Choosing Appropriate Estimands in Clinical Trials

Lack of adherence to study protocol and missing data are often unavoidable in clinical trials, and both increase the need to differentiate between the ideal treatment effect if the medication is taken as directed and the treatment effect in presence of the actual adherence pattern. In this regard, estimands have become the focus of attention. An estimand is simply that which is being estimated. In the context of treatment benefit, an estimand may address either efficacy or effectiveness aspects. Defining the estimand of interest is an essential step to take before deciding on trial design and primary analysis. The choice of estimand has consequences for various other factors to be considered during any clinical trial's planning phase. This study presents a process chart including all aspects to consider during planning. After deciding on the primary estimand, the trial design should be specified, followed by the primary analysis. Both should appropriately address the chosen estimand. Finally, sensitivity analyses should be taken into account. Provided are suggestions for all the planning steps involved, especially on choosing between efficacy and effectiveness, and relevant examples from clinical practice to illustrate them. It is recommended that one bear in mind the process chart during planning of any clinical trial and give reasonable justification for each decision in the study protocol.