title: Use of statistical models for evaluating antibody response as a correlate of protection against varicella.
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.
authors.affiliation: Clinical Biostatistics, Merck Research Laboratories, Merck & Co., West Point, PA 19486, USA. Ivan_Chan@Merck.com
authors.forename: Ivan S F
authors.initials: IS
authors.lastname: Chan
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.forename: Holly
authors.initials: H
authors.lastname: Matthews
authors.forename: Christina
authors.initials: C
authors.lastname: Chan
authors.forename: Rupert
authors.initials: R
authors.lastname: Vessey
authors.forename: Jerald
authors.initials: J
authors.lastname: Sadoff
authors.forename: Joseph
authors.initials: J
authors.lastname: Heyse
mesh_terms: D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D002644:Chickenpox / Q000276:immunology* / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D007223:Infant; D008297:Male; D018448:Models, Immunological; D015233:Models, Statistical; D014481:United States; D014611:Vaccination / Q000379:methods*; D015164:Vaccines, Inactivated / Q000276:immunology / Q000592:standards; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines