Representation of the population in need for pivotal clinical trials in lymphomas.

Despite the advances in cancer outcomes, significant health disparities persist. Several new agents have been recently approved for treatment of lymphomas, leading to improved outcomes. Extending the benefits of these new agents starts by adequate enrollment of all affected patient populations. This study aimed to evaluate the extent to which randomized controlled trials (RCTs) match the demographic and geographic diversity of the population affected by lymphoma. Two Food and Drug Administration databases, clinicaltrials.gov, and relevant primary manuscripts were reviewed for drug approval data and demographic representation in RCTs for classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma. Maps showing the distribution and frequency of trial participation relative to disease burden, insurance status, and racial representation were created. Black, Hispanic, and female patients were significantly underrepresented in the RCTs for lymphoma compared with that for the disease burden (3.6% [95% confidence interval (CI), 2.8-5.4] vs 14.6% [95% CI, 13.8-15.3]; 6.7% [95% CI, 5.5-7.9] vs 16.3% [95% CI, 15.5-17.1]; and 39.1% [95% CI, 37.3-40.9] vs 42.7% [95% CI, 42.3-43.1], respectively). White and male patients were overrepresented. More counties with higher mortality rates and racial minority representation had low access to the trials, particularly for cHL in the southern region of the United States. There are significant racial misrepresentations in pivotal RCTs in the United States, and geographic distribution of these trials may not provide easy access to all patients in need. Disparities in enrollment should be corrected to make results applicable to all populations.

Global Trial Representation and Availability of Tyrosine Kinase Inhibitors for Treatment of Chronic Myeloid Leukemia.

Background: Evaluating clinical trial representation for countries with different socio-demographic index (SDI) and tyrosine kinase inhibitor (TKI) availability for chronic myeloid leukemia (CML). Methods: CML incidence rates (IRs) and disability-adjusted life years (DALYs) (1999-2019) from the Institute of Health Metrics and Evaluation were analyzed. Trials investigating TKI use in CML were obtained from ClinicalTrials.gov. Site data for eligible trials (N = 30) and DALYs were analyzed. TKI approvals, DALYs, and IRs were summarized by SDI. Results: North America (NA) had significant decreases in annual percent change (APC) in DALYs and incidence rates from 1999 to 2004. IRs were highest in Europe and Central Asia (ECA) and NA, while DALYs were highest in South Asia (SAsia) and Sub-Saharan Africa (SSA). Countries in the high-SDI quintile were likely to have lower DALYs than lower-SDI quintiles. Differences in regional DALYs vs. sites in TKI trials were significant for SAsia, SSA, and ECA. High-SDI countries were included in all 30 trials, and TKI approvals were prominent in high-SDI (142) vs. low-SDI (14) countries. Conclusions: The inclusion of disproportionately affected countries during the design of and recruitment into clinical trials should occur, as should TKI availability. The lack of representation demonstrates healthcare disparities.

Are Pivotal Clinical Trials for Drugs Approved for Leukemias and Multiple Myeloma Representative of the Population at Risk?

PURPOSE: There are significant disparities in care and outcomes for patients with leukemias and multiple myeloma (MM). To evaluate the extent to which clinical trials (CTs) match the demographic and geographic diversity of populations affected by leukemias and MM. METHODS: CTs leading to drug approval were identified from the US Food and Drug Administration databases. Demographic and geographic data were collected from ClinicalTrials.gov and primary manuscripts. Standard descriptive statistics were used to summarize the data in frequencies and proportions, including 95% CIs, by race, ethnicity, sex, and malignancy subtypes. RESULTS: A total of 41 (67.2%) trials leading to drug approval reported data on race and 20 (48.8%) on ethnicity. These trials included 13,731 patients, of whom 11,209 (81.6%) were White. Among minorities, Asian-Pacific Islanders and Blacks had the highest representation in chronic myeloid leukemia, 147 (12.7%) and 61 (5.3%), and lowest in chronic lymphocytic leukemia, 55 (3%) and 20 (1.1%), respectively. Proportions for Blacks, Native Americans, and Hispanics were significantly low, reflecting under-representation in trials compared with the proportion in the general population. Females were also under-represented in acute myeloid leukemia (44.7% v 60.5%, P < .0001), and males in MM (55.3% v 60.2%, P < .0001) and chronic myeloid leukemia (55.2% v 62.9%, P < .0001). The geographic distribution of trials showed inadequate regional and state participation compared with mortality for all malignancies except MM. CONCLUSION: There are significant demographic and geographic under-representation and imbalances in pivotal CTs leading to drug approvals for leukemias and MM compared with the population affected. These disparities need to be addressed to make results applicable to all relevant populations.