Evaluation of a Health State Staging System Defined by Loss of Independence in Amyotrophic Lateral Sclerosis: Assessment in a Second Dataset

OBJECTIVE: To assess a proposed amyotrophic lateral sclerosis (ALS) health state staging system that reflects loss of independence on relevant functions of swallowing, breathing, communicating and walking/self-care. BACKGROUND: Prognosis in ALS is receiving increased attention with multiple proposals to provide a clearly defined, discrete, and mutually exclusive health state staging system reflecting the clinical progression of ALS. A co-operative international working group has been established to facilitate these efforts and develop general principles for ALS staging systems. DESIGN/METHODS: We evaluated one proposed staging system that relies upon ALS Functional Rating Scale (ALSFRS) changes in 4 key domains: swallowing, walking/self-care, communicating, and breathing. Impaired functions in each domain were determined by specific ALSFRS item score thresholds. Stages were defined by the number of domains lost (stratified by domain): Stage 0 – functional involvement but no loss of independence on any domain; Stages 1-4 – independence lost in 1-4 domains; Stage 5 – death. We applied this system to data from a randomized ALS creatine study and fit linear mixed models to determine mean trajectories of SF-36 functional health domains by ALS stage. RESULTS: Data from all 175 participants were analyzed. The mean age of ALS onset was 56.3 years (SD=11.1), 67.4% males with mean follow-up of 13.5 months (SD=6.4). At baseline, the distribution of ALS staging was stage 0 (n=108), 1 (n=45), or 2 (n=22). The mean total SF-36 score decreased (p CONCLUSIONS: This proposed ALS staging approach partitions patients into potentially relevant progression stages, associated with decline in health-related quality of life and an increased risk of death. Independent validation is required to ascertain whether ALS disease progression is appropriately defined to allow the evaluation of therapeutics9 effects on different ALS health states. Supported by: Biogen Idec, Inc. Disclosure: Dr. Hammond has nothing to disclose. Dr. Young has received personal compensation for activities with Biogen Idec, Novartis, Schering, and Teva Neuroscience. Dr. Chio has received personal compensation for activities with Biogen Idec and Cytokinetics. Dr. Van den Berg has received personal compensation for activities with Baxter, Biogen Idec and Cytokinetics as a consultant and/or participant on an advisory board. Dr. Al-Chalabi has received personal compensation for activities with Biogen Idec and Cytokinetics Inc as a consultant. Dr. Al-Chalabi receives research support from MNDA, ALS Association and ALS Therapy Alliance. Dr. Berry has received personal compensation for activities with Biogen Idec and Oakstone Publishing. Dr. Berry has received research support from the Muscular Dystrophy Association and ALS Therapy Alliance. Dr. Brooks has received personal compensation for activities with Biogen Idec, Avanir Pharmaceuticals, Acorda Therapeutics, Cytokinetics, Synapse, and the National Institute of Neurological Disorders and Stroke. Dr. Brooks has received research support from Biogen Idec, Avanir Pharmaceuticals, Cytokinetics, Neuraltus, GlaxoSmithKline, Inc., and the National Institute of Neurological Disorders and Stroke. Dr. Shefner has received personal compensation for activities with Biogen-Idec and Glaxo SmithKline as a member of the advisory boards, and from Cytokinetics, Inc as a consultant. Dr. Shefner has received personal compensation in an editorial capacity for the Neuromuscular Section Editor of UpToDate. Dr. Shefner has received research funding from NIH, the ALS Association, the ALS Therapy Alliance, MDA, Glaxo Smith Kline, Isis Pharmaceuticals, Biogen-Idec, Cytokinetics, Inc., and Sanofi Pharmaceuticals. Dr. Turner has received personal compensation for activities with Biogen Idec. Dr. Williams has received personal compensation for activities with Biogen Idec as an employee. Dr. Williams holds stock and/or stock options in Biogen Idec. Dr. Li has received personal compensation for activities with Biogen Idec as an employee. Dr. Kerr has received personal compensation for activities with Biogen Idec as an employee and holds stock options in Biogen.