PUTTING TRIALS ON TRIAL - THE COSTS AND CONSEQUENCES OF SMALL TRIALS IN DEPRESSION - A SYSTEMATIC REVIEW OF METHODOLOGY

Study objective-To determine why, despite 122 randomised controlled tr ials, there is no consensus about whether the selective serotonin reup take inhibitors or tricyclic and related antidepressants should be use d as first line treatment of depression. Design-Systematic review of a ll RCTs comparing selective serotonin reuptake inhibitors and tricycli c or heterocyclic antidepressants. Main results-The shortcomings ident ified in the 122 trials were as follows: (1) there was inadequate desc ription of randomisation, (2) the outcomes used were mainly observer r ated measurements of depression, and studies failed to use quality of life measures or perform economic evaluations, (3) doses of tricyclic antidepressants were inadequate, (4) generalisability of studies was p oor (including a reliance on secondary care settings and inadequate fo llow up), and (5) there were statistical shortcomings such as low stat istical power, failure to use intention to treat analyses, and the ten dency to make multiple comparisons. Conclusions-Future RCTs should be designed to inform policy makers and address these methodological shor tcomings.