Demographic characteristics of participants in clinical trials to treat Alzheimer disease, 2008–2023
Year: 2023
Type: article
Abstract: Over 6.5 million Americans are estimated to live with Alzheimer disease, which disproportionately affects women and members of the Black and Hispanic communities.1 Despite the significant burden of Alzheimer disease, only recently have drugs intended to slow Alzheimer disease progression entered the market. Nonetheless, these approvals were met with controversy, reasons among which included the exclusion of older adults and low enrollment of Black participants in some pivotal trials supporting approval.2 Whether these patterns were exceptional or common among Alzheimer disease trials is unknown. To investigate potential disparities in trial participation, we characterized the demographic characteristics of participants of all completed clinical trials of drugs to treat Alzheimer disease. We performed a cross-sectional analysis of completed Phase 2–4 clinical trials of drugs to treat Alzheimer disease with start date after January 1, 2008 and primary completion date prior to March 10, 2023, when the search was conducted. Using ClinicalTrials.gov, we identified and characterized trials by phase, disease severity, indication, and size. We identified whether the trials reported results through ClinicalTrials.gov or through a publication, using a two-step process of searching PubMed for matching trials by NCT number and by trial name. We abstracted participant demographic characteristics, including mean age, sex, race, and ethnicity, from the data source with the most complete information. We calculated the participation-to-prevalence ratio (PPR), the ratio between the proportion of a demographic subgroup among trial participants to that among the patient population.3 We used previously published demographic characteristics from a 100% Medicare Fee-For-Service (FFS) population of people with Alzheimer disease to determine the denominator.4 A PPR between 0.8 and 1.2 was considered adequate representation.3 Ninety-five percent confidence intervals were calculated using t-tests. Analyses were conducted using R version 4.1.2. The study was determined to be exempt by the Duke Health Institutional Review Board. We identified 277 completed Phase 2–4 trials of 159 drugs to treat Alzheimer disease, enrolling over 80,000 patients (Table 1). Two hundred seven (74.7%) trials released results, whether through ClinicalTrials.gov or publication. Of these, 184 (88.9%) reported mean age, 202 (97.6%) reported sex, 134 (48.4%) reported race, and 67 (32.4%) reported ethnicity. The mean of mean age was 72.7 (SD 4.1). In the 202 (97.6%) studies reporting sex, men were overrepresented (mean 44.3%, PPR 1.33 [95% CI 1.27–1.38]) (Figure 1). In the 113 (54.6%) trials with complete reporting of race, Black participants were underrepresented (mean 4.8%, PPR 0.49 [95% CI 0.30–0.68]) and Asian participants were overrepresented (mean 10.0%, PPR 3.45 [95% CI 1.93–4.97]). Only 66 (31.9%) trials included complete reporting of ethnicity, with a mean of 10.7% Hispanic participants (PPR 1.39, 95% CI 0.92–1.85). When restricting to 88 trials that enrolled only in the United States, trends were similar except for the reversal of Asian representation to underrepresentation. Clinical trials of drugs to treat Alzheimer disease enrolled participants who were not representative of the Medicare Fee-For-Service population, with younger mean age, underrepresentation of Black participants, and overrepresentation of Asian participants, mirroring findings in other disease areas.5-7 Previous studies have identified potential explanatory factors including variation by demographic characteristics in recruitment sources, specific trial exclusion criteria, and overall likelihood of inclusion.8-10 These factors must continue to be addressed to ensure representative trial participation, and to close knowledge gaps that threaten to exacerbate disparities for older adults and Black adults experiencing a greater burden of disease. Study limitations include dependence on public results reporting to identify trial participant characteristics; limitations intrinsic to using Medicare claims algorithms to identify adults with Alzheimer dementia; and inability to distinguish between different stages of dementia severity. The National Institute on Aging and Food and Drug Administration have long made it a priority to enhance diversity in clinical trials, including for Alzheimer disease. Nonetheless, gaps in representativeness of participants in trials of Alzheimer disease therapeutics persist. Clinicians and patients should be aware of the ongoing need to tailor recruitment efforts for participants in trials for Alzheimer disease. All authors were responsible for the conception and design of this work. Dr. Zhang was responsible for the acquisition of data, drafted the manuscript, and performed the statistical analysis. All authors participated in the analysis and interpretation of the data and critically revised the manuscript for important intellectual content. Dr. Zhang is the guarantor. This project was supported by the National Institute on Aging though the Duke Creating ADRD Researchers for the Next Generation—Stimulating Access to Research in Residency (CARiNG-StARR) Program (R38AG065762). Dr. Zhang is also a member of the Junior Investigator Intensive Program of the US Deprescribing Research Network, which is funded by the National Institute on Aging (R24AG064025). Dr. Anderson reports additional research funding from the National Institute on Aging, American Heart Association, and US Deprescribing Research Network outside of the submitted work. The research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health. The sponsor was not involved in the design, collection, analysis, or interpretation of the data, or in the writing or submission of the manuscript for publication. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health.
DOI: 10.1111/jgs.18645
Language: English
Topic: Ethics in Clinical Research
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4388223231