Objective:

This study describes the development of the Limb Girdle Muscular Dystrophy Health Index (LGMDHI), a disease-specific patient-reported outcome measure designed for therapeutic trials. 

Background:

Limb girdle muscular dystrophy (LGMD) is a group of rare muscular dystrophies caused by mutations in genes needed for muscle maintenance, repair and normal function. As therapeutic trials for LGMD take place, an objective measure of patient-reported disease burden is needed. 

Design/Methods:

Participants were recruited from three LGMD registries: Coalition to Cure Calpain-3 (https://www.curecalpain3.org/registry/), the Jain Foundation (https://dysferlinregistry.jain-foundation.org/), and the Global FKRP (https://www.fkrp-registry.org/); and from the ongoing GRASP-LGMD consortium natural history study. All participants were aged >18 years and had a diagnosis of genetically confirmed or clinically diagnosed LGMD. An initial survey was used to determine the importance and prevalence of 161 symptoms. Using survey data, expert review, factor analysis, and test-retest reliability we developed the LGMDHI.

Results:

In total, 163 individuals completed the initial survey. Following expert review, survey questions were eliminated based on a lack of perceived responsiveness to intervention (24), lack of generalizability (22), vague wording (7), unclear language (4), and redundancy (2). Subscales were created based on expert review and exploratory factor analysis. Test-retest reliability of the LGMDHI and its subscales was conducted with 32 participants. Five questions were eliminated due to a Cohen’s kappa below 0.5. Intraclass correlation coefficient (ICC) scores for the final subscales ranged from 0.61 to 0.96. The final version of the LGMDHI consists of 15 subscales and 97 questions that measure the 15 symptomatic themes of greatest importance to individuals with LGMD.

Conclusions:

The LGMDHI provides a valid and reliable outcome measure to assess patient-reported disease burden in LGMD. On behalf of the GRASP-LGMD Consortium.