Inclusion of unexposed subjects improves the precision and power of self-controlled case series method

J Biopharm Stat. 2022 Mar;32(2):277-286. doi: 10.1080/10543406.2021.1998099. Epub 2021 Nov 15.

Abstract

The self-controlled case series is an important method in the studies of the safety of biopharmaceutical products. It uses the conditional Poisson model to make comparison within persons. In models without adjustment for age (or other time-varying covariates), cases who are never exposed to the product do not contribute any information to the estimation. We provide analytic proof and simulation results that the inclusion of unexposed cases in the conditional Poisson model with age adjustment reduces the asymptotic variance of the estimator of the exposure effect and increases power. We re-analysed a vaccine safety dataset to illustrate.

Keywords: Asymptotic variance; conditional Poisson model; drug safety; self-controlled case series; vaccine safety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Humans
  • Research Design*
  • Time Factors