Perils of randomised controlled trial survival extrapolation assuming treatment effect waning: why the distinction between marginal and conditional estimates matters

A long-term, constant, protective treatment effect is a strong assumption when extrapolating survival beyond clinical trial follow-up, hence sensitivity to treatment effect waning is commonly assessed for economic evaluations. Forcing a HR (hazard ratio) to 1 does not necessarily estimate loss of individual-level treatment effect accurately due to HR selection bias. A simulation study was designed to explore the behaviour of marginal HRs under a waning conditional (individual-level) treatment effect and demonstrate bias in forcing a marginal HR to 1 when the estimand is ‘survival difference with individual-level waning’.
Source: Value in Health - Category: International Medicine & Public Health Authors: Tags: Methodology Source Type: research