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

Alzheimer's and Dementia: Translational Research and Clinical Interventions - Tập 5 - Trang 308-318 - 2019
Dan Li1, Samuel Iddi1,2, Paul S. Aisen1, Wesley K. Thompson3, Michael C. Donohue1
1Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego, CA, USA
2Department of Statistics, University of Ghana, Legon-Accra, Ghana
3Department of Psychiatry, University of California, San Diego, CA, USA

Tóm tắt

AbstractIntroductionClinical 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.MethodsMultivariate 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.ResultsWe 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.DiscussionGiven the relative inefficiency of time to progression, it should be avoided as a primary analysis approach in clinical trials of preclinical Alzheimer's disease.

Tài liệu tham khảo

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Alzheimer's and Dementia: Translational Research and Clinical Interventions

Tập 5

308-318

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