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 trials, there is no consensus about whether the selective serotonin reuptake inhibitors or tricyclic and related antidepressants should be used as first line treatment of depression. DESIGN Systematic review of all RCTs comparing selective serotonin reuptake inhibitors and tricyclic or heterocyclic antidepressants. MAIN RESULTS The shortcomings identified in the 122 trials were as follows: (1) there was inadequate description of randomisation, (2) the outcomes used were mainly observer rated 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 poor (including a reliance on secondary care settings and inadequate follow up), and (5) there were statistical shortcomings such as low statistical power, failure to use intention to treat analyses, and the tendency to make multiple comparisons. CONCLUSIONS Future RCTs should be designed to inform policy makers and address these methodological shortcomings.