Design and estimation for evaluating principal surrogate markers in vaccine trials.
Design and estimation for evaluating principal surrogate markers in vaccine trials.
复制标题
DOI：
10.1111/biom.12014
复制
发表时间：
2013-06
期刊：
影响因子：
1.9
通讯作者：
Wolfson J
中科院分区：
文献类型：
--
作者：
Huang Y;Gilbert PB;Wolfson J
In vaccine research, immune biomarkers that can reliably predict a vaccine’s effect on the clinical endpoint (i.e., surrogate markers) are important tools for guiding vaccine development. This paper addresses issues on optimizing two-phase sampling study design for evaluating surrogate markers in a principal surrogate framework, motivated by the design of a future HIV vaccine trial. To address the problem of missing potential outcomes in a standard trial design, novel trial designs have been proposed that utilize baseline predictors of the immune response biomarker(s) and/or augment the trial by vaccinating uninfected placebo recipients at the end of the trial and measuring their immune biomarkers. However, inefficient use of the augmented information can lead to counterintuitive results on the precision of estimation. To remedy this problem, we propose a pseudo-score type estimator suitable for the augmented design and characterize its asymptotic properties. This estimator has superior performance compared with existing estimators and allows calculation of analytical variances useful for guiding study design. Based on the new estimator we investigate in detail the problem of optimizing the sampling scheme of a biomarker in a vaccine efficacy trial for efficiently estimating its surrogate effect, as characterized by the vaccine efficacy curve (a causal effect predictiveness curve) and by the predicted overall vaccine efficacy using the biomarker.
登录
查看更多内容
影响因子：
1.9
作者：
Wolfson, Julian;Gilbert, Peter
通讯作者：
Gilbert, Peter
影响因子：
1.9
作者：
Gilbert, Peter B.;Hudgens, Michael G.
通讯作者：
Hudgens, Michael G.
影响因子：
1.2
作者：
Gilbert, Peter B.;Hudgens, Michael G.;Wolfson, Julian
通讯作者：
Wolfson, Julian
影响因子：
1.9
作者：
Frangakis, CE;Rubin, DB
通讯作者：
Rubin, DB
影响因子：
1.9
作者：
Hudgens MG;Gilbert PB
通讯作者：
Gilbert PB