Lola A. Fashoyin-Aje, MD, MPH
A review of the 2019 Drug Trials Snapshots Report1 from the U.S. Food and Drug Administration (FDA) showed that although female participation in clinical trials grew to 72% from 56% in the FDA’s 2018 Drug Trials Snapshots Report,2 ethnic minority participation in clinical trials actually declined from the previous year: 9% Black or African American, 9% Asian, and 18% Hispanic vs 11% Black or African American, 10% Asian, and 14% Hispanic, respectively. The percentage of White participation in clinical trials ticked up slightly from 69% in 2018 to 72% in 2019.
The lack of participation by racial and ethnic minority patients in cancer treatment trials is even more pronounced. Despite efforts by the FDA to encourage greater inclusion of minority patients in clinical trials,3 recent analyses found that between 4% and 6% of cancer treatment trial participants are Black and between 3% and 6% are Hispanic, although they represent 15% and 13% of all patients diagnosed with cancer, respectively.4,5 Moreover, analysis by ProPublica of clinical trial participation for 24 of the 31 cancer drugs approved by the FDA since 2015 found that fewer than 5% of the participants were Black.6
The lack of diversity in cancer clinical trials is not limited to Black and Hispanic patients. Reporting from ProPublica has shown that although Asians were well represented in clinical trials in some foreign countries, they were enrolled in less than 2% of United States–based trials. And Native Americans, who make up about 1% of the population, were not represented in nearly two-thirds of clinical trials.6
There are many consequences of low participation by racial and ethnic minority patients in clinical trials. They include a reduction in access to potentially life-saving therapies for these patients, insufficient understanding of the role biology plays in cancer treatment effectiveness, and the inability to ensure drug efficacy across different patient populations.
“I cannot stress enough the importance for trial sponsors to prospectively define enrollment targets—and to ensure that they are set across the life cycle of drug development….”— Lola A. Fashoyin-Aje, MD, MPH
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To explore these issues, The ASCO Post talked with Lola A. Fashoyin-Aje, MD, MPH, Acting Deputy Director of the Division of Oncology 3 in the Office of Oncologic Diseases and Associate Director for Science and Policy to Address Disparities in the Oncology Center of Excellence at the FDA and a member of ASCO’s Health Equity Committee. In a wide-ranging interview, Dr. Fashoyin-Aje discusses how the FDA is working to improve minority participation in clinical studies, its partnership with ASCO to expand eligibility criteria for clinical trial accrual, and outreach in minority communities to improve access to oncology care.
Ensuring Representation of Minority Patients in Clinical Trials
Low participation in clinical trials by Black and Hispanic patients who experience a higher incidence and mortality from some cancers compared with the overall population7 may limit the generalizability of the clinical trial results. Please talk about how such underrepresentation impacts clinical trial results, and what the FDA is doing to improve clinical trial participation by minority patients.
Underrepresentation of racial and ethnic subgroups in clinical trials is a long-standing and well-documented problem. This observation applies to all clinical trials, including those that are submitted to the FDA to support the approval of cancer therapeutics.
For patients with life-threatening diseases like cancer, for whom clinical trials may offer the best option for treatment, the underrepresentation of racial and ethnic minorities may reflect a lack of access for these patients to potentially promising anticancer therapies compared with their White counterparts. In addition, inadequate representation of any clinically important subgroup in drug trials leads to insufficient data to conduct analyses that may point to important differences among subgroups, in terms of both the drug’s activity and underlying differences in the natural history of the disease across subgroups, including racial and ethnic minority patients.
The clinical trial provides the optimal mechanism to assess a therapy’s effects, and it yields important information to facilitate the safe and effective use of the drug once we approve it. Unfortunately, for most trials that we review, there is a missed opportunity to evaluate the role that race and ethnicity may or may not play in the outcomes under investigation.
Although the FDA does not conduct clinical trials, the agency has published guidance documents outlining its expectations that trial sponsors will enroll participants who reflect the demographics of clinically relevant patient populations, taking into consideration factors such as race, ethnicity, sex, and age. We regularly discuss these expectations with trial sponsors during our interactions in the course of a drug’s development, and we are moving to formalize those discussions to ensure more consistency in our approach. Stakeholders, including patients, are asking us to report on sponsors’ specific measures to address minority representation in clinical studies, and we hope a more formal process will help us track these efforts.
The FDA has also led efforts to address underrepresentation in clinical trials in specific diseases, to identify practices that may be adopted to address this issue from the regulatory standpoint—for example, when there is evidence of racial differences in the underlying biology or presentation of a disease. In addition, the FDA regularly collaborates with external stakeholders on research and policy efforts, including broadening eligibility criteria, which we know represent significant barriers to clinical trial enrollment for patients who are racial and ethnic minorities. We have also worked on efforts to catalog institutional practices that have led to the successful inclusion of racial and ethnic minorities in clinical trials.
Assessing a Drug’s Safety and Efficacy Across Patient Populations
Do drugs that are predominantly tested in White patients affect minority patients differently?
The short answer is we do not know in most cases, because we do not have sufficient data to support any conclusions. We recognize that race is an imperfect marker or proxy to use to assess drug effectiveness or drug safety. However, race could indirectly reflect covariates that are important in evaluating drug efficacy or safety. In some cases, disease phenotypes may be enriched in subgroups defined by race, and more understanding could identify the specific biologic factor that is at play.
For example, in multiple myeloma, we see a certain cytogenetic profile that more commonly occurs in African American patients than White patients, which may be indicative of differences in the biology of the disease by race. This is not to suggest that any differences would be exclusive to any racial or ethnic group, so race alone does not explain any differences that may be observed, but differences may be enriched in subgroups defined by race.
In the early clinical investigations of the epidermal growth factor receptor (EGFR) inhibitor gefitinib, we observed better responses among Asian patients than Western patients. We now know this was due to the presence of EGFR mutations in this population. Ultimately, drugs that target this pathway were found to be beneficial to patients with this mutation in the United States. This is an example that points to the benefits and efficiencies afforded by more diverse enrollment in clinical trials.
Partnering With ASCO to Increase Trial Eligibility Criteria
How is the FDA working with ASCO to improve cancer care for minority patients and reduce health-care inequity?
ASCO has a number of initiatives that are specifically focused on addressing racial inequities in cancer care. The FDA is a key partner in these initiatives, providing the regulatory perspective for a more comprehensive approach to addressing this issue and also learning from other stakeholders working on these initiatives.
ASCO’s Health Equity Committee and its task forces are doing important work on measures that address disparities in clinical trial enrollment and data collection on racial and ethnic minority patients and sexual and gender minority patients, as well as other demographic groups, such as older adults who historically have been underrepresented in clinical research. We are also honored to be working with ASCO on its new initiative with the Association of Community Cancer Centers, which is designed to identify and implement strategies and practical solutions to increase the participation of racial and ethnic minority patients in cancer clinical trials.
In addition, we have successfully collaborated with ASCO to broaden eligibility criteria for clinical trial enrollment in other areas, which has led to a number of guidance documents. We have additional guidance recommendations under review and are moving a step farther by assessing how to operationalize these recommendations within a particular clinical disease setting.
In summary, the FDA has tremendous overlap with ASCO in terms of its interest in improving access to clinical trials for traditionally underserved populations. We collaborate on initiatives that specifically focus on these groups and on other efforts that have implications for addressing gaps in data on these populations.
Inclusion of LGBTQ Patients in Clinical Studies
Although national cancer registries do not collect data on the sexual orientation or gender identity of cancer survivors, it is estimated that there are more than 1 million LGBTQ survivors of cancer in the United States.8 Do you know the rate of LGBTQ patients in cancer clinical trials? What is the FDA doing to increase study participation by these patients?
Sexual and gender minorities are woefully underserved in health care in general, including cancer care, largely because there is no standard practice of collecting data on these subgroups in typical medical practice, let alone in clinical trials. Clinical trial data submitted to the FDA are reported in a binary fashion according to sex as assigned at birth. Information regarding gender identity is not included in the data sets we receive, so I cannot report on the participation rate.
I am a member of ASCO’s Sexual and Gender Minorities task force, which is trying to identify best practices for collecting data in medical practice, including in clinical trials. There are published reports of the barriers these patients face, and we need to do better as a research community to characterize these barriers and their impact on outcomes and, more importantly, effectively address them.
We have taken proactive steps in the FDA Oncology Center of Excellence to learn from experts on some of these issues more broadly, with the aim of identifying measures that we can implement at the FDA.
Mitigating Racial Disparities in Clinical Trial Design
What can the FDA do to mitigate racial disparities in clinical trial designs and encourage more minority patients to participate in these studies?
The key clinical trial design issue that has the potential to impact minority patient accrual is trial entry criteria. We have worked on outlining our expectations in the guidance documents mentioned previously.
In addition, the Oncology Center of Excellence has an external engagement program, which leverages the expertise of the FDA staff to engage with communities, with the goal of promoting clinical research participation. These efforts emphasize a dialogue about cancer well before an individual is facing a cancer diagnosis. They are also designed to provide opportunities for community members who are not typically involved with the FDA to learn about how their perspectives inform our regulatory work. We have also extended this outreach to different patient groups to hear about the challenges they are facing during the COVID-19 pandemic.
GUEST EDITOR
Diversity in Oncology explores the issues of inequities in oncology care for minority racial/ethnic populations, how to curb gender bias and sexual harassment in oncology and reduce implicit bias in medicine, and how to increase diversity in the oncology workforce. The column is guest edited by Karen M. Winkfield, MD, PhD, Chair of ASCO’s Diversity Inclusion Task Force and Associate Professor of Radiation Oncology and Associate Director for Community Outreach and Engagement at Wake Forest Baptist Comprehensive Cancer Center in Winston-Salem, North Carolina.
The FDA has been working for many years to address disparities in clinical trial participation. The leadership within the Oncology Center of Excellence is committed to attaining these goals by more consistently and formally requesting that sponsors specify the measures they are taking to improve diversity in clinical trials and the collection of data on underrepresented subgroups of patients, as well as to report on whether these measures are achieving their intended goals.
I cannot stress enough the importance for trial sponsors to prospectively define enrollment targets—and to ensure they are set across the life cycle of drug development, from early clinical studies through the postapproval setting. Where appropriate or feasible, this should include the use of other data sources, such as real-world data, to help address knowledge gaps or inform hypothesis testing in underrepresented minority patients.
DISCLOSURE: Dr. Fashoyin-Aje reported no conflicts of interest.
REFERENCES
1. U.S. Food and Drug Administration: 2019 Drug Trials Snapshots Summary Report. Available at www.fda.gov/media/135337/download. Accessed September 10, 2020.
2. U.S. Food and Drug Administration: 2018 Drug Trials Snapshots Summary Report. Available at www.fda.gov/media/120253/download. Accessed September 10, 2020.
3. U.S. Food and Drug Administration: Enhancing the diversity of clinical trial populations: Eligibility criteria, enrollment practices, and trial designs guidance for industry. Available at www.fda.gov/media/127712/download?utm_campaign=CDER%20Guidance&utm_medium=email&utm_source=Eloqua. Accessed September 10, 2020.
4. Loree JM, Anand S, Dasari A, et al: Disparity of race reporting and representation in clinical trials leading to cancer drug approvals from 2008 to 2018. JAMA Oncol 5:e191870, 2019.
5. Duma N, Vera Aguilera J, Paludo J, et al: Representation of minorities and women in oncology clinical trials: Review of the past 14 years. J Oncol Pract 14:e1-e110, 2018.
6. Chen C, Wong R: Black patients miss out on promising cancer drugs. ProPublica, September 19, 2018. Available at www.propublica.org/article/black-patients-miss-out-on-promising-cancer-drugs. Accessed September 10, 2020.
7. American Cancer Society: Cancer Facts & Figures for African Americans 2019–2021. Available at www.cancer.org/research/cancer-facts-statistics/cancer-facts-figures-for-african-americans.html. Accessed September 10, 2020.
8. National LGBT Cancer Network: The LGBT community’s disproportionate cancer burden. Available at https://cancer-network.org/cancer-information/cancer-and-the-lgbt-community/the-lgbt-communitys-disproportionate-cancer-burden. Accessed September 10, 2020.
