Responsiveness of clinical outcome measures in Charcot-Marie-Tooth disease

Background and purpose: Charcot-Marie-Tooth disease (CMT) is a veryslowly progressive neuropathy which makes it difficult to detect diseaseprogression over time and to assess intervention efficacy. Experience fromcompleted clinical trials with ascorbic acid and natural history studies confirmdifficulties in detecting such changes. Consequently, sensitive-to-change out-come measures (OMs) are urgently needed.Methods: The relative responsiveness of clinical scales of the ItalianUKascorbic acid trial (placebo arm) were assessed by using the standardizedresponse mean (SRM), which is the ratio of the paired scores mean changeover time to the standard deviation of the score change (0 is worst responsive-ness).Results: Little worsening of OM scores was found over 2 years. In detail, theprimary OM of the trial, the CMT Neuropathy Score version 1 (CMTNSv1),showed low responsiveness (SRM 0.13). Some CMTNS items showed slightlygreater responsiveness (CMT Examination Score 0.17; CMTNS Signs 0.19).Myometric assessments of handgrip and foot dorsiflexion strength were themost responsive (SRM 0.31 and 0.38, respectively). Amongst the othermeasures, the nine-hole peg test, which assesses upper limb functioning,showed the best sensitivity to change (SRM 0.28).Conclusions: Overall these OMs showed low or negligible responsiveness,confirming the need to improve current OMs and to develop novel ones forprognostic and interventional studies. However, handgrip and foot dorsiflexionmyometry are worth retaining for future trials as they were the most respon-sive and are likely to be clinically relevant for patients.