Discussing diversity in clinical trials with Clinical Ambassador’s Allison Kalloo
Many factors, such as age, biological sex, disabilities, chronic comorbidities, geographical location, gender identity, race, and ethnic background, can influence how individuals react to certain drugs, medical devices, and treatment plans.
People of color, however, have been (and continue to be) particularly underrepresented in clinical research. We spoke with Allison Kalloo from Clinical Ambassador about the historical underrepresentation of communities of color in clinical trials and what steps are being taken to increase racial diversity in research, particularly for COVID-19 prevention and vaccine clinical trials.
Discussing diversity in clinical trials with Clinical Ambassador’s Allison Kalloo
Can you discuss the historical underrepresentation of communities of color in clinical trials? Why does this matter?
Underrepresentation among communities of color in clinical trials has significant reverberations in the past, and if we are not careful, it will in the longer term as well. By way of a silver lining, the flood of recent coverage of disproportionate burden seen in coronavirus morbidity and mortality statistics has also brought attention to persistent disparities in myriad health conditions that predispose minorities to worse COVID outcomes. However, the potential of such a pandemic silver lining to enhance attention toward solutions is tempered by hesitance and distrust regarding clinical trials among communities of color. The barriers to minorities being vaccinated today are indistinguishable from the reasons for historical underrepresentation in clinical trials. And it matters because when all people do not participate in what is considered the gold standard in medicine, equity in healthcare is a nonstarter. And if science makes progress without all of us, is it really progress?
The reasons for hesitance among communities of color are hearty ones, and while there is an argument to be made that objections to participating are outdated and survive in large part due to an echo chamber, these issues that have been cited ad nauseum are not without historical justification. Many reasons that persist are rooted in institutional racism and implicit bias within the medical system and our larger society. These challenges include functional barriers to access and lack of exposure to these options in healthcare settings.
Patients of color are also less likely to be face-to-face with providers who discuss participation in clinical trials. Research by the National Institutes of Health indicates that clinicians are less likely to discuss clinical trials with patients of color. Furthermore, recruitment campaigns lack reach not only because they aren’t getting into the right hands, but because they are less likely to be culturally appropriate. Patient recruitment is often approached as a one-size-fits-all proposition, and does not address differences in language and health literacy. Beyond these very real issues, people of color who may not necessarily be familiar with the infamous Tuskegee Syphilis Experiment or why medical hero Henrietta Lacks is a household name are nonetheless acquainted with historical racism in health care which too many Black and Brown people still experience today.
Another barrier falls under study design, and for Black and Brown people who wrestle with social determinants of health, having comorbidities, or pre-existing conditions, summarily excludes these individuals from participation at the gate. Other prohibitive study factors can be the location or distance to trial sites, work, and caregiving constraints, and sometimes a lack of access to technology, especially for decentralized trials and hybrids that require data input and monitoring.
When you’re a person of color, there can be a swirling mix factoring into one’s access, perceptions, trust, and willingness to participate in clinical trials.
Typically, how diverse are clinical trials today?
The FDA has explicitly stated that “to further promote and protect public health, it is important that people who are in clinical trials represent the populations most likely to use the potential medical product.” As such, the agency issued final guidance with recommendations on designing and executing clinical trials of drugs and biologics that include people with different demographic characteristics, including race and ethnicity. Further, a ProPublica article published in 2018 explored the issue of lack of diversity in cancer drug trials, noting “stark” and “widespread” underrepresentation of African Americans in these trials — even when the type of cancer being studied disproportionately affects this community.
The article compiled data showing that Black Americans made up less than 5% of the clinical trials for 24 of the cancer drugs approved between 2015 and 2018. But as part of the Food and Drug Administration Safety and Innovation Act (FDASIA), the FDA has made this data public on the Drug Trials Snapshot since 2015. This web page details the demographic breakdown of the participants in clinical trials on which the agency bases its new drug approvals (NDAs). During that period of time, it was reported that approximately 25% of the new compounds that were FDA-approved had enough data on people of color to make a determination. Yet these drugs were approved for market. But for whom?
Why is diversity especially important for COVID-19 prevention and vaccine trials?
The disproportionate impact of COVID-19 on communities of color coupled with a hesitancy to trust the medical establishment makes this a health conundrum of epic proportions. Black and Brown people are at highest risk of exposure to coronavirus often by virtue of having the largest proportion of jobs on the frontlines and as essential workers. These and other social determinants of health also result in higher rates of transmission, more severe cases, and higher mortality from coronavirus for people of color. Consequently, diverse racial/ethnic representation in COVID-19 vaccine trials is that much more crucial. It’s important to know whether and to what extent drugs and vaccines affect different racial subgroups. There is abundant literature describing variance in pharmacodynamics across many therapeutic areas, and in addition to possible differences in drug metabolism that need to be understood, there are other underlying experiences and environmental exposures for communities of color which scientists have yet to tease apart.
Common sense allows us to agree with the overarching conclusion of a whitepaper from the Endocrine Society that, “scientifically, it makes no sense to develop new treatments among populations of patients who are different from those who will be using them.” The facts could not be simpler: We don’t know what we don’t know. Until people of color are a significant part of all clinical trials being conducted, best practices for our care will only be a pipe dream. Allowing providers to continue to shoot in the dark is not acceptable to me.
Along with that is the need for a reckoning within communities of color that science is the help we have routinely prayed for, that solutions are not going to fall from the sky, and that clinical trials are the way these data are gathered and analyzed and safe discoveries are made. Participation in clinical trials and agreeing to be vaccinated are the only viable ways we meet the urgent demands of this pandemic, and are the only solutions to addressing the underlying conditions that make coronavirus the dystopian poster child for health disparities. Ideally speaking, trials should enroll people of color in percentages that match disparities statistics, i.e. where a disproportionate number of study slots are reserved for those facing disproportionate risk in pursuit of equitable representation. But we are far from that being a realistic possibility.
What steps are being taken to increase racial diversity in trials, particularly for COVID-19 prevention and vaccine trials? What do you hope to see more of in the future?
Broadly speaking, the FDA has called for more intensive efforts to increase diversity in clinical trials, rising to meet the demand of COVID-19 vaccines. That has taken the form of creating a public-facing education and outreach campaign, issuing recommendations that industry design protocols with fewer exclusion criteria that block people of color from participating, and systematically collecting demographic data. But, these initiatives still lack oversight, milestones or consequences for failure to comply. The National Institutes of Health (NIH) has had a federal mandate in place since 1993 calling for the inclusion of women and minorities in clinical trials; however, this mandate continues to lack “teeth.” For real change to take place, both agencies need mandates and guidances that evolve into regulations that can be enforced. There are reports of both Pfizer and Moderna being intentional about including more people of color in their trials, with Moderna even slowing down enrollment to allow more minority enrollment.
The industry as a whole seems to be acknowledging their role in underrepresentation by looking more closely at site selection, marketing channels, and creative that can better address the needs of more diverse patient populations. There is an undeniable need for more industry training in diversity, equity, and inclusion (DEI) for all staff members — regardless of whether departments are patient-facing — to weave these principles into the workstream of the entire organization. Equally impactful is making sure that community efforts are generously sponsored by industry in order to deliver cohesion, consistency, and trustworthiness in communities of color. It is important for industry to acknowledge that underrepresented populations generally receive information about clinical research better from familiar, trusted sources. Then, industry has to allow for the development of language that resonates with these communities. Forming true collaboratives and supporting community efforts will be crucial moving forward, and tremendous opportunities exist for industry to show up, engage in the community and develop real relationships when there is no study hanging in the balance.
There are many opportunities to improve the patient experience by optimizing patient centricity across the board. The only way to gather authentic data about what patients will respond to is to systematically sample patient feedback directly, whether in the form of focus groups, interviews, surveys, or mock trials — all of which Clinical Ambassador happens to provide in our roster of services.
What are some common missteps you see companies making when it comes to finding diverse populations to participate in trials?
I just happen to have a list of missteps I see industry companies making when it comes to finding diverse participants. They include:
- Seeing us as monolithic within our subgroups.
- Not asking patients or caregivers their opinions when they can make a difference in protocol design.
- Going through the motions of surveying patient recommendations but failing to implement them.
- Using the word “subject” rather than patient or participant.
- Not compensating study participants well.
- Not compensating recruitment partners fairly or equitably.
- Undermining our trust by not extending trust to us.
- Expecting experts to work on spec for recruitment projects.
- Waiting too long to begin to strategize and not starting early enough.
- Failing to identify target audiences (patients) early.
- Failing to outsource relationship development to local experts.
- Relying only on churches for community outreach.
- Relying only on physicians for referrals.
- Not providing adequate resources for recruitment campaigns.
- Not involving communities of color in recruitment strategies.
- Failing to ask patients what they want or need to participate.
- Dismissing ideas that deviate from the industry status quo, comfortable, or familiar measures.
- Failing to accept feelings of discomfort.
- Failing to deal with systemic racism or to acknowledge it.
- Having little willingness to work with research naïve sites or investigators.
- Being removed from the community until you need something or a study is hanging in the balance.
- Believing that decentralized trials give you an “out” for connecting with human beings.
Clinical Ambassador hopes to be a lighthouse that people use to navigate doubt around clinical trials. We rely on a variety of tested communication methods to help get the right messages across to the right people in the right way. And we get real people to weigh in and direct that. I think the most effective ways of doing that will be for industry to more fully resource grassroots efforts that can humanize and complement the move toward decentralized trials and other virtual study interfaces, which COVID is now normalizing. Human interaction is more essential than ever, not less. We need more visible efforts from industry in that vein so that it can earn trust. Become trustworthy. Finally, there are countless untapped opportunities for communication innovation and better reach.
I’m perpetually hopeful that the industry will develop an appetite for implementation of the recommendations that come from the communities they need to better engage. And when COVID-19 is under control and the news cycle moves on, the new normal of industry best practices in DEI must demonstrate staying power. We need to ensure that we are not starting from scratch with engaging communities of color each time a study or health crisis emerges.
The issue of diversity and clinical trial participation is critically important. Better treatments and potential cures will continue to be elusive for some segments of the population if trial populations don’t reflect the real world.