A Study on Statistical Methods for Evaluation of Vaccine Immunogenicity Bridging Studies
Date Issued
2008
Date
2008
Author(s)
Chen, Ting-Huei
Abstract
4,908 females were diagnosed with cervical cancer and about 932 died from this disease in 2003. It is now recognized that persistent human papillomavirus (HPV) infections are the major cause of cervical cancer. In recent years, the quadrivalent vaccine against HPV has now been licensed for use within Taiwan. The company claims that the HPV vaccine efficacy can be applied to the female 9-26 years of age. Their pivotal trials conducted to evaluate both antibody titer measurement and clinical endpoints such as incidence of HPV infection or related disease only in females 16-26 years of age. On the other hand, for the females 9-15 years of age, the immunogenicity bridging studies is conducted to measure their quantity of antibody titer, not including the clinical endpoints observation. Since the mean titer of the females 9-15 years of age is higher than that of the females 9-26 years of age, the company claimed the vaccine efficacy observed in the females 16-26 years of age can be bridged to the females 9-15 years of age. owever, this claim does not have any statistical inference but only with the observations of the average measurements of the quantity of the antibody titers. In order to test the validity of the claimed vaccine efficacy for the females 9-15 years of age in a scientific manner, the main objective of this thesis is to develop a statistical method to test whether the vaccine efficacy established in the females 16-26 years of age, can be applied to the females 9-15 years of age, through immunogenicity bridging studies. Under the assumption that the relationship between the incidence of the clinical end points and the measurement of quantity of anti-HPV antibody titers is the same for both age groups, we fit a logistic regression prediction model to the dataset of the subjects of the females 16-26 years of age. Then based on the estimated prediction model, we can predict the incidence of the clinical endpoints of the subjects of the females 9-15 years of age by their antibody measurement and the estimated the proportions of the occurrence of clinical endpoints in the females 9-15 years of age. We proposed a procedure to test the hypothesis that the proportion of the clinical endpoints in the females of age 9-15 years is less than that of age 16-26 years. The hypothesis testing is based on the bootstrapping method. A simulation study was conducted to empirically examine the size and power of the proposed method. A numerical dataset illustrates the application of the proposed method.
Subjects
Cervical cancer
HPV
vaccine efficacy
logistic regression
bootstrapping
SDGs
Type
thesis
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