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Proposal 1088

Title of the Proposed Research

A study to identify risk factors that modify Rotarix efficacy and influence the time to rotavirus gastroenteritis among vaccinated and unvaccinated African infants.

Lead Researcher

Joann Gruber

Affiliation

University of North Carolina at Chapel Hill

Funding Source

None

Potential Conflicts of Interest

Research Assistant at Merck (Jan-Dec 2014) working on analysis related to Merck’s rotavirus vaccine (RotaTeq)

Data Sharing Agreement Date

4 September 2015

Lay Summary

Rotavirus infections are the world’s leading cause of severe diarrhea in children under five years of age [1, 2]. Each year there are 140 million cases of rotavirus infection in children under five with 26 million of these cases requiring clinic visits or hospitalizations [1]. Despite similar rates of infection in developed and developing countries, rotavirus-associated mortality disproportionately affects children in developing countries, where 80-90% of rotavirus-associated deaths occur [1, 6].

Vaccination against rotavirus is considered the most promising intervention to prevent infection and reduce the burden of disease [4, 11, 12]. As of 2009, universal rotavirus vaccination of infants was recommended by the World Health Organization [13]. Two live, oral rotavirus vaccines are available for use across the globe—Rotarix and RotaTeq. Doses are administered two or three times, depending on the vaccine type, around 2, 4, and 6 months of age [11]. While rotavirus vaccine trials have shown high protective efficacy (85-96%) against severe rotavirus gastroenteritis in high income countries [14-16], the efficacy has been much lower (40-59%) in trials conducted in GAVI-eligible countries in Africa and Asia [17-19]. This lower vaccine efficacy reported in developing countries is similar to study results for other live oral vaccines [20-22]. Although this is a common theme in developing countries, the reason for lower efficacy is not well understood.

I purpose to analyze risk factors that modify Rotarix vaccine efficacy and influence time to rotavirus gastroenteritis among African infants. I am a PhD student in epidemiology at the University of North Carolina and propose to do this work as my dissertation. The study participants will be 2,089 infants who participated in a clinical trial of Rotarix sponsored by GlaxoSmithKline. For the first research aim, I will utilize the randomized design of the clinical trial to identify risk factors that modify the effect of Rotarix in developing countries. The second research aim will be time-to-event analysis. Each risk factor will be analyzed as a potential exposure variable influencing the time to occurrence of breakthrough case of rotavirus (any severity and severe). Aim 3 will use the results of Aim 1 and Aim 2 to predict the effectiveness of Rotarix in developing countries. Potential risk factors analyzed will depend on the data collected during the study; however, I propose the following as a guide. Risk factors will be age at vaccination, breastfeeding status, nutrition status, birth weight, gestational age at birth, and co-administration of vaccines and medicines at time of vaccination. Two peer reviewed publication will be submitted summarizing the results. Understanding how clinical and demographic risk factors influence rotavirus vaccine efficacy can help to improve efficacy in developing countries.

Study Data Provided

Study GSK-102248: Multi-Center Study to Assess the Efficacy, Safety and Immunogenicity of 2 or 3 Doses of GSK Biologicals' Oral Live Attenuated Human Rotavirus (HRV) Vaccine Given Concomitantly With Routine EPI Vaccinations in Healthy Infants
Study GSK-111274: Multi-Center Study to Assess the Efficacy, Safety and Immunogenicity of 2 or 3 Doses of GSK Biologicals' Oral Live Attenuated Human Rotavirus (HRV) Vaccine Given Concomitantly With Routine EPI Vaccinations in Healthy Infants

Statistical Analysis Plan

This will be added after the research is published.

Publication Citation

The publication citation will be added after the research is published.