Endpoint selection and relative (versus absolute) risk reporting in published medication trials.

BACKGROUND

The use of surrogate and composite endpoints, disease-specific mortality as an endpoint, and relative (rather than absolute) risk reporting in clinical trials may produce results that are misleading or difficult to interpret.

OBJECTIVE

To describe the prevalence of these endpoints and of relative risk reporting in medication trials. DESIGN AND MAIN MEASURES: We analyzed all randomized medication trials published in the six highest impact general medicine journals between June 1, 2008 and September 30, 2010 and determined the percentage using these endpoints and the percentage reporting results in the abstract exclusively in relative terms.

KEY RESULTS

We identified 316 medication trials, of which 116 (37%) used a surrogate primary endpoint and 106 (34%) used a composite primary endpoint. Among 118 trials in which the primary endpoint involved mortality, 32 (27%) used disease-specific mortality rather than all-cause mortality. Among 157 trials with positive results, 69 (44%) reported these results in the abstract exclusively in relative terms. Trials using surrogate endpoints and disease-specific mortality as an endpoint were more likely to be exclusively commercially funded (45% vs. 29%, difference 15% [95% CI 5%-26%], P = 0.004, and 39% vs. 16%, difference 22% [95% CI 6%-37%], P = 0.007, respectively). Trials using surrogate endpoints were more likely to report positive results (66% vs. 49%, difference 17% [95% CI 5%-28%], P = 0.006) while those using mortality endpoints were less likely to be positive (46% vs. 62%, difference -16% [95% CI -27%--4%], P = 0.01).

CONCLUSIONS

The use of surrogate and composite endpoints, endpoints involving disease-specific mortality, and relative risk reporting is common. Articles should highlight the limitations of these endpoints and should report results in absolute terms.