• Andrea C Tricco, Wasifa Zarin, Roberta Cardoso, Areti-Angeliki Veroniki, Paul A Khan, Vera Nincic, Marco Ghassemi, Rachel Warren, Jane P Sharpe, Andrea V Page, and Sharon E Straus.
• Knowledge Translation Program, Li Ka Shing Knowledge Institute, St Michael's Hospital, 209 Victoria Street, East Building, Toronto, M5B 1W8, ON, Canada triccoa@smh.ca.
• BMJ. 2018 Oct 25; 363: k4029.

ObjectiveTo compare the efficacy, effectiveness, and safety of the herpes zoster live attenuated vaccine with the herpes zoster adjuvant recombinant subunit vaccine or placebo for adults aged 50 and older.DesignSystematic review with bayesian meta-analysis and network meta-analysis.Data SourcesMedline, Embase, and Cochrane Library (inception to January 2017), grey literature, and reference lists of included studies.Eligibility Criteria For Study SelectionExperimental, quasi-experimental, and observational studies that compared the live attenuated vaccine with the adjuvant recombinant subunit vaccine, placebo, or no vaccine in adults aged 50 and older. Relevant outcomes were incidence of herpes zoster (primary outcome), herpes zoster ophthalmicus, post-herpetic neuralgia, quality of life, adverse events, and death.Results27 studies (22 randomised controlled trials) including 2 044 504 patients, along with 18 companion reports, were included after screening 2037 titles and abstracts, followed by 175 full text articles. Network meta-analysis of five randomised controlled trials found no statistically significant differences between the live attenuated vaccine and placebo for incidence of laboratory confirmed herpes zoster. The adjuvant recombinant subunit vaccine, however, was statistically superior to both the live attenuated vaccine (vaccine efficacy 85%, 95% credible interval 31% to 98%) and placebo (94%, 79% to 98%). Network meta-analysis of 11 randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more adverse events at injection sites than the live attenuated vaccine (relative risk 1.79, 95% credible interval 1.05 to 2.34; risk difference 30%, 95% credible interval 2% to 51%) and placebo (5.63, 3.57 to 7.29 and 53%, 30% to 73%, respectively). Network meta-analysis of nine randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more systemic adverse events than placebo (2.28, 1.45 to 3.65 and 20%, 6% to 40%, respectively).ConclusionsUsing the adjuvant recombinant subunit vaccine might prevent more cases of herpes zoster than using the live attenuated vaccine, but the adjuvant recombinant subunit vaccine also carries a greater risk of adverse events at injection sites.Protocol RegistrationProspero CRD42017056389.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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