APPLICATION OF THE MEDIATION ANALYSIS APPROACH TO CANCER PREVENTION TRIALS RELATING TO CANCER SEVERITY

In a cancer prevention trial, an outcome such as cancer severity cannot be evaluated in individuals who do not develop cancer. In such a situation, the principal stratification approach has been applied. Under this approach, the Principal Strata Effect (PSE) has been considered, which is defined as the effect of treatment on the outcome among the subpopulation in which individuals would have developed cancer under either treatment arm. However, in this study, the author does not apply this approach to the situation. Instead, the author discusses the mediation analysis approach, in which Natural Direct and Indirect Effects (NDE and NIE) are considered. This approach has an advantage as it considers two possible mechanisms of treatment control of cancer severity: The first is that the treatment may prevent an individual from getting cancer, which could be regarded as control of cancer severity; the second is that even if the treatment does not prevent an individual from getting cancer, it may still impair the cancer severity. The former mechanism corresponds to the NIE and the latter corresponds to the NDE, although the PSE can consider only the latter mechanism. Methodologies proposed in the context of vaccine trials are applied to data from a randomized prostate cancer prevention trial.