Augmented case-only designs for randomized clinical trials with failure time endpoints

Biometrics
James Y DaiCharles Kooperberg

Abstract

Under suitable assumptions and by exploiting the independence between inherited genetic susceptibility and treatment assignment, the case-only design yields efficient estimates for subgroup treatment effects and gene-treatment interaction in a Cox model. However it cannot provide estimates of the genetic main effect and baseline hazards, that are necessary to compute the absolute disease risk. For two-arm, placebo-controlled trials with rare failure time endpoints, we consider augmenting the case-only design with random samples of controls from both arms, as in the classical case-cohort sampling scheme, or with a random sample of controls from the active treatment arm only. The latter design is motivated by vaccine trials for cost-effective use of resources and specimens so that host genetics and vaccine-induced immune responses can be studied simultaneously in a bigger set of participants. We show that these designs can identify all parameters in a Cox model and that the efficient case-only estimator can be incorporated in a two-step plug-in procedure. Results in simulations and a data example suggest that incorporating case-only estimators in the classical case-cohort design improves the precision of all estimated parameters;...Continue Reading

References

Jan 1, 1990·American Journal of Epidemiology·B Langholz, D C Thomas
Jul 17, 1999·Lifetime Data Analysis·T M Therneau, H Li
Apr 14, 2000·Lifetime Data Analysis·O BorganJ Pogoda
Feb 7, 2003·The New England Journal of Medicine·William E Evans, Howard L McLeod
Sep 2, 2004·Nature Reviews. Drug Discovery·Richard Weinshilboum, Liewei Wang
Sep 21, 2006·Biometrics·E Vittinghoff, D C Bauer
Nov 18, 2008·Lancet·M Juliana McElrathUNKNOWN Step Study Protocol Team
Dec 26, 2009·Genome Medicine·Sharon J PitteriRoss L Prentice
Jan 9, 2010·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Ross L PrenticeDennis G Ballinger
Mar 27, 2010·Biometrics·Eric J Tchetgen Tchetgen, James Robins
Feb 16, 2011·Annals of Internal Medicine·Holly JanesWilliam E Barlow
Jul 10, 2012·American Journal of Epidemiology·James Y DaiCharles Kooperberg
Jul 5, 2013·Methods in Molecular Biology·Rosane Charlab, Lei Zhang

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