A simple method for principal strata effects when the outcome has been truncated due to death

In randomized trials with follow-up, outcomes such as quality of life may be undefined for individuals who die before the follow-up is complete. In such settings, restricting analysis to those who survive can give rise to biased outcome comparisons. An alternative approach is to consider the "principal strata effect" or "survivor average causal effect" (SACE), defined as the effect of treatment on the outcome among the subpopulation that would have survived under either treatment arm. The authors describe a very simple technique that can be used to assess the SACE. They give both a sensitivity analysis technique and conditions under which a crude comparison provides a conservative estimate of the SACE. The method is illustrated using data from the ARDSnet (Acute Respiratory Distress Syndrome Network) clinical trial comparing low-volume ventilation and traditional ventilation methods for individuals with acute respiratory distress syndrome.