OBJECTIVES: New drug approvals decisively rely on the relative efficacy (RE) of intervention drugs versus standard of care in clinical trials. To investigate whether and how the RE is associated with baseline demographic characteristics in clinical trials.

METHODS: Two-arms, randomized controlled clinical trials (RCTs) registered on ClinicalTrials.gov from November 1999 to June 2020 were included as sample trials if both sex or race composition at baseline and overall survival (OS) hazard ratios (HRs) were reported. The primary outcome was whether the OS HR comparing the intervention arm to the control arm was smaller than 1 or not and multivariate logistic regression was used to explore its associations with sex and race. The secondary outcome was the HR itself and its associated p-value and linear regression was used to explore their associations with sex and race.

RESULTS: In this cross-sectional analysis of 590 RCTs involving 336,647 participants, all trials reported intention-to-treat (ITT) participant numbers by sex while 357 (61%) reported ITT participant numbers by race. Comparing trials with HR<1 to trials with HR≥1, 56% vs 53% participants were male, 71% vs 77% were White, 20% vs 15% were Asian, and 2.6% vs 3.5% were Black. Higher male participation (odds ratio [OR], 1.009; 95% confidence interval [CI], 0.999 to 1.019; P=0.067) and higher Asian participation (OR, 1.010; 95% CI, 0.999 to 1.022; P=0.088) were associated with an increase in the odds of HR<1 at the 10% significance level. Higher White participation (OR, 0.986; 95% CI, 0.975 to 0.998; P=0.027) and higher Black participation (OR, 0.936; 95% CI, 0.857 to 1.023; P=0.143) were associated with a decrease in the odds of HR<1.

CONCLUSIONS: The results suggest that the RE in RCTs is associated with sex and race. New drug therapy approvals may be biased when based on pivotal trials that are unrepresentative of the real-world patient population.