By Allison Proffitt 

September 9, 2021 | If you can’t measure it, you can’t improve it. 

Researchers from Beth Israel Deaconess Medical Center (BIDMC) took this well-known business maxim and applied it to clinical trials in a new paper published in the Journal of the American Heart Association. They reviewed investigators’ planning documents in federally-funded cardiovascular disease trials run between 2000 and 2019 to determine whether various recruitment strategies impacted the number of Black participants enrolled. 

There is an established need to increase the enrollment of Black participants in clinical trials to ensure that the scientific literature guiding clinical practice better reflects the diversity of individuals in the United States, said corresponding author Stephen Juraschek, MD, PhD, a clinician researcher in the Division of General Medicine and Primary Care, Section for Research, at BIDMC and assistant professor of medicine at Harvard Medical School (HMS), in a press release announcing the work. “Otherwise the care of Black Americans is informed by data predominantly from non-Black participants.”

The NIH has focused on the inclusion of women and underrepresented populations in its funded research since 1994, and there have been broad efforts to increase Black adult clinical research participation. But those efforts have often focused on addressing community mistrust, transportation challenges, and socio-economic factors. The BIDMC researchers believe investigators themselves hold responsibility and wanted to quantify their efforts. 

Juraschek and colleagues—including first author Anagha Prasanna of HMS—examined the published study protocols of 62 federally-funded cardiovascular interventional clinical trials looking for strategies used to increase diversity in trials, and then compared those intentions to actual enrollments. They found a link between defining recruitment targets for underrepresented populations and higher enrollment of Black participants, but recruitment targets were rarely met. 

The authors set a benchmark of 25% for their study, reasoning that 25% is approximately equivalent to the burden of mortality in cardiovascular disease among Black adults. That benchmark is about twice the percentage of black adults in the US population. 

Based on that benchmark, the researchers found that Black participants are still underrepresented in cardiovascular disease trials, and enrollment rates have not greatly improved. 

“There seemed to be some minor improvements over time, but these did not meet our threshold for a statistically significant difference,” Juraschek clarified for Clinical Research News. Though he did point out that this study, “began in 2000, so compared to more historic periods there may have been improvements.” 

Protocol Insights 

The research team looked at each study’s recruitment strategies, including active and passive recruitment, community-based recruitment, electronic medical record-based recruitment, and healthcare provider referrals. Active recruitment included direct outreach to potential participants initiated by the research team as opposed to passive recruitment, in which participants had to initially express interest based on informational ads. 

The team found that, among the 100 NIH-funded trials that met their study criteria, 62 had protocols outlining recruitment efforts available. Among the 90% of trials that reported active recruitment strategies, 5% of trial protocols explicitly mentioned community members as being part of the trial design process, and just 3% of trials had community members outside of academic medical institutions as co-authors. Nearly a quarter of the trials did not specify what percentage of enrollees identified as Black. Trials that did not define recruitment targets often had an inadequate representation of Black participants. While 21% of studies explicitly mentioned target goals for recruitment of historically underrepresented populations, just one trial met its goal for enrolling Black participants. 

Moving Forward 

The authors did have recommendations for improvement, and they emphasized investigators’ roles ensuring change.

“The investigators implement the trials, so they are ultimately responsible,” Juraschek said. “However, trial sponsors and the NIH can guide the investigators along. For example, the NIH introduced demographic enrollment tracking which has been a step in the right direction. Perhaps the next step is greater scrutiny of recruitment plans. Maybe even requiring trials investigators submit their plans as part of the NIH progress report could be helpful in this regard.” 

The authors argued that earlier consideration for diversity is needed. “We think that recruitment goals and strategies should be discussed early as the researchers build their study teams and data management systems for tracking participant engagement,” Juraschek said. 

The NIH does require annual reporting on participant demographics, he pointed out, but including specifics about diversity strategies and goals within trial protocols would make it easier to observe how researchers are approaching recruitment and if they are meeting their own recruitment goals. “Often there are unconscious biases that we are not aware of,” Juraschek said. “More standardization in study planning documents would allow external researchers to study how researchers are approaching efforts for inclusive recruitment and their relative success.” 

Diversity and Real World Data 

Others argue that big health equity issues like these cannot be solved through better trial enrollment. Dan Riskin, CEO of Verantos, was not involved in the study, and he commented on the findings for Clinical Research News. “Bringing up the question is critical,” Riskin said, but issues of health equity are much bigger. 

“At a higher level, it isn’t just about health equity in race and randomized trials. It’s about health equity in the overall healthcare system,” Riskin argued. “Can we really understand which subgroup is doing better in which ways? Can we move beyond just race or just gender or just age and say there are a lot of characteristics that influence how someone does in the health system and which therapy is most effective? For that, no amount of tweaking of randomized trials and improving enrollment approaches will ever get those answers. That has to be an approach where we use routinely collected data to improve care.” 

Verantos, of course, is a real-world evidence company. The company platform integrates heterogenous real-world data sources and leverages data science and artificial intelligence along with advanced data sources such as electronic health records to generate RWE capable of supporting clinical assertions. And Riskin sees these capabilities as key toward gathering more diverse health data and ensuring equity in the future. 

“The amount of routinely collected information is orders of magnitude larger than the amount of information for randomized trials. That’s where we’re going to get health equity,” he said. “That’s where we’re going to say: actually patients who were poorer or who were this race or that gender did better with this treatment. That’s really the only way out of this hole.” 

To that end, Riskin puts the responsibility for improvement on all players in the healthcare ecosystem—including patients. “Ultimately the patient is responsible. Ultimately Congress and NIH and the pharmaceutical firms and health systems are responding to pressure when enough patients get together. People should be demanding health equity and better data and tailored care,” he said.

But he also acknowledged that this is a heavy lift for patients.

“I think everyone in the industry—myself included—has an obligation when we join this field to really try to deliver the best care to patients regardless of whether they are demanding it. That’s an important part of the field that makes it different from technology or finance or other industries.”