Development, reliability and validity of the Charcot‐Marie‐Tooth disease Pediatric Scale (CMTPedS)

Abstract

In children with Charcot-Marie-Tooth disease (CMT), growth and development, offset by deterioration of strength and function greatly complicate measurement of disease severity, progression and response to treatment. There is a need for accurate, sensitive and disease-relevant measures of young children and adolescents with CMT to enable accurate assessment of baseline performance, monitor disease severity longitudinally, and determine responses to existing and novel interventions. The aim of this project was to develop and validate a multidimensional neuropathy scale for children with CMT, known as the CMT Pediatric Scale (CMTPedS). As part of the Inherited Neuropathies Consortium, the CMTPedS underwent a thorough development process, including: (1) definition of the construct; (2) generation of the item pool; (3) choice of scoring format; (4) peer-review (face validity); (5) pilot testing; (6) standardized training; (7) inter-rater reliability of four international centers assessing eight children with CMT; (8) multicenter implementation. Findings of the development process were: (1)the CMTPedS is a composite scale with eight domains capturing symptoms, foot and ankle involvement, hand dexterity and strength, sensation, balance, motor function; (2) a large pool of items generated from the literature were reduced based on disease-specificity, functional/patient-relevance, reliability/validity, published norms, test duration and ease of interpretation; (3) items were collapsed to 5-point Likert scales using z-scores based on age/gender and limb dominance norms; (4) quality, appropriateness and suitability of items were peer-reviewed by 23 expert clinicians/researchers/patient representatives at the 168th ENMC International Workshop; (5) pilot-tested on four children with CMT to check for administration problems, item instructions, order and duration; (6) clinicians from USA, UK, Italy and Australia trained through workshops, online manual and video resources; (7) all items exhibited good to excellent inter-rater reliability (ICC2,4 0.78-0.99); (8) a multicenter natural history study of children with all types of CMT aged 3-17 years is underway, with 110 children recruited to date. Implementation and psychometric validation of the CMTPedS continues. We plan to apply the final CMTPedS as the primary outcome in clinical trials of rehabilitative, pharmacological and surgical interventions.