Abstract
When one arm in a trial has a worse early endpoint such as recurrence, a data‐monitoring committee might recommend that all participants are offered the apparently superior treatment. The resultant crossover makes it difficult to measure differences between arms thereafter, including for longer‐term endpoints such as mortality and disease‐specific mortality. In this paper, we consider estimators of the efficacy of treatment on those who would not cross over if randomised to the apparently inferior arm. Binomial and proportional hazards maximum likelihood estimators are developed. The binomial estimator is applied to analysis of a breast cancer treatment trial and compared with intention‐to‐treat and inverse probability weighting estimators. Full and partial likelihood proportional‐hazard model estimators are assessed through computer simulations, where they had similar bias and variance. The new efficacy estimators extend those for all‐or‐none compliance to this important problem. © 2017 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd
Highlights
Unplanned crossover occurs in randomised trials when participants decide to switch treatment arms
Equivalent versions of A3 and A4 have been used by all-or-none compliance estimators [7]
The binomial model extends straightforwardly to an exponential model, but a proportional-hazards model is more flexible, and so we focus on it
Summary
Unplanned crossover occurs in randomised trials when participants decide to switch treatment arms. We consider trials with selective crossover in one arm arising due to results from early efficacy endpoints, such as when initial results from a trial or other concurrent trials lead a data-monitoring committee to recommend that all participants are offered the apparently superior treatment The traditional inferential method for a trial with selective crossover is an intention-to-treat (ITT) analysis This maintains the randomised balance of all causal factors other than the treatment, but it is likely to attenuate the estimated effect of treatment, because some participants in the control arm receive the intervention.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
