Background

Respiratory syncytial virus (RSV) causes outbreaks of respiratory tract infection in the winter months in the UK. It is the leading cause of lower respiratory tract infection (LRTI) in infants and can lead to hospitalisation, particularly in those who are premature or who have chronic lung disease (CLD) or congenital heart disease (CHD). There are currently two licensed specific therapies in the UK: ribavirin and palivizumab. Palivizumab is a monoclonal antibody designed to provide passive immunity against RSV and thereby prevent or reduce the severity of RSV infection. It is licensed for the prevention of serious lower LRTI caused by RSV in children at high risk. While it is recognised that a policy of using palivizumab for all children who meet the licensed indication does not meet conventional UK standards of cost-effectiveness, most clinicians feel that its use is justified in some children. The purpose of this review is to determine if we can identify subgroups in whom palivizumab is cost-effective.

Objective

This review aims to systematically examine the scientific evidence about the effectiveness and cost-effectiveness of palivizumab for the prevention of RSV in children and to look at prognostic factors to determine if it is possible to identify subgroups among which there are important differences in cost-effectiveness.

Methods

We systematically reviewed the literature about the effectiveness and cost-effectiveness of prophylaxis with palivizumab. Bibliographic databases were searched from inception to March 2007 with no date limits or language restrictions. Current economic evaluations were analysed to identify which parameters were driving the different cost-effectiveness estimates. A probabilistic decision-analytical model was built to assess the cost-effectiveness of prophylaxis with palivizumab for children at risk of RSV infection and the parameters populated with the best available estimate thought to be most applicable to the UK context. Data to inform parameters in our model were systematically sought from the identified trial data and pragmatically identified from observational studies in the wider literature. Meta-analyses were carried out where appropriate.

Results

Conclusion

Prophylaxis with palivizumab is clinically effective for reducing the risk of serious LRTI caused by RSV infection and requiring hospitalisation in high-risk children, but if used unselectively in the licensed population the ICER is over £60,000/QALY, which is double that considered to represent good value for money in the UK (the current willingness-to-pay threshold is about £30,000/QALY). The BrumEE shows that prophylaxis with palivizumab may be cost-effective (based on a threshold of £30,000/QALY, but the threshold for decision-makers may vary, particularly for this type of patient group) for children with CLD when the children have two or more additional risk factors.

Our economic evaluation is limited by the quality and quantity of the primary data available and the pragmatic rather than systematic methods used to identify parameter values. Future research should initially focus on reviewing systematically the major uncertainties for patient subgroups with CLD and CHD (e.g. mortality rates for RSV infection in children not given palivizumab prophylaxis) and then on primary research to address the important uncertainties that remain.

Publication

• Wang D, Cummins C, Bayliss S, Sandercock J, Burls A. Immunoprophylaxis against respiratory syncytial virus (RSV) with palivizumab in children: a systematic review and economic evaluation. Health Technol Assess 2008;12(36). [PubMed: 19049692]

NIHR Health Technology Assessment Programme

The Health Technology Assessment (HTA) Programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care.

The research findings from the HTA Programme directly influence decision-making bodies such as the National Institute for Health and Clinical Excellence (NICE) and the National Screening Committee (NSC). HTA findings also help to improve the quality of clinical practice in the NHS indirectly in that they form a key component of the 'National Knowledge Service'.

The HTA Programme is needs led in that it fills gaps in the evidence needed by the NHS. There are three routes to the start of projects.

First is the commissioned route. Suggestions for research are actively sought from people working in the NHS, from the public and consumer groups and from professional bodies such as royal colleges and NHS trusts. These suggestions are carefully prioritised by panels of independent experts (including NHS service users). The HTA Programme then commissions the research by competitive tender.

Second, the HTA Programme provides grants for clinical trials for researchers who identify research questions. These are assessed for importance to patients and the NHS, and scientific rigour.

Third, through its Technology Assessment Report (TAR) call-off contract, the HTA Programme commissions bespoke reports, principally for NICE, but also for other policy-makers. TARs bring together evidence on the value of specific technologies.

Some HTA research projects, including TARs, may take only months, others need several years. They can cost from as little as £40,000 to over £1 million, and may involve synthesising existing evidence, undertaking a trial, or other research collecting new data to answer a research problem.

The final reports from HTA projects are peer reviewed by a number of independent expert referees before publication in the widely read journal series Health Technology Assessment.

Criteria for inclusion in the HTA journal series

Reports are published in the HTA journal series if (1) they have resulted from work for the HTA Programme, and (2) they are of a sufficiently high scientific quality as assessed by the referees and editors.

Reviews in Health Technology Assessment are termed 'systematic' when the account of the search, appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others.

The research reported in this issue of the journal was commissioned by the HTA Programme as project number 06/29/01. The contractual start date was in November 2006. The draft report began editorial review in July 2007 and was accepted for publication in April 2008. As the funder, by devising a commissioning brief, the HTA Programme specified the research question and study design. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors' report and would like to thank the referees for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

The views expressed in this publication are those of the authors and not necessarily those of the HTA Programme or the Department of Health.

Editor-in-Chief: Professor Tom Walley

Series Editors: Dr Aileen Clarke, Dr Peter Davidson, Dr Chris Hyde, Dr John Powell, Dr Rob Riemsma and Professor Ken Stein