Abstract:

OBJECTIVE: Multiple outcomes are commonly analyzed in randomized trials. Interpretation of the results of trials with many outcomes is not always straightforward. We characterize the prevalence and factors associated with multiple outcomes in reports of clinical trials of depression, methods used to account for these outcomes, and concordance between published analyses and original protocol specifications. METHODS: A PubMed search for randomized controlled depression trials that included multiple outcomes published between January 2007 and October 2008 in 6 medical journals. Original study protocols were reviewed where available. Parallel data collection by 2 abstractors was used to determine trial registration information, the number of outcomes, and analytical method. RESULTS: Of the 55 included trials, nearly half of the papers reported more than 1 primary outcome, while almost all (90.9%, n = 50) reported more than 2 combined primary or secondary outcomes. Relatively few of the studies (5.8%, n = 3) adjusted for multiple outcomes. While most studies had published protocols in clinical trial registries (76.4%, n = 42), many did not specify outcomes in the protocol (n = 11) and a number had discrepancies with the published report. CONCLUSIONS: Multiple outcomes are prevalent in randomized controlled depression trials and appropriate statistical analyses to account for these methods are rarely used. Not all studies filed protocols, and there were discrepancies between these protocols and published reports. These issues complicate interpretability of trial results, and in some cases may lead to spurious conclusions. Promulgation of guidelines to improve analysis and reporting of multiple outcomes is warranted.