Validation of the Upper Extremity Reachable Work Space (RWS) as a clinical outcome assessment (COA) for FSHD Clinical Trials


Clinical Other

Poster Number: 22


Jay Han, MD, Gregorij Kurillo, Maya Hatch, PhD, Alina Nicorici Lewis, Vicky Chan, Craig McDonald, MD, Diego Cadavid, MD


1. UC Irvine, School of Medicine, Department of Physical Medicine and Rehabilitation, 3. University of California Irvine, 5. UC Irvine, School of Medicine, Department of Physical Medicine and Rehabilitation, 6. UC Davis, 7. Fulcrum Therapeutics

Background: FSHD is characterized by slowly progressive descending weakness and accumulation of physical disability. Patients consistently rank difficulty with the use of the shoulder and proximal arm as the most prevalent and severe impairment leading to limitations in their daily activities. However, the lack of reliable, valid, and sensitive outcome measures for the shoulder and proximal arm is a significant barrier for FSHD clinical trials.

Methods: We examined all key criteria for validity of the RWS for the context of use of measuring upper extremity functional changes in FSHD clinical trials. These included face validity, concurrent validity, criterion validity, appropriateness, acceptability, feasibility, interpretability, precision, reliability, and responsiveness.

Results: There has been extensive development of the RWS. The measure of the RWS is the relative surface area or RSA, which provides a continuous variable normalized to an individual’s arm length. It shows excellent test-retest reliability with only a mild practice effect. Multicenter studies involving over 11 international clinical sites and over 300 FSHD patients have established its feasibility, cost-effectiveness, and acceptability. The clinical meaningfulness has been established based on strong correlations with individual’s self-reported upper extremity function in the context of daily living activities. Concurrent validity has been demonstrated based on robust correlations with established clinical disability scores and impairment versus healthy controls. Initial results of longitudinal change show responsiveness to disease progression over a year.

Conclusions: The RWS is a well-studied COA that measures how patients with FSHD function. Extensive work over the last decade provides substantial evidence of validation across all major criteria. Two ongoing phase 2 clinical trials of the p38a/b inhibitor Losmapimod for treatment of FSHD at its root cause are using the RWS as COA.