Sensitivity analysis for principal stratum direct effects, with an application to a study of physical activity and coronary heart disease.

SUMMARY: In many studies, the aim is to learn about the direct exposure effect, that is, the effect not mediated through an intermediate variable. For example, in circulation disease studies it may be of interest to assess whether a suitable level of physical activity can prevent disease, even if it fails to prevent obesity. It is well known that stratification on the intermediate may introduce a so-called posttreatment selection bias. To handle this problem, we use the framework of principal stratification (Frangakis and Rubin, 2002, Biometrics 58, 21-29) to define a causally relevant estimand--the principal stratum direct effect (PSDE). The PSDE is not identified in our setting. We propose a method of sensitivity analysis that yields a range of plausible values for the causal estimand. We compare our work to similar methods proposed in the literature for handling the related problem of "truncation by death."