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Flexible modelling of vaccine effect in self-controlled case series models

Ghebremichael-Weldeselassie, Yonas; Whitaker, Heather J. and Farrington, C. Paddy (2016). Flexible modelling of vaccine effect in self-controlled case series models. Biometrical Journal, 58(3) pp. 607–622.

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The self-controlled case-series method (SCCS), commonly used to investigate the safety of vaccines, requires information on cases only and automatically controls all age-independent multiplicative confounders, while allowing for an age dependent baseline incidence.
Currently the SCCS method represents the time-varying exposures using step functions with pre-determined cut-points. A less prescriptive approach may be beneficial when the shape of the relative risk function associated with exposure is not known a priori, especially when exposure effects can be long-lasting. We therefore propose to model exposure effects using flexible smooth functions. Specifically, we used a linear combination of cubic M-splines which, in addition to giving plausible shapes, avoids the integral in the log-likelihood function of the SCCS model. The methods, though developed specifically for vaccines, are applicable more widely. Simulations showed that the new approach generally performs better than the step function method. We applied the new method to two data sets, on febrile convulsion and exposure to MMR vaccine, and on fractures and thiazolidinedione use.

Item Type: Journal Item
Copyright Holders: 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
ISSN: 1521-4036
Project Funding Details:
Funded Project NameProject IDFunding Body
The Open University (OU)Not SetThe Open University (OU)
Wolfson research merit awardNot SetRoyal Society
Not SetHGXF A4468MRC
Keywords: M-splines; Risk function; Self-controlled case series; Smoothing; Vaccines
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Mathematics and Statistics
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 46255
Depositing User: Heather Whitaker
Date Deposited: 10 May 2016 10:04
Last Modified: 06 May 2019 19:09
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