The amyotrophic lateral sclerosis-health index (ALS-HI): development and evaluation of a novel outcome measure

Abstract

Objective: The identification of effective therapeutics for ALS necessitates valid and responsive outcome measures to track disease progression and therapeutic gain in clinical trial settings. The Amyotrophic Lateral Sclerosis-Health Index (ALS-HI) is a multifaceted, disease-specific patient-reported outcome measure (PRO) designed to measure ALS symptomatic disease burden in adults with ALS. Methods: Through a national cross-sectional study of individuals with ALS, we identified the most important symptoms in ALS. These symptoms were incorporated into the ALS-HI, a measure that quantifies the multifaceted disease burden in ALS. We performed factor analysis, qualitative patient interviews, test-retest reliability assessment, and known groups analysis to evaluate and validate the ALS-HI. Results: The cross-sectional study included 497 participants with ALS who identified the most important symptoms to include in the ALS-HI. Fifteen participants beta tested the ALS-HI and found it to be clear, easy to use, and relevant. Twenty-one participants engaged in a test-retest reliability study, which indicated the reliability of the instrument (intraclass correlation coefficient = 0.952 for full instrument). The final ALS-HI and its subscales demonstrated a high internal consistency (Cronbach’s α = 0.981 for full instrument) and an ability to differentiate between groups with dissimilar disease severity. Conclusions: This research supports use of the ALS-HI as a valid, sensitive, reliable, and relevant PRO to assess the multifactorial disease burden faced by adults with ALS. The ALS-HI has potential as a mechanism to track disease progression and treatment efficacy during therapeutic trials.

Keywords:

• Amyotrophic lateral sclerosis
• patient-reported outcome measure
• disease burden
• symptom assessment
• therapeutic trial

Acknowledgements

The authors thank the patients who participated in the various stages of this research. The authors acknowledge Sumaira Hussain, BSc (University of Miami Miller School of Medicine, Department of Neurology, Miami, FL) for assistance with patient recruitment through the CReATe Consortium.

Declaration of interest

Christine Zizzi has provided consultation to Recursion Pharmaceuticals. Joanne Wuu reports grants from the National Institutes of Health. Richard Bedlack receives research support from the Amyotrophic Lateral Sclerosis Association, Orion, MediciNova, and Healey Center. He has provided consultation to AB Science, Alexion, the Amyotrophic Lateral Sclerosis Association, Amylyx, Apellis, Biogen, Black Swan, Brainstorm Cell, Corcept, Cytokinetics, GenieUs, Guidepoint, ITF Pharma, Mallinkrodt, New Biotic, PTC, Orphazyme, Shinkei, and Woolsey Pharma. Volkan Granit has provided consultation to Amylyx Pharmaceuticals. He is an employee of Biohaven Pharmaceuticals. Michael Benatar reports remuneration for ad hoc consulting for Alector, Annexon, Arrowhead, Biogen, Novartis, Orphazyme and UniQure. He serves as the global academic lead for the ATLAS study (Biogen). The University of Miami has licensed intellectual property to Biogen for the design of the ATLAS study. He reports grants from the ALS Association, the Muscular Dystrophy Association, and the National Institutes of Health. He has a provisional patent pending (Determining Onset of Amyotrophic Lateral Sclerosis), and he serves as a member of the Board of Trustees for the ALS Association. 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, and the Marigold Foundation. He receives grant support from the Department of Defense, Duchenne UK, Parent Project Muscular Dystrophy, Recursion Pharmaceuticals, SwanBio Therapeutics, the National Institute of Neurological Disorders and Stroke, the Muscular Dystrophy Association, the Friedreich’s Ataxia Research Alliance, Cure Spinal Muscular Atrophy, and the Amyotrophic Lateral Sclerosis Association. He is the director of the University of Rochester’s Center for Health and Technology. All other authors have no conflicts of interest to declare.

Disclaimer

This work was funded by a grant from the ALS Association and was conducted in collaboration with CReATe Consortium and the Centers for Disease Control and Prevention (CDC)/Agency for Toxic Substances and Disease Registry (ATSDR). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of CDC/ATSDR.

Data availability statement

Any anonymized data not included in the article or supplemental material will be shared, according to good clinical practice, with qualified investigators upon request.