Are participants in gout medication registration clinical trials representative of people with gout in the general population?

Background: Ensuring clinical trial participants are representative of the target population is important for the generalizability of trial findings. This study aimed to determine if phase 3 clinical trials of gout medications approved by the US Food and Drug Administration (FDA) included participants representative of the US general population with gout. Methods: Gout therapeutics were identified by searching the FDA and CenterWatch websites. Data from phase 3 clinical trials of FDA approved gout medications between 2009 and 2023 were analyzed. Demographic variables (sex, age, and ethnicity) and comorbidities (hypertension, myocardial infarction, heart failure, nephrolithiasis, chronic kidney disease, BMI >= 30 kg/m2, and diabetes) were extracted and compared with published data from the 2007-2008 and 2015-2016 US National Health and Nutrition Examination Survey (NHANES). Data were pooled using a random effects model and presented as a percentage with a 95 % confidence interval. Results: Twelve phase 3 clinical trials were included, covering febuxostat, colchicine, pegloticase, lesinurad, and canakinumab. Compared to the NHANES gout population, clinical trials over-represented men, younger individuals, and White ethnicity participants. Under-representation was observed for clinical trial participants with hypertension, prior myocardial infarction, nephrolithiasis, and diabetes, while those with a BMI >= 30 kg/m2 were over-represented. Conclusions: FDA approved gout medication trials since 2009 have not enrolled a study population that is representative of the US general population with gout, particularly regarding age, ethnicity, and cardiometabolic comorbidities. For broader applicability, future phase 3 trials should ensure the greater inclusion of women, older individuals, diverse ethnicities, and those with common gout-associated comorbid conditions.