Sample Size Calculations in Acute Stroke Trials: A Systematic Review of Their Reporting, Characteristics, and Relationship With Outcome

Abstract

Background and Purpose— Only a few randomized controlled trials in acute stroke have shown a treatment-related benefit. Inadequate trial design, especially low sample size, may partly explain this failure. We investigated sample size calculations (SSCs) in a systematic review of acute stroke trials. Methods— Full reports of nonconfounded randomized controlled trials that recruited patients within 1 week of stroke onset and were published before the end of 2001 were identified from the Cochrane Library and other bibliographic databases. Information on the SSC and outcome event rates was collected for each trial. Results— Of 189 identified trial reports, 57 (30%) reported ≥1 components of the SSC, phase II 14/129 (11%) versus phase III 43/60 (72%) ( P Conclusions— Too few trial publications report the assumptions underlying their SSC. Most trials were underpowered, ie, power <0.90, used inappropriate assumptions for event rates, and were grossly overoptimistic in their expectation of treatment effect. These deficiencies will together have resulted in trials being far too small and reduced their chance of being able to detect real treatment effects.