@article{56e4a08960d145a3b65c779c499b1956,
title = "The relative efficiency of time-to-threshold and rate of change in longitudinal data",
abstract = "Randomized, placebo-controlled trials often use time-to-event as the primary endpoint, even when a continuous measure of disease severity is available. We compare the power to detect a treatment effect using either rate of change, as estimated by linear models of longitudinal continuous data, or time-to-event estimated by Cox proportional hazards models. We propose an analytic inflation factor for comparing the two types of analyses assuming that the time-to-event can be expressed as a time-to-threshold of the continuous measure. We conduct simulations based on a publicly available Alzheimer's disease data set in which the time-to-event is algorithmically defined based on a battery of assessments. A Cox proportional hazards model of the time-to-event endpoint is compared to a linear model of a single assessment from the battery. The simulations also explore the impact of baseline covariates in either analysis.",
keywords = "Linear mixed models, Longitudinal data, Marginal linear models, Power, Survival analysis",
author = "Donohue, {M. C.} and Gamst, {A. C.} and Thomas, {R. G.} and R. Xu and L. Beckett and Petersen, {R. C.} and Weiner, {M. W.} and P. Aisen",
note = "Funding Information: The Alzheimer's Disease Neuroimaging Initiative (ADNI), which began in 2004, is a collaborative project funded by National Institute on Aging and National Institute of Bioimaging and Bioengineering, the pharmaceutical and imaging industry, and several foundations (see years, and is ideal for a more complex, clinically realistic simulation of our comparison of interest. Namely, we will simulate clinical trials to determine which experimental design can more efficiently detect a hypothesized intervention to slow cognitive and functional decline in a population with MCI. www.adni-info.org ). The study design and baseline characteristics are described in Ref. [23] . Briefly, the objective of ADNI is to study the rate of change of cognition, function, brain structure, and biomarkers in 200 elderly controls, 400 subjects with MCI, and 200 with Alzheimer's disease. For this analysis, publicly available data were downloaded from the ADNI web site adni.loni.ucla.edu on November 30, 2009. The data set contains repeated continuous measures of key assessments and progression events at 6-month intervals over 2 to 3 Funding Information: We are grateful to the reviewers and editor for their insightful suggestions. We are also grateful to the ADNI community, including the collaborators at all of the cores, sites, and laboratories; and to the ADNI volunteers and their families. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) ( National Institutes of Health Grant U01 AG024904 ). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., as well as non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the U.S. Food and Drug Administration. Private sector contributions to ADNI 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 California, Los Angeles. This research was also supported by NIH grants P30 AG010129 , K01 AG030514 , and the Dana Foundation . ",
year = "2011",
month = sep,
doi = "10.1016/j.cct.2011.04.007",
language = "English (US)",
volume = "32",
pages = "685--693",
journal = "Contemporary Clinical Trials",
issn = "1551-7144",
publisher = "Elsevier Inc.",
number = "5",
}