The Limb Girdle Muscular Dystrophy Health Index (LGMD-HI).

Limb girdle muscular dystrophy (LGMD) is a debilitating disease and the fourth most common muscular dystrophy. This study describes the development of the LGMD-Health Index (LGMD-HI). Participants were aged >18 years and recruited from three LGMD registries and GRASP-LGMD consortium. The initial instrument, comprised of 16 thematic subscales and 161 items, underwent expert review resulting in item removal as well as confirmatory factor analysis followed by inter-rater reliability and internal consistency of the subscales. Following expert review, one subscale and 59 items were eliminated. Inter-rater reliability was assessed and five items were removed due to Cohen's kappa <0.5. The final subscales had high internal consistencies with an average Cronbach alpha of 0.92. Test re-test reliability of the final instrument was high (intraclass correlation coefficient=0.97). Known groups validity testing showed a statistically significant difference in LGMD-HI scores amongst subjects based on ambulation status (28.7 vs 50.0, p < 0.0001), but not sex, employment status, or genetic subtype. The final instrument is comprised of 15 subscales and 97 items. The LGMD-HI is a disease-specific, patient-reported outcome measure designed in compliance with published FDA guidelines. This instrument is capable of measuring burden of disease with no significant variation based on LGMD subtype.
Competing Interests: Declaration of competing interest Chad Heatwole receives royalties for the use of multiple disease specific instruments. He has provided consultation to Biogen Idec, Ionis Pharmaceuticals, aTyr Pharma, AMO Pharma, Acceleron Pharma, Cytokinetics, Expansion Therapeutics, Harmony Biosciences, Regeneron Pharmaceuticals, Astellas Pharmaceuticals, AveXis, Recursion Pharmaceuticals, IRIS Medicine, Inc., Takeda Pharmaceutical Company, Scholar Rock, Avidity Biosciences, Novartis Pharmaceuticals Corporation, SwanBio Therapeutics, Neurocrine Biosciences, Sanofi, Lupin Pharmaceuticals, Vertex, and the Marigold Foundation. He receives grant support from the Department of Defense, Duchenne UK, Parent Project Muscular Dystrophy, Recursion Pharmaceuticals, Swan Bio Therapeutics, the National Institute of Neurological Disorders and Stroke, the Muscular Dystrophy Association, the Friedreich's Ataxia Research Alliance, Cure Spinal Muscular Atrophy, the Amyotrophic Lateral Sclerosis Association, and the Michael J. Foxx Foundation. He is the director of the University of Rochester's Center for Health and Technology. Nicholas Johnson has received grant funding from NINDS (4K23NS091511; R01NS104010), CDC (DD19-002) and the FDA (7R01FD006071-02). He receives royalties from the CCMDHI and the CMTHI. He receives research funds from Dyne, AveXis, CSL Behring, Vertex Pharmaceuticals, Fulcrum Therapeutics, ML Bio, Sarepta, and Acceleron Pharma. He has provided consultation for AveXis, AMO Pharma, Strongbridge BioPharma, Acceleron Pharma, Fulcrum Therapeutics, Dyne, Avidity, Arthex, and Vertex Pharmaceuticals. He receives licensing fees from the University of Rochester for the CCMDHI and CMTHI. He has received stock options from ML Bio.
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