Use of statistical models for evaluating antibody response as a correlate of protection against varicella

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Abstract
In vaccine clinical trials, humoral antibody responses are often used to measure the effect of a vaccine because they correlate with a vaccine's protective efficacy against the target disease. While the concept of a correlate of protection usually refers to establishing a protective level of antibody titre, identifying a clear‐cut value is often impossible because vaccine efficacy is not related solely to the antibody titre. We propose examining the relationship between disease protection and the whole distribution of antibody responses rather than a single cut‐off level. In particular, we use failure‐time models to estimate the relationship between long‐term disease breakthroughs and primary antibody responses after vaccination. We apply these models to show that the varicella antibody response measured by glycoprotein enzyme‐linked immunosorbent assay 6 weeks after vaccination strongly correlate with protection against varicella (chickenpox); we used 7‐year follow‐up data from children who received one dose of a live attenuated varicella (Oka/Merck) vaccine. In addition, we explore the potential use of these models to predict long‐term disease breakthrough rates and to estimate the predicted vaccine efficacy of a similar varicella vaccine made with a modified manufacturing process. Copyright © 2002 John Wiley & Sons, Ltd.