Cost effectiveness of palivizumab for RSV prevention in high-risk children in the Netherlands. Economic evaluation of possible prevention of RSV-related hospitalizations in premature infants in Germany. Economic evaluation of palivizumab in children with congenital heart disease: a Canadian perspective. Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. Cost-effectiveness analysis of palivizumab as respiratory syncytial virus prophylaxis in preterm infants in Sweden. Palivizumab for immunoprophylaxis of respiratory syncytial virus (RSV) bronchiolitis in high-risk infants and young children: a systematic review and additional economic modelling of subgroup analyses. Cost effectiveness of palivizumab for respiratory syncytial virus prophylaxis in high-risk children: a UK analysis. Economic analysis of palivizumab in infants with congenital heart disease. [Methodological aspects of economic evaluation in pediatrics: illustration by RSV infection prophylaxis in the French setting].
Respiratory syncytial virus (RSV) is a common pathogen that is the leading cause of lower respiratory tract infections in young children. High-risk children are at risk of severe infection, which may require hospitalisation. RSV is also associated with a high risk for respiratory morbidity and mortality, which may have long-term clinical and economic consequences.
                To assess the cost effectiveness of palivizumab, a humanised monoclonal antibody, used as prevention against severe respiratory syncytial virus (RSV) infection requiring hospitalisation, in the indication of preterm infants and infants with preterm/bronchopulmonary dysplasia and in the second indication of children with congenital heart disease in the Dutch healthcare setting.
                A decision-tree model was used to estimate the cost effectiveness of palivizumab, used as a preventative treatment against severe respiratory syncytial virus (RSV) infection, in high-risk groups of children in the Netherlands. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. Data sources included published literature, the palivizumab pivotal trials, official price/tariff lists and national population statistics. The study was conducted from the perspective of society in the Netherlands.
                The use of palivizumab results in undiscounted incremental cost-effectiveness ratios of €12,728/QALY and €4,256/QALY in preterm/bronchopulmonary dysplasia and congenital heart disease indications, respectively. Inclusion of indirect costs leads to even more favourable cost-effectiveness outcomes. The study is limited by a number of conservative assumptions. It was assumed that palivizumab only affects the occurrence of RSV hospitalisation and does not influence the severity of the RSV infection. Another assumption was that international clinical trial data and data on utilities could be applied to the Dutch healthcare setting.
                Palivizumab provides cost-effective prophylaxis against RSV in high-risk infants. The use of palivizumab in these children results in positive short- and long-term health-economic benefits. Palivizumab (Synagis, MedImmune Inc./Abbott Laboratories) has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in premature infants. The cost-effectiveness ratio of this prophylaxis, however, has not been evaluated in the German health-care system to date. The aim of the study was to assess the costs and benefits of Palivizumab among premature infants </=35 weeks with different risk factors. Projecting a societal perspective, we used decision analysis to compare the strategies of a prophylaxis with and without Palivizumab. Probabilities and costs of hospitalization were derived from a retrospective, population-based cohort study on 1,103 prematurely born infants primarily admitted to nine neonatologic care units in southern Germany between November 1998 and October 1999. Costs of prophylaxis were based on hospital sources. Efficacy of prophylaxis and estimates of RSV mortality were derived from the literature. Effectiveness was defined as the number of averted hospitalizations. The cost-effectiveness ratio of Palivizumab varied strongly among the different risk groups. While demonstrating no net cost savings related to RSV prophylaxis for any of the risk groups analyzed, Palivizumab showed the best cost-effectiveness ratio among male infants with chronic lung disease, discharge from primary neonatal care between October and December, and the presence of siblings visiting a day-care group. One averted hospitalization in this high-risk group was associated with costs of Euro 6,639 (number needed to treat (NNT): 4). For infants in other risk groups, the ratios varied from Euro 25,288 (NNT: 8) to Euro 204,684 (NNT: 54) per hospitalization averted. The cost-effectiveness ratios were sensitive to varying assumptions about probabilities and costs of rehospitalization, efficacy, and costs of Palivizumab prophylaxis.
                The results of this cost-effectiveness analysis do not justify the widespread use of Palivizumab among preterm infants. Lowering the costs of prophylaxis would be the most direct way to improve the cost-effectiveness ratio of Palivizumab. Respiratory syncytial virus (RSV) is a common cause of bronchiolitis in infants. In children with congenital heart disease (CHD), it is associated with significant morbidity and mortality. Palivizumab is a monoclonal antibody that reduces the number of RSV-associated hospitalizations in children with CHD. We sought to assess cost savings and cost-effectiveness of palivizumab in children < 2 years old with hemodynamically significant CHD in a provincially administered RSV prophylaxis program.
                A cohort of children who received palivizumab (N = 292) from 2003-2007 was compared to a historical cohort of children (N = 412) from 1998-2003 who met the eligibility criteria for palivizumab prior to initiation of the prophylaxis program. Direct and indirect costs and benefits were determined.
                The direct and indirect costs in the historical cohort were $838 per patient season compared to $9130 per patient season in the palivizumab cohort. Risk of admission was reduced by 42%, and days in hospital were reduced by 83%. The incremental cost of the RSV prophylaxis program was $8292 per patient for 1 RSV season. The incremental cost to prevent 1 day of hospitalization was $15,514. The cost of palivizumab accounted for 87.9% of the cost of prophylaxis.
                Palivizumab is clinically effective; however, the cost was exceptionally high relative to the outcomes in this population. Given the financial constraints in a public health care setting, more strict criteria for patient selection or reduced drug costs would improve the cost-effectiveness of RSV prophylaxis.
                Copyright © 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. To evaluate the safety, tolerance, and efficacy of palivizumab in children with hemodynamically significant congenital heart disease (CHD).
                A randomized, double-blind, placebo-controlled trial included 1287 children with CHD randomly assigned 1:1 to receive 5 monthly intramuscular injections of 15 mg/kg palivizumab or placebo. Children were followed for 150 days. The primary efficacy end point was antigen-confirmed respiratory syncytial virus (RSV) hospitalization.
                Palivizumab recipients had a 45% relative reduction in RSV hospitalizations (P=.003), a 56% reduction in total days of RSV hospitalization per 100 children (P=.003), and a 73% reduction in total RSV hospital days with increased supplemental oxygen per 100 children (P=.014). Adverse events were similar in the treatment groups; no child had drug discontinued for a related adverse event. Serious adverse events occurred in 55.4% of palivizumab recipients and 63.1% of placebo recipients (P<.005); none were related to palivizumab. Twenty-one children (3.3%) in the palivizumab group and 27 (4.2%) in the placebo group died; no deaths were attributed to palivizumab. The rates of cardiac surgeries performed earlier than planned were similar in the treatment groups.
                Monthly palivizumab (15 mg/kg IM) was safe, well-tolerated, and effective for prophylaxis of serious RSV disease in young children with hemodynamically significant CHD. To investigate the cost-effectiveness of palivizumab vs. no prophylaxis for respiratory syncytial virus (RSV) infection in preterm infants in Sweden.
                A probabilistic Markov model was populated using a nationwide register linkage and data from the literature. Cost-effectiveness was investigated from a societal perspective over a lifetime for infants born at <29 weeks of gestation. Palivizumab was modelled using assumptions for its direct effect on RSV hospitalization risk and an indirect effect (via decreased RSV hospitalization) on subsequent asthma and mortality during the epidemic. Costs and effects were discounted by 3%.
                In the base case, prophylaxis resulted in an additional 0.102 quality-adjusted life-year (QALY) at a cost of 20,000 SEK relative to no prophylaxis (incremental cost-effectiveness ratio [ICER] 195,000 SEK/QALY). The probability of prophylaxis being cost-effective was 99% at a willingness-to-pay of 500,000 SEK/QALY. Assumptions about a causal association between RSV infection and subsequent asthma had a moderate impact, while exclusion of the indirect prophylaxis effect on mortality increased the ICER to 492,000 SEK/QALY. When excluding both of these, prophylaxis was not cost-effective.
                Based on a willingness-to-pay of 500,000 SEK/QALY, palivizumab was found to be cost-effective compared with no prophylaxis for infants born at <29 weeks if severe RSV infection was assumed to increase subsequent asthma or mortality risk.
                © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica. Respiratory syncytial virus (RSV) is a seasonal infectious disease, with epidemics occurring annually from October to March in the UK. It is a very common infection in infants and young children and can lead to hospitalisation, particularly in those who are premature or who have chronic lung disease (CLD) or congenital heart disease (CHD). Palivizumab (Synagis®, MedImmune) 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 respiratory tract infection 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.
                To use systematic review evidence to estimate the cost-effectiveness of immunoprophylaxis of RSV using palivizumab in different subgroups of children with or without CLD or CHD who are at high risk of serious morbidity from RSV infection.
                A systematic review of the literature and an economic evaluation was carried out. The bibliographic databases included the Cochrane Library [Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] and five other databases, from inception to 2009. Research registries of ongoing trials including Current Controlled Trials metaRegister, Clinical Trials.gov and the National Institute for Health Research Clinical Research Network Portfolio were also searched.
                Searches were conducted for prognostic and hospitalisation studies covering 1950-2009 (the original report searches conducted in 2007 covering the period 1950-2007 were rerun in August 2009 to cover the period 2007-9) and the database of all references from the original report was sifted to find any relevant studies that may have been missed. The risk factors identified from the systematic review of included studies were analysed and synthesised using stata. The base-case decision tree model developed in the original HTA journal publication [Health Technol Assess 2008;12(36)] was used to derive the cost-effectiveness of immunoprophylaxis of RSV using palivizumab in different subgroups of pre-term infants and young children who are at high risk of serious morbidity from RSV infection. Cost-effective spectra of prophylaxis with palivizumab compared with no prophylaxis for children without CLD/CHD, children with CLD, children with acyanotic CHD and children with cyanotic CHD were derived.
                Thirteen studies were included in this analysis. Analysis of 16,128 subgroups showed that prophylaxis with palivizumab may be cost-effective [at a willingness-to-pay threshold of £30,000/quality-adjusted life-year (QALY)] for some subgroups. For example, for children without CLD or CHD, the cost-effective subgroups included children under 6 weeks old at the start of the RSV season who had at least two other risk factors that were considered in this report and were born at 24 weeks gestational age (GA) or less, but did not include children who were > 9 months old at the start of the RSV season or had a GA of > 32 weeks. For children with CLD, the cost-effective subgroups included children < 6 months old at the start of the RSV season who were born at 28 weeks GA or less, but did not include children who were > 21 months old at the start of the RSV season. For children with acyanotic CHD, the cost-effective subgroups included children < 6 months old at the start of the RSV season who were born at 24 weeks GA or less, but did not include children who were > 21 months old at the start of the RSV season. For children with cyanotic CHD, the cost-effective subgroups included children < 6 weeks old at the start of the RSV season who were born at 24 weeks GA or less, but did not include children who were > 12 months old at the start of the RSV season.
                The poor quality of the studies feeding numerical results into this analysis means that the true cost-effectiveness may vary considerably from that estimated here. There is a risk that the relatively high mathematical precision of the point estimates of cost-effectiveness may be quite inaccurate because of poor-quality inputs.
                Prophylaxis with palivizumab does not represent good value for money based on the current UK incremental cost-effectiveness ratio threshold of £30,000/QALY when used unselectively in children without CLD/CHD or children with CLD or CHD. This subgroup analysis showed that prophylaxis with palivizumab may be cost-effective (at a willingness-to-pay threshold of £30,000/QALY) for some subgroups. In summary, the cost-effective subgroups for children who had no CLD or CHD must contain at least two other risk factors apart from GA and birth age. The cost-effective subgroups for children who had CLD or CHD do not necessarily need to have any other risk factors. Future research should be directed towards conducting much larger, better powered and better reported studies to derive better estimates of the risk factor effect sizes.
                This report was funded by the HTA programme of the National Institute for Health Research. To assess the cost effectiveness of palivizumab (a preventative treatment against severe respiratory syncytial virus [RSV] infection) in children at high risk of hospitalisation, i.e. preterm infants < or = 35 weeks gestation, children with bronchopulmonary dysplasia (BPD) and children with congenital heart disease (CHD).
                A decision tree model was developed employing data sources from the published literature, palivizumab clinical trials, official UK price/tariff lists and national population statistics. The comparator was no prophylaxis. The primary perspective of the study was that of the UK NHS. In a societal perspective scenario analysis, the future lost productivity of a child resulting from RSV-related mortality (indirect costs) was also included. The cost of administration of palivizumab, hospital care for RSV infections and the cost of asthma treatment were included. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. The primary efficacy outcome in the palivizumab clinical trials was the number of RSV hospitalisations avoided, which was extrapolated to effectiveness outcomes, i.e. number of life-years gained and number of QALYs. Costs and effects were discounted by 3.5%.
                In preterm infants and children with BPD, prophylaxis with palivizumab compared with no prophylaxis had an incremental cost-effectiveness ratio (ICER) of 7042 pounds/QALY without discounting outcomes, increasing to 16,720 pounds/QALY after discounting. In babies with CHD, the use of palivizumab resulted in an ICER of 2427 pounds/QALY without discounting outcomes and 6664 pounds/QALY after discounting. One-way sensitivity analyses and probabilistic sensitivity analyses confirmed the robustness of the model. A scenario analysis showed that the inclusion of indirect costs leads to further improvement in the cost-effectiveness outcomes for palivizumab.
                This study suggests that palivizumab prophylaxis against severe RSV infection in children at high risk may be cost effective from the NHS perspective (vs no prophylaxis), and that the positive clinical and economic benefits may persist beyond one RSV season. Palivizumab has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations by 45% in children with congenital heart disease (CHD). The American Academy of Pediatrics has recommended that infants with hemodynamically significant CHD be considered for palivizumab. However, the economic implications of palivizumab prophylaxis in the CHD population have not been evaluated. In the present study, we sought to examine the cost savings and cost utility of RSV prophylaxis with palivizumab in children with CHD.
                Probabilities of hospitalization and efficacy of prophylaxis were based on published results. Costs of hospitalization were derived from a published analysis of bronchiolitis hospitalization costs from a consortium of children's hospitals. A hypothetical cohort of 10,000 CHD patients (half of whom would receive palivizumab) was created to calculate cost-savings and cost-utility. To assess cost utility, we assumed that by reducing hospitalization, palivizumab would reduce RSV-related hospital mortality, generally reported to be 3% in CHD patients. Sensitivity analysis was performed.
                On the basis of a protocol of 5 monthly doses of palivizumab, the cost of prophylaxis for 1 RSV season was calculated as 6160 dollars per patient. After accounting for impact on direct and indirect costs of hospitalization, administration of palivizumab to 5000 CHD patients would result in a net loss of 20,415,753 dollars. If one assumes that palivizumab confers a survival benefit, then the cost of life-year saved is 100,338 dollars and cost of quality-adjusted life-year saved is 114,337 dollars.
                The cost of palivizumab prophylaxis was high relative to benefits realized. Given the large number of CHD patients who might be considered candidates for RSV prophylaxis (>6000 patients per year in United States) routine use of palivizumab in young children with hemodynamically significant CHD needs to be evaluated further. The methodological approach of the economic evaluation of drugs in pediatrics is illustrated by the case study of the prophylaxis for RSV infections using palivizumab in the French setting. The indications for the reimbursement of this treatment have been restricted to premature children with bronchopulmonary dysplasia (BPD) or hemodynamically significant congenital-heart disease. A model was developed primarily using the results of the pivotal clinical studies on palivizumab. Unit costs were estimated (2006 values) in both societal and payer's perspectives. An assumption was made and discussed on the benefits of the prophylaxis on mortality. Based on the different data available and the estimated costs and benefits, different cost-effectiveness ratios (CERs) were estimated from both the society's and payer's points of view. A discount rate of 3% was applied to benefit. The CER obtained in the most unfavorable case is considered acceptable for the innovative-medical technologies in the French-healthcare system. Some of the parameters used by the model will be illustrated from the EPIPAGE study data from 2 of the 9 regions involved in this study: this evaluation suggests that the children not having an RSV infection during their 1st year of life will continue to require significantly fewer hospitalizations in the following years. These additional evaluations also suggest that the model overestimates the costs of the treatment with regard to the true medical situation. This could be explained by the model not using the children's exact weight or the real number of injections because the children had been discharged from the maternity ward based on their date of birth and the epidemic period. In spite of these factors, RSV prophylaxis using palivizumab in premature children with BPD or hemodynamically significant congenital-heart disease can be considered cost-effective in France.
There is evidence that palivizumab prophylaxis is effective in reducing the frequency of hospitalisations due to RSV infection, i.e. in reducing the incidence of serious lower respiratory tract RSV disease in children with chronic lung disease, congenital heart disease, or those born preterm. 
Results from economic evaluations of palivizumab prophylaxis are inconsistent across studies, ranging from highly cost-effective to not cost-effective, implying that economic findings must be interpreted with caution. The availability of low-cost palivizumab would reduce its inequitable distribution, so that RSV prophylaxis would be available to the poorest countries where children are at greatest risk.