Revised Airlie House consensus guidelines for design and implementation of ALS clinical trials

Objective 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). Methods A consensus committee comprising 140 key members of the international ALS community (ALSresearchers,clinicians,patientrepresentatives,researchfundingrepresentatives,industry, andregulatoryagencies)addressed9areasofneedwithinALSresearch:(1)preclinicalstudies; (2) biological and phenotypic heterogeneity; (3) outcome measures; (4) disease-modifying andsymptomaticinterventions;(5)recruitmentandretention;(6)biomarkers;(7)clinicaltrial phases;(8)beyondtraditionaltrialdesigns;and(9)statisticalconsiderations.Assignedto1of8 sections, committee members generated a draft set of guidelines based on a “background” of developinga(pre)clinicalquestionanda“rationale”outliningtheevidenceandexpertopinion. 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). Results 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 dataavailablefromDryad(appendicese-3–e-5,doi.org/10.5061/dryad.32q9q5d).Theauthors prioritized 15 guidelines with the greatest potential to improve ALS clinical research. Conclusion The revised Airlie House ALS Clinical Trials Consensus Guidelines should serve to improve clinicaltrialdesignandacceleratethedevelopmentofeffectivetreatmentsforpatientswithALS.