@article{9f90840104b442178b3d31cb7c3c8f18,
title = "Stochastic optimization of adaptive enrichment designs for two subpopulations",
abstract = "An adaptive enrichment design is a randomized trial that allows enrollment criteria to be modified at interim analyses, based on a preset decision rule. When there is prior uncertainty regarding treatment effect heterogeneity, these trial designs can provide improved power for detecting treatment effects in subpopulations. We present a simulated annealing approach to search over the space of decision rules and other parameters for an adaptive enrichment design. The goal is to minimize the expected number enrolled or expected duration, while preserving the appropriate power and Type I error rate. We also explore the benefits of parallel computation in the context of this goal. We find that optimized designs can be substantially more efficient than simpler designs using Pocock or O{\textquoteright}Brien-Fleming boundaries.",
keywords = "Clinical trials, optimization, simulated annealing, treatment effect heterogeneity",
author = "{For the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative} and Aaron Fisher and Michael Rosenblum",
note = "Funding Information: This work was supported by the Patient-Centered Outcomes Research Institute (Grant number ME-1306-03198) and the U.S. Food and Drug Administration (Grant number HHSF223201400113C). Data collection and sharing for this project was funded by the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer{\textquoteright}s Association; Alzheimer{\textquoteright}s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer{\textquoteright}s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. This work is solely the responsibility of the authors and does not represent the views of the above people and agencies. Funding Information: This work was supported by the Patient-Centered Outcomes Research Institute (Grant number ME-1306-03198) and the U.S. Food and Drug Administration (Grant number HHSF223201400113C). Data collection and sharing for this project was funded by the Alzheimer?s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer?s Association; Alzheimer?s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer?s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. This work is solely the responsibility of the authors and does not represent the views of the above people and agencies. We thank Daniel Hanley and Michela Gallagher for providing summary statistics from the MISTIE and ADNI data, respectively. Publisher Copyright: {\textcopyright} 2018, {\textcopyright} 2018 The Author(s). Published by Taylor & Francis.",
year = "2018",
month = sep,
day = "3",
doi = "10.1080/10543406.2018.1489401",
language = "English (US)",
volume = "28",
pages = "966--982",
journal = "Journal of biopharmaceutical statistics",
issn = "1054-3406",
publisher = "Taylor and Francis Ltd.",
number = "5",
}