Schwarz 2017.
| Methods |
Study design: phase 3, randomised, open‐label Duration: 12 months after the second dose |
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| Participants |
Inclusion criteria Setting: outpatient Country: 20 centres in Canada (n = 2), Germany (n = 15), and the USA (n = 3) Number: 828 participants; treatment (N = 413), control (N = 415) Participants' health status: healthy participants Age: mean 63.4 years Sex: 51.8% female Other relevant information: aged ≥ 50 years 92% Caucasian (understood to be white) Exclusion criteria "They were excluded if they had taken (or planned to take) any investigational or non‐registered drug or vaccine, or any non study vaccine, from 30 days before study inclusion through 30 days after the second dose of HZ/su, had received influenza vaccine or had received long‐term treatment with immunosuppressant drugs or immune‐modifying drugs within 6 months before study inclusion, had received a previous VZV or HZ vaccination, or had a history of HZ" |
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| Interventions |
Treatment group
Control group
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| Outcomes | "Primary outcomes: To evaluate the vaccine response rate (VRR) to HZ/su 1 month after the second dose of the vaccine in the coadministration group, to demonstrate the non‐inferiority of anti‐gE geometric mean concentrations (GMCs) after the second dose of HZ/su in coadministration versus control group, and to demonstrate the non‐inferiority of IIV4 immunogenicity in coadministration versus control groups for each vaccine strain by comparing the geometric mean titers (GMTs) of hemagglutination inhibition (HI) antibodies Secondary outcomes: to assess the non‐inferiority of HI antibody seroconversion rates (SCRs) in the coadministration group for each IIV4 strain versus those in control group, to assess IIV4 immunogenicity for each strain in terms of GMT and in terms of the age group–specific (age 50 to 64 or ≥ 65 years) Center for Biologics Evaluation and Research (CBER) criteria for seroprotection rates (SPRs) and SCRs [17], and to evaluate the safety and reactogenicity of both vaccines when co administered or sequentially administered Safety: Solicited local reactions were injection site pain, redness, and swelling; solicited general reactions were arthralgia, fatigue, fever, gastrointestinal symptoms (nausea, vomiting, diarrhoea, abdominal pain), head‐ ache, myalgia, and shivering. Reactogenicity of the herpes zoster subunit (HZ/su) and quadrivalent seasonal inactivated influenza (IIV4) immunizations. Solicited local and general reactions are presented for the total vaccinated cohort. The coadministration (Coadmin) group received the first dose of HZ/su and the IIV4 vaccine on day 0 and the second dose of HZ/su at month 2. The control group received the IIV4 vaccine on day 0, the first dose of HZ/su at month 2, and the second dose of HZ/su dose at month 4. A, Local reactions occurring in the coadministration group within 7 days after coadministration of the first dose of HZ/su (HZ) and IIV4 or in the control group within 7 days after each vaccine was administered separately are shown for each arm. Reactions for the coadministration group were recorded concurrently for 7 days after day 0; reactions for the control group were recorded for 7 days after day 0 for IIV4 and 7 days after the first dose of HZ/su was administered at month 2. B, General reactions occurring within 7 days after the first dose of HZ/su and IIV4 coadministration in the coadministration group or within 7 days after each vaccine was administered separately in the control group. General reactions for the coadministration group were recorded for 7 days after day 0 and were attributable to both vaccines given at the same time; reactions for the control group were recorded for 7 days after day 0 for IIV4 and 7 days after the first dose of HZ/su was administered at month 2, and so were attributable to each vaccine given separately. GI, gastrointestinal symptoms. C, General reactions occurring within 7 days after administration of the second dose of HZ/su in each group. Reactions were recorded in month 2 for the coadministration group and in month 4 for the control group. A local reaction for redness or swelling was recorded if the diameter was ≥20 mm; it was recorded as grade 3 intensity if the diameter was >100 mm. Fever was recorded if the oral temperature was ≥37.5°C; it was recorded as grade 3 intensity if it was >39.0°C. Other general reactions were recorded if they were mild or easily tolerated (no interference in normal daily activity), moderate (discomfort that interfered with normal daily activity), or severe (grade 3; significant discomfort that prevented normal daily activity). Error bars represent 95% confidence intervals" |
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| Purpose of the study | To evaluate the immunogenicity and safety of an adjuvant herpes zoster subunit vaccine when co‐administered with a quadrivalent seasonal inactivated influenza vaccine (IIV4) in a phase 3, open‐label, randomised clinical trial in adults aged ≥ 50 years | |
| Funding sources | GSK Biologicals | |
| Conflicts of interest | "C. C., M. D., K. G., M. L. F., L. O., and P. V. d. S. are employees, and O. G., T. C. H., and H. L. are former employees of the GSK group of companies. C.C., O.G., T. C. H., L. O., and H. L. hold shares in the GSK group of companies as part of their actual or former employee remuneration. T. C. H. is the co inventor of a patent application related to the vaccine used in this study. T.C.H. is currently paid as a consultant for GSK and that H.L. is employed by Pfizer Inc and holds stock as part of his remuneration. T. F. S. reports receiving personal fees from GSK." | |
| Notes | No ITT analyses As there were many graphics in the journal article publication, we extracted data from clinicaltrials.gov/ct2/show/results/NCT01954251. |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Randomised 1:1 to 1 of the 2 parallel study arms using a central Internet‐based randomisation system (GSK Vaccines)" |
| Allocation concealment (selection bias) | Unclear risk | Not described |
| Blinding (performance bias and detection bias) All outcomes | High risk | Open‐label |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Open‐label |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | "Diary cards were provided to subjects at each vaccination to collect the solicited and unsolicited adverse events" |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Many outcomes were reported only as graphs. |
| Selective reporting (reporting bias) | Low risk | All data on effectiveness and adverse events proposed in the methodology were presented in the results for both groups. |
| Other bias | Unclear risk | Insufficient information |