Crossover and survival

CROSSOVER AND SURVIVAL

DSU Report
Assessing methods for dealing with treatment switching in randomised clinical trials (July 2010)

Related publication
J Morden, P Lambert, N Latimer, K Abrams, A Wailoo. Assessing methods for dealing with treatment switching in randomised clinical trials: A simulation study
BMC Medical Research Methodology 2011; Vol 11:4

Background:
We investigat methods used to analyse the results of clinical trials with survival outcomes in which some patients switch from their allocated treatment to another trial treatment. These include simple methods which are commonly used in medical literature and may be subject to selection bias if patients switching are not typical of the population as a whole. Methods which attempt to adjust the estimated treatment e ffect, either through adjustment to the hazard ratio or accelerated failure time models, are also considered. A simulation study was conducted to assess the performance of each method in a number of di fferent scenarios.

Results: 16 di fferent scenarios were identi ed which di ffered by the proportion of patients switching, underlying prognosis of switchers and size of true treatment effect. 1000 datasets were simulated for each of these and all methods applied. Selection bias was observed in naive methods when the diff erence in survival between switchers and non-switchers was large. A number of methods, particularly the AFT method of Branson and Whitehead were found to give less biased estimates of the true treatment eff ect in these situations.

Conclusions: Simple methods are often not appropriate to deal with treatment switching. Alternative methods such as the Branson & Whitehead method to adjust for switching should be considered.


Note: a technical support document (TSD) is currently in progress (expected publication Spring 2014) building on research carried out since this report was published.