Authors' objectives

To quantify the efficacy of BCG vaccine against tuberculosis (TB).

Searching

MEDLINE was searched using the terms 'BCG vaccine', 'tuberculosis' and 'human'. Bibliographies of retrieved studies and review papers were examined for additonal material, and the World Health Organization (WHO) and the Centre for Disease Control and Prevention (CDC) were contacted for unpublished trials. Studies and trials in any language were considered.

Study selection

Assessment of study quality

Two readers evaluated study validity. The readers recorded study design, age range of population, number of patients enrolled, location of study, strain and dose of BCG used, route of administration, years of follow-up or time since immunisation, outcomes measured, efficacy of design, and items for assessing potential bias in study design and diagnosis. Potential bias was assessed using a scoring system, which for trials, assessed the method of vaccine assignment to study population, equality of surveillance among control and treatment arm, criteria used to diagnose TB, and preparation of BCG vaccine. In the case-control studies, potential bias was examined in data collection, and the criteria used to collect information. Two readers independently evaluated study validity and any discrepancies were resolved by a third reviewer.

Data extraction

Two readers extracted the data independently and any differences were resolved by a third reviewer.

Methods of synthesis

Results of the review

Of the 70 studies reviewed, 26 were included: 14 prospective trials (n= 360,000; 7 RCTs, 2 trials with alternate allocation and 4 trials with systematic allocation; details were only provided for 13 studies) and 12 case-controls (n=1,414; details were only provided for 10 studies).

In the 13 prospective trials, the relative risk (RR) of TB was 0.49 (95% confidence interval, CI: 0.34, 0.70) for vaccine recipients, compared with nonrecipents (protective effect of 51%). In the 10 case-control studies, the odds ratio (OR) for TB was 0.50 (95% CI: 0.39, 0.64), or a 50% protective effect. Seven trials reporting deaths from TB showed a protective effect from BCG vaccine of 71% (RR 0.29, 95% CI: 0.16, 0.53), and 5 studies reporting on meningitis showed a protective effect from BCG vaccine of 64% (OR 0.36, 95% CI: 0.18, 0.70). Geographic latitude of the study site and study validity score explained 66% of the heterogeneity among trials in a random-effects regression model.

Authors' conclusions

On average, BCG vaccine significantly reduces the risk of TB by 50%. Protection is observed across many populations, study designs and forms of TB. Age at vaccination did not enhance predictiveness of BCG efficacy. Protection against death from TB, meningitis and disseminated disease is higher than for total TB cases, although this result may reflect reduced error in disease classification rather than greater BCG efficacy.

CRD commentary

There are some inconsistencies in the reporting of the number of included studies: the abstract reports 14 trials, Table 1 describes 15 (maybe 3 Comstock papers are linked), but design details are provided for only 13; similarly, the abstract reports 12 case studies but presents data on 10. The study failed to provide adequate details of the scoring system applied in the validity assessment. The paper does not provide enough detail of the study population or the geographic location of the studies. Geographic latitude of the study site and study validity explained 66% of the heterogeneity in the random-effects regression model. Apart from the presentation inconsistencies noted above, this is a well-conducted meta-analysis.

Funding

US Centres for Disease Control and Prevention.

Bibliographic details

Colditz G A, Brewer T F, Berkey C S, Wilson M E, Burdick E, Fineberg H V, Mosteller F. Efficacy of BCG vaccine in the prevention of tuberculosis: meta-analysis of the published literature. JAMA 1994; 271(9): 698-702. [PubMed: 8309034]

Indexing Status

Subject indexing assigned by NLM

MeSH

BCG Vaccine; Humans; MEDLINE; Research Design; Tuberculosis /prevention & control; United States

AccessionNumber

11995003437

Database entry date

31/07/1996

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.