title: The DIAN-TU Next Generation Alzheimer's prevention trial: Adaptive design and disease progression model.
abstract: The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) trial is an adaptive platform trial testing multiple drugs to slow or prevent the progression of Alzheimer's disease in autosomal dominant Alzheimer's disease (ADAD) families. With completion of enrollment of the first two drug arms, the DIAN-TU now plans to add new drugs to the platform, designated as the Next Generation (NexGen) prevention trial.
  
  
  
  In collaboration with ADAD families, philanthropic organizations, academic leaders, the DIAN-TU Pharma Consortium, the National Institutes of Health, and regulatory colleagues, the DIAN-TU developed innovative clinical study designs for the DIAN-TU NexGen prevention trial.
  
  
  
  Our expanded trial toolbox consists of a disease progression model for ADAD, primary end point DIAN-TU cognitive performance composite, biomarker development, self-administered cognitive assessments, adaptive dose adjustments, and blinded data collection through the last participant completion.
  
  
  
  These steps represent elements to improve efficacy of the adaptive platform trial and a continued effort to optimize prevention and treatment trials in ADAD.
authors: Department of Neurology, Washington University in St Louis, St Louis, MO, USA. Electronic address: batemanr@wustl.edu.
authors: Randall J
authors: RJ
authors: Bateman
authors: Department of Radiology, Washington University in St Louis, St Louis, MO, USA.
authors: Tammie L
authors: TL
authors: Benzinger
authors: Berry Consultants, Austin, TX, USA.
authors: Scott
authors: S
authors: Berry
authors: Department of Neurology, Washington University in St Louis, St Louis, MO, USA.
authors: David B
authors: DB
authors: Clifford
authors: Department of Neurology, Washington University in St Louis, St Louis, MO, USA.
authors: Cynthia
authors: C
authors: Duggan
authors: Department of Neurology, Washington University in St Louis, St Louis, MO, USA.
authors: Anne M
authors: AM
authors: Fagan
authors: Department of Neurology, Washington University in St Louis, St Louis, MO, USA.
authors: Kathleen
authors: K
authors: Fanning
authors: Indiana Alzheimer Disease Center, Indiana University, Indianapolis, IN, USA.
authors: Martin R
authors: MR
authors: Farlow
authors: Department of Neurology, Washington University in St Louis, St Louis, MO, USA.
authors: Jason
authors: J
authors: Hassenstab
authors: Department of Neurology, Washington University in St Louis, St Louis, MO, USA.
authors: Eric M
authors: EM
authors: McDade
authors: Department of Neurology, Washington University in St Louis, St Louis, MO, USA.
authors: Susan
authors: S
authors: Mills
authors: Department of Neurology, Washington University in St Louis, St Louis, MO, USA.
authors: Katrina
authors: K
authors: Paumier
authors: Berry Consultants, Austin, TX, USA.
authors: Melanie
authors: M
authors: Quintana
authors: Memory and Aging Program, Butler Hospital, Brown Medical School, Providence, RI, USA.
authors: Stephen P
authors: SP
authors: Salloway
authors: Department of Neurology, Washington University in St Louis, St Louis, MO, USA.
authors: Anna
authors: A
authors: Santacruz
authors: Alzheimer's Disease Research Center, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
authors: Lon S
authors: LS
authors: Schneider
authors: Department of Biostatistics, Washington University in St Louis, St Louis, MO, USA.
authors: Guoqiao
authors: G
authors: Wang
authors: Department of Biostatistics, Washington University in St Louis, St Louis, MO, USA.
authors: Chengjie
authors: C
authors: Xiong
mesh_terms: D000465:Algorithms; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D035843:Biomedical Research; D002986:Clinical Trials as Topic / Q000379:methods*; D003072:Cognition Disorders / Q000209:etiology / Q000628:therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008962:Models, Theoretical; D009483:Neuropsychological Tests; D055818:Public-Private Sector Partnerships; D012107:Research Design
chemical_list: D014150:Antipsychotic Agents
keywords: Adaptive clinical trial; Alzheimer's disease; Alzheimer's prevention trial; Amyloid; Autosomal dominant Alzheimer's disease; Biomarkers; Cognitive composite; DIAN-TU; Disease progression model; Dose adjustment; Tau