title: Using proportion of similar response to evaluate correlates of protection for vaccine efficacy.
abstract: A question of interest in many vaccine clinical development programmes is whether vaccine-induced serum antibody level can be used as a correlate of vaccine efficacy; that is, whether serum antibody levels induced by a candidate vaccine can reliably predict the risk of breakthrough disease. Traditionally, analyses to answer this question have been based on modelling the incidence of breakthrough disease as a function of antibody level, among vaccinated subjects in clinical trials. The Proportion of Similar Response (PSR) method will be described and explored, and compared to the Receive Operator Characteristics (ROC) curve as a graphical tool and the area under the ROC (AUROC) as a summary measure in the context of evaluating correlates of protection. A way to use PSR analysis as complementary to Youden's index as a simple and elegant method to determine the discriminatory ability of a test and to set an optimal threshold value will be presented. In addition, the relationships among PSR and other measures of overlap and discrimination will be described. An example based on a clinical trial from a development programme for a vaccine against human papillomavirus (HPV) will be presented.
authors.affiliation: McNeil Consumer Healthcare, Division of McNeil - PPC, Inc., Fort Washington, PA, USA kgiacole@its.jnj.com.
authors.forename: Katherine E D
authors.initials: KE
authors.lastname: Giacoletti
authors.affiliation: Merck Research Labs, North Wales, PA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Heyse
mesh_terms: D019540:Area Under Curve; D056808:Biostatistics; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D006801:Humans; D016015:Logistic Models; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000494:pharmacology; D012372:ROC Curve; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014612:Vaccines / Q000494:pharmacology*
chemical_list: D053918:Papillomavirus Vaccines; D014612:Vaccines