Bmc Med Res Methodol
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Bmc Med Res Methodol · May 2019
ReviewAre non-constant rates and non-proportional treatment effects accounted for in the design and analysis of randomised controlled trials? A review of current practice.
Most clinical trials with time-to-event primary outcomes are designed assuming constant event rates and proportional hazards over time. Non-constant event rates and non-proportional hazards are seen increasingly frequently in trials. The objectives of this review were firstly to identify whether non-constant event rates and time-dependent treatment effects were allowed for in sample size calculations of trials, and secondly to assess the methods used for the analysis and reporting of time-to-event outcomes including how researchers accounted for non-proportional treatment effects. ⋯ Our review confirmed that when designing trials with time-to-event primary outcomes, methodologies assuming constant event rates and proportional hazards were predominantly used despite potential efficiencies in sample size needed or power achieved using alternative methods. The Cox proportional hazards model was used almost exclusively to present inferential results, yet testing and reporting of the pivotal assumption underpinning this estimation method was lacking.