Tyring 2007.

Methods	Study design: randomised clinical trial, blinded to participant, investigator, and sponsor Duration: 42 days postvaccination
Participants	Inclusion criteria Setting: outpatient Country: 18 sites in the USA, Canada, the UK, Germany, and Belgium Number: 692 participants; treatment (N = 459), control (N = 233) Participants' health status: healthy participants with varicella history‐positive (or resident for more 30 years in a country with endemic VZV infection), herpes zoster history‐negative Age: mean 64.4 years Sex: ˜ 59.3% female Other relevant information: aged ≥ 50 years 92.6% Caucasian (understood to be white) Exclusion criteria History of hypersensitivity reaction to any component of the vaccine; prior receipt of any varicella or zoster vaccine; recent receipt of immune globulin or blood products, or both; live or inactivated vaccine during the study period; known immune dysfunction; concomitant use of antiviral therapy with activity against herpesviruses; and participation in an investigational drug or vaccine study within 30 days prior to vaccination
Interventions	Treatment group Higher‐potency LZV (frozen) SC (˜ 207,000 pfu/0.65 mL dose); N = 459 Control group Lower‐potency LZV (frozen) SC (˜ 58,000 pfu/0.65 mL dose); N = 233
Outcomes	Herpes zoster or herpes zoster‐like rash, varicella or varicella‐like rash, local and systemic clinical adverse events and tolerability of both interventions
Purpose of the study	"To compare the safety and tolerability profile of a higher potency zoster vaccine (˜207,000 plaque forming units (PFU)/0.65‐mL dose) with that of a lower potency vaccine (˜58,000 PFU/0,65‐mL dose)"
Funding sources	Merck Research Laboratories
Conflicts of interest	Nickoya D Bundick, Jianjun Li, Ivan SF Chang, Jon E Stek, and Paula W Annunziato are representatives of Merck & Co Inc, West Point, PA, USA.
Notes	Lower‐potency zoster vaccine in this study was similar to vaccine potencies studied in Oxman 2005. Randomised 2:1 ratio to receive 1 injection of each 3 participants were discontinued from the study: 2 participants were lost to follow‐up in the higher‐potency zoster vaccine group, and 1 participant in the lower‐potency zoster vaccine group withdrew consent prior to completion of the follow‐up period, but was included in the safety analyses. No ITT analyses (the participants who completed the study were considered)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Low risk	Blinded participants, investigator, and sponsor
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The 2 potency formulations were indistinguishable in appearance. All participants received a single 0.65 mL subcutaneous injection of either the higher‐potency zoster vaccine or the lower‐potency zoster vaccine.
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	The adverse events prespecified in the methods section were reported in the results for both higher‐potency and lower‐potency zoster vaccines.
Other bias	Unclear risk	Insufficient information