Estimating effects when outcomes are truncated by death

A common situation arises when one wants to estimate the effect of a treatment or exposure at some time point t in an observational cohort or randomised trial. For example, what is the mean difference in some outcome Y at time t between the two groups of interest. To make things a bit simpler, let’s suppose that subjects were allocated to the two groups (e.g. two treatments A and B) randomly, as in a randomised trial. Now suppose that some of the subjects die before time t, such that their outcome Y is not observed. Then we can no longer compare Y between the two groups in all subjects, because some values of Y are missing, or truncated by death.

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Matching analysis to design: stratified randomization in trials

Yesterday I was re-reading the recent nice articles by Brennan Kahan and Tim Morris on how to analyse trials which use stratified randomization. Stratified randomization is commonly used in trials, and involves randomizing in a certain way to ensure that the treatments are assigned in a balanced way within strata defined by chosen baseline covariates.

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Combining bootstrapping with multiple imputation

Multiple imputation (MI) is a popular approach to handling missing data. In the final part of MI, inferences for parameter estimates are made based on simple rules developed by Rubin. These rules rely on the analyst having a calculable standard error for their parameter estimate for each imputed dataset. This is fine for standard analyses, e.g. regression models fitted by maximum likelihood, where standard errors based on asymptotic theory are easily calculated. However, for many analyses analytic standard errors are not available, or are prohibitive to find by analytical methods. For such methods, if there were no missing data, an attractive approach for finding standard errors and confidence intervals is the method of bootstrapping. However, if one is using MI to handle missing data, and would ordinarily use bootstrapping to find standard errors / confidence intervals, how should these be combined?

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