The DIAN-TU Next Generation Alzheimer's prevention trial: Adaptive design and disease progression model

Randall J. Bateman, Tammie L. Benzinger, Scott Berry, David B. Clifford, Cynthia Duggan, Anne M. Fagan, Kathleen Fanning, Martin Farlow, Jason Hassenstab, Eric M. McDade, Susan Mills, Katrina Paumier, Melanie Quintana, Stephen P. Salloway, Anna Santacruz, Lon S. Schneider, Guoqiao Wang, Chengjie Xiong

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Introduction: 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. Methods: 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. Results: 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. Conclusion: These steps represent elements to improve efficacy of the adaptive platform trial and a continued effort to optimize prevention and treatment trials in ADAD.

Original languageEnglish (US)
JournalAlzheimer's and Dementia
DOIs
StateAccepted/In press - 2016

Fingerprint

Disease Progression
Alzheimer Disease
Pharmaceutical Preparations
Social Adjustment
National Institutes of Health (U.S.)
Biomarkers
Organizations

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

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Geriatrics and Gerontology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Cite this

Bateman, R. J., Benzinger, T. L., Berry, S., Clifford, D. B., Duggan, C., Fagan, A. M., ... Xiong, C. (Accepted/In press). The DIAN-TU Next Generation Alzheimer's prevention trial: Adaptive design and disease progression model. Alzheimer's and Dementia. https://doi.org/10.1016/j.jalz.2016.07.005

The DIAN-TU Next Generation Alzheimer's prevention trial : Adaptive design and disease progression model. / Bateman, Randall J.; Benzinger, Tammie L.; Berry, Scott; Clifford, David B.; Duggan, Cynthia; Fagan, Anne M.; Fanning, Kathleen; Farlow, Martin; Hassenstab, Jason; McDade, Eric M.; Mills, Susan; Paumier, Katrina; Quintana, Melanie; Salloway, Stephen P.; Santacruz, Anna; Schneider, Lon S.; Wang, Guoqiao; Xiong, Chengjie.

In: Alzheimer's and Dementia, 2016.

Research output: Contribution to journalArticle

Bateman, RJ, Benzinger, TL, Berry, S, Clifford, DB, Duggan, C, Fagan, AM, Fanning, K, Farlow, M, Hassenstab, J, McDade, EM, Mills, S, Paumier, K, Quintana, M, Salloway, SP, Santacruz, A, Schneider, LS, Wang, G & Xiong, C 2016, 'The DIAN-TU Next Generation Alzheimer's prevention trial: Adaptive design and disease progression model', Alzheimer's and Dementia. https://doi.org/10.1016/j.jalz.2016.07.005
Bateman, Randall J. ; Benzinger, Tammie L. ; Berry, Scott ; Clifford, David B. ; Duggan, Cynthia ; Fagan, Anne M. ; Fanning, Kathleen ; Farlow, Martin ; Hassenstab, Jason ; McDade, Eric M. ; Mills, Susan ; Paumier, Katrina ; Quintana, Melanie ; Salloway, Stephen P. ; Santacruz, Anna ; Schneider, Lon S. ; Wang, Guoqiao ; Xiong, Chengjie. / The DIAN-TU Next Generation Alzheimer's prevention trial : Adaptive design and disease progression model. In: Alzheimer's and Dementia. 2016.
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abstract = "Introduction: 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. Methods: 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. Results: 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. Conclusion: These steps represent elements to improve efficacy of the adaptive platform trial and a continued effort to optimize prevention and treatment trials in ADAD.",
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AU - Paumier, Katrina

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AU - Santacruz, Anna

AU - Schneider, Lon S.

AU - Wang, Guoqiao

AU - Xiong, Chengjie

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