Diversity in Heart Failure Trials Still Falls Short

Heart failure trials continue to suffer from a lack of adequate representation of certain groups, including older patients, women, and racial/ethnic minorities, according to a review of studies published since 2001.

The mean age of enrolled patients and the proportion of women have not increased over time, researchers led by Ayman Samman Tahhan, MD (Emory University, Atlanta, GA), report in a study published online August 22, 2018, ahead of print in JAMA Cardiology. What’s more, even though the proportion of racial/ethnic minorities has grown, that could simply be a reflection of reporting biases and the increasing globalization of study sites.

Still, there are some signs that initiatives on the part of government and industry sponsors aimed at improving enrollment of underrepresented groups is working, study co-author Muthiah Vaduganathan, MD (Brigham and Women’s Hospital, Boston, MA), told TCTMD.

He pointed out, for example, that trials funded by the US National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) enrolled larger proportions of women and people from racial/ethnic minority groups than trials with other sources of funding. Also, discrepancies between representation in trials and in real-world cohorts are not as great as they once were.

“The efforts from the NIH and from industry sponsors show that everyone’s thinking about this,” Vaduganathan said, noting that problems with representation in trials are not unique to heart failure. “Everyone wants to see an improvement in enrollment of these groups and really capture representative enrolled subsets, but there’s some inherent challenges that it just takes time to overcome.”

Prior research has shown that older patients, women, and racial/ethnic minorities, despite dealing with a disproportionate share of the heart failure burden, have traditionally been underrepresented in clinical trials, raising questions about the generalizability of the results. But in recent years, government funders and industry have made efforts to correct that imbalance.

To see if those efforts are paying off within heart failure specifically, Samman Tahhan, Vaduganathan, and colleagues reviewed trials that included more than 400 patients and published results between 2001 and 2016. The investigators identified 118 trials that enrolled a total of 215,508 patients; most of the trials (80%) exclusively enrolled patients with reduced ejection fraction.

Across all trials, the mean age of the patients was 65 and the proportion of women was 27%. Neither of those figures changed significantly during the study period.

Less than half of the trials (47%) reported the racial/ethnic makeup of the patient population, but among those that did, 22% of patients were nonwhite. That percentage increased from 13% in 2001-2004 to 30% in 2013-2016 (P = 0.01).

The authors note, however, that those numbers could be inflated by reporting biases stemming from the fact that most trials did not provide information on race/ethnicity.

Vaduganathan pointed out, too, that the rise in the proportion of nonwhite participants over time is primarily explained by the move toward globalization of study sites, with more trials being done in Asia in particular. Indeed, the percentage of Asian participants increased from 1% to 20% over time, whereas a smaller gain was seen for American Indians/Alaskan Natives (3% to 9%) and a decline was seen for black participants (8% to 5%).

Parsing the results further, some differences emerged in terms of heart failure type, funding source, type of intervention studied, and primary region of enrollment.

Of note, trials of patients with chronic heart failure with preserved ejection fraction enrolled older patients and were more likely to include women than trials of patients with chronic heart failure with reduced ejection fraction or acute heart failure.

Also, trials conducted primarily in North America and those performed across multiple regions enrolled younger patients than did those performed in Western Europe. Proportions of women and nonwhite participants were higher in North American trials.

“Some encouraging trends. Still lots of work to do,” Vaduganathan said.

He highlighted two main strategies that should be used to improve representation in clinical trials moving forward.

Some encouraging trends. Still lots of work to do. Muthiah Vaduganathan

First, “we need to have standardized reporting of especially race and ethnic profiles in trials,” he said, noting that the US Food and Drug Administration has released a document that could aid in that effort. “I think adoption of similar forms in clinical protocols would be very helpful,” Vaduganathan said.

And second, he said, enrollment at US study sites should be incentivized. “I think it’s going to be very challenging to mirror representation of populations within the United States if clinical trials are being conducted almost entirely outside the US,” Vaduganathan explained. “So I think that either we further incentivize clinical investigators and study sites to enroll within the United States or we conduct subsequent postapproval studies only in the United States to more closely mirror the patients we’re seeing in clinical practice.”