Estimands and Their Role in Clinical Trials

Abstract

ABSTRACTThe National Research Council (NRC) highlighted the need to more clearly distinguish between the target of estimation (“estimand”) and the method of estimation (“estimator”) in clinical trials. While the NRC report on “The Prevention and Treatment of Missing Data in Clinical Trials” focuses on issues arising due to missing data, a framework to coherently align trial objectives and corresponding estimands is valuable in a broader sense. The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) has reinforced this by tasking a working group to develop an addendum to the ICH-E9 guideline “Statistical Principles for Clinical Trials.” In this article, we motivate the need for change, propose a structured framework to bridge trial objectives with proper inference tools, and discuss how it may impact the role of statisticians involved in clinical trial design and analysis.