Estimation of intervention effects using first or multiple episodes in clinical trials: The Andersen-Gill model re-examined

Abstract

Randomized trials of interventions against infectious diseases are often analyzed using data on first or only episodes of disease, even when subsequent episodes have been recorded. It is often said that the Andersen-Gill (AG) model gives a biased estimate of intervention effect if there is event dependency over time. We demonstrate that, in the presence of event dependency, an effective intervention may have an indirect effect on disease risk at time tj via its direct effect on disease risk at time ti, i