Minority, Female, and Older Patients Remain Underrepresented in ACS Clinical Trials

Does patient representation in trials of acute coronary syndrome (ACS) correlate with epidemiologic studies of patients with the condition? According to recent results published in JAMA Cardiology, older patients, women, and black patients continue to be underrepresented in ACS clinical trials.

“This situation raises concerns,” the study authors pointed out, “because biological differences associated with age, sex, or race/ethnicity may alter outcomes, responsiveness to therapy, and, in turn, the relative balance of safety and efficacy.”

To better understand where these representation gaps exist, in hopes of coming up with solutions to close those gaps, the team of investigators systematically reviewed randomized clinical trials that were published between 2001 and 2018 in the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, Circulation, European Heart Journal, Journal of the American College of Cardiology, and BMJ. The results were then divided into 6 periods: 2001-2003, 2004-2006, 2007-2009, 2010-2012, 2013-2015, and 2016-2018.

Altogether, they analyzed 460 trials that had 1,067,520 participants and a median 21 sites (interquartile range, 5-73). Overall, of the total participants, women accounted for just 26.8% (range, 0.3%-100%), blacks for 3.7% (range, 0.2%-58.4%), Hispanics for 7.8% (range, 1.4%-53.5%), Asians for 9.6% (range, 0-45.1%), and nonwhites for 15.0% (range, 0-96.0%).

Diving deeper, the numbers of women enrolled in clinical trials actually decreased between 2001-2006 and 2013-2018 by almost 12%: from 27.8% to 24.9%. Meanwhile, rates of ethnic and racial minority reporting remained low in these same periods, with just 17.8% and 18.9% of trials, respectively, reporting such numbers. Black clinical trial participants, in particular, stayed level: 5.2% (range, 2.8%) and 4.9% (range, 0.2%-48.7%). More than 75% of clinical trials did not report any race/ethnicity data.

In addition, despite participants being older in epidemiologic studies in the United States and Europe—the mean (SD) ages were 66.4 (14.8) years and 70.0 (13.5) years, respectively—the mean (SD) overall age for the clinical trials reviewed was just 62.9 (10.7) years. “Assuming a normal distribution, only 12.9% of enrolled participants were older than 75 years,” the authors said.

“These data suggest that, despite substantial efforts put forth by the US Congress, the National Institutes of Health/National Heart, Lung, and Blood Institute, the FDA, professional societies, and industry, contemporary ACS trials continue to have inadequate representation and incomplete reporting on these key demographic subsets,” they concluded.

Possible reasons for the underinclusion of these groups in clinical trials include strict qualification criteria, comorbidities, insurance coverage, economic constraints, and lack of access to the necessary technology.

What can be done, then? The FDA already has requirements to report on minorities’ results in drug efficacy trials; on effectiveness data via sex, age, and racial/ethnic subgroup; and for women to be included in all federally funded clinical trials.

With this not seeming to be enough, however, the authors believe that trial recruitment efforts must increase their efforts to target women and minorities and for there to be mandatory reporting of race/ethnicity data in journals and on websites, in order for studies to appear.

Reference

Tahhan AS, Vaduganathan M, Greene SJ, et al. Enrollment of older patients, women, and racial/ethnic minority groups in contemporary acute coronary syndrome clinical trials: a systematic review [published online March 25, 2020]. JAMA Cardiol. doi: 10.1001/jamacardio.2020.0359.