Variance estimation for reference-based multiple imputation – the debate continues

Reference-based imputation methods have become a popular approach to handling missing data in clinical trials after patients experience what is nowadays referred to as an intercurrent event. Roughly speaking, these approaches impute such missing data in one treatment group (e.g. those in the active treatment group) based to some extent on estimates of parameters from another treatment group (e.g. the control treatment group). The approach was proposed in a paper by my colleague James Carpenter and others in 2013.

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