Authors' objectives

To address the question of how effective and cost-effective palivizumab (Synagis) is, compared with placebo or alternative prophylaxis, in the prevention of respiratory syncytial virus (RSV) infection in infants at high risk of infection.

Searching

The following databases were searched for reviews and primary studies: MEDLINE (from 1966 to 2000), CINAHL, the Cochrane Database of Systematic Reviews, the Cochrane Controlled Trials Register, EMBASE (from 1980 to 2000), DARE, NHS EED and HTA. The databases were searched in October 2000 and revisited in January 2001 to check for more recent papers.

The MeSH and textwords 'MEDI-493', 'palivizumab', 'Synagis', 'RSV' and 'respiratory syncytial virus' were used with the following search (adapted for each platform): ("MEDI-493".mp) OR ("palivizumab".mp) OR ("Synagis".mp) AND (respiratory syncytial virus, human/or respiratory syncytial viruses/) OR ("RSV".mp).

The searches were inclusive, rather than restrictive. Reviews and primary studies with relevant subject matter were identified by inspection of the titles and abstracts, and by obtaining papers where necessary. Papers written in any language were considered.

The Internet was searched, in particular, the FDA Centre for Drug Evaluation and Research site. Abstracts from the World Congress on Lung Health and 10th European Respiratory Society Annual Congress, and from the 94th, 95th and 96th American Thoracic Society International Conferences were handsearched, as were recent copies of Paediatric Respiratory Reviews). Abbott Laboratories (the manufacturer of palivizumab) and subject experts were contacted for further references. Citations in all the papers obtained were checked for additional references.

A search for economic analyses of palivizumab was also conducted.

Study selection

Assessment of study quality

Information relating to the quality of the included studies was collected. This included whether: the study addressed a clearly focused question; the participants were randomised to treatment groups; the randomisation method was specified; the inclusion and exclusion criteria were specified; there was clear definition of the treatment groups; intention to treat analysis was used; and loss to follow-up was reported. The quality assessment was undertaken independently by two researchers. It was not stated how any disagreements were resolved.

Data extraction

Two reviewers independently extracted the data and resolved any differences by discussion.

Methods of synthesis

Results of the review

One large randomised, double-blind, placebo-controlled, multicentre trial with a total of 1,502 participants was included in the review.

The results demonstrated a 55% reduction in the risk of hospitalisation attributable to RSV with palivizumab (95% confidence interval, CI: 38, 72, P=0.0004). Statistically-significant decreases in hospitalisation were seen in both subgroups: children with BPD experienced a 39% reduction (95% CI: 20, 58, P=0.038), while premature infants without BPD experienced a 78% reduction (95% CI: 66, 90, P<0.001). Trends in reduction of RSV hospitalisation rates were similar in all of the countries participating in the study, i.e. USA, UK and Canada. In general, palivizumab appeared to be effective in both patients who are premature but do not have BPD, and those who are premature and have BPD. However, the greatest effect was within the subset of premature patients without BPD.

Children randomised to palivizumab had significantly fewer total days (per 100 children) of RSV hospitalisation (P<0.001), days with increased oxygen (P<0.001), and days with a lower respiratory illness score of at least three (P<0.001).

Cost information

The authors state that insufficient data on quality of life made it inappropriate for them to conduct a cost-utility analysis. However, the evidence on effectiveness obtained from the trial identified, along with the cost data on hospitalisation, allowed a cost-effectiveness analysis of palivizumab in comparison with placebo to be carried out.

The economic analysis was based on effectiveness data from the RCT and cost data on hospitalisation. The base-case incremental cost effectiveness ratio was found to be £43,000 per hospital admission prevented, and £96,000 per life-year gained if used for all children who meet the licensed indication.

Authors' conclusions

Palivizumab appeared to be effective in preventing serious lower respiratory tract infection caused by RSV and requiring hospitalisation in high-risk infants. However, in our base-case cost-effectiveness model, palivizumab was not good value for money if used in all children who meet the licensed indication. This is not how the drug is currently used by clinicians in the UK; they reserve it for those children at greatest risk.

CRD commentary

The authors stated their review question and the inclusion criteria clearly. The literature search was adequate and included handsearches of abstracts from conferences, and contact with the manufacturers of palivizumab and subject experts, in an attempt to identify grey literature. No analyses were conducted to assess publication bias. No language restrictions were applied.

The validity of the individual studies was systematically assessed. The authors did not report details relating to the decision-making process for selecting the studies, such as how many of the reviewers were involved, whether the studies were examined independently, or whether the reviewers were blinded to the source.

Details of the studies were reported thoroughly in the text, with the results presented in tabular format and supplemented by a narrative discussion.

Only one study was identified that was eligible for inclusion in the review, which is a potential source of bias. However, the authors' conclusions appear to be justified.

Implications of the review for practice and research

Practice: The authors state that the recommendation for the use of palivizumab (Synagis), in the prevention of RSV infection in infants at high risk of infection, was borderline. It is reasonable to assume that if hospital admission can be prevented then mortality may also fall. However, although the trial results were consistent with such a fall, the trial was not large enough to demonstrate a statistically significant reduction in the death rates in high-risk infants. The panel do not see any reason to change the current usage in high-risk cases at tertiary centres.

Research: The authors state that a systematic review of the prognostic factors for hospital admission should be undertaken. This should permit the development of clinical guidelines, to enable clinicians to identify the most appropriate children to be treated with palivizumab.

Funding

The review was conducted by people funded by the NHS.

Bibliographic details

Simpson S, Burls A. A systematic review of the effectiveness and cost-effectiveness of palivizumab (Synagis) in the prevention of respiratory syncytial virus (RSV) infection in infants at high risk of infection Birmingham: University of Birmingham, Department of Public Health and Epidemiology. West Midlands Development and Evaluation Service Report; 30. 2001.

Original Paper URL

http://www.birmingham.ac.uk/Documents/college-mds/haps/projects/WMHTAC/REPreports/2001/Palivizumab_final_post_panel.pdf

Indexing Status

Subject indexing assigned by CRD

MeSH

Adrenal Cortex Hormones /therapeutic use; Antibodies, Monoclonal /therapeutic use; Antiviral Agents /therapeutic use; Bronchodilator Agents /therapeutic use; Child; Child, Preschool; Emergency Medical Services; Hospitalization; Infant; Respiratory Syncytial Virus Infections /drug therapy /epidemiology; Respiratory Tract Infections /drug therapy /epidemiology

AccessionNumber

12002008213

Database entry date

31/01/2003

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.