Functional Loss and Mortality in Randomized Clinical Trials for Amyotrophic Lateral Sclerosis: To Combine, or Not to Combine—That is the Estimand. Issue 4 (17th February 2022)

• Record Type: Journal Article
• Authors: van Eijk, Ruben P.A.; Roes, Kit C.B.; de Greef‐van der Sandt, Inez; van den Berg, Leonard H.; Lu, Ying
• Is Part Of: Clinical pharmacology & therapeutics. Volume 111:Issue 4(2022)
• Page Start: 817
• Page End: 825
• Publication Date: 2022-02-17
• Subjects: Pharmacology -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1002/cpt.2533
• Languages: English
• ISSNs: 0009-9236

Abstract

Abstract : Amyotrophic lateral sclerosis is a rapidly progressive disease leading to death in, on average, 3–5 years after first symptom onset. Consequently, there are frequently a non‐negligible number of patients who die during the course of a clinical trial. This introduces bias in end points such as daily functioning, muscle strength, and quality of life. In this paper, we outline how the choice of strategy to handle death affects the interpretation of the trial results. We provide a general overview of the considerations, positioned in the estimand framework, and discuss the possibility that not every strategy provides a clinically relevant answer in each setting. The relevance of a strategy changes as a function of the intended trial duration, hypothesized treatment effect, and population included. It is important to consider this trade‐off at the design stage of a clinical trial, as this will clarify the exact research question that is being answered, and better guide the planning, design, and analysis of the study.