Handling rescue therapy in myasthenia gravis clinical trials: why it matters and why you should care

TL;DR

This paper explains how to properly handle rescue therapy in myasthenia gravis trials to avoid misleading results and improve patient care.

Contribution

The paper introduces strategies aligned with ICH guidelines for defining treatment effects in MG trials involving rescue therapy.

Findings

Failure to address rescue therapy can bias estimates and increase false positives in MG trials.

Strategies based on the estimand framework can rigorously define treatment effects in MG trials.

Statistical methods for estimating treatment effects are outlined for different rescue therapy scenarios.

Abstract

Myasthenia gravis (MG) clinical trials typically allow rescue therapy during follow‐up in the event of marked worsening of MG symptoms. Failure to appropriately address rescue therapy in defining treatment effects and planning statistical analyses may yield biased estimates, increase false positive rates, or decrease statistical power – all of which increase the risk that inaccurate information influences patient care. In alignment with recent International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines, we review strategies based on the estimand framework that produce rigorously defined treatment effects in MG trials where rescue therapy may be administered. We also discuss the interpretation, clinical relevance, and pitfalls of each strategy in the context of MG trials, suggesting circumstances in which a strategy would or would not be appropriate. Finally, we outline available statistical methods for estimating treatment effects based on each strategy. As primary endpoints and statistical analyses for trials must be defined prior to conducting the study, it is necessary to consider how to address rescue therapy during study planning.

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