NETSCC, HTA 26th July 2009

Transcription

1 NETSCC, HTA 26 th July 2009

2 HTA 06/29/02 1 Title of the project: Palivizumab for immunoprophylaxis of respiratory syncitial virus (RSV) bronchiolitis in high risk infants, additional subgroup analysis 2 Name of TAR team and project lead TAR team: Project lead: Post held: Official address: West Midlands Health Technology Assessment Collaboration (WMHTAC), University of Birmingham Catherine Meads Deputy Director of WMHTAC Department of Public Health, Epidemiology and Biostatistics, University of Birmingham, Edgbaston, Birmingham B15 2TT Telephone number: Fax number: address: c.a.meads@bham.ac.uk 3 Plain English Summary Respiratory syncytial virus (RSV) is a very common infection in young children, with up to half of all infants becoming infected by the age of one. A proportion of children with RSV are seriously affected by the virus and may need to be hospitalised due to life-threatening complications such as bronchiolitis (inflammation of the smaller airways of the lung) and pneumonia. Children who are at high risk of hospitalisation for these reasons include premature babies, children with chronic lung disease due to abnormal development of the lungs or cystic fibrosis, children who were born with certain types of heart problems and children who have limited resistance to disease due to a weakened immune system. As many as one in five of these high risk infants may need to be hospitalised and some may require admission to an intensive care unit. RSV is a seasonal disease, with epidemics occurring annually from October to March in the UK. Beyond supportive care (such as mechanical assistance with breathing, intravenous fluids and oxygen) the only treatment available for RSV infection is ribavirin. Ribavarin may be of some benefit after infection but its use requires hospitalisation which increases the risk of spreading the infection, it is costly and has a number of unwanted side effects. Strategies to prevent infection are therefore of considerable interest. Attempts to develop a vaccine to prevent RSV infection have so far been unsuccessful but another type of product, palivizumab (sold under the brand name of Synagis) may be useful in preventing or reducing the severity of RSV infection and is available for use in the UK. Common side effects of palivizumab include injection site reactions and fever. Rare side effects, occurring in less than one Protocol 27/07/2009 1

3 in a hundred children, include infections, blood disorders, respiratory problems, rash, diarrhoea and vomiting. This additional subgroup analysis aims to address the best way for the health service to use palivizumab in children with CHD who are at high risk of developing serious complications following RSV infection. 4 Decision problem 4.1 Purpose of the report To estimate the cost-effectiveness of immunoprophylaxis of RSV using palivizumab (a monoclonal antibody) in different subgroups of children with CHD who are at high risk of serious morbidity from RSV infection. 4.2 Intervention Synagis is indicated for the prevention of serious lower respiratory tract disease requiring hospitalisation caused by respiratory syncytial virus (RSV) in children at high risk for RSV disease. The marketing authorisation specifies the following high risk groups: Children born at 35 weeks of gestation or less and less than 6 months of age at the onset of the RSV season Children less than 2 years of age and requiring treatment for bronchopulmonary dysplasia within the last 6 months. Children less than 2 years of age and with haemodynamically significant congenital heart disease. The recommended dose of palivizumab is 15 mg/kg of body weight, injected intramuscularly, given once a month during anticipated periods of RSV risk in the community. Where possible, the first dose should be administered prior to commencement of the RSV season. Subsequent doses should be administered monthly throughout the RSV season. To reduce risk of rehospitalisation, it is recommended that children receiving palivizumab who are hospitalised with RSV continue to receive monthly doses of palivizumab for the duration of the RSV season. For children undergoing cardiac bypass, it is recommended that a 15 mg/kg injection of palivizumab be administered as soon as stable after surgery to ensure adequate palivizumab serum levels. Subsequent doses should resume monthly through the remainder of the RSV season for children that continue to be at high risk of RSV disease. Protocol 27/07/2009 2

4 4.3 Relevant comparators No prophylactic treatment 4.4 Population and relevant sub-group 1. The population is infants at high risk of hospitalisation, morbidity or death due to RSV infection, including children less than 2 years of age, and with haemodynamically significant congenital heart disease. This group will be stratified by age to find out whether administration is cost effective for any age group. 2. Using the whole dataset, further analysis of other potential risk groups as follows will be done, depending on the number of additional studies found and the time available. age less than six weeks at the start of the RSV season, male gender, multiple births, exposure to passive smoke, lack of, or minimal, breast feeding, overcrowding in the family home, parental education, and family history of atopy Comment [v1]: Should this be early weaning i.e. before three months old? 4.5 Key factors to be addressed This subgroup analysis will investigate cost-effectiveness only. 5 Report methods The original HTA monograph on this was HTA 2008;12(36) A systematic review of the additional evidence needed for modelling will be undertaken using the original search strategies updated to July The relevant studies are prognostic studies of morbidity due to RSV. The inclusion criteria will be the same as originally employed. Similar methods of inclusion and data extraction will be done as per the original project. 5.1 Methods of analysis/synthesis Additional included studies will be listed and described. Data will be tabulated and discussed in a narrative review with new and original studies combined. Heterogeneity will be explored if possible. The economic evaluation model described in the original HTA monograph will be used to perform the sub-group analyses. The evidence from the additional included Protocol 27/07/2009 3

5 studies will be synthesised and the values of the parameters required by the model will be derived from the additional included studies and the original studies. The cost-effectiveness results for children with CHD who are at high risk of serious morbidity from RSV infection will be tabulated. 6 Expertise in this TAR team The West Midlands Health Technology Assessment Collaboration (WMHTAC) is an organisation involving several universities and academic groups who collaboratively produce health technology assessments and systematic reviews. Four of the original team for this HTA have since left the University of Birmingham but we retain the archive for the work, including the searches used and the model. The new searches will be conducted in house and staff systematic reviewers will be used to apply the original inclusion and exclusion criteria to the new list of studies. DeChao Wang was the original modeller for this project and is currently available on a freelance basis to carry out the additional modelling work. He will undertake the data extraction, modelling and writing the report. The project will be managed by Dr Catherine Meads who will take overall responsibility for project management and the quality of the final report. 7 Competing interests of authors None 8 Timetable/milestones Submission of protocol: 15 th July 2009 Submission of final report: 15 th September Protocol 27/07/2009 4