weight-based dosing is important because when medications are dosed for the average patient, it is often modeled for a man. This may be the explanation as to why women have two to three times more adverse events compared with men, according to the debate.
Women are often eager to participate in clinical trials, but some trial sponsors think that it is troublesome to enroll women, as they are more difficult, Redberg said. Another issue may be that most principal investigators are men. According to an FDA analysis, the lack of women is not seen in trials focused on hypertension or atrial fibrillation, but rather in trials on unstable angina, CAD and HF.
Clinical trials sometimes consider women as a subgroup, although 52% of the global population consists of women, according to the debate.
Sex-specific labeling for medications is important, especially when the risk for bleeding, for example, is higher in women compared with men, participants said. Many drugs, including glycoprotein IIb/IIIa inhibitors, do not include these details in their labeling, but the FDA has changed a few labels to accommodate this need, according to the debate.
Focus on women representation
Matching the number of men and women in clinical trials based on disease prevalence may be the route to take, but it proposes fairness and scientific issues because if women are fairly represented, other subgroups like race would also need to be fairly represented, according to the debate.
“We have to make a decision, and we never have all the information we’d like to have,” Unger said. “If we did, our job would be pretty easy, just enroll 5 million people in the trial and we’ll know everything, but we can’t do that.”
The idea of a participation-to-prevalence ratio does not make up for sample size because although proportion may represent the percentage of disease, it does not represent enough women in the trial, Redberg said.
An important group of women that should be included more in clinical trials are women who are pregnant, of childbearing age and lactating.
“If there’s ever a clinical situation where we think that this drug is going to be used in a pregnant woman for a nonpregnancy-related condition, we have to know if it’s safe,” Redberg said. “If we don’t have data on those, then we’re really practicing blindly because I can’t in good conscience prescribe the drug, and then if I don’t, maybe it would have been safe and effective, and women will not have the benefit of the drugs.” – by Darlene Dobkowski
References:
FDA Office of Women’s Health. The Great Debate: What is Enough ... Women in Clinical Trials. May 16, 2018. Retrieved from https://www.fda.gov/ForConsumers/ByAudience/ForWomen/ucm606138.htm.
Scott PE, et al. J Am Coll Cardiol. 2018; doi:10.1016/j.jacc.2018.02.070.
Disclosures: Gottlieb, Redberg and Unger report no relevant financial disclosures.