Refining clinical trial inclusion criteria to optimize the standardized response mean of the CMTPedS.

Kayla M D Cornett,Trupti Bhandari,Manoj P Menezes,Tim Estilow,Sabrina W Yum,Emanuela Pagliano,Richard S Finkel,Matilde Laura,David N Herrmann,Rosemary R Shy,Joshua Burns,Paula Bray,Isabella Moroni,Katy J Eichinger,Michael E Shy,Francesco Muntoni,Davide Pareyson,Mary M Reilly

doi:10.1002/acn3.51145

Abstract

The CMT Pediatric Scale (CMTPedS) is a reliable, valid, and responsive clinical outcome measure of disability in children with CMT. The aim of this study was to identify the most responsive patient subset(s), based on the standardized response mean (SRM), to optimize the CMTPedS as a primary outcome measure for upcoming clinical trials. Analysis was based on a 2‐year natural history data from 187 children aged 3–20 years with a range of CMT genetic subtypes. Subsets based on age (3–8 years), disability level (CMTPedS score 0–14), and CMT type (CMT1A) increased the SRM of the CMTPedS considerably. Refining the inclusion criteria in clinical trials to younger, mildly affected cases of CMT1A optimizes the responsiveness of the CMTPedS.

Highlights

The CMT Pediatric Scale (CMTPedS) is a reliable, valid, and sensitive clinical outcome measure of disease severity in children and adolescents aged 3–20 years.[1]
Recent natural history data shows significant progression over 2 years at a rate of 2.4 Æ 4.9 (14%) for all genetic subtypes of CMT (P < 0.001) and 1.8 Æ 4.2 (12%) for CMT1A (P < 0.001).[2]. This rate of progression was significant, due to the slowly progressive nature and phenotypic variability[3] of CMT there is value determining if there are subsets of patients that are more responsive on the CMTPedS to maximize power, and reduce sample size, in clinical trials by refining the inclusion criteria
The importance of early intervention has been shown in other progressive neuromuscular conditions such as Spinal Muscular Atrophy where intervening early and even presymptomatically has the best results.[7,8]

Summary

Introduction

The CMT Pediatric Scale (CMTPedS) is a reliable, valid, and sensitive clinical outcome measure of disease severity in children and adolescents aged 3–20 years.[1]. An SRM >0.8 is considered to indicate large responsiveness, 0.5–0.8 moderate, and 0.2–

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