This commentary takes up Pearl's welcome challenge to clearly articulate the scientific value of principal stratification estimands that we and colleagues have investigated, in the area of randomized placebo-controlled preventive vaccine efficacy trials, especially trials of HIV vaccines. After briefly arguing that certain principal stratification estimands for studying vaccine effects on post-infection outcomes are of genuine scientific interest, the bulk of our commentary argues that the "causal effect predictiveness" (CEP) principal stratification estimand for evaluating immune biomarkers as surrogate endpoints is not of ultimate scientific interest, because it evaluates surrogacy restricted to the setting of a particular vaccine efficacy trial, but is nevertheless useful for guiding the selection of primary immune biomarker endpoints in Phase I/II vaccine trials and for facilitating assessment of transportability/bridging surrogacy.
Bibliographical noteFunding Information:
Author Notes: We thank the reviewer for extraordinarily insightful comments that led to major improvements. This research was supported by NIH NIAID grant 2 R37 AI054165-08 and NIAID HIV Vaccine Trials Network grant 5 U01 AI068635-05.
- causal inference
- principal stratification
- vaccine trial