Keywords: estimands, causal inference, ICH E9 addendum
Defining the estimand of interest in a clinical trial is crucial to align its planning, design, conduct, analysis, and interpretation. The need for more precise specifications of estimands was highlighted by the Steering Committee of the International Council for Harmonization (ICH) in 2014, which endorsed a Concept Paper with the goal of developing a new regulatory guidance, suggested to be an addendum to ICH guideline E9.
The estimand discussions have highlighted that some established paradigms in the pharmaceutical industry, at least when it comes to the statistical concepts and principles, may need to be adapted and expanded in line with the scientific questions that are of interest to patients, prescribers, regulators, payers, and the sponsors. We will use two case studies to illustrate the benefits of the estimand framework in facilitating the specification of the scientific question. Moreover, we will touch upon associated statistical methods and the required assumptions.