Vink 2017.

Methods	Study design: randomised, open‐label Duration: 12 months after the last dose
Participants	Inclusion criteria Setting: outpatient Country: Japan, single centre Number: 60 participants; treatment (N = 30), control (N = 30) Participants' health status: healthy participants Age: mean 61.9 years Sex: 50% female Other relevant information: aged ≥ 50 years 100% Asians Exclusion criteria "i) any investigational or non‐registered drug/vaccine within 30 days; ii) any immunosuppressants or immune‐modifying drugs within 6 months before study start; iii) allergic to any vaccine component, iv) history of herpes zoster, v) previously vaccinated against herpes zoster or varicella. vi) underlying illness, pregnancy, or planning to get pregnant"
Interventions	Treatment group HZ/su subcutaneous in deltoid region (2 doses with a 2‐month interval, 0.5 mL per dose); N = 30 Control group HZ/su intramuscular in deltoid region (2 doses with a 2‐month interval, 0.5 mL per dose); N = 30 Observation: 50 mg of recombinant VZV gE combined with the AS01B Adjuvant System per dose
Outcomes	Cases of herpes zoster Safety and reactogenicity: Injection site reactions (pain, swelling, redness, pruritus at the injection site and impaired movement/range of motion of the vaccinated arm) and systemic symptoms (fatigue, fever, gastrointestinal symptoms, headache, myalgia, and shivering) recorded 7 days after each injection All unsolicited adverse events were recorded for 30 days after each injection. Serious adverse events at 12 months after last dose Study withdrawals and medical conditions Dropouts
Purpose of the study	"This study was conducted to evaluate the safety and immunogenicity of the HZ/su candidate vaccine in Japanese adults 50 years old or older when HZ/su was administered SC compared to IM"
Funding sources	GlaxoSmithKline Biologicals SA, Rixensart, Belgium and Japan Vaccine Company, Tokyo, Japan
Conflicts of interest	"Peter Vink and Martine Douha are employees of the GlaxoSmithKline group of companies and, as such, are compensated by GSK for work both related and unrelated to the submitted work. Peter Vink receives GSK stock equity as part of his compensation. Himal Lal and Thomas Heineman were employees of GSK and received salary and stock as compensation at the time of the study design, conduct, and interpretation of data and writing of manuscript. Himal Lal is currently an employee of Pfizer. Thomas Heineman is currently an employee of Genocea Biosciences. Masayuki Ogawa and Masahiro Eda are employees of the Japan Vaccine Company. Masanari Shiramoto declares having no potential conflicts of interest."
Notes	ITT analyses In the publication of the results on ClinicalTrials.gov data "per participant" are provided. This is where we obtained the data for analyses. In the journal article the data were published as "per dose" and not "per participant". We extracted the published data from clinicaltrials.gov/ct2/show/results/NCT01777321.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	High risk	Open‐label RCT
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label RCT
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label RCT
Incomplete outcome data (attrition bias) All outcomes	Low risk	Clear patient flow
Selective reporting (reporting bias)	Low risk	All data that the authors proposed in their methodology were presented in the results.
Other bias	Unclear risk	Insufficient information

AE: adverse event or adverse experiences
 AMP: Alternative Manufacturing Process
 AS01: liposome‐based adjuvant system containing the immunoenhancers 3‐O‐desacyl‐4′‐monophosphoryl lipid A (MPL) and the saponin QS‐21 (Quillaja saponaria Molina, fraction 21)
 Adjuvant gE/AS01_B: 50 μg purified gE with adjuvant B (1 mg dioleoyl phosphatidylcholine, 250 μg cholesterol, 50 μg MPL, and 50 μg QS‐21)
 Adjuvant gE/AS01_E: 50 μg purified gE with adjuvant E (500 μg dioleoyl phosphatidylcholine, 125 μg cholesterol, 25 μg MPL, and 25 μg QS‐21)
 AS01_B: adjuvant B composed of 1 mg dioleoyl phosphatidylcholine, 250 μg cholesterol, 50 μg MPL, and 50 μg QS‐21
 AS01_E: adjuvant E composed of 500 μg dioleoyl phosphatidylcholine, 125 μg cholesterol, 25 μg MPL, and 25 μg QS‐21
 Elderly or older adults: aged ≥ 60 years old
 Frozen: −15 °C or colder
 gE: recombinant subunit VZV composed of glycoprotein E
 gE/saline: unadjuvanted gE
 GSK: GlaxoSmithKline
 HLZV or heat LZV: heat‐treated LZV
 HZ: herpes zoster
 HZ/su: herpes zoster subunit vaccine
 ID: identification
 IIV4: inactivated quadrivalent influenza vaccines
 IM: intramuscular
 ISRs: injection site adverse reactions
 ITT: intention‐to‐treat
 Live zoster vaccine AMP: Alternative Manufacturing Process of live attenuated zoster vaccine
 LZV or ZV: live zoster vaccine (live attenuated Oka varicella zoster virus vaccine)
 mo: month
 MPL: immunoenhancer 3‐O‐desacyl‐4′‐monophosphoryl lipid A
 MSD: Merck Sharp & Dohme Corp
 NNTB: number needed to treat for an additional beneficial outcome
 NNTH: number needed to treat for an additional harmful outcome
 PCR: polymerase chain reaction
 pfu: plaque‐forming units
 pIMDs: potential immune‐mediated diseases
 PPSV23 or pneumo‐23 vaccine: 23–valent pneumococcal polysaccharide vaccine
 QS‐21: immunoenhancer saponin Quillaja saponaria Molina, fraction 21
 RCT: randomised controlled trial
 Refrigerated: 2 °C to 8 °C
 RZV or HZ/su or GSK 1437173A: adjuvant recombinant zoster vaccine (contains 50 µg of recombinant VZV glycoprotein E, and the liposome‐based AS01_B adjuvant system contains 50 µg of 3‐O‐desacyl‐4′‐monophosphoryl lipid A (MPL) and 50 µg Quillaja saponaria Molina, fraction 21 (QS21))
 SAEs: serious adverse events
 SC: subcutaneously or subcutaneous
 TDaPV: tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine
 VZV: varicella zoster virus
 V212: heat‐treated VZV vaccine
 Zoster vaccine 1‐mo schedule: ZV 2 doses given 1 month apart
 Zoster vaccine 3‐mo schedule: ZV 2 doses given 3 months apart