Lal 2015.
| Methods |
Study design: randomised, double‐blind, placebo controlled Duration: mean follow‐up of 3.2 years |
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| Participants |
Inclusion criteria Setting: outpatient Country: 18 countries in Europe, North America, Latin America, Asia, and Australia Number: 15,411 participants; treatment (N = 7698), control (N = 7713) Participants' health status: healthy participants Age: mean age ˜ 62.4 years Sex: ˜ 61.2% female Other relevant information: aged ≥ 50 years ˜ 71.5% Caucasian (understood to be white) The majority from Europe: 51.2% Exclusion criteria A history of herpes zoster, previously vaccinated against varicella or herpes zoster, or had an immunosuppressive condition |
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| Interventions |
Treatment group
Control group
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| Outcomes |
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| Purpose of the study | "The primary objective of the study was to evaluate overall vaccine efficacy in reducing the risk of herpes zoster, as compared with placebo. Secondary objectives included determining the vaccine efficacy in reducing the incidence of herpes zoster in each age group (50 to 59 years, 60 to 69 years, and ≥70 years) and HZ/su safety and reactogenicity profiles." | |
| Funding sources | GlaxoSmithKline Biologicals | |
| Conflicts of interest | “The authors’ affiliations are as follows: GSK Vaccines, King of Prussia, PA (H.L., T.C.H.); Westmead Millennium Institute for Medical Research, Westmead, NSW, and the University of Sydney, Sydney — both in Australia (A.L.C.); GSK Vaccines, Wavre, Belgium (O.G., T.Z.); Faculty of Military Health Sciences, University of Defense, Hradec Kralove, Czech Republic (R.C.); Vaccine Research Unit, Fundación para el Fomento de la Investigación Sanitaria y Biomédica, Valencia, Spain (J.D.‐D., J.P.‐B.); Department of Family Medicine, Taipei Veterans General Hospital, and National Yang Ming University School of Medicine ‐ both in Taipei, Taiwan (S.‐J.H.); University of Colorado Anschutz Medical Campus, Aurora (M.J.L.); Advanced Medical Research Institute of Canada, Sudbury, ON (J.E.M.); Tartu University Hospital, Tartu, Estonia (A.P.); Vaccine Research Center, University of Tampere, Tampere, Finland (T.V.); Department of Dermatology, Aichi Medical University, Nagakute, Aichi, Japan (D.W.); and Centro de Referencia de Imunobiológicos Especiais, Universidade Federal de São Paulo, São Paulo (L.W.).” | |
| Notes |
We used the available data for efficacy by age ≥ 60 years (a total of 8,122 participants) and contacted the authors requesting adverse events by age, however the data were not provided. We therefore used the adverse events published for ≥ 50 years (a total of 15,411 participants). A total of 16,160 participants were enrolled, of which 749 were excluded from the efficacy analyses, mostly due to deviations from Good Clinical Practice standards at 2 study centres (involving 726 participants). The remaining 15,411 participants constituted the total vaccinated cohort for analysis, of which 14,759 (95.8%) were included in the modified vaccinated cohort, however we did not consider this last cohort since we used ITT analysis. Efficacy analysis only used data from participants aged 60 and over. Most participants received 2 doses of the study vaccines (95.6% of herpes zoster subunit vaccine recipients and 96.4% of placebo recipients). "A reactogenicity subgroup of participants. This subgroup included all participants who were 70 years of age or older and randomly selected participants in the two other age groups (50 to 59 years and 60 to 69 years). The participants rated the intensity of the solicited reactions on a scale from 0 (absent) to 3 (preventing normal everyday activities). Unsolicited adverse events were recorded for 30 days after each dose. Serious adverse events were recorded in all participants for up to 12 months after the second dose. Such events that were considered to be related to the study vaccine or study participation, any events resulting in death, and potentially immune‐mediated diseases were evaluated in all participants over the entire study period. (A full list of potentially immune‐mediated diseases is provided in the Supplementary Appendix.)" We contacted the authors of this study asking for details about why the participants did not receive dose 2. We received a response, but the authors could not provide this information because "the ZOE‐50 study, which was the subject of the NEJM report, is still ongoing and consequently blinded at the subject level. Therefore, information on the specific reasons for non‐receipt of the second vaccine or placebo dose is not presently available". |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "We randomly assigned participants in a 1:1 ratio to receive either vaccine or placebo using an online centralized randomization system" |
| Allocation concealment (selection bias) | Unclear risk | Despite the sequence and random number generation being appropriate, there were no details about allocation. |
| Blinding (performance bias and detection bias) All outcomes | Low risk | "Because the appearance of the reconstituted HZ/su vaccine differed from the placebo solution, injections were prepared and administered by study staff who did not participate in any study assessment" |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | "Because the appearance of the reconstituted HZ/su vaccine differed from the placebo solution, injections were prepared and administered by study staff who did not participate in any study assessment" |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | "The investigators, participants, and those who were responsible for the evaluation of any study end point were unaware of whether vaccine or placebo had been administered" |
| Incomplete outcome data (attrition bias) All outcomes | High risk | No clear participant flow; the number of participants randomised to each group is not described for all outcomes |
| Selective reporting (reporting bias) | Low risk | All data that the authors proposed in their methodology were described in the results. |
| Other bias | Unclear risk | Insufficient information |