cb‐Schink 2014.

Study characteristics
Methods	Matched cohort study, Germany
Participants	Claims data of more than 17 million insures in the German Pharmacoepidemiological Research Database. All children born between 1 January 2004 and 31 December 2008 who received a 1st dose of MMRV vaccine were matched to children vaccinated with MMR, MMR+V and MMR or MMR+V.
Interventions	MMRV: Priorix‐Tetra (GSK) compared to MMR and V vaccines (MMR+V). Vaccinations were identified by outpatient codes used for reimbursement of administration of vaccines. For MMR and V vaccines, these codes cover all brands available in Germany from different manufacturers. Vaccine dispensations in the pharmacy could not be considered, as physicians generally use vaccines kept in their own medical practices.
Outcomes	Febrile convulsions: diagnosis of FC, i.e. an ICD‐10‐GM code R56.0 in any of the hospital diagnoses 2 outcome definitions: The primary outcome “FC narrow” was defined as hospitalisation where no alternative plausible cause of FC. This endpoint included: (i) all hospitalisations with FC as main discharge diagnosis; (ii) all hospitalisations with FC as main admission diagnosis and without a main discharge diagnosis of an infectious disease (except measles, mumps, rubella, or chickenpox) or a neurological condition; (iii) all hospitalisations with FC as secondary or ancillary diagnosis and a main discharge diagnosis coded as complication following immunisation (ICD‐10‐GM code “T88.0 infection following immunization” or “T88.1 other complications following immunization, not elsewhere classified”). Due to exclusion of alternative causes of FC in this outcome definition, it was assumed that it would have higher specificity, but lower sensitivity. The secondary outcome “FC Jacobsen”: only hospitalisations for FC with a neurological condition coded as main discharge diagnosis were excluded. Consequently, “FC Jacobsen” included: (i) all hospitalisations with FC as main discharge diagnosis; (ii) all hospitalisations with FC as main admission diagnosis and without a main discharge diagnosis of a neurological condition; and (iii) all hospitalisations with FC as secondary or ancillary diagnosis and with a main discharge diagnosis coded as complication following immunisation. “FC narrow” cases are a subset of “FC Jacobsen” cases.
Funding Source	Pharmaceutical industry
Notes	Conclusions: this study in children younger than 5 years, 90% of them between 11 and 23 months, shows a risk of FC similar in magnitude for Priorix‐Tetra as has previously been reported for ProQuad, suggesting a class effect for these quadrivalent vaccines.
Risk of bias
Bias	Authors' judgement	Support for judgement
PCS/RCS ‐ exposed cohort selection	Low risk	Adequate ‐ German Pharmacoepidemiological Research Database
PCS/RCS ‐ non‐exposed cohort selection	Low risk	Adequate ‐ German Pharmacoepidemiological Research Database
PCS/RCS ‐ comparability	Low risk	Adequate ‐ matched for age, sex, a prior FC, hospitalisation for an infectious disease 15 days before until 30 days after vaccination, administration of other vaccines 30 days prior to 30 days after immunisation with MMRV, MMR, or MMR+V, and calendar month of vaccination to take into account the seasonality of infectious diseases
PCS/RCS ‐ assessment of outcome	Low risk	Adequate ‐ medical record
Summary Risk of Bias assessment	Low risk	Plausible bias is unlikely to have seriously altered the results.