Trial and Error: The Systemic Challenges of Clinical Trial Enrollment

Mariam Eskander, MD, MPH

Equitable clinical trial enrollment remains a concern for many patients, clinicians, and researchers. A study presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting investigated how social vulnerability and race influence clinical trial enrollment among patients with the top 5 deadliest cancers.

In this large, nationwide study, only 1.4% of patients participated in a clinical trial. Patients with Medicaid insurance and those living in socially vulnerable neighborhoods were less likely to enroll in a clinical trial. The negative impact of social vulnerability on enrollment was more pronounced among Black patients than White patients.

These findings suggest that addressing social determinants of health may be important for increasing racial diversity in clinical trials. There also appears to be additional barriers to clinical trial enrollment for Black patients, even when accounting for social vulnerability.

Efforts to address these disparities may help improve the generalizability of clinical trial results and ensure that all patients have the opportunity to participate in potentially lifesaving research.

In an interview with Targeted Oncology^TM, Mariam Eskander, MD, MPH, surgical oncologist and assistant professor in the Department of Surgery, Division of Surgical Oncology, Section of Gastrointestinal Oncology at Rutgers Cancer Institute, discussed the critical findings and implications from this study presented at ASCO.

Targeted Oncology: What are some of the biggest limitations when it comes to clinical trial enrollment?

Eskander: There are lots of limitations at different levels. We can start at the systemic and structural level: There is limited trial availability, so trials for different cancers and for [patients] with different stages, like how many trials are available and what hospitals offer those trials. Generally, and our study found this, patients are more likely to enroll in a clinical trial when they are seen in an academic center.

From a resource perspective, there are limitations in terms of having the research staff and the funding to open a trial at a specific hospital. There are also challenges around having the consents in different languages so that [patients] from all backgrounds can join the trial. From the provider's perspective, does the provider know what trials are available for that patient and where to send them? Are providers unbiased in who they offer a trial to?

From a patient perspective, there are lots of limitations. There are issues of trust, I think. In order to enroll in a trial, a patient needs to have trust that this trial is the right path for them, especially because it's called a clinical trial. There is some uncertainty. There are barriers around transportation getting to the trial site. There are barriers around missing work and the commitments to be on trial. There were insurance barriers in the past, but there are not anymore.

What is social vulnerability?

There are a lot of ways to define social vulnerability, and we use the novel index that is specific to the Vizient clinical database, and this index is called the Vizient Vulnerability Index. It is defined at the census level, which is very good because census tracts are homogenous, as opposed to ZIP codes and counties [which] are very heterogeneous. It identifies drivers of health. It has 9 domains of which 3 I mentioned already, but a couple of other ones are housing and social environment. It tries to give a global view of the structural resources available in a neighborhood. The 9 domains altogether encompass 43 components. It [considers] many things about that neighborhood. We divided the index into quartiles from least vulnerable to most vulnerable, and that was the exposure, social vulnerability in quartiles at the census tract level.

Could you summarize the methodology of this research?

The question we were interested in was whether social vulnerability at the neighborhood level has an impact on clinical trial enrollment, and we studied patients with 5 different cancers. These are the top 5 causes of cancer related death in the United States. They are breast, prostate, lung, colorectal, and pancreas cancer. We use a claims database called the Vizient Clinical Database. The Vizient Clinical Database has inpatient and outpatient claims data and includes 98% of academic centers, and several hundred cancer hospitals and community hospitals. It is quite representative of the landscape around hospitals in the US.

We identified patients enrolled in clinical trials using a special billing code for a clinical trial, and then we compared patients who were enrolled in trials and patients who are not enrolled with respect to their different demographics, including race, ethnicity, and social vulnerability. Then, we were also interested in the interaction between race and social vulnerability as it relates to clinical trial enrollment.

Could you summarize your findings?

The major finding is that high social vulnerability—patients who live in socially vulnerable neighborhoods—are less likely to enroll in a clinical trial, and this has a greater impact for Black patients than White patients. Then, we identified 3 domains of social vulnerability that were most associated with barriers to clinical trial enrollment, and those were education, transportation, and neighborhood resources.

What is the importance of having diversity in clinical trials?

I think it is extremely important. I think this study shows that beyond racial diversity, economic diversity is also important, making sure that people who come from less wealthy backgrounds and more vulnerable areas [who] also may not be represented on trials and faced specific hurdles to being on trial. I think, in general, representation is important, both from a racial standpoint or socioeconomic standpoint, because we know that in the United States, the [patients] who bear the burden of cancer and the burden of cancer mortality are those patients, right? They are the patients of color; they are the low-income patients. Clinical trial enrollment is both a symptom of disparities and a potential solution to disparities. If we can get [patients] new and improved treatments up front, it may reduce some of that burden of mortality that we see in those populations and then from a representation.

Another point is that if a specific racial group is not represented in trials, we cannot extrapolate the findings of trials to those patients. Historically, some of our big landmark trials in cancer have been made up of [close to] 90% White [patients] and a handful of Black [patients] and a handful of Hispanic [patients]. It is hard to extrapolate those results to people of color when no one on this study was a person of color. There are potentially underlying biologic or epigenetic differences between people of different racial groups, and we need to have those people all represented in the studies where we study cancer therapy.

From an equity standpoint, it is just unjust. It is unjust not to represent [fewer] wealthy people and people of color on trials. I think our study highlights the socio-economic piece, as well and how important it is to make sure that our trials are reaching patients who may have less access to care.

The final piece about the interaction between race and social vulnerability is also important, because it suggests that if we help get low-income [patients] and socially vulnerably [patients] on trials, we may also see increases in racial diversity on trials, which is important. To break down that interaction a little bit more, we found that when [patients] were very socially vulnerable, like in that fourth quartile of social vulnerability, it decreased the odds of enrollment if [they] were Black. It did so more for Black patients than it did for White patients. The impact of high social vulnerability was higher. I think race and class, there is always some overlap there. If we want true equity in our trials and equity and access to new, potentially lifesaving treatments, we have to not only recruit and build relationships with all patient populations, but also focus on interventions that bring trials to people in socially vulnerable neighborhoods. We need to do things from a policy level, work on education and making sure that patients in the neighborhood have access to preschool and graduate with high rates from high school, improving access to transportation, whether it is public or private, improving food deserts and park access, and all the structural things we know are associated with poverty. From a political perspective, working hard to get our patients transportation to appointments, working hard to educate our patients, improve the messaging around trials. We need to also do that, both at a structural and at a personal level.

REFERENCE:

Perati SR, Mohayya SM, Shippey E, et al. Social vulnerability and clinical trial enrollment: The next frontier of health equity. J Clin Oncol. 2024;42(suppl 16)1508. doi:10.1200/JCO.2024.42.16_suppl.1508