Sex differences in perceived risks, distrust, and willingness to participate in clinical trials: a randomized study of cardiovascular prevention trials.

BACKGROUND Multiple sex differences exist in cardiovascular disease burden and treatment efficacies; adequate participation of both sexes is crucial to clinical research. METHODS A multicenter, double-blind, randomized study evaluated sex and trial scenarios on willingness to participate (WTP) in cardiovascular prevention trials and examined sex differences in perceived risks and distrust. Hypothetical trial scenarios randomized multifactorial vignettes of adverse effects, trial durations, sponsors, financial incentives, and conflicts of interest. RESULTS With 783 participants across 13 clinical centers, women showed lower distrust of medical researchers, perceived greater risk of myocardial infarction, and perceived greater risk of harm from trial participation than men. Men had 15% greater WTP than women (33.1% vs 28.7%; relative risk [RR], 1.15; 95% confidence interval [CI], 1.02-1.31); adjusting for explanatory mediators, we found that sex differences in perceived risks and benefits explained the sex gap in WTP. Although greater perceived probability of harm (RR, 0.41; 95% CI, 0.23-0.72), health benefit (RR, 2.99; 95% CI, 1.63-5.46), and quality of care (RR, 1.71; 95% CI, 1.12-2.61) strongly predicted WTP (for perceived probabilities >or=80% vs <20%) similarly in both sexes, and perceptions of distrust and myocardial infarction risk predicted WTP differently between sexes (P<or=.01 for interactions), age, history of coronary artery disease, hypertension, and diabetes mellitus increased WTP in men but not in women (P<or=.05 for sex interactions). Compared with no financial conflict, disclosure of investigator patent ownership increased WTP in women, while it decreased WTP in men (P=.02 for sex interaction). Monetary incentives were overall more effective on WTP in women (P=.03 for sex interaction). CONCLUSIONS In this multicenter study, women perceived greater risk of harm and myocardial infarction and showed lower WTP in cardiovascular prevention trials. Evidence underscores the importance of sex in influencing clinical trial enrollment.