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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Intradermal hepatitis B vaccination: a systematic review and meta-analysis

L Sangare, L Manhart, D Zehrung, and CC Wang.

Review published: 2009.

CRD summary

This review compared levels of seroprotection achieved by hepatitis B vaccine delivered intradermally and intramuscularly. The authors appeared to conclude that intradermal vaccination remained an attractive alternative to intramuscular vaccination. Overall, the results of this review should be treated with caution as the review had several methodological flaws and the authors did not state a clear conclusion.

Authors' objectives

To compare the level of seroprotection achieved by reduced-dose hepatitis B vaccine delivered intradermally with that achieved by standard-dose hepatitis vaccine delivered intramuscularly.

Searching

MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched in December 2008 for articles in any language. Search terms were reported. Reference lists of relevant articles were searched.

Study selection

Prospective studies that assessed intradermal hepatitis B vaccination in participants who were immunocompetent and naïve to hepatitis B vaccination were eligible for inclusion. Studies had to measure seroprotection one to six months after last dose and have at least 60% follow-up.

The included studies were mostly conducted in healthy adult care workers and considered intradermal vaccine alone or intradermal injection compared with intramuscular vaccine. Studies in neonates and children were included. The dosing schedule for intradermal vaccine varied and the most common dose was three doses of 2ug given at zero, one and six months. The most common dosing schedule for intramuscular vaccine was three doses of 20ug given at zero, one and six months. The type of vaccine used included Gen Hevac B, Engerix B, HB-Vax, and Heptervax-B.

Two authors independently undertook the selection process. Disagreements were resolved through discussion.

Assessment of study quality

Study validity was assessed considering four factors: method of allocation, allocation concealment, sample size, and follow-up rates. No quality scores were assigned. The authors did not state how many reviewers performed quality assessment.

Data extraction

Data were extracted on the number of participants with seroprotection (defined as the proportion of patients with anti-HBs ≥10mLU/mL measured at one to six months after the last dose) and used to calculate relative risks (RRs). One author undertook data extraction.

Methods of synthesis

A narrative synthesis was undertaken that grouped studies according to study type. Where data were deemed homogeneous, pooled relative risks together with the 95% confidence intervals (CI) were calculated using a random-effects meta-analysis. Statistical heterogeneity was assessed using the Χ2 test. Subgroups were explored narratively based on gender of participants and children/infants.

Results of the review

Thirty-three prospective studies were included in the review: 13 before-and-after studies (n=3,588), seven quasi-experimental studies (n=1,764); and 13 randomised controlled trials (RCTs) (n=2,040). Sample size of included studies ranged from 24 to 1,406 participants. The authors reported that all studies were deemed to be of similar quality.

Meta-analysis (five RCTs, n=757 participants): Participants who received hepatitis B vaccination intradermally were 14% less likely to achieve seroprotection than those who received the vaccine intramuscularly (RR 0.86, 95% CI 0.77 to 0.95). The level of heterogeneity was statistically significant (Χ2=12.06, p=0.017).

Narrative synthesis: The 13 before-and-after studies reported seroprotection rates that ranged from 68% to 100% with intradermal vaccine. In the seven quasi-experimental studies seroprotection ranged from 41% to 100% with intradermal vaccine and 87.5% to 100% with intramuscular vaccine. In the 13 RCTs, the rate of seroprotection was generally lower in the intradermal vaccine group compared with the intramuscular group.

Children and infants (six studies): In the four comparative studies, intradermal vaccine was associated with lower seroprotection than intramuscular vaccine (41% to 98% compared with 94% to 100%). In two before-and-after studies, intradermal vaccine offered 93% to 100% seroprotection. Overall, the rates of seroprotection in children and adults were higher than in adults.

Gender (six studies): The seroprotection offered by intradermal injection was marginally higher in adult females (89% to 100%) than adult males (64% to 100%).

Authors' conclusions

The authors appeared to conclude that intradermal vaccine remained an attractive alternative to intramuscular vaccines. The authors also stated that seroprotection was highest among females and children, which suggested that these populations may be most appropriate for future intradermal vaccine developments.

CRD commentary

Inclusion criteria for the review were broadly defined. A limited search was undertaken for published articles in any language, which may mean that relevant unpublished studies were missed. Publication bias was not assessed. Two authors independently performed study selection to minimise selection bias. Only one author performed data extraction, which may have introduced error and bias to the analysis. Quality assessment was not based on a validated tool and no details were provided, which made quality assessment of the included studies difficult. Both a narrative synthesis and random-effects meta-analysis were undertaken. There was significant heterogeneity in the meta-analysis results, which the authors did not explore. The authors’ conclusions were difficult to disentangle from general discussion. The results of the meta-analysis demonstrated that intradermal vaccine offered lower seroprotection than that offered by intramuscular vaccine, which did not support the authors’ statement that intradermal vaccine remained an attractive alternative to intramuscular vaccine. Overall, the authors' results should be treated with caution as the review had several methodological flaws and the authors did not state a clear conclusion.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors stated that future studies should focus on rigorous study design to enhance comparability of results and evaluate the efficacy of intradermal vaccination using novel administration techniques. The authors stated that seroprotection was highest among females and children, which suggested that these populations may be most appropriate for future intradermal vaccine developments.

Funding

Not stated.

Bibliographic details

Sangare L, Manhart L, Zehrung D, Wang CC. Intradermal hepatitis B vaccination: a systematic review and meta-analysis. Vaccine 2009; 27(12): 1777-1786. [PubMed: 19200451]

Indexing Status

Subject indexing assigned by NLM

MeSH

Child; Child, Preschool; Data Interpretation, Statistical; Female; Hepatitis B /immunology /prevention & control; Hepatitis B Vaccines /administration & dosage /therapeutic use; Humans; Infant; Infant, Newborn; Injections, Intradermal; Male; Randomized Controlled Trials as Topic; Reproducibility of Results

AccessionNumber

12009103846

Database entry date

22/09/2010

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 19200451

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