Inequitable Racial and Ethnic Representation in Duchenne Muscular Dystrophy Clinical Trials

Abstract

Objective

We investigated the racial and ethnic distribution of participants in Duchenne muscular dystrophy (DMD) phases II and III clinical trials.

Methods

A total of 36 DMD phases II and III clinical trials were analyzed for racial and ethnic information. Publicly available demographic information was collected from DMD phases II and III clinical trials registered between 2005 and 2018 from the clinical trials database (clinicaltrials.gov). Clinical trial participation was also analyzed based on geographic location (international vs. United States) and funding source (industry vs. academia).

Results

White participants accounted for 84% of study participants in DMD phases II and III clinical trials in both multinational studies and within the continental United States. Among the 36 trials, 22% (8/36) did not report racial data, and 44% (16/36) did not report ethnicity. Most DMD phases II and III clinical trials were funded by industry (89%) compared with the National Institutes of Health (3%) and other sources (8%).

Conclusion

White participants are most represented in DMD phases II and III clinical trials. The documentation of racial and ethnic information in DMD clinical trials is insufficient. These data highlight the need for further approaches to diversify and include equitable representation in DMD clinical trials.

Keywords

health equity - muscular dystrophy - clinical trials

Introduction

Duchenne muscular dystrophy (DMD) is an X-linked recessive, progressive, and fatal genetic disease despite FDA-approved medications. Boys are primarily affected by this disease, and the characteristic features of DMD include progressive skeletal and cardiac muscle weakness and premature death due to cardiorespiratory failure.[1] The rarity of DMD and lack of awareness among pediatric specialists can result in a diagnostic odyssey, which can delay firmly establishing the diagnosis and commencing treatment.[2] [3] [4]

With the promise of several disease-modifying therapies in DMD, there is a renewed interest in ensuring that early diagnosis as well as commencement of treatment are implemented as early as possible. However, recent publications have brought to attention marked racial and ethnic disparities in both diagnosis and treatment of DMD.[2] [5] [6] These disparities include later age at initial evaluation and diagnosis and delayed treatment initiation in non-White patients, as well as earlier loss of ambulation in those of lower socioeconomic status.[3] Furthermore, in one study investigating the representation in DMD observational and natural history studies, Barnard et al reported that a large majority of participants included White individuals with minimal representation of all other groups.[7]

Against this backdrop of inequitable representation in natural history studies, we hypothesized that White participants are likely to be overrepresented in phases II and III DMD clinical trials. We investigated our hypothesis by analyzing open-access data from clinicaltrials.gov. Specifically, we compared representation within the continental United States versus international phases II and III DMD clinical trials, as well as the inclusive efforts of the National Institutes of Health (NIH) and industry partners.

Methods

Study Population

We used the clinical trials database (clinicaltrials.gov) to collect the demographic information of participants filtered to include both DMD phases II and III clinical trials ([Supplementary Table S1], available in online version only). We searched for “DMD” and included only “completed” and “with results” studies between 2005 and 2018.

Data Extraction

Demographic information compiled from the studies included (1) race, (2) ethnicity, and (3) nation of enrollment. Race was categorized into the following, as indicated in clinicaltrials.gov: American Indian, Asian, Native Hawaiian, Black or African American, White, more than one, unknown or not reported, and not collected. Ethnicity was categorized into the following: Hispanic or Latino, non-Hispanic or Latino, and unknown. Additional data obtained included NCT number, title of study, and start date of clinical trial.

Geographic Comparisons

Due to expected geographic differences in enrollment of diverse participants, we compared non-White representation within the continental United States with other single-country and multinational clinical trial studies. Multinational clinical trials included enrollment from the following countries: Australia, Belgium, Canada, the Czech Republic, Greece, Israel, the Netherlands, Spain, Sweden, and the United Kingdom. In addition to U.S.-only studies, there were several single-nation studies from the United Kingdom, Japan, and Italy.

Results

Racial and Ethnic Representation in Multinational DMD Clinical Trials

[Fig. 1] provides a diagrammatic scheme of our study. A total of 36 DMD phases II and III trials between 2005 and 2018 were evaluated for racial and ethnic composition. Of the 36 trials that were examined, 42% (15/36) were multinational studies; 44% were U.S.-only (16/36), and 14% (5/36) were single-national (Japan, United Kingdom, Belgium, or Italy-only). White participants accounted for 84% of subjects enrolled in both multinational and single-nation studies ([Fig. 2]). Of the rest of the study participants, 7% were Asian, 2% were Black or African American, 2% were more than one race, 0.3% were Native Hawaiian, and 0.2% were American Indian or Alaska Native. Additionally, for both multinational and single-nation studies, 22% (8/36) did not report racial information, and 44% (16/36) did not report ethnicity. Of the reported ethnicity groups, 10% were Hispanic or Latino, and 25% were unknown.

Fig. 1 Schematic of data extraction from phases II and III Duchenne Muscular Dystrophy Clinical Trials and their demographic distribution.

Fig. 2 Racial representation in Duchenne muscular dystrophy participants from multinational phases II and III interventional clinical trials versus in the United States.

Race and Ethnicity Representation in U.S.-Only DMD Clinical Trials

In DMD phase II/III trials conducted within the continental United States (16/36), White participants were overwhelmingly represented (87%). Of the non-White participants, 4% were Asian, 3% were Black or African American, 3% unknown or not reported, 2% more than one race, 0.8% were Native Hawaiian or Pacific Islander, and 0% were American Indian or Alaska Native ([Fig. 2]). Among the 16 U.S.-only trials, 38% (6/16) did not report ethnicity, and 25% (4/16) did not report racial information. Of the 62% who did report ethnicity, 13% were Hispanic or Latino, and 3% unknown.

Trials Grouped by Funding Source

Most studies (89%) were funded by industry, whereas the rest were funded by “other sources (8%) and the NIH (3%).”

Discussion

Equitable racial and ethnic representation not only in DMD clinical trials, but in medical research, improves the generalizability, cost effectiveness, innovative potential, and accrual value of research data. Beyond improving accessibility to efficacious medical interventions, equitable representation decreases health disparities and improves societal health.[8] Recent lived experiences are increasingly raising awareness regarding the importance of social drivers of health. We extended this observation to investigate racial and ethnic representation in a rare neuromuscular disease, DMD. DMD affects all races and ethnicities. Yet, disparities in the time to diagnosis and access to care have been reported in DMD.[2] [3] [4]

We were interested in evaluating whether there was equitable representation in DMD clinical trials. Our analysis from the clinicaltrials.gov database found that White participants are overwhelmingly represented in DMD phases II and III clinical trials. Not only were race and ethnicity frequently not reported, but many racial categories are amorphous catch-all terms that do not capture the multiplicity among these groups, obscuring the generalizability of clinical trial findings. It is also important to note that the suggested categories for race and ethnicity were established in the United States, which may not sufficiently capture race and/or ethnicity as defined in countries outside of the United States. The FDA is addressing this concern by expanding these categorizations with detailed grouping by geographic region, though more granular details may be added contingent on being traceable to the five minimum standard categories for race and ethnicity.[8]

Disproportionate representation of White participants illuminates the need for a more inclusive blueprint to recruit a more heterogeneous cohort into both observational and interventional trials in DMD. It also raises a multitude of questions: Is this disparate composition due to an inability to adequately provide information to these groups? What, if any, are the barriers to enrollment for these groups? What can the health care system do to improve access and enrollment for these populations?

The long-lasting effects of health disparities on children are particularly significant, given their influence on health throughout adulthood, educational success, and financial security.[9] Bodicoat et al conducted a literature review regarding barriers to inclusion and strategies to improve inclusion in clinical trials. Among the fifteen recommendations made, the three most central recommendations include improving the cultural competency and sensitivity of clinical trial staff, establishing a diverse community advisory panel, and increasing recruitment of staff from marginalized populations.[10] Another article organized an interventional framework that addresses the question of how to reduce health inequities, demonstrating that common interventions fall into four broad categories: strengthening individuals, strengthening communities, improving living and working conditions, and promoting health macro-policies.[11] Other strategies that could encourage participation are to reduce the intensity of clinical trial visits by combining in-person visits with remote assessments. Such an approach can reduce the burden of clinical trial participation while being more inclusive of participants from different racial and ethnic backgrounds. Further, participation in clinical trials in DMD can be “competitive,” with a very small number of study subjects being enrolled. This “first-come-first-enroll” may also add to inequities.

We considered some strategies to improve trial participation among non-English speaking participants. One strategy to improve the recruitment and enrollment process is to host focus groups for nonnative English speakers to ask questions and clarify logistics. Another approach may include developing translation algorithms for websites so they can be translated to other languages (i.e., translation to Spanish for clinical trials in North America).

There is a significant lack of representation of non-White study participants in DMD interventional trials. In addition, the reporting of race and ethnicity in phases II and III clinical trials is insufficient. These data warrant further investigation regarding approaches to diversify and include equitable representation in DMD clinical trials. Preliminarily proposed strategies include focus groups, translation services, and the establishment of a community advisory panel.

Conflict of Interest

Mathula Thangarajh reports receiving consultant fees from NS Pharma and Biogen.

Acknowledgments

Mathula Thangarajh acknowledges the support by VCU Wright Center for Clinical & Translation Research (CCTR) Clinical and Translational Science Award UM1TR004360, K12TR004364, NIH R21TR004007 and MDA Award Number 952826.

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Publication History

Received: 07 April 2025

Accepted: 02 July 2025

Accepted Manuscript online:
03 July 2025

Article published online:
19 August 2025