Efficacy, effectiveness, and safety of herpes zoster vaccines in adults aged 50 and older: systematic review and network meta-analysis

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Abstract

Objective

To compare the efficacy, effectiveness, and safety of the herpes zoster live attenuated vaccine with the herpes zoster adjuvant recombinant subunit vaccine or placebo for adults aged 50 and older.

Design

Systematic review with bayesian meta-analysis and network meta-analysis.

Data sources

Medline, Embase, and Cochrane Library (inception to January 2017), grey literature, and reference lists of included studies.

Eligibility criteria for study selection

Experimental, quasi-experimental, and observational studies that compared the live attenuated vaccine with the adjuvant recombinant subunit vaccine, placebo, or no vaccine in adults aged 50 and older. Relevant outcomes were incidence of herpes zoster (primary outcome), herpes zoster ophthalmicus, post-herpetic neuralgia, quality of life, adverse events, and death.

Results

27 studies (22 randomised controlled trials) including 2 044 504 patients, along with 18 companion reports, were included after screening 2037 titles and abstracts, followed by 175 full text articles. Network meta-analysis of five randomised controlled trials found no statistically significant differences between the live attenuated vaccine and placebo for incidence of laboratory confirmed herpes zoster. The adjuvant recombinant subunit vaccine, however, was statistically superior to both the live attenuated vaccine (vaccine efficacy 85%, 95% credible interval 31% to 98%) and placebo (94%, 79% to 98%). Network meta-analysis of 11 randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more adverse events at injection sites than the live attenuated vaccine (relative risk 1.79, 95% credible interval 1.05 to 2.34; risk difference 30%, 95% credible interval 2% to 51%) and placebo (5.63, 3.57 to 7.29 and 53%, 30% to 73%, respectively). Network meta-analysis of nine randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more systemic adverse events than placebo (2.28, 1.45 to 3.65 and 20%, 6% to 40%, respectively).

Conclusions

Using the adjuvant recombinant subunit vaccine might prevent more cases of herpes zoster than using the live attenuated vaccine, but the adjuvant recombinant subunit vaccine also carries a greater risk of adverse events at injection sites.

Protocol registration

Prospero CRD42017056389.

Related collections

Most cited references 40

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Evaluation of inconsistency in networks of interventions.

Areti Angeliki Veroniki, Haris Vasiliadis, Julian P.T. Higgins … (2013)

The assumption of consistency, defined as agreement between direct and indirect sources of evidence, underlies the increasingly popular method of network meta-analysis. No evidence exists so far regarding the extent of inconsistency in full networks of interventions or the factors that control its statistical detection. In this paper we assess the prevalence of inconsistency from data of 40 published networks of interventions involving 303 loops of evidence. Inconsistency is evaluated in each loop by contrasting direct and indirect estimates and by employing an omnibus test of consistency for the entire network. We explore whether different effect measures for dichotomous outcomes are associated with differences in inconsistency, and evaluate whether different ways to estimate heterogeneity affect the magnitude and detection of inconsistency. Inconsistency was detected in from 2% to 9% of the tested loops, depending on the effect measure and heterogeneity estimation method. Loops that included comparisons informed by a single study were more likely to show inconsistency. About one-eighth of the networks were found to be inconsistent. The proportions of inconsistent loops do not materially change when different effect measures are used. Important heterogeneity or the overestimation of heterogeneity was associated with a small decrease in the prevalence of statistical inconsistency. The study suggests that changing the effect measure might improve statistical consistency, and that an analysis of sensitivity to the assumptions and an estimator of heterogeneity might be needed before reaching a conclusion about the absence of statistical inconsistency, particularly in networks with few studies.

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Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses.

Fujian Song, Douglas G. Altman, Anne-Marie Glenny … (2003)

To determine the validity of adjusted indirect comparisons by using data from published meta-analyses of randomised trials. Direct comparison of different interventions in randomised trials and adjusted indirect comparison in which two interventions were compared through their relative effect versus a common comparator. The discrepancy between the direct and adjusted indirect comparison was measured by the difference between the two estimates. Database of abstracts of reviews of effectiveness (1994-8), the Cochrane database of systematic reviews, Medline, and references of retrieved articles. 44 published meta-analyses (from 28 systematic reviews) provided sufficient data. In most cases, results of adjusted indirect comparisons were not significantly different from those of direct comparisons. A significant discrepancy (P<0.05) was observed in three of the 44 comparisons between the direct and the adjusted indirect estimates. There was a moderate agreement between the statistical conclusions from the direct and adjusted indirect comparisons (kappa 0.51). The direction of discrepancy between the two estimates was inconsistent. Adjusted indirect comparisons usually but not always agree with the results of head to head randomised trials. When there is no or insufficient direct evidence from randomised trials, the adjusted indirect comparison may provide useful or supplementary information on the relative efficacy of competing interventions. The validity of the adjusted indirect comparisons depends on the internal validity and similarity of the included trials.

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Is Open Access

Is network meta-analysis as valid as standard pairwise meta-analysis? It all depends on the distribution of effect modifiers

Jeroen P Jansen, Huseyin Naci (2013)

Background In the last decade, network meta-analysis of randomized controlled trials has been introduced as an extension of pairwise meta-analysis. The advantage of network meta-analysis over standard pairwise meta-analysis is that it facilitates indirect comparisons of multiple interventions that have not been studied in a head-to-head fashion. Although assumptions underlying pairwise meta-analyses are well understood, those concerning network meta-analyses are perceived to be more complex and prone to misinterpretation. Discussion In this paper, we aim to provide a basic explanation when network meta-analysis is as valid as pairwise meta-analysis. We focus on the primary role of effect modifiers, which are study and patient characteristics associated with treatment effects. Because network meta-analysis includes different trials comparing different interventions, the distribution of effect modifiers cannot only vary across studies for a particular comparison (as with standard pairwise meta-analysis, causing heterogeneity), but also between comparisons (causing inconsistency). If there is an imbalance in the distribution of effect modifiers between different types of direct comparisons, the related indirect comparisons will be biased. If it can be assumed that this is not the case, network meta-analysis is as valid as pairwise meta-analysis. Summary The validity of network meta-analysis is based on the underlying assumption that there is no imbalance in the distribution of effect modifiers across the different types of direct treatment comparisons, regardless of the structure of the evidence network.

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Author and article information

Contributors

Andrea C Tricco:

ORCID: http://orcid.org/0000-0002-4114-8971

Role: scientist and associate professor

Wasifa Zarin: Role: research manager

Roberta Cardoso: Role: research coordinator

Areti-Angeliki Veroniki: Role: scientist

Paul A Khan: Role: research coordinator

Vera Nincic: Role: research coordinator

Marco Ghassemi: Role: research coordinator

Rachel Warren: Role: research assistant

Jane P Sharpe: Role: research assistant

Andrea V Page: Role: staff physician and assistant professor

Sharon E Straus: Role: professor and interim physician in chief

Journal

Journal ID (nlm-ta): BMJ

Journal ID (iso-abbrev): BMJ

Journal ID (publisher-id): BMJ-UK

Journal ID (hwp): bmj

Title: The BMJ

Publisher: BMJ Publishing Group Ltd.

ISSN (Print): 0959-8138

ISSN (Electronic): 1756-1833

Publication date Collection: 2018

Publication date (Electronic): 25 October 2018

Volume: 363

Electronic Location Identifier: k4029

Affiliations

[1 ]Knowledge Translation Program, Li Ka Shing Knowledge Institute, St Michael’s Hospital, 209 Victoria Street, East Building, Toronto, M5B 1W8, ON, Canada

[2 ]Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, M5T 3M7, ON, Canada

[3 ]Division of Infectious Diseases, Mount Sinai Hospital, Joseph and Wolf Lebovic Health Complex, Toronto, ON, Canada

[4 ]Department of Medicine, University of Toronto, Toronto, ON, Canada

[5 ]St Michael’s Hospital, Toronto, ON, Canada

Author notes

Correspondence to: A C Tricco triccoa@ 123456smh.ca (or @atricco on Twitter)

Author information

Andrea C Tricco http://orcid.org/0000-0002-4114-8971

Article

Publisher ID: tria044865

DOI: 10.1136/bmj.k4029

PMC ID: 6201212

PubMed ID: 30361202

SO-VID: 8d71c1b1-5a87-4ede-977f-1760c53fbc46

License:

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

Efficacy, effectiveness, and safety of herpes zoster vaccines in adults aged 50 and older: systematic review and network meta-analysis

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Abstract

Objective

Design

Data sources

Eligibility criteria for study selection

Results

Conclusions

Protocol registration

Related collections

Vaccines

Most cited references 40

Evaluation of inconsistency in networks of interventions.

Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses.

Is network meta-analysis as valid as standard pairwise meta-analysis? It all depends on the distribution of effect modifiers

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