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.
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.
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.
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.