CONGENITAL MYOPATHIES (CNM): P.138The CHOP INTEND scale (Children's Hospital of Philadelphia infant test of neuromuscular disorders) in X-linked myotubular myopathy: content validity and psychometric performance

Abstract

XLMTM is a rare, congenital neuromuscular disorder characterized by extreme hypotonia, respiratory failure, and premature death. The CHOP INTEND is a measurement tool developed to assess motor function in patients with spinal muscular atrophy type I (SMAI), and successfully used in clinical trials to assess treatment response. As SMA I patients have a similar phenotype to infants with XLMTM, this study evaluated the CHOP INTEND as a measure of motor function in children with XLMTM. A literature review and qualitative interviews were completed (11 clinical experts, 5 caregivers); findings were used to determine content validity and develop a conceptual model of XLMTM, which were also assessed in a Delphi panel (7 clinical experts). Inter-rater reliability was evaluated among 15 physical therapists, with agreement between the ratings assessed based on independent review of videotaped assessments. The conceptual model of XLMTM includes body function and structural impairments (neuromuscular, pulmonary, musculoskeletal, gastrointestinal), as well as disease impacts (development skills, activities of daily living, caregiver burden). Concepts related to motor function map to most CHOP INTEND items. Caregiver descriptions of their child's function also align with items evaluated in the CHOP INTEND. The Delphi panel achieved consensus on the conceptual model of XLMTM and the appropriateness of the CHOP INTEND to assess motor function in XLMTM. Finally, the inter-rater reliability was supported with an intraclass correlation coefficient of 0.938 (95% CI: .902-.965). Results from this study suggest that the CHOP INTEND is a valid and reliable assessment tool for children with XLMTM, and support the appropriateness of its use in the ASPIRO gene therapy clinical trial as a co-primary endpoint. Next steps include evaluation of the psychometric performance of the CHOP INTEND in this population.