db‐MacDonald 2014.

Study characteristics
Methods	Person‐time cohort, Canada. From 2006 to 2012
Participants	Children 12 to 23 months of age in the province of Alberta For each vaccine administered, the authors compared the incidence of seizures in the 42‐day “observation period” following administration (comparable with clinical trials of Priorix‐Tetra and the postlicensure study of ProQuad) and the 7‐ to 10‐day “peak period” (when previous studies have indicated that febrile seizure risk is expected to be highest) with the incidence in the 42 days preceding vaccination (control period) using a risk interval analysis.
Interventions	MMRV (Priorix‐Tetra) (administered from mid‐2010 onward) and MMR+V (2006 onward)
Outcomes	Data on seizure events were obtained from the physician claims database ICD‐9 780.3* for convulsions and the ambulatory care and hospital discharge databases (ICD‐10, Canadian version, codes R56.0* for febrile convulsions), using coding consistent with other studies of febrile seizures after vaccination.
Funding Source	Government
Notes	Conclusion: combining MMR and varicella into a single vaccine decreases pain for children and distress for parents, thus addressing common barriers to vaccine uptake, and may improve vaccine coverage levels and decrease immunisation delivery costs. These potential benefits must be balanced by the increased risk (albeit small) of febrile seizures with the combination vaccine. Febrile seizures are typically self‐limiting and rarely have long‐term effects, but they can be extremely distressing for parents, may precipitate acute care visits, and may undermine confidence in immunisation programmes. It is a matter for debate whether the choice of separate versus combination vaccine is a policy decision or a choice for parents to make in consultation with their vaccination provider. If MMRV continues to be offered for first‐dose administration, it might be advisable to counsel parents regarding antipyretic use if children experience a fever within the peak risk period.
Risk of bias
Bias	Authors' judgement	Support for judgement
SCCS/PTC ‐ case selection	Low risk	Adequate ‐ independent validation
SCCS/PTC ‐ exposure	Low risk	Adequate ‐ secure record
SCCS/PTC ‐ observation and exposure risk period	Low risk	Adequate ‐ observation periods are well‐defined, exposure period appears to be well‐documented
SCCS/PTC ‐ comparability	Low risk	Adjusted for age and calendar year
Summary Risk of Bias assessment	Low risk	Plausible bias is unlikely to have seriously altered the results.