Chlibek 2013.

Methods	Study design: RCT phase II, parallel group, placebo controlled, double‐blind Duration: 1 year after the last vaccination (14 months)
Participants	Inclusion criteria Setting: outpatient Country: 12 centres: USA (n = 7); Spain (n = 4), the Czech Republic (n = 1) Number: 410 participants; treatment (N = 372), control (N = 38) Participants' health status: healthy participants Age: mean age ˜ 65 years Sex: ˜ 57% female Other relevant information: aged ≥ 50 years ˜ 90% of participants were Caucasian (understood to be white) Exclusion criteria "Participants were excluded if they were using any investigational or non‐registered drug or vaccine within 30 days preceding the first dose of study vaccine or any non‐replicating vaccines within 2 weeks of enrolment, were receiving chronic (> 14 consecutive days) immunosuppressants or other immune‐modifying drugs within 3 months prior to enrolment (for corticosteroids, ≥0.5 mg/kg/day prednisone or equivalent), were previously vaccinated against herpes zoster or varicella, had a history of herpes zoster, allergic disease or reactions likely to be exacerbated by any component of the vaccine, had a confirmed or suspected immunosuppressive or immunodeficient condition, were administered immunoglobulins or any blood products within the 3 months preceding the first injection of study vaccine or planned to receive them during the study period, or had an acute disease at enrolment. In addition, women could not be pregnant or had to be using birth control or be of non‐childbearing potential"
Interventions	Treatment group 2 doses 2 months apart 50 μg purified adjuvant gE/AS01B 0.5 mL IM (N = 150) gE/AS01B 2 doses 2 months apart 50 μg purified adjuvant gE/AS01E 0.5 mL IM (N = 149) 2 doses 2 months apart 50 μg purified gE/saline 0.5 mL IM (N = 73) Control group 2 doses 2 months apart saline 0.5 mL IM (N = 38)
Outcomes	Participants with solicited general symptoms (fatigue, fever (recorded as temperature), headache, gastrointestinal symptoms, and myalgia) between days 0 and 6 Participants with solicited local reactions (pain, redness and swelling at the injection site) between days 0 and 6 Participants with unsolicited symptoms between days 0 and 29 after each dose Participants with temperature scored grade 3 (> 39.0 °C) Participants with other symptoms scored grade 3 for prevents normal activity Participants with redness and swelling at the injection site scored grade 3 (> 100 mm) Severe adverse events were collected for 1 year after the last vaccination and were defined as events that resulted in death, were life‐threatening, required hospitalisation or prolongation of existing hospitalisation, resulted in disability/incapacity, caused a congenital anomaly/birth defect in the child of a study participant, or could have jeopardised the participant or required medical or surgical intervention.
Purpose of the study	Immunogenicity and reactogenicity of recombinant gE in a representative older adult population
Funding sources	GlaxoSmithKline Biologicals SA, Belgium
Conflicts of interest	"R. C. has been the principal investigator in clinical studies supported by the GlaxoSmithKline group of companies and Novartis. He has also been a scientific consultant to Baxter, GSK, Novartis, Aventis Pasteur, and Pfizer and received sponsorship from GSK and Aventis Pasteur to attend scientific meetings. J. M. B. has been the principal investigator in clinical studies supported by GSK and Sanofi Pasteur MSD. He has also been a scientific consultant to GSK, Novartis, Sanofi Pasteur MSD, and Pfizer. H. C. has been principal investigator in clinical studies with GSK and other pharmaceutical companies M. L. R. D. has been the principal investigator in clinical studies supported by GSK and has received investigator fees from the Fundación Puerta de Hierro. E. L., J. F. M., and T. C. H. are employed by the GlaxoSmithKline group of companies. T. C. H. receives stock equity in GSK as part of his compensation. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed."
Notes	"Of the 410 subjects, 395 completed the study. Of the 15 participants who discontinued the study early, 2 withdrew due to treatment related AEs (1 participants each in the gE/AS01E and gE/AS01B groups) and 2 withdrew for SAEs not considered treatment related (digestive tract haemorrhage in the gE/AS01E group and myocardial infarction in the gE/AS01B group), 2 vaccine‐related adverse events led to withdrawal from the study: 1 subject treated with gE/AS01B withdrew due to malaise beginning on the day of vaccination, and 1 participants treated with gE/AS01E withdrew due to injection site redness that lasted > 2 weeks. 2 lost to follow‐up (gE/AS01B), 8 consent withdrawal (4 in the gE/AS01B, 2 in the gE/AS01E, 1 in the gE/saline and 1 after second dose of vaccine in the group gE/AS01B). 1 protocol violation (gE/AS01E)" The only unsolicited symptom reported by > 3% of participants in any group was chills, which was reported by 5% (8/150) of participants treated with gE/AS01B and 2% (3/149) of those treated with gE/AS01E; this was not reported in participants treated with gE/saline or saline alone. No vaccine‐related serious adverse events or cases of herpes zoster were reported through month 14 of the study. We asked the study authors about adverse events by age or vaccination, but the response we received reiterated only the published data.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"The randomisation was made using an algorithm that stratified by country, minimized for age, and included a block size of 11"
Allocation concealment (selection bias)	Low risk	"Treatments were allocated at each site using a central randomisation system on the Internet"
Blinding (performance bias and detection bias) All outcomes	Low risk	"The person in charge of the vaccination accessed the randomisation system on Internet using the subject number and age"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Both vaccine recipients and observers responsible for evaluations were blinded to which formulation was administered"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"Both vaccine recipients and observers responsible for evaluations were blinded to which formulation was administered"
Incomplete outcome data (attrition bias) All outcomes	Low risk	The patient flow is clear.
Selective reporting (reporting bias)	Low risk	The adverse events originally defined by the authors were presented for all groups.
Other bias	Unclear risk	Insufficient information