Mitigating bias in observational vaccine effectiveness studies using simulated comparator populations: application to rotavirus vaccination in the UK



Hungerford, Daniel ORCID: 0000-0002-9770-0163, Vivancos, Roberto, Read, Jonathan M, Bonnett, Laura J ORCID: 0000-0002-6981-9212, Bar-Zeev, Naor ORCID: 0000-0003-0570-4624, Iturriza-Gomara, Mirren ORCID: 0000-0001-5816-6423, Cunliffe, Nigel A ORCID: 0000-0002-5449-4988 and French, Neil ORCID: 0000-0003-4814-8293
(2018) Mitigating bias in observational vaccine effectiveness studies using simulated comparator populations: application to rotavirus vaccination in the UK. Vaccine, 36 (45). 6674 - 6682.

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Abstract

Background:Measuring vaccine effectiveness (VE) relies on the use of observational study designs.However, achieving robust estimates of direct and indirect VE is frequently compromised by bias, partic-ularly when using syndromic diagnoses of low-specificity.Methods:In order to mitigate confounding between the measured outcome and vaccine uptake, we devel-oped a method to balance comparator populations using individual-level propensity scoring derived fromthe vaccine-exposed population, and applied it to the unexposed comparator population. Indirect VE wasestimated by comparing the unvaccinated vaccine-exposed group with a propensity score-simulatedunvaccinated, unexposed group. Direct VE was derived by removing indirect VE from the overall VE.We applied this method to an evaluation of the effectiveness of infant rotavirus vaccination in the UK.Using a general practice cohort of 45,259 live births between May 2010 and December 2015, we calculatedindirect and direct VE against consultations for acute gastroenteritis using conventional and vaccination-propensity adjustment comparator populations.Results:The overall VE during the rotavirus-season (January-May) calculated using mixed-effects Coxregression was 30% [95% confidence intervals (95% CI: 25,35%)]. Use of conventional comparator popula-tions resulted in implausible VE estimates 14% (95% CI: 41,7%) for direct and 29% (95% CI: 14,42%) forindirect effects. Applying our alternative method, direct VE was 26% (95% CI: 1,45%) and indirect VE was 8%(95% CI: 19,29%).Conclusions:Estimating VE using propensity score simulated comparator populations, particularly forstudies using routine health data with syndromic, low-specificity endpoints will aid accurate measure-ment of the broader public health impact of a vaccine programme.Ó2018 The Authors. Published by Elsevier Ltd. ThisisanopenaccessarticleundertheCCBYlicense

Item Type: Article
Uncontrolled Keywords: Rotavirus vaccines, Gastroenteritis, Vaccine effectiveness, Epidemiologic methods, Bias, Propensity score
Depositing User: Symplectic Admin
Date Deposited: 08 Oct 2018 09:31
Last Modified: 27 Nov 2020 10:16
DOI: 10.1016/j.vaccine.2018.09.051
Open Access URL: https://www.sciencedirect.com/science/article/pii/...
Related URLs:
URI: http://livrepository.liverpool.ac.uk/id/eprint/3027173