From the Department of Neurology (L.H.v.d.B.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Neurology (E.S.), Mayo Clinic, Rochester, MN; Department of Neurology (G.G.), University of Kansas Medical Center, Kansas City; Department of Medicine (E.A.M.), Massachusetts General Hospital, Biostatistics Center, Harvard Medical School, Boston; Department of Neurology (J.A., H.M.), Columbia University, Eleanor and Lou Gehrig ALS Center, New York, NY; Department of Neurology (R.H.B.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (M.B.), University of Miami, FL; Neurological Clinical Research Institute (J.D.B.), Massachusetts General Hospital, Boston; Rita Levi Montalcini Department of Neuroscience (A.C.), University of Torino, Italy; Centre Constitutif SLA (P.C.), Université de Tours, France; Department of Neurology (A.G.), Clinical Research Unit, Montreal Neurological Institute, Neurosurgery, McGill University, Montreal, Canada; National Institute of Neurological Disorders and Stroke (A.K.G.), National Institutes of Health, Bethesda, MD; ALS Center (C.L.-H.), University of California San Francisco; Department of Neuroscience (C.J.M.), Sheffield Institute for Translational Neuroscience, University of Sheffield, UK; Department of Neurology (E.P.P.), Section of ALS & Related Disorders, Cleveland Clinic, OH; Department of Neurology (J.R.), The Center for Restorative Neurology, Loma Linda University School of Medicine, CA; Department of Neurology and Laboratory of Neuroscience (V.S.), Istituto Auxologico Italiano, IRCCS, Milan; Department of Pathophysiology and Transplantation (V.S.), "Dino Ferrari" Centre, Università degli Studi di Milano, Milan, Italy; Nuffield Department of Clinical Neurosciences (M.R.T.), University of Oxford, UK; Neuromuscular Diseases Unit/ALS Clinic (M.W.), Kantonsspital St. Gallen, Switzerland; Carolinas Neuromuscular/ALS-MDA Care Center (B.R.B.), Charlotte; Department of Neurology (B.R.B.), Carolinas Medical Center, University of North Carolina School of Medicine, Charlotte; Forbes Norris ALS Treatment and Research Center (R.G.M.), California Pacific Medical Center San Francisco; and Department of Neurosciences (R.G.M.), Stanford University, CA.
Neurology. 2019 Apr 2;92(14):e1610-e1623. doi: 10.1212/WNL.0000000000007242. Epub 2019 Mar 8.
To revise the 1999 Airlie House consensus guidelines for the design and implementation of preclinical therapeutic studies and clinical trials in amyotrophic lateral sclerosis (ALS).
A 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).
In 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.
The 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.
修订 1999 年爱丽舍共识指南，以设计和实施肌萎缩侧索硬化症（ALS）的临床前治疗研究和临床试验。
一个由 140 名国际 ALS 社区的关键成员（ALS 研究人员、临床医生、患者代表、研究资助代表、行业和监管机构）组成的共识委员会，解决了 ALS 研究的 9 个需求领域：（1）临床前研究；（2）生物学和表型异质性；（3）结果测量；（4）疾病修饰和症状干预；（5）招募和保留；（6）生物标志物；（7）临床试验阶段；（8）超越传统试验设计；和（9）统计考虑。委员会成员被分配到 8 个部分中的 1 个，根据提出（临床前）问题的背景和概述证据和专家意见的理由，生成了一组指南草案。在爱丽舍会议中心进行了为期两天的面对面研讨会之后，采用改良 Delphi 流程制定了共识研究指南草案，随后根据公众的意见进行了审查和修改。统计专家起草了一份单独的统计考虑文件（第 9 节）。
在本报告中，我们总结了 112 条指南及其相关背景和理由。完整的指南列表、统计考虑因素以及术语表可在 Dryad 上找到（附录 e-3-e-5，doi.org/10.5061/dryad.32q9q5d）。作者确定了 15 条最有可能改善 ALS 临床研究的指南作为优先事项。
修订后的爱丽舍 ALS 临床试验共识指南应有助于改善临床试验设计，并加速为 ALS 患者开发有效治疗方法。
