(M0930-02-12) Sex, Racial, and Ethnic Representation in COVID-19 Vaccine Clinical Trials Conducted in US - A Systematic Review Compared to 2020 US Census Data

Purpose: Vaccines and drugs typically undergo approval processes based on established safety and efficacy, validated through the rigorous randomized clinical trials. However, the limited diversity in clinical trials, especially for vaccines, has persisted for decades¹, raising concerns that the efficacy observed in these trials may not be applicable or effective for all populations²_. This underrepresentation contributes to vaccine hesitancy and lack of trust in the medical establishment, particularly in minority communities³. This underscores the critical importance of inclusion efforts in future trials despite the heightened challenges involved. To enhance enrollment of underrepresented groups, the NIH Revitalization Act of 1993 mandated the appropriate inclusion of women and racial/ethnic minority groups in clinical trials. However, decades later, inclusion rate of such populations has remained persistently low⁴. Various regulatory bodies worldwide have developed plans to bolster inclusion efforts and enhance the reporting of demographic data. However, the efficacy of these initiatives has yet to be conclusively evaluated ⁵. As of March 10, 2024, 677 million people across the world has been confirmed infected by SARS-CoV-2, with 96 million cases and more than 1 million COVID-19–related deaths in the US alone ⁶, and the actual number of cases may be much higher. To assess the diversity of enrollment in clinical trials, demographic data (pertaining to race, ethnicity and sex) focus on trials of COVID-19 Vaccine from completed studies within the past three years were analyzed.

Methods: This work utilized data from interventional all covid-19 vaccine trials conducted between January 2020 and December 2023, which were registered and reported on ClinicalTrials.gov. Retrieved data from those trials for which results had been posted as of March 2024 (Figure 1). Enrollment data categorized by demographic variables (race, ethnicity and sex) were abstracted for analysis. Based on common federal classifications⁷, race was delineated into seven following mutually exclusive categories: American Indian or Alaska Native; Asian; Black of African American; Native Hawaiian or Other Pacific Islander; White; More than one race; Other, unknown, or missing. Ethnicity was classified as Hispanic/Latino versus non-Hispanic/non-Latino. Sex was classified as Female, Male. Additionally, we also characterized studies by phase, which combined phases categorized as the higher phase (e.g., phases 1/2 reported as Phase 2). Location of clinical sites (US and non-US) were also recorded. US population data from US censuses was used as reference for comparision⁸.

Results: Table 1 presents the number and percentage of participants in each demographic group compared with US census data from 2020 and 2022. Of all US-based trials reporting race, White and Black or African American participants were slightly overrepresented ( < 1% difference) compared to 2020 data, American Indian and Alaska Native participants were overrepresented ( >4% difference), Asian and mixed-race participants appeared to be underrepresented independent of year of the census ( >1.4% difference). Hispanic or Latino participants were overrepresented, i.e. 22.0% vs 18.2%. Regarding gender, female adult participants were slightly underrepresented, accounted for 46.0% of participants compared with 50.8% to 50.4% of the US population. When analyzed by study phase, in trials with an unidentified phase, the race/ethnicity distribution varied wildly from other phases and population in 2020, likely due to incomplete race information collection. For studies with an identified phase, the demographic distribution is less varied (Figure 2). Data for non-US trials are presented for information purposes only, considering data from those studies should also be used for drug submission in US. However, the study’s demographic depends on the demographic distribution of the clinical site’s area and study population restriction.

Conclusion: In this cross-sectional review study, the distribution of race/ethnicity in the non-U.S. differed from the U.S. trials because some of the studies were conducted in countries/areas with specific demographic characteristics. For trials conducted in US, Asian and more than one race participants were slightly underrepresented, White, Black or African American and American Indian or Alaska Native adults were overrepresented with the US population. Hispanic/ were overrepresented while females were underrepresented. Females have historically been both underrepresented and overrepresented in clinical trials.^9,10 However, it’s worth highlighting that our findings might not reflect the true diversity in clinical trials for COVID-19 Vaccines or the industry in general. Among a thousand trials, there are 30% of studies with available results for the public. Additionally, limitations in data reporting, such as varied race/ethnicity reporting standards, missing or incomplete information pose challenges in accurately assessing the demographic representation. This suggests that improving racial/ethnic diversity in vaccines studies requires efforts from different parties and must be incorporated at all stages from trial planning to reporting, to address vaccine hesitancy, provide education, and counter safety concerns about vaccines by ensuring equitable representation in definitive clinical trials.

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2. Ramamoorthy A, Pacanowski MA, Bull J, Zhang L. Racial/ethnic differences in drug disposition and response: review of recently approved drugs. Clin Pharmacol Ther. 2015;97(3):263-273.
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5. US Food and Drug Administration. FDA action plan to enhance the collection and availability of demographic subgroup data. Published August 2014. Accessed September 15, 2020.
6. https://coronavirus.jhu.edu/map.html
7. Hong Xiao, etc., Sex, Racial, and Ethnic Representation in COVID-19 Clinical Trials, A Systematic Review and Meta-analysis, JAMA Intern Med. 2023;183(1):50-60.
8. https://data.census.gov/table/ACSDP5Y2020.DP05
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10. Khan SU, Khan MZ, Raghu Subramanian C, et al. Participation of women and older participants in randomized clinical trials of lipid-lowering therapies: a systematic review. JAMA Netw Open. 2020;3(5):e205202

Figure 1. Selection of Studies Included in Analysis

Figure 2. Demographic Representation Comparison between US Census and COVID-19 studies in US
(between 2020 - 2023)

Table 1. Race/Ethnicity and Sex Representation in Registered Vaccine Clinical Trials in ClinicalTrials.gov