The FDA looks to address a lack of diversity in cancer drug trials.
In clinical trials evaluating the effects of cancer drugs on patient populations, there has been a long-standing, consistent lack of diversity that is representative of the US patient populations likely to receive the treatment.1-3 Additionally, landmark oncology trials frequently fail to report the racial diversity of their patient populations, with one study finding that only 33% of the trials reviewed over a 14-year period reported on ethnicity,1 and a second finding that trials leading to FDA oncology drug approvals reported race only 63% of the time between 2008 and 2018.2
When race and ethnicity are reported, Black and Hispanic patients are consistently underrepresented when compared with the burden of cancer incidence faced by these populations, and investigators have observed that recruitment of members of racial minority groups in cancer clinical trials has decreased over time.1,2
The Importance of Diversity and Representation in Drug Trials
In an interview with Pharmacy Times®, Lola Fashoyin-Aje, MD, MPH, associate director of the Science & Policy to Address Disparities program at the FDA’s Oncology Center of Excellence (OCE), discussed the importance of promoting inclusion of members of racial and ethnic minority groups in cancer drug development, and the potential impact of that lack of adequate representation on patient health.3
“The whole goal of representation is to be able to generate data that reflect the variability in the study population,” Fashoyin-Aje said. “Things like race and ethnicity, they’re not really biological constructs; they’re sociopolitical constructs. However, they tend to track with certain ancestry, which can sometimes reflect certain genetic or genomic factors that contribute to a drug’s effect or its safety.”3
A homogeneous patient population during clinical trials testing drugs, Fashoyin-Aje explained, can result in a study that fails to appropriately account for differences among the patient population that will ultimately receive these treatments. Because the purpose of a clinical trial is to study the effects of a drug on patients in a controlled environment, failing to properly include minority groups in a study leaves potentially critical health interactions unexamined.3
Sources, Influences, and Potential Solutions
Several sources contribute to this lack of diversity, and other factors involving the structural ecosystem, patient level, and drug development exacerbate the problem further. Although efficient drug development can result in patients receiving treatment faster, decisions made in the interest of speed can make the problem worse if they are not thoughtfully deployed.
Fashoyin-Aje noted that an emphasis on speed during clinical trials can result in smaller patient populations, which decreases the likelihood of appropriately representing each subgroup.3
“Probably the largest factors have to do with not having a plan that is thought about in terms of how we’re going to enroll these underrepresented subgroups in the trial at the outset and how we can address the barriers that may preclude their enrollment or make it difficult for them to enroll,” Fashoyin-Aje said.3
According to Fashoyin-Aje, the problem is also partially rooted in how these trials are designed around the toxicity of the drugs in use. Investigators and trial sponsors are likely to select trial participants who have very few comorbidities in the interest of producing data that will allow for a greater level of ease and clarity during analysis. For the investigators, choosing patients free of medical conditions that could interact with and alter the effect of the drug makes it easier to study the baseline effects of the medication.
However, this can also result in the exclusion of populations that, because of social determinants of health, have a higher rate of the comorbid conditions the investigators are avoiding when selecting the trial population.3
“The downside to that is that you’re studying the trial in a population that does not reflect who will be receiving the drug once it’s approved, so one has to be very thoughtful at the outset—particularly in the design phase—to ensure that we are enrolling a diverse population for the cancer trials,” Fashoyin-Aje said.3
Currently, the FDA’s OCE is attempting to counteract this lack of diversity in trial populations. The FDA has issued guidance on how to collect and present data on diverse populations that represent subgroups based on sex, age, race, and ethnicity. Guidance has also been issued for how to enhance diversity of drug trial populations, and the OCE has taken action on this issue.3
“Our efforts are focusing on the engagement of stakeholders who really have a stake in representation,” Fashoyin-Aje said. “This includes our patients, our providers, professional organizations, and so many [others]. Engaging with them to provide transparency regarding what we’re seeing in terms of diversity can then help inform their policies and their research programs, but also vice versa.”3
The Future of Diversity in Cancer Drug Trials
Fashoyin-Aje is hopeful that ongoing recognition of the lack of diversity as an obstacle to accurate data in clinical trials will lead to sustained remedies. She also explained that she hopes perfectionism will not thwart efforts to ensure inclusivity in clinical research. Although work toward change may be imperfect and incomplete, each step forward reduces the impact that a lack of representation can have on patients' health, Fashoyin-Aje noted.3
“I think what we saw with the COVID-19 pandemic was that it was a catalyst for broader and greater awareness of the need to address disparities and to ensure that there is appropriate representation of all subgroups in clinical research,” Fashoyin-Aje said. “My hope is that those efforts are going to be sustained, and that we continue to learn and refine strategies to promote inclusion and representation, but also to start to understand how that actually adds value to the research that we’re conducting. I think that that’s something that’s not well articulated. We tend to focus on the fact that there is not enough, but we don’t focus so much on when there is appropriate representation, how it adds value to the research.”3