The Future of Diversity in Clinical Trials: Real-World Evidence

This episode of tHEORetically Speaking features real-world evidence experts Alexandrina Balanean, MPH; Parisa Asgarisabet, PhD; and Danielle Gentile, PhD from Cardinal Health discussing the problems caused by lack of diverse representation in clinical trials.

The underrepresentation of disproportionately burdened groups limits information on therapeutic response, safety, and efficacy to a small subset of the population—which tends to be healthier, more well-educated, and financially advantaged. However, recent findings show that real-world evidence (RWE) may be able to help with this underrepresentation. Listen in to learn more about these findings and what it may mean for the future of RWE.

Cardinal Health Real-World Evidence and Insights uncovers actionable insights through deep data and unique research methods. Through our group purchasing organization (GPO) and electronic medical record (EMR)-agnostic provider networks, our market-leading physician-led chart abstraction solution, our innovative practice research network and our regulatory expertise, we can support your real-world data (RWD) and real-world evidence (RWE) needs and give you the access and efficiency you need to craft a stronger product value story. We work with key stakeholders to critically analyze data and deliver clinically and scientifically meaningful results to inform all phases of the product lifecycle.

Reach out to us with your RWD and RWE needs by visiting cardinalhealth.com/RWE.

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What is the problem we are facing today with the lack of diversity in clinical trials, and how does it contribute to health disparities?

Alexandrina Balanean, MPH:
Clinical trials are meant to study treatments for the population as a whole, but their findings are based on data from about the 5% or so who actually participate – and this is a largely homogeneous group. About 85% are white and the proportions of women, children, and older adults having the diseases being studied are not adequately represented in the trials. So potential risks and adverse events that are more common in these populations won’t be studied.

This can contribute to health disparities in many ways. For example, underrepresented populations tend to be in under resourced communities. They may be more likely to have comorbidities and unhealthy exposures and behaviors leading to treatment-related adverse events. Not having regular access to quality health care increases emergency department use.

Also, many clinical trials are federally funded, so our tax dollars are wasted when they end early because they can’t enroll enough participants. Along with higher mortality, worse patient outcomes, and lost work productivity, this costs hundreds of billions of dollars every year. On top of all of this, socioeconomic status is a sensitive topic because patients may hesitate to self-report financial hardship, which more often correlates with non-White race, female sex, and older age. So clinical trial coordinators try to recruit patients whom they think will meet these strict study criteria and have the interest, understanding, and financial means to participate which is how we get the underrepresented samples in most clinical trials today.

How can RWD help with this problem then? And what are some of the limitations of RWD when it comes to this problem?

Danielle Gentile, PhD:
RWE is a great supplement to randomized control trial (RCT) data because it involves real patients in real-world settings who are truly receiving that treatment without the guise of an RCT having such strict definitions of who can participate.

The main limitation of real-world evidence is that we are not able to randomly assign patients to different treatments, making it less possible to isolate the treatment effect from potential confounders.

Cardinal Health Real-World Evidence and Insights recently completed a study comparing RWE, RCT, and Surveillance, Epidemiology, and End Results (SEER) national cancer registry data. Could you elaborate on what you wanted to learn from this study?

Danielle Gentile, PhD:
Sure! So some background on this study is that we had three different sources of data. The first source was real-world evidence data, and that was matched to the closest RCT comparator using the eligibility criteria of the RCT. The third comparator is the SEER registry database, which serves as a comparator for the US population although it was a proxy for the US population.

When we compared those three sources, we found that in general, people who were within the RWD tended to be older and more ethnically and racially diverse than those who are participating in randomized control trials.

With those results in mind, what do you think is the next step for using RWE to overcome lack of diversity in clinical trials? And what should sponsors keep in mind when leveraging RWE?

Parisa Asgarisabet, PhD:
So RWD can help overcome this issue of lack of diversity in two distinct ways. One, with providing supplementary evidence when diversity is an issue, and two, with providing means to improve the diversity in clinical trials. RWD are more representative of the target population for medical treatments, and generating evidence from these data can help us overcome limitations of clinical trials, helping us understand how well or poorly treatments are working in real life.

We can understand the safety of adverse events more clearly, and once we identify these rare adverse events that were not identified in clinical trials, we can plan to prevent them from happening. This can reduce emergency room visits, reduce hospitalizations, and eventually reduce their healthcare costs. We can also understand whether the treatment effect is any different across racial or ethnic groups, male versus female, as well as across age groups and other subgroups.

Deeper understanding of this treatment heterogeneity creates opportunities for research and hypothesis generation, and ultimately improves innovation.

RWE can also be used to improve the diversity in clinical trials. We can use it to find centers that have more diverse patients, and this is more important in the rare disease area as this can also improve the recruitment of the patients – which as Alex mentioned, is an issue in clinical trials. One day of extended clinical trials costs significantly, and this can be used to improve the recruitment of the patients.

Any final key takeaways that you would like to share with us?

Danielle Gentile, PhD:
My key takeaway is that while randomized control trials are still the gold standard because they’re able to assign patients randomly to different conditions so that we can isolate that treatment effect, real world evidence is an excellent supplement because it allows us to see how well the treatment is working in the real world with patients of all kinds especially diverse patients which are needed within RCT.

Alexandrina Balanean, MPH:
Underrepresentation in clinical trials hurts all of us, not only the patients who are underrepresented.

Parisa Asgarisabet, PhD:
I would say that diversity in clinical trials means diversity in all aspects. This would be diversity in race and ethnicity, sex, age, health status, socioeconomic status, and all other aspects that may affect the health outcome.