The ALSFRS-R Summit: a global call to action on the use of the ALSFRS-R in ALS clinical trials

Abstract

The Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) was developed more than 25 years ago as an instrument to monitor functional change over time in patients with ALS. It has since been revised and extended to meet the needs of high data quality in ALS trials (ALSFRS-R), however a full re-validation of the scale was not completed. Despite this, the scale has remained a primary outcome measure in clinical trials. We convened a group of clinical trialists to discuss and explore opportunities to improve the scale and propose alternative measures. In this meeting report, we present a call to action on the use of the ALSFRS-Revised scale in clinical trials, focusing on the need for (1) harmonization of the ALSFRS-R administration globally, (2) alignment on a set of recommendations for clinical trial design and statistical analysis plans (SAPs), and (3) use of additional outcome measures.

Keywords:

• Clinical trial design
• clinical trial outcome measures
• functional rating scale
• harmonization
• statistical analysis

Acknowledgements

Medical writing assistance for this manuscript was provided by KTP (Knowledge Translation Partners), Montreal, Canada.

Disclosure statement

Dr Adriano Chiò serves on scientific advisory boards for Mitsubishi Tanabe, Biogen, Roche, Denali Pharma, Cytokinetics, Lilly, and Amylyx Pharmaceuticals. I have also received a research grant from Biogen. I have disclosed these interests fully to Taylor & Francis, and I have in place a plan for managing any potential conflicts arising from these disclosures. Catherine Cummings, MBA, CAE has received honoraria from Mitsubishi Tanabe Pharma—Canada. I have disclosed these interests fully to Taylor & Francis, and I have in place a plan for managing any potential conflicts arising from these disclosures. The International Alliance of ALS/MND Associations receives funding, educational grants, and consulting fees from the following companies: Alexion, Amylyx, Apellis, Biogen, Cytokinetics, Ionis, Mitsubishi Tanabe Pharma, QurAlis, Sanofi,UCB, Wave Life Therapies. Dr Philip Van Damme (PVD) has served on advisory boards for Biogen, CSL Behring, Alexion Pharmaceuticals, Ferrer, QurAlis, Cytokinetics, Argenx, UCB, Muna Therapeutics, Alector, Augustine Therapeutics, VectorY, Zambon, Amylyx (paid to institution). PVD has received speaker fees from Biogen and Amylyx (paid to institution). PVD is supported by the E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders (from CSL Behring, paid to institution). I have disclosed these interests fully to Taylor & Francis, and I have in place a plan for managing any potential conflicts arising from these disclosures. Dr Christina Fournier has received consulting fees from QurAlis and institutional research funding from Amylyx, Biogen, Corcept, Denali, Mitsubishi Tanabe, QurAlis, I have disclosed these interests fully to Taylor & Francis, and I have in place a plan for managing any potential conflicts arising from these disclosures. Dr Angela Genge is the Chief Medical Officer for QurAlis and has received funding, educational grants, and consulting fees from the following companies: Alexion, AL-S Pharma, Amicus Therapeutics, Amylyx, Anelixis, Anexon, Apellis, Atlantic Research Group, Biogen, Calico, Cytokinetics, Eli Lilly, Ionis, Medtronic, Mitsubishi Tanabe Pharma, Orion, QurAlis, RA Pharma, Roche, Sanofi Genzyme, UCB, Wave Life Therapies. I have disclosed these interests fully to Taylor & Francis, and I have in place a plan for managing any potential conflicts arising from these disclosures. Dr Julian Grosskreutz has served on scientific advisory boards for Biogen, Alexion, UCB and Amylyx Pharmaceuticals. He has disclosed these interests fully to Taylor & Francis and has in place a plan for managing any potential conflicts arising from these disclosures. Dr Chris McDermott is supported by the NIHR Biomedical Research Center Sheffield and an NIHR Research Professorship award. I have disclosed these interests fully to Taylor & Francis, and I have in place a plan for managing any potential conflicts arising from these disclosures. John Polzer is a consultant with QurAlis. I have disclosed these interests fully to Taylor & Francis, and I have in place a plan for managing any potential conflicts arising from these disclosures. Kristiana Salmon is an employee of QurAlis. I have disclosed these interests fully to Taylor & Francis, and I have in place a plan for managing any potential conflicts arising from these disclosures. Dr Jeremy Shefner has received personal compensation from: Amylyx; Cytokinetics; Denali; GSK; Mitsubishi Tanabe Pharma America; Neurosense; Orthogonal; RRD; Acurastem; Revalasio; Apellis; Swanbio; Novartis; Sanofi. He has received research funding from: AB Sciences; Acorda Therapeutics; Alector; Amylyx; Biogen; Cytokinetics Incorporated; Ionis; Mitsubishi Tanabe Pharma America; Quralis; PTC; Sanofi; Wave; Myolex. I have disclosed these interests fully to Taylor & Francis, and I have in place a plan for managing any potential conflicts arising from these disclosures. Corey Straub is an employee of QurAlis. I have disclosed these interests fully to Taylor & Francis, and I have in place a plan for managing any potential conflicts arising from these disclosures. The following authors report no competing interests: Dr Ammar Al-Chalabi, Dr Jinsy Andrews, Dr Leonard van den Berg, Dr James Berry, Dr Vanessa Bertone, Tommy Bunte, Dr Jesse M Cedarbaum, Dr Mathias Couillard, Dr Ruben van Eijk, Dr Jonathon Glass, Gale Kittle.

Additional information

Funding

Amylyx Pharmaceuticals provided funding to support the medical writing on this manuscript.