Lal 2018.

Methods	Study design: phase 3, randomised, multicentre, open‐label Duration: 12 months post‐dose 2
Participants	Inclusion criteria Setting: outpatient Country: USA and Estonia Number: 354 participants; treatment (N = 235), control (N = 119) Participants' health status: healthy participants Age: mean ˜ 64.2 years Sex: 69.5% female Other relevant information: aged ≥ 50 years Majority of Caucasian/European (understood to be white) Exclusion criteria "Female participants had to be of non‐child bearing potential or have a negative pregnancy test on the day of vaccination and meet the contraceptive requirements as outlined in the protocol. Adults were excluded from participation in the study if they had taken any investigational or non‐registered product other than the study vaccine, were administered or planned to receive a live or non replicating vaccine for the protocol‐specified time period, had a history of HZ, received previous vaccination against varicella or HZ, or had a history of reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. Chronic administration of immunosuppressants or other immune‐modifying drugs within 6 months prior to the first vaccine dose, or any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy also resulted in exclusion."
Interventions	Treatment group RZV (2 doses: first dose month 0 and second dose month 6) IM (N = 119) RZV (2 doses: first dose month 0 and second dose month 12) IM (N = 116) Control group RZV (2 doses: first dose month 0 and second dose month 2) IM (N = 119)
Outcomes	Suspected herpes zoster cases Solicited local and general symptoms within 7 days after each vaccination Unsolicited adverse events within 30 days after each vaccination Serious adverse events during the course of the entire study 12 months post‐dose 2, for each participant Potential immune‐mediated diseases during the course of the entire study 12 months post‐dose 2, for each participant Dropouts (consent withdrawal, lost to follow‐up, or others) Death
Purpose of the study	Immunogenicity, reactogenicity, and safety following administration of 2 HZ/su doses at intervals longer than 2 months (2 doses 6 months apart and 2 doses 12 months apart)
Funding sources	GlaxoSmithKline Biologicals SA
Conflicts of interest	“LC, BG, LO, CVA are employees, and TCH and HL former employees, of the GSK group of companies. BG, TCH, HL, LO hold shares in the GSK group of companies as part of their current or former employee remuneration. HL is employed by Pfizer Inc and receives stock as part of his remuneration. TCH is the co‐inventor of a patent application related to the vaccine used in this study and is currently a consultant for the GSK group of companies. AP declares that she has no conflict of interest.”
Notes	For data analyses, only clinical safety outcomes were used. The intensity of all AEs was graded on a scale from 1 to 3. Grade 3 solicited symptoms were defined as ‘‘preventing normal every day activity” (pain, headache, fatigue, gastrointestinal symptoms, myalgia, shivering); surface diameter > 100 mm (redness/swelling); tympanic/oral/axillary temperature > 39.0 °C (fever). Grade 3 unsolicited AEs were also defined as ‘‘preventing normal, every day activities”. All solicited local reactions were considered causally related to vaccination. The causality of all other AEs was assessed by the investigator. We contacted Dr Lal requesting details about the reasons for the dropouts and if there was any consent withdraw. He promptly sent us a table with these data.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"1:1:1, to receive 2 doses of HZ/su according to a 0, 2‐month (group [Gr] 0–2), 0, 6‐month (Gr 0–6) or 0, 12‐month (Gr 0–12) schedule, using an online centralized randomisation system"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	High risk	Open‐label study
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label study
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Clear patient flow
Selective reporting (reporting bias)	Low risk	All of the adverse events listed in the methods section were described in the results.
Other bias	Unclear risk	Insufficient information