Why Diversity is More Important Than Ever for Clinical Trials

Why Diversity is More Important Than Ever for Clinical Trials

The COVID pandemic is shining a light on a long-standing and well-documented issue in clinical trials – a lack of diversity. Currently, it’s putting critical research like the COVID vaccine at risk, as trials struggle to recruit Black and Latinx participants, despite the fact that more than half of COVID cases have been among Black or Latinx people.

Recently, we spoke with Makeda Robinson, MD, PhD, about the importance of diversity in clinical trials and how the industry can approach this complex topic. Dr. Robinson is an infectious disease specialist who received her MD and PhD in Microbiology and Immunology from Stanford University. Dr. Robinson shares straightforward, research-based content about understanding and staying safe during COVID on YouTube and Instagram.

Understanding the problem

The lack of diversity in clinical trials is not a new problem but, like many other issues with clinical trials, is one highlighted by the harsh reality of the pandemic. The impact of the issue, however, is difficult to understate. According to research from Clinical Research Pathways, a non-profit organization focused on increasing diversity in clinical research, African Americans make up only 5% of clinical trial participants, despite representing 13.4% of Americans. The disparity is even more extreme with the Hispanic and Latinx communities, who represent 18.1% of the population and 1% of clinical trial participants.

Even in trials related to diseases that disproportionately affect people of color, these communities are underrepresented. “Take multiple myeloma, for example,” says Dr. Robinson. “African-Americans are twice as likely to be diagnosed with multiple myeloma than white Americans. However, the clinical trial designs for new therapies don’t always reflect these real-world differences. A recent study for a multiple myeloma drug (Ninlaro) that has now been approved by the FDA enrolled 13 African-American patients, constituting 1.8% of their participants. So, even though we have the data showing that this disease will likely impact minority communities disproportionately, we’re not necessarily enrolling even equivalent numbers of African-Americans into these studies.”

This is critically important because clinical trials and clinical research make up the basis of our standards of care. Research and clinical trials are how we determine appropriate dosages, identify side effects and drug interactions, and make necessary calculations for life-saving decisions in medicine.

“The findings from clinical trials can often be the first steps towards the development of new standards of care. The outcomes from these studies start to anchor our ideas about best practices for the treatment of disease. Once we have certain standards in place, they can start to become dogma, and we begin to become more anchored in how we think about treatment and disease,” says Dr. Robinson. “As the medical community begins to develop algorithms around these findings, this information is then learned, disseminated, and set as the rule that all groups will then be treated by. This is why it’s so important to be thoughtful about designing these clinical trials, so that the data that we’re generating leads to accurate and efficacious treatment decisions.”

It can be a time-consuming task to reevaluate and reshape these narratives to be more inclusive, which is why it’s so crucial we tackle this issue, especially as we look at the ramifications that COVID-19 will have on our health for years to come.

As with many societal issues, however, the reasons for this lack of diversity are complex. Why people of color don’t participate in clinical trials is because of an array of issues around unequal access to healthcare resources, historical failures in protecting people of color during research, and overall disparities in the health of people of color.

“In clinical trials, they’re looking for ‘healthy sick people’,” points out Dr. Robinson. “They want patients that have disease X and only disease X, because they’re trying to draw the clearest line between intervention and outcome. But if you have other medical issues, there’s concern that these other factors may influence your response and possibly the outcome of the intervention. Knowing that in the African- American community, 40% of the adult population has high blood pressure, along with increased risk of diabetes and kidney disease, oftentimes these co-morbidities can be a barrier to these populations getting into clinical trials, because their baseline health is compromised.”

Disconcertingly, there are some trials where African-Americans are over represented. “There are higher rates of African-Americans that are enrolled in studies that do not require informed consent,” says Dr. Robinson. “With studies that are focused on emergency interventions, such as different CPR procedures, African-Americans are actually disproportionately highly enrolled into those studies. I think embedded in that is a lot of the conversation around why African-Americans are not enrolled at appropriate numbers in the majority of studies with a more traditional study design such as cancer clinical trials or the ongoing studies for SARS-CoV-2 vaccines and therapies. It comes down to the issue of mistrust and access, which I think are two huge barriers to enrollment of people of color into many of these clinical trials.”

Overcoming the barriers

Overcoming such a complex and deeply-rooted issue is no easy feat. Dr. Robinson sees a few areas where the industry can focus to break down barriers to clinical trial involvement for under-represented communities. The first is by focusing on increasing awareness about clinical trials, with both communities of color and physicians working in those communities. Dr. Robinson points out that often, physicians outside of the major academic medical centers may not be as informed about the clinical trial options available to their patient populations, which makes it difficult for them to provide that information to their patients. These local physicians have often built trust within their communities and can be a great source of information for their patients, so ensuring they have information about clinical trials and an understanding the eligibility requirements can help create trusted advocates and partnerships between community healthcare systems and research institutions.

The second is to increase access to clinical trials. Dr. Robinson points out that even small things can be barriers to participation in a clinical trial, such a gas, transportation, and parking. With a significant shift towards virtual visits as part of the COVID pandemic, this could be an opportunity to remove some of the logistical barriers that make it challenging for some people to participate in a clinical trial.

If the patient is not required have to come into the hospital as frequently, this can often remove a huge upfront time, energy, and financial investment for the patient. Being able to have the conversation remotely and then finding logistical approaches to allow the patient to receive any blood draws or therapies in their community prevents them from needing to travel to a specific hub to be part of the trial.

Finally, sites can get more intentional with their trial design and recruitment efforts. By proactively building diversity as a key goal into their trial design and metrics, sponsors and sites can invest in tools and relationships that can make it easier to recruit people of color into not just a single trial but provide access to other trials that may be appropriate for them in the future, strengthening our ability as an industry to continue efficacious and unbiased research.

Diversify more than just patients

Diversifying the patients involved in clinical trials is just one piece of the puzzle, however. There is under-representation in other areas of the clinical trial process that are just as important to consider.

As part of tackling this issue, trial participants need to see people that look like them as part of the trial process. This means increasing diversity in the clinical trials staff as well as the physicians conducting the research. “Having the people managing the clinical trial also be more diverse helps participants because they’re seeing somebody who looks like them invested in the clinical trial, which can engender a trusting relationship.” says Dr. Robinson.
This is a challenge because there is a significant under-representation of people of color among physicians. Only 4.1% of physicians are Black, and 4.4% are Hispanic or Latinx. If you look at the National Institutes of Health (NIH)-funded physician researchers, only 1.5% are Black, and 4.6% are Hispanic or Latinx. Principal investigators can play a role in combating this lack of diversity as well, by being more intentional about building relationships and collaborating with African-American and Latinx physicians on research.

It doesn’t stop there, either. Diversification of the editors and review boards that make decisions about what research is funded and published in respected journals can also be part of the solution. The more we can diversify the perspectives of everyone involved in clinical trials and research, the more we can create an inclusive industry.

Opportunity in the COVID-19 pandemic

The current pandemic is shining a spotlight on the importance of getting this right. COVID-19 is affecting black and brown communities more severely. Given how quickly we are trying to develop and deploy treatments for COVID-19, it’s crucial that communities of color are represented appropriately in the research. This is compounded by a few factors, such as the fact that many of the co-morbidities known to be associated with severe COVID-19 infection are disproportionately higher in communities of color. These populations are also unfortunately less likely to have jobs that allow them to work from home, and they are more likely to live in multigenerational homes. These factors all increase the potential exposure and transmission of the virus to vulnerable populations. However, there is still more to learn about this through efforts to understand the underpinnings of the increased severity and mortality rates seen in African-American and Latinx populations when infected with COVID-19.

But it’s also an opportunity to better incorporate these communities into clinical research and engage them in the process for the long term. COVID-19 vaccine and therapeutics trials could serve as an excellent opportunity to involve underrepresented communities in important research studies. This could also allow researchers and research organizations to build important relationships with those communities for future studies. “There are a lot of opportunities for those who have already been infected with COVID to donate blood and plasma,” says Dr. Robinson. “While we are still learning about the efficacy of convalescent plasma as a treatment, these recovered patients can teach us a lot about the natural history of the disease and help save lives through blood donation.” Engaging these communities now could serve to hasten our efforts in finding effective treatments for COVID-19 and strengthen our clinical trials programs for years to come.

The role technology can play

Technology and data collection can also play an important role in addressing this issue. Dr. Robinson points to the FDA’s snapshots database, which collects demographic data about the participants in studies for FDA-approved drugs.

“Collecting the data is the first step,” says Dr. Robinson. “One important way to start to make a difference is through the development of collaborations between clinical trials and information technology. Utilizing emerging data science technologies can shine a light on how we can improve in a rapid and evolving fashion.”

This consolidation of data also creates opportunities for national networks, allowing trials to reach geographic and demographic communities that are currently not engaged in clinical trials. “If you’re running a trial in an area where you know you don’t have an appropriately diverse population to draw from, you can potentially start to reach those populations. Even looking at the issue of urban versus rural populations, there are many people in rural areas that don’t necessarily get access to the clinical trials because of these barriers to access. We now have a better ability to target and identify people in different locations and in ways where they may not have to uproot their lives to be close to a specific center or hub where it’s happening.”

The rise of artificial intelligence (AI) could further this impact, if used appropriately. Currently, the datasets that algorithms are based on can be flawed, for all the same reasons that clinical trials are flawed. Incomplete or skewed data can create biased AI, entrenching our societal biases. But knowing that gives us an opportunity to mitigate and overcome it. As AI develops, we’ll be able to use it to identify and eradicate biases in data, but only with an industry focus on prioritizing issues around diversity and the value of tackling inequity in healthcare writ large.

Systemic problems require systemic solutions

As with any systemic issue, individual and even organizational commitments to change will only get us so far. Systemic problems require systemic solutions. Achieving true diversity across clinical research will require industry policies to push for meaningful change, quickly. The NIH has started this process, requiring demographic breakdowns of trial participants and justifications if groups are underrepresented. The Food and Drug Administration (FDA) has also issued draft guidance encouraging sponsors and researchers to broaden eligibility criteria, make trial participation less burdensome, and adopt retention practices that enhance inclusiveness. These initiatives are a start, but will require an industrywide commitment to prioritize diversity to see meaningful change soon.

Final thoughts

Increasing diversity in clinical trials provides us an opportunity to demystify the experience for all potential trial volunteers. “My hope would be that the new normal will include people feeling closer to the clinical trials process,” says Dr. Robinson. “It doesn’t have to always feel like this is something happening in an ivory tower academic center. By democratizing clinical trials in a way that people feel more connected to them, we can give people a sense of agency and proactivity in their health experience. They can realize that this is part of the ongoing process of improving medicine for everyone.” Acknowledging long standing barriers to participation are important, but now more than ever, we have so many tools at our disposal to begin to tear down the walls between patients and research.

About Dr. Makeda Robinson

Dr. Makeda Robinson obtained her MD and PhD from Stanford University. She is a recipient of a Howard Hughes Medical Institute Medical Fellowship and is a Jackie Robinson Foundation Scholar. Her research has taken her around the world, where she has studied malaria treatments in Ethiopia and Traditional Chinese and Western Medicine approaches in China. She is currently working with clinical cohorts in Colombia utilizing innovative single-cell technologies to discover transcriptomic signatures predictive of severe dengue and identifying Zika virus-host interactions associated with pathogenesis. Her research has been published in several top journals including Cell Reports and PNAS and highlighted in Nature Medicine.

You can follow her on YouTubeTwitter, and Instagram to find and share her content for understanding COVID-19 and staying safe during the pandemic.