Design and estimation for evaluating principal surrogate markers in vaccine trials

Ying Huang, Peter B. Gilbert, Julian Wolfson

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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 article 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 counter-intuitive 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.

Original languageEnglish (US)
Pages (from-to)301-309
Number of pages9
JournalBiometrics
Volume69
Issue number2
DOIs
StatePublished - Jun 1 2013

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Marker Vaccines
Surrogate Markers
Vaccines
Vaccine
Biomarkers
Vaccine Efficacy
biomarkers
vaccines
Estimator
experimental design
Two-phase Sampling
Potential Outcomes
Sampling
AIDS Vaccines
Causal Effect
Curve
Sampling Design
Immune Response
vaccine development
Sampling Studies

Keywords

  • Closeout placebo vaccination
  • Estimated likelihood
  • Immune correlate
  • Principal surrogate
  • Pseudo-score
  • Two-phase sampling design

Cite this

Design and estimation for evaluating principal surrogate markers in vaccine trials. / Huang, Ying; Gilbert, Peter B.; Wolfson, Julian.

In: Biometrics, Vol. 69, No. 2, 01.06.2013, p. 301-309.

Research output: Contribution to journalArticle

Huang, Ying ; Gilbert, Peter B. ; Wolfson, Julian. / Design and estimation for evaluating principal surrogate markers in vaccine trials. In: Biometrics. 2013 ; Vol. 69, No. 2. pp. 301-309.
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