Project

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Carriage and immunological outcomes in vaccine trials: implications for meta-analysis and reporting

English title Carriage and immunological outcomes in vaccine trials: implications for meta-analysis and reporting
Applicant Egger Matthias
Number 138490
Funding scheme Project funding (Div. I-III)
Research institution Institut für Sozial- und Präventivmedizin Universität Bern
Institution of higher education University of Berne - BE
Main discipline Methods of Epidemiology and Preventive Medicine
Start/End 01.03.2012 - 28.02.2014
Approved amount 322'909.00
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Lay Summary (English)

Lead
Lay summary

Background
The World Health Organization estimates that 1.4 million deaths each year among children under 5 years of age are due to diseases that could be prevented by routine vaccination. Decisions about the use of vaccines should be based on available evidence which comes from vaccine studies. Data from such studies are found by performing systematic reviews and are analysed using a method to combine data from multiple studies, called meta-analysis.

Goals
We aim to improve methods for the analysis and interpretation of data found in systematic reviews of vaccines. This will help us to make recommendations for researchers conducting systematic reviews and meta-analyses of vaccine effects. The results of such reviews will then be more easily understood by policy makers.


Methods of investigationWe will simulate data for several types of outcomes which are often measured in vaccine studies. Data will be simulated to represent data from multiple hypothetical studies of vaccine effects. We will used this simulated data to examine how best to perform meta-analysis, and how results of these meta-analyses can be interpreted. We will test our findings from simulated data against real data which we have from previously conducted systematic reviews and meta-analyses of vaccine effects. We will then develop a checklist and recommendations about key analysis, interpretation and reporting issues for meta-analyses of vaccines to aid future reviews and meta-analyses.

Importance and impact
This research will allow us to make recommendations on the design, conduct, synthesis and interpretation of data from vaccine studies and meta-analyses. Ultimately, the outputs will help policy makers to make more informed evidence based decisions about the introduction and use of new vaccines.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Comparing Haemophilus influenzae type b conjugate vaccine schedules: a systematic review and meta-analysis of vaccine trials.
Low Nicola, Redmond Shelagh M, Rutjes Anne W S, Martínez-González Nahara A, Egger Matthias, di Nisio Marcello, Scott Pippa (2013), Comparing Haemophilus influenzae type b conjugate vaccine schedules: a systematic review and meta-analysis of vaccine trials., in The Pediatric infectious disease journal, 32(11), 1245-56.
Direct and indirect effects of screening for Chlamydia trachomatis on the prevention of pelvic inflammatory disease: a mathematical modeling study.
Herzog Sereina A, Heijne Janneke C M, Scott Pippa, Althaus Christian L, Low Nicola (2013), Direct and indirect effects of screening for Chlamydia trachomatis on the prevention of pelvic inflammatory disease: a mathematical modeling study., in Epidemiology (Cambridge, Mass.), 24(6), 854-62.
Completeness of reporting in randomized controlled trials of 3 vaccines: a review of adherence to the CONSORT checklist.
Scott Pippa, Ott Franziska, Egger Matthias, Low Nicola (2012), Completeness of reporting in randomized controlled trials of 3 vaccines: a review of adherence to the CONSORT checklist., in The Pediatric infectious disease journal, 31(12), 1286-94.

Collaboration

Group / person Country
Types of collaboration
National Institute for Public Health and the Environment (RIVM) Netherlands (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dr. Kari Auranen, National Institute for Health and Welfare (THL) Finland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dr. Thomas Gsponer, Institute of Social and Preventive Medicine (ISPM) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz Austria (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Epidemics 4 Poster Timing of the assessment of bacterial carriage as an outcome in vaccine trials 19.11.2013 Amsterdam, Netherlands Low Nicola Minling; Scott Pippa; Gsteiger Sandro;
WHO Ad Hoc Expert Consultation on Hib Vaccines schedules Individual talk What is the effect of Hib vaccination schedules on critical disease outcomes 03.10.2013 Geneva, Switzerland Scott Pippa; Low Nicola Minling;


Abstract

Background The World Health Organization estimates that 1.4 million deaths each year among children under 5 years of age are due to diseases that could be prevented by routine vaccination. Vaccines that prevent transmission of the infectious agent protect not only the vaccinated individual but also those that they would have infected if they had not received vaccine. There is little known about how indirect effects contribute to between trial heterogeneity when synthesizing evidence in meta-analysis, and how they should be dealt with and reported.Goals The overall goal of this project is to address key issues in the analysis and interpretation of data from randomized trials of vaccine effects that will contribute to recommendations for researchers conducting systematic reviews and meta-analyses of vaccine effects such that their results are more easily understood by policy makers and other users of reviews. Methods of investigationObjective 1: To determine appropriate effect measures for carriage and immunological response and sources of between trial heterogeneity trials of pneumococcal conjugate vaccines (PCV).We will construct a transmission dynamic model to investigate the behaviour of cross-sectional measures of the effect of PCV on pneumococcal carriage, and identify other potential sources of between trial heterogeneity. Model outputs will be compared to data from individual trials and to the output of a different model. For immunological outcomes we will use Monte Carlo methods to simulate datasets reflecting different scenarios for distributions of immunological data from trials. Results will be compared to empirical data. Objective 2: To determine sources of heterogeneity that have the greatest influence in meta-analyses and meta-regression analyses of vaccine trials in practice. We will use existing empirical datasets that we have collated and identify new datasets to explore the influence of the sources of heterogeneity identified in Objective 1. Objective 3: To identify lessons for future conduct and reporting of vaccine trials using carriage and immunological outcomes. We will develop a checklist and recommendations about key analysis, interpretation and reporting issues for meta-analyses of vaccines following stakeholder consultation using a modified Delphi process.Timescale October 2011 to September 2013.Importance and impact This project will triangulate methods and provide and in-depth investigation into issues specific to the design of vaccine trials and interpretation of meta-analyses and systematic reviews of the effects of vaccines. This will allow us to make recommendations on the design, conduct, synthesis and interpretation of data from trials and meta-analyses. Ultimately, the outputs will help policy makers to make more informed evidence based decisions about the introduction and use of new vaccines.
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