title: Power/sample size calculations for assessing correlates of risk in clinical efficacy trials.
abstract: In a randomized controlled clinical trial that assesses treatment efficacy, a common objective is to assess the association of a measured biomarker response endpoint with the primary study endpoint in the active treatment group, using a case-cohort, case-control, or two-phase sampling design. Methods for power and sample size calculations for such biomarker association analyses typically do not account for the level of treatment efficacy, precluding interpretation of the biomarker association results in terms of biomarker effect modification of treatment efficacy, with detriment that the power calculations may tacitly and inadvertently assume that the treatment harms some study participants. We develop power and sample size methods accounting for this issue, and the methods also account for inter-individual variability of the biomarker that is not biologically relevant (e.g., due to technical measurement error). We focus on a binary study endpoint and on a biomarker subject to measurement error that is normally distributed or categorical with two or three levels. We illustrate the methods with preventive HIV vaccine efficacy trials and include an R package implementing the methods. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Vaccine and Infectious Disease and Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle, 98109, Washington, U.S.A.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Gilbert
authors.affiliation: Vaccine and Infectious Disease and Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle, 98109, Washington, U.S.A.
authors.forename: Holly E
authors.initials: HE
authors.lastname: Janes
authors.affiliation: Vaccine and Infectious Disease and Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle, 98109, Washington, U.S.A.
authors.forename: Yunda
authors.initials: Y
authors.lastname: Huang
mesh_terms: D016915:AIDS Vaccines; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012306:Risk; D018401:Sample Size; D016896:Treatment Outcome
chemical_list: D016915:AIDS Vaccines
keywords: case-cohort design; case-control design; immune response biomarkers; measurement error; principal stratification; two-phase sampling design; vaccine efficacy trial