The relative efficiency of time-to-progression and continuous measures of cognition in presymptomatic Alzheimer’s disease

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dc.contributor.authorIddi, S.
dc.contributor.authorLi, D.
dc.contributor.authorAisen, P.S.
dc.contributor.authorThompson, W.K.
dc.contributor.authorDonohue, M.C.
dc.date.accessioned2019-12-12T16:45:27Z
dc.date.available2019-12-12T16:45:27Z
dc.date.issued2019-07-18
dc.descriptionResearch Articleen_US
dc.description.abstractIntroduction: Clinical trials on preclinical Alzheimer’s disease are challenging because of the slow rate of disease progression.We use a simulation study to demonstrate that models of repeated cognitive assessments detect treatment effects more efficiently than models of time to progression. Methods: Multivariate continuous data are simulated from a Bayesian joint mixed-effects model fit to data from the Alzheimer’s Disease Neuroimaging Initiative. Simulated progression events are algorithmically derived from the continuous assessments using a random forest model fit to the same data. Results: We find that power is approximately doubled with models of repeated continuous outcomes compared with the time-to-progression analysis. The simulations also demonstrate that a plausible informative missing data pattern can induce a bias that inflates treatment effects, yet 5% type I error is maintained. Discussion: Given the relative inefficiency of time to progression, it should be avoided as a primary analysis approach in clinical trials of preclinical Alzheimer’s disease.en_US
dc.description.sponsorshipcollection and sharing for this project was funded by the 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 organizations: 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 Inc. The Canadian Institutes of Health Research provided 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 Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.en_US
dc.identifier.otherhttps://doi.org/10.1016/j.trci.2019.04.004
dc.identifier.urihttp://ugspace.ug.edu.gh/handle/123456789/34163
dc.language.isoenen_US
dc.publisherAlzheimer's & Dementia: Translational Research & Clinical Interventionsen_US
dc.relation.ispartofseries5;2019
dc.subjectClinical trial simulationsen_US
dc.subjectAlzheimer’s diseaseen_US
dc.subjectCox proportional hazards modelen_US
dc.subjectLongitudinal dataen_US
dc.subjectMixed model of repeated measures (MMRM)en_US
dc.titleThe relative efficiency of time-to-progression and continuous measures of cognition in presymptomatic Alzheimer’s diseaseen_US
dc.typeArticleen_US

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