Vermeulen 2012

Methods	Randomised, double‐blind, placebo‐controlled, multicentre study: United States (5 sites) and the Netherlands (1 site) Duration: 6 months after the second vaccination
Participants	N = 209 healthy participants ≥ 60 years with a history of varicella and no prior HZ The mean age at enrolment was 68.7 years for the ZV group and 70.7 years for the placebo group, ˜48% ≥ 70 years old and 8% ≥ 80 years old > 60% women Almost all white participants (97.1% in both groups)
Interventions	1. Lyophilised zoster vaccine (frozen) SC (∼23,000 pfu); N = 104 2. Placebo SC; N = 105
Outcomes	Adverse events (AEs), both injection site and/or systemic. Swelling, redness, pain or tenderness or rash at the injection site, or varicella(‐like) rash or HZ(‐like) rash, any serious AEs (SAEs)
Purpose of the Study	"To examine the safety, tolerability and immunogenicity after 1 and 2 doses of zoster vaccine in adults 60 years of age and older"
Funding sources	Merck Sharp Dohme Corp
Notes	The first and second doses were administered 42 days apart (post‐vaccination 1 and post‐vaccination 2) 1 participant withdrew consent before vaccination in the vaccine group Discontinued after first vaccination vaccine group: clinical AE = 3, withdrew consent = 1, no participants lost follow‐up or due to protocol deviation, other = 2 Discontinued after first vaccination placebo group: 1 participant due to clinical AE, no participants lost to follow‐up, 1 withdrew consent, 1 participant due to protocol deviation and 1 for other reason Discontinued after second vaccination vaccine group: only 1 participant due to clinical AE Discontinued after second vaccination placebo group: 1 to lost follow‐up and 2 for other reasons No ITT analysis
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Subjects were randomised in a 1:1 ratio to receive 2 doses of either ZV or placebo, according to a computer‐generated, study‐centre specific allocation schedule"
Allocation concealment (selection bias)	Low risk	"Allocation numbers were assigned sequentially by the study site personnel to subjects who met the study eligibility criteria, beginning with the lowest number available at the study centre, after informed consent and medical history had been obtained. The allocation schedule was generated by a sponsor statistician not otherwise associated with the ZV program"
Blinding (performance bias and detection bias) All outcomes	Low risk	"The subject, investigator, clinical study site personnel, and sponsor personnel directly involved in the study were blinded to whether the subject received zoster vaccine or placebo. They remained blinded until all subjects completed the study"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"The clinical materials were prepared by an unblinded vaccine coordinator at each clinical site, because of differences in the turbidity of the study vaccine and placebo. Each vial of vaccine or placebo was labelled with a subject‐specific allocation number. The unblended vaccine coordinator reconstituted the study vaccine/placebo and wrapped the syringe in an opaque label containing subject allocation number and time of reconstitution. The unblinded vaccine coordinator did not have any contact with the subject and did not disclose the contents of the syringe to the person administering the study vaccine/placebo"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Low risk	Clear patient flow
Selective reporting (reporting bias)	Low risk	All adverse events listed by the authors were described in their results for both vaccinations
Other bias	Unclear risk	Not described