Equity in clinical trials for HIV-associated cryptococcal meningitis: A systematic review of global representation and inclusion of patients and researchers.

Background: It is essential that clinical trial participants are representative of the population under investigation. Using HIV-associated cryptococcal meningitis (CM) as a case study, we conducted a systematic review of clinical trials to determine how inclusive and representative they were both in terms of the affected population and the involvement of local investigators. Methods: We searched Medline, EMBASE, Cochrane, Africa-Wide, CINAHL Plus, and Web of Science. Data were extracted for 5 domains: study location and design, screening, participants, researchers, and funders. Data were summarised and compared over 3 time periods: pre-antiretroviral therapy (ART) (pre-2000), early ART (2000 to 2009), and established ART (post-2010) using chi-squared and chi-squared for trend. Comparisons were made with global disease burden estimates and a composite reference derived from observational studies. Results: Thirty-nine trials published between 1990 and 2019 were included. Earlier studies were predominantly conducted in high-income countries (HICs) and recent studies in low- and middle-income countries (LMICs). Most recent studies occurred in high CM incidence countries, but some highly affected countries have not hosted trials. The sex and ART status of participants matched those of the general CM population. Patients with reduced consciousness and those suffering a CM relapse were underrepresented. Authorship had poor representation of women (29% of all authors), particularly as first and final authors. Compared to trials conducted in HICs, trials conducted in LMICs were more likely to include female authors (32% versus 20% p = 0.014) but less likely to have authors resident in (75% versus 100%, p < 0.001) or nationals (61% versus 93%, p < 0.001) of the trial location. Conclusions: There has been a marked shift in CM trials over the course of the HIV epidemic. Trials are primarily performed in locations and populations that reflect the burden of disease, but severe and relapse cases are underrepresented. Most CM trials now take place in LMICs, but the research is primarily funded and led by individuals and institutions from HICs. Author summary: It is essential that clinical trial participants are representative of the population under investigation. Similarly, research must meaningfully include researchers who are from and/or based in the location where the study is being conducted, both to ensure that the research matches the local need but also to promote equity in research. Using clinical trials in HIV-associated cryptococcal meningitis as a case study, we conducted a systematic review to determine how inclusive and representative trials have been across the course of the HIV epidemic. We identified 39 studies. There was a geographical shift with trials moving from the USA to Africa and Asia over time. We found that recent trials were conducted in areas heavily affected by cryptococcal meningitis, but we did identify geographical areas and patient groups that have been underrepresented. We also found inequality within authorship that was skewed towards male researchers from high-income countries. These findings outline areas for our discipline to focus on. We can also use this study as a benchmark from which to monitor our progress over time. This is a broad methodology that could be adopted and adapted by other research groups. [ABSTRACT FROM AUTHOR]