Diversity, equity, and inclusion in clinical trials was a hot topic in several abstracts presented at the recent Annual Meeting of the American Society of Hematology (ASH). Be it in terms of lacking representation of minority ethnic groups in clinical trial design, or the disparity in outcome indicators across different groups. Such issues are noticeable in indications like acute lymphoblastic leukemia (ALL).
Focusing on some of the potential disparities in children, adolescents, and young adults from minority ethnic backgrounds with ALL, the insights brought up by ASH abstracts #337 and #211 inspired expert ideas on how to how to improve such disparities. Researchers say that companies and institutions should pay close attention to clinical site locations to ensure that the sites are reflective of indications and their incidence in different populations. Additionally, collecting sociodemographic data of individual subjects could equally provide greater insight into some of the factors playing a role in a disparity in clinical trial outcomes.
ASH abstract argues for hotspot states
Institutions and companies can make their research more inclusive and insightful by focusing on clinical site locations, researchers tells Clinical Trials Arena. Taking part in preparing and presenting abstract #337 at this year’s ASH, Stanford University Medical Centre associate professor of medicine Dr Lori Muffly says matching clinical sites with areas representative of specific populations could mitigate enrollment disparity. Professionals could focus on what Muffly called “hotspot states”, which are areas with a high incidence of ALL, including states with large Hispanic populations such as California or Texas.
The abstract focused on the enrollment characteristics and outcomes of Hispanic and African American adolescent and young adult (AYA) subjects (age 18 – 40) with ALL. These patients took part in CALGB 10403 (NCT00558519), a Phase II clinical trial sponsored by the Alliance for Clinical Trials in Oncology. This population and data was subsequently compared to US population-wide data.
Despite that ALL remains a cancer with a higher incidence amongst a specific ethnic group, with over 40% of AYA (18 – 40 years in this case) ALL subjects grouped as Hispanic, Muffly says she has seen a discrepancy between the actual incidence of the indication and the enrolment of such individuals in clinical studies. More specifically, Muffly notes an underrepresentation of Hispanic subjects within the CALGB 10403 study, which led her to the abstract, she adds. Indeed, although this was a country-wide study, it only featured 45 subjects, about 15.3%, identified as Hispanic, despite they making up over 40% of AYA ALL subjects.
Fully omitting states such as Florida or Texas could have been an influential factor in causing a disparity of enrolment of Hispanic subjects.
Matching disease incidence and epidemiology with geography could be a way how to improve disparity of enrolment, Muffly says. This could be by considering areas with significant populations of respective minority groups. In case of CALGB 10403, Muffly notes the study focused a great deal of its clinical sites within the American Midwest, fully omitting states such as Florida or Texas, which could have been an influential factor in causing a disparity of enrolment of Hispanic subjects.
According to insights from GlobalData’s Pharma Intelligence Center, such disparities in enrollment appear to be much wider than in the case of the CALGB 10403 study. In 123 US-held ALL trials between 2004 and 2018, about 10.8% of subjects identified as Hispanic.
Linking disparity of enrolment and worse outcomes
While outcome disparity in clinical trial populations remains a complex topic, minimal enrollment of specific populations affected by a disease could be one of the reasons why some treatments are perhaps not as effective in those populations as they could have been, notes University of California San Francisco School of Medicine assistant professor of pediatrics Dr Lena Winestone. In simpler terms, if the appropriate populations are not represented, then the results could perhaps not be generalizable to that population, she adds.
Winestone has taken part in producing the #211 abstract presented at ASH 2021. The paper focused on racial, ethnic, and socioeconomic factors and their role in causing outcome disparities in a cohort of children and AYAs (age 0 – 30.99) with ALL who have taken part in the Children’s Oncology Group trials between the years 2004 and 2019. The paper examined the health outcomes of this cohort of newly-diagnosed ALL subjects. The paper found that non-Hispanic White subjects had the highest 5-year event-free (EFS) and overall survival (OS) rates, attaining 87.4% and 93.3%, respectively. In contrast, Hispanic subjects had an EFS of 82.8% and an OS of 90%, while non-Hispanic Black patients had an EFS of 81.9% and 89.8%.
Determining the causes for such disparities remains complicated and is likely an interplay of social determinants together with disease prognosticators, Winestone says. However, making sure that all populations are well-represented remains essential to allowing researchers and institutions to understand the factors playing a role in driving health inequities, notes Harvard Medical School assistant professor of pediatrics Dr. Kira Bona. If there are insufficient representative data from trials, professionals will not be able to ensure trial findings are generalisable to all populations and to intervene properly to improve equity in outcomes, she adds.
Reducing inequities also require a more systematic approach to collecting social determinants of health data for individual patients.
Yet to Bona, diversifying enrollment in clinical trials on its own is inadequate, reducing inequities also require a more systematic approach to collecting social determinants of health data for individual patients, which would allow professionals to understand modifiable links between such factors and outcome disparities.
Inequitable access to and enrollment on clinical trials is even more pronounced in adult populations, owing to the different models of healthcare delivery as compared to pediatric oncology necessitated by much larger overall number of adults affected by cancer, Bona says. Partly owing to fewer numbers of children affected by ALL, care can be focused in more centralized institutions, she adds, which can facilitate equitable trial participation.
According to data from GlobalData’s intelligence centre, in 21 trials with a cohort aged 25 and under between 2004 and 2018, about 13.7% of subjects were identified as Hispanic and 9.15% as African American. In case of the COG trials studied in the paper, 65.6% of the cohort identified as Non-Hispanic White, whereas 20.6 percent were grouped as Hispanic and 7.2% as Non-Hispanic Black.