In an analysis of 118 clinical trials since 2001, investigators found females and minorities comprised just 27% and 22% of the total patient population, respectively.
Ayman Samman Tahhan, MD
While racial and ethnic minorities, older patients, and women bear the brunt of disproportionate burdens regarding heart failure (HF), they are often underrepresented in clinical trials. With such inclusion disparities in research among the HF general population, doubts surrounding accurate assessments of therapies’ risks and benefits based on differing demographic profiles arise.
In a recent study led by Ayman Samman Tahhan, MD, cardiology fellow at Emory University, the severity of the gaps in HF patient representation was not only further uncovered, but could possibly be explained with more context as to what factors affect specific minority groups.
“For example, elderly individuals tend to have comorbid and chronic conditions that would be a barrier for enrollment,” Tahhan said in an interview with MD Magazine®. “Premenopausal women tend to not enroll in clinical trials due to concerns about effects on their childbearing years, and some trials even exclude premenopausal women. For racial and ethnic minorities, problems are often due to geographic distributions of centers.”
In order to glean these conclusions, Tahhan and his team evaluated over 215,508 patients with HF from January 2001 to December 2016, amounting to an inclusion of 118 international clinical trials garnered from online databases. Of the 118 included trials, only those enrolling more than 400 patients qualified for inclusion in the study. Included patients with HF were divided into those with reduced ejection fraction (HFrEF), preserved ejection fraction (HFrEF), and acute HF (AHF).
Mean patient age was 65 years, with 27% of the sampled population being women.
Exclusively at North America sites—which were involved in 91% of multiregional trials—disparities were hardly less severe. The mean age of HFrEF patients was 69 years, and 73 years for both HFpEF and AHF patients. The proportion of HFpEF female patients (56%) was also higher than the proportion of HFrEF female patients (24%) and the AHF female patients (32%).
Investigators also noted that although distribution of racial/ethnic groups was reported in 55% of the trials, just 22% of the total participants were not white.
“This highlights underrepresentation of these minority population in which we know the burden of HF is higher,” Tahhan explained. “More black patients have heart failure in comparison to white patients, for example. We know that those specific minorities have a higher burden of disease, yet we’re not able to enroll them in clinical trials to see if therapies are working in these populations.”
It’s common for clinicians to extrapolate from the results of trials with real-world implications, Tahhan noted, but these sources often lack data for the most affected populations.
“If we’re going to treat with therapeutic options to HF patients, we need to make sure our data and trials are applicable to those populations,” Tahhan said. “Otherwise, we are not really following evidence-based medicine.”
Despite the inequality of representation in the HF general population, Tahhan and his colleagues also found that these disparities are lessening. The mean age of participants increased from 64 years in 2001 to 2004, to 65 years in 2013 to 2016. The percentage of women also increased from 26% to 29% same time periods, as did non-white patient enrollment—from 13% to 30%.
These are direct efforts in response to the growing issues of health disparity, Tahhan explained. He noted how the National Institutes of Health recently began enrolling more women and black patients into its own trials to improve population representation—a decision mirrored by other organizations and institutions.
“The gap that we saw that was being reduced in the population was being driven by industrial trials; it wasn’t truly an improvement in the representation of black and Hispanics,” Tahhan said. “There are specific nuances in the indicated closing gaps to consider.”
That said, challenges still remain. Older patients face barriers in trial-specific inclusion/exclusion criteria, trial durations, financial costs, and other factors. Women were similarly burdened by costs, as well as therapeutic indications and trial locations. Racial and ethnic minorities face poor documentation; less than half of the HF trials reported data regarding the distribution of race/ethnicity and categories.
Looking forward, Tahhan and his team concluded that future studies related to HF must require more adequate descriptions of age, sex, and race/ethnicity. Additionally, efforts to improve representative patient participation need to be renewed—specifically, incentives are needed for North American sites in global HF clinical trials.
Lastly, they called for concerted, multilevel interventions to improve site-based enrollment of underrepresented minorities. In researching and treating heart failure, there is an abundance of registry data, and a need across all populations. There is no need to restrict clinical trials to geographic areas with less racial or ethnic representation.
“Collaboration between all the funding agencies—the industry, the community, and the centers—are necessary to ensure that we are enrolling minority patients and that the trials representative of the general population,” Tahhan said. “I think collaboration is the key here, especially when we have registries.”
The study, “Enrollment of Older Patients, Women, and Racial and Ethnic Minorities in Contemporary Heart Failure Clinical Trials,” was published in JAMA Cardiology on Wednesday.