TY - JOUR
T1 - Revised Airlie House consensus guidelines for design and implementation of ALS clinical trials
AU - Van Den Berg, Leonard H.
AU - Sorenson, Eric
AU - Gronseth, Gary
AU - Macklin, Eric A.
AU - Andrews, Jinsy
AU - Baloh, Robert H.
AU - Benatar, Michael
AU - Berry, James D.
AU - Chio, Adriano
AU - Corcia, Philippe
AU - Genge, Angela
AU - Gubitz, Amelie K.
AU - Lomen-Hoerth, Catherine
AU - Mcdermott, Christopher J.
AU - Pioro, Erik P.
AU - Rosenfeld, Jeffrey
AU - Silani, Vincenzo
AU - Turner, Martin R.
AU - Weber, Markus
AU - Brooks, Benjamin Rix
AU - Miller, Robert G.
AU - Mitsumoto, Hiroshi
N1 - Funding Information:
The Article Processing Charge was funded by Columbia University.
Funding Information:
L. van den Berg serves on scientific advisory boards for the Biogen Idec, Cytokinetics, and Sarepta; received an educational grant from Shire; serves on the editorial boards of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, the Journal of Neurology, Neurosurgery and Psychiatry, and the Journal of Neuromuscular Diseases; and receives research support from the Prinses Beatrix Spierfonds, Netherlands ALS Foundation, The European Community’s Health Seventh Framework Programme (grant agreement 259867), The Netherlands Organisation for Health Research and Development (Vici Scheme, JPND [SOPHIA, STRENGTH, NETCALS, ALSCare]). E. Sorenson reports no disclosures relevant to the manuscript. G. Gronseth receives compensation from the American Academy of Neurology for activities related to being associate editor ofNeurology®, a member of the editorial advisory board for Brain & Life, and chief methodologist for guideline development. J. Andrews: consultant for Cytokinetics, Biohaven, and Anelixis Therapeutics; received research grant funding from Neuraltus and Roche. R. Baloh reports no disclosures relevant to the manuscript. M. Benatar receives support from NIH (U54NS092091) for the CReATe Consortium. CReATe is part of Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), NCATS. This consortium is funded through collaboration between NCATS and the NINDS. J. Berry consulted for MT Pharma and Denali Therapeutics and has received research support from Voyager Therapeutics, GSK, Cytokinetics, Brainstorm Cell Therapeutics, ALS One, ALS Association, Muscular Dystrophy Association, and NIH. A. Chio served on scientific advisory boards for Biogen Idec, Cytokinetics, Neuraltus, Ital-farmaco, and Mitsubishi Tanabe. A. Genge consults for the following entities: Sanofi, Biogen, Novartis, ALS Pharma, AB Sciences, Wave Life Sciences, CSL Behring, Cytokinetics, Ana-lexis, Orion, and Revalesio. A. Gubitz reports no disclosures. The findings and conclusions in this manuscript are the opinions of the authors and may not necessarily represent the official position of the National Institute of Neurological Disorders and Stroke. C. Lomen-Hoerth reports no disclosures relevant to the manuscript. E. Macklin served as a DSMB member and a Steering Committee member and received research funding from Acorda Therapeutics, served as a DSMB member for Shire Human Genetic Therapies, consultant to Myolex Inc., and Dr. Macklin’s institution received research funding on his behalf from the Adolph Coors Foundation, the ALS Association, Autism Speaks, Cedars-Sinai Research Institute, the Michael J. Fox Foundation, and the Salah Foundation. C. McDermott: funded by the NIHR Sheffield Biomedical Research Centre (BRC). The views expressed are those of the author and not necessarily those of the NHS, the NIHR, or the Department of Health. P. Corcia: consultant for Roche. E. Pioro receives support from the Samuel J. and Connie M. Frankino Charitable Foundation, receives clinical trial and research funding from NIH/CDC, ALS Association, Iron Horse Diagnostics, and serves as consultant to Avanir Pharmaceuticals, Inc., Otsuka America, Inc., MT Pharma America, Inc., and Cytokinetics, Inc. J. Rosenfeld: consultant and speaker for MT Pharma and Strongbridge Biopharma; research funding, principal investigator for Mallinckrodt Pharma, FLEX Pharma. V. Silani serves on the scientific advisory board for Cytokinetics; V.S. serves on the editorial boards of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, European Neurology, Frontiers in Neurology. M. Turner received funding from the Medical Research Council & Motor Neurone Disease Association Lady Edith Wolfson Senior Fellowship (MR/ K01014X/1); paid consultancy for Genentech Inc. on ALS biomarkers (2017) and anonymous clients through GLG Consulting on the topic of ALS diagnosis, management, and biomarkers (2016–2018); scientific advisory board member of Orphazyme (2018); paid-in-kind for undertaking independent neurofilament study in ALS (kits provided by EUROIMMUN UK, 2017–2018). M. Weber served on scientific advisory boards for Biogen Idec, Merz Pharma Switzerland, CSL Behring, Pharnext, and Mitsubishi Tanabe. B. Rix Brooks has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Mitsubishi Tanabe Pharma USA, Avanir, Biogren, and Biohaven. Dr. Brooks has received research support from MediciNova, Bio-haven, Orion, Neuraltus, Cytokinetics, Santhera, Biogen, ITP Pharma, Acceleron, and Centers for Disease Control. R. Miller reports no disclosures relevant to the manuscript. H. Mitsumoto received grants from CDC/ATSDR, MDA, SPF, NIH, ALSA, Adams Foundation, MNDA; advisory board: Cytokinetics, Mitsubishi-Tanabe, Biohaven, Sunovion, and Denali. Go to Neurology.org/N for full disclosures.
Publisher Copyright:
© American Academy of Neurology.
PY - 2019/4/2
Y1 - 2019/4/2
N2 - ObjectiveTo revise the 1999 Airlie House consensus guidelines for the design and implementation of preclinical therapeutic studies and clinical trials in amyotrophic lateral sclerosis (ALS).MethodsA consensus committee comprising 140 key members of the international ALS community (ALS researchers, clinicians, patient representatives, research funding representatives, industry, and regulatory agencies) addressed 9 areas of need within ALS research: (1) preclinical studies; (2) biological and phenotypic heterogeneity; (3) outcome measures; (4) disease-modifying and symptomatic interventions; (5) recruitment and retention; (6) biomarkers; (7) clinical trial phases; (8) beyond traditional trial designs; and (9) statistical considerations. Assigned to 1 of 8 sections, committee members generated a draft set of guidelines based on a "background" of developing a (pre)clinical question and a "rationale" outlining the evidence and expert opinion. Following a 2-day, face-to-face workshop at the Airlie House Conference Center, a modified Delphi process was used to develop draft consensus research guidelines, which were subsequently reviewed and modified based on comments from the public. Statistical experts drafted a separate document of statistical considerations (section 9).ResultsIn this report, we summarize 112 guidelines and their associated backgrounds and rationales. The full list of guidelines, the statistical considerations, and a glossary of terms can be found in data available from Dryad (appendices e-3-e-5, doi.org/10.5061/dryad.32q9q5d). The authors prioritized 15 guidelines with the greatest potential to improve ALS clinical research.ConclusionThe revised Airlie House ALS Clinical Trials Consensus Guidelines should serve to improve clinical trial design and accelerate the development of effective treatments for patients with ALS.
AB - ObjectiveTo revise the 1999 Airlie House consensus guidelines for the design and implementation of preclinical therapeutic studies and clinical trials in amyotrophic lateral sclerosis (ALS).MethodsA consensus committee comprising 140 key members of the international ALS community (ALS researchers, clinicians, patient representatives, research funding representatives, industry, and regulatory agencies) addressed 9 areas of need within ALS research: (1) preclinical studies; (2) biological and phenotypic heterogeneity; (3) outcome measures; (4) disease-modifying and symptomatic interventions; (5) recruitment and retention; (6) biomarkers; (7) clinical trial phases; (8) beyond traditional trial designs; and (9) statistical considerations. Assigned to 1 of 8 sections, committee members generated a draft set of guidelines based on a "background" of developing a (pre)clinical question and a "rationale" outlining the evidence and expert opinion. Following a 2-day, face-to-face workshop at the Airlie House Conference Center, a modified Delphi process was used to develop draft consensus research guidelines, which were subsequently reviewed and modified based on comments from the public. Statistical experts drafted a separate document of statistical considerations (section 9).ResultsIn this report, we summarize 112 guidelines and their associated backgrounds and rationales. The full list of guidelines, the statistical considerations, and a glossary of terms can be found in data available from Dryad (appendices e-3-e-5, doi.org/10.5061/dryad.32q9q5d). The authors prioritized 15 guidelines with the greatest potential to improve ALS clinical research.ConclusionThe revised Airlie House ALS Clinical Trials Consensus Guidelines should serve to improve clinical trial design and accelerate the development of effective treatments for patients with ALS.
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U2 - 10.1212/WNL.0000000000007242
DO - 10.1212/WNL.0000000000007242
M3 - Article
C2 - 30850440
AN - SCOPUS:85064219744
VL - 92
SP - E1610-E1623
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 14
ER -