Rethinking Composite End Points in Clinical Trials: Insights From Patients and Trialists

BACKGROUND—Many clinical trials use composite end points to reduce sample size, but the relative importance of each individual end point within the composite may differ between patients and researchers. METHODS AND RESULTS—We asked 785 cardiovascular patients and 164 clinical trial authors to assign 25 “spending weights” across 5 common adverse events comprising composite end points in cardiovascular trialsdeath, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. We then calculated end point ratios for each participant’s ratings of each nonfatal end point relative to death. Whereas patients assigned an average weight of 5 to death, equal or greater weight was assigned to myocardial infarction (mean ratio, 1.12) and stroke (ratio, 1.08). In contrast, clinical trialists were much more concerned about death (average weight, 8) than myocardial infarction (ratio, 0.63) or stroke (ratio, 0.53). Both patients and trialists considered revascularization (ratio, 0.48 and 0.20, respectively) and hospitalization (ratio, 0.28 and 0.13, respectively) as substantially less severe than death. Differences between patient and trialist end point weights persisted after adjustment for demographic and clinical characteristics (P