Development of a Clinically Relevant Outcome Measure for FSHD Therapeutic Trials

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DESCRIPTION (provided by applicant): Facioscapulohumeral muscular dystrophy (FSHD) is the second most common adult muscular dystrophy. The recently discovered genetic and molecular underpinnings of FSHD suggest unique opportunities for therapeutic intervention. Meanwhile, the U.S. Food and Drug Administration (FDA) have identified validated patient reported outcome measures as an acceptable and at times preferred mechanism for determining therapeutic benefit. While novel genetic and symptomatic therapies are rapidly being developed for FSHD, trial readiness in the form of valid, responsive, FSHD-specific, patient-relevant outcomes for this disease are lacking. If FSHD clinical trial readiness is not addressed, the development and study of promising FSHD therapies and interventions will be hindered. This proposal will develop, test, and validate a disease-specific patient reported outcome measure for use in FSHD therapeutic trials. Specific Aim 1: To use data from our cross-sectional study of 328 facioscapulohumeral muscular dystrophy (FSHD) patients to develop the FSHD-Health Index, a comprehensive question set capable of detecting meaningful change in multiple areas of FSHD patients' health. Specific Aim 2: To optimize the FSHD-Health Index using qualitative interviews. Specific Aim 3: To evaluate and maximize the responsiveness of the FSHD-Health Index through a 12 month longitudinal study of FSHD patients. Specific Aim 4: To evaluate the test-retest reliability of the FSHD-Health Index and determine its ability to differentiate between FSHD cohorts with different disease severity. Future Directions: Specific Aim 5: To use the FSHD-Health Index: 1) In anticipated FSHD therapeutic trials; and, 2) As a model for the development of additional disease-specific instruments for common musculoskeletal disorders. This study will be conducted in close collaboration with The Fields Center for FSHD Research, the National Registry of FSHD patients, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), industry partners, and with FSHD clinical and basic science researchers. We anticipate that findings from this proposal will enable clinicians and investigators to incorporate a valid patient relevant endpoint in FSHD clinical trials.