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]. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. The IMpact-RSV Study Group. Cost-effectiveness of respiratory syncytial virus prophylaxis in various indications. Cost effectiveness of palivizumab in children with congenital heart disease in Germany. Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: a noninferiority trial. Palivizumab for respiratory syncytial virus prophylaxis in high-risk infants: a cost-effectiveness analysis. Cost effectiveness of palivizumab in Spain: an analysis using observational data. Cost-effectiveness of respiratory syncytial virus prophylaxis among preterm infants. Cost-effectiveness analysis of palivizumab in premature infants without chronic lung disease. Cost-effectiveness of palivizumab for respiratory syncytial virus infection in high-risk children, based on long-term epidemiologic data from Austria. The cost-effectiveness of palivizumab for respiratory syncytial virus prophylaxis in premature infants with a gestational age of 32-35 weeks: a Canadian-based analysis . A randomized controlled trial of motavizumab versus palivizumab for the prophylaxis of serious respiratory syncytial virus disease in children with hemodynamically significant congenital heart disease. [The efficiency (cost-effectiveness) of palivizumab as prophylaxis against respiratory syncytial virus infection in premature infants with a gestational age of 32-35 weeks in Spain]. Cost-utility analysis of palivizumab in Italy: results from a simulation model in the prophylaxis of respiratory syncytial virus infection (RSV) among high-risk preterm infants. Cost-effectiveness of palivizumab in infancy. Cost-effectiveness of palivizumab against respiratory syncytial viral infection in high-risk children in Austria. Cost-effectiveness analysis of the use of palivizumab in the prophylaxis of preterm patients in Mexico. Cost-effectiveness of palivizumab in New Zealand. The cost effectiveness of palivizumab in term Inuit infants in the Eastern Canadian Arctic. Changing costs and the impact on RSV prophylaxis. Cost-effectiveness analysis of palivizumab among pre-term infant populations covered by Medicaid in the United States. Use of surfactant for prophylaxis versus rescue treatment of respiratory distress syndrome: experience from an Italian-Bulgarian trial. Safety, tolerability, pharmacokinetics, and immunogenicity of motavizumab, a humanized, enhanced-potency monoclonal antibody for the prevention of respiratory syncytial virus infection in at-risk children. The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome.
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. To determine the safety and efficacy of prophylaxis with palivizumab in reducing the incidence of hospitalization because of respiratory syncytial virus (RSV) infection in high-risk infants.
                A randomized, double-blind, placebo-controlled trial was conducted at 139 centers in the United States, the United Kingdom, and Canada. During the 1996 to 1997 RSV season, 1502 children with prematurity (less than or equal to 35 weeks) or bronchopulmonary dysplasia (BPD) were randomized to receive 5 injections of either palivizumab (15 mg/kg) or an equivalent volume of placebo by intramuscular injection every 30 days. The primary endpoint was hospitalization with confirmed RSV infection. Children were followed for 150 days (30 days from the last injection). Those with hospitalization as a result of RSV infection were evaluated for total number of days in the hospital, total days with increased supplemental oxygen, total days with moderate or severe lower respiratory tract illness, and incidence and total days of intensive care and mechanical ventilation. The incidence of hospitalization for respiratory illness not caused by RSV and the incidence of otitis media were also evaluated. The placebo and palivizumab groups were balanced at entry for demographics and RSV risk factors. Ninety-nine percent of children in both groups completed the protocol and approximately 93% received all five scheduled injections.
                Palivizumab prophylaxis resulted in a 55% reduction in hospitalization as a result of RSV (10.6% placebo vs 4.8% palivizumab). Children with prematurity but without BPD had a 78% reduction in RSV hospitalization (8.1% vs 1.8%); children with BPD had a 39% reduction (12.8% vs 7.9%). When gender, entry age, entry weight, BPD, and gestational age were included in a logistic regression model, the effect of prophylaxis with palivizumab remained statistically significant. The palivizumab group had proportionally fewer total RSV hospital days, fewer RSV hospital days with increased oxygen, fewer RSV hospital days with a moderate/severe lower respiratory tract illness, and a lower incidence of intensive care unit admission. Palivizumab was safe and well tolerated. No significant differences were observed in reported adverse events between the two groups. Few children discontinued injections for related adverse events (0.3%). Reactions at the site of injection were uncommon (1.8% placebo vs 2.7% palivizumab); the most frequent reaction was mild and transient erythema. Mild or moderate elevations of aspartate aminotransferase occurred in 1.6% of placebo recipients and 3.6% of palivizumab recipients; for alanine aminotransferase these percentages were 2.0% and 2.3%, respectively. Hepatic and renal adverse events related to the study drug were similar in the two groups.
                Monthly intramuscular administration of palivizumab is safe and effective for prevention of serious RSV illness in premature children and those with BPD. To evaluate the cost-effectiveness of immunoprophylaxis against respiratory syncytial virus (RSV) infections with palivizumab based on actual cost and observed incidence rates in various pediatric risk groups.
                Decision tree analysis comparing children with various combinations of the following indications: chronic lung disease, congenital heart disease, or prematurity (≤32 weeks gestation), and children with none of these indications. One-way sensitivity analyses and Monte Carlo simulations were used to quantify parameter uncertainty.
                Florida during the 2004-2005 RSV season.
                A total of 159,790 Medicaid-eligible children aged 0 to 2 years.
                Palivizumab prophylaxis compared with no prophylaxis. OUTCOMES MEASURE: Incremental cost (2010 US dollars) per hospitalization for RSV infection avoided.
                The mean cost of palivizumab per dose ranged from $1661 for infants younger than 6 months of age to $2584 for children in their second year of life. Among preterm infants younger than 6 months of age without other indications, immunoprophylaxis with palivizumab cost $302,103 (95% confidence interval, $141,850-$914,798) to prevent 1 RSV-related hospitalization. Given a mean cost of $8910 for 1 RSV-related hospitalization in this subgroup, palivizumab would be cost-neutral at a per-dose cost of $47. Incremental cost-effectiveness ratios for the other subgroups ranged from $361,727 to more than $1.3 million per RSV-related hospitalization avoided in children up to 2 years of age with chronic lung disease and no additional risk factors. Younger age and multiple indications were associated with improvements in the incremental cost-effectiveness ratio.
                The cost of immunoprophylaxis with palivizumab far exceeded the economic benefit of preventing hospitalizations, even in infants at highest risk for RSV infection. To assess the cost effectiveness of palivizumab, a humanised monoclonal antibody, used as prevention against severe respiratory syncytial virus (RSV) infection requiring hospitalisation, in infants with haemodynamically significant congenital heart disease (CHD) in the German healthcare setting.
                A decision-tree model was used to estimate the cost effectiveness of palivizumab for a hypothetical cohort of patients. 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 (primary analysis) and the healthcare purchaser (secondary analysis).
                From the societal perspective, use of palivizumab results in an incremental cost-effectiveness ratio (ICER) of €2,615 per quality-adjusted life-year (QALY) without discounting, which increases to €9,529/QALY after discounting. From the perspective of the German healthcare purchaser, use of palivizumab results in an ICER of €4,576/QALY without discounting, which increases to €16,673/QALY after discounting. Probabilistic sensitivity analyses confirmed the robustness of the model. 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 German healthcare setting.
                This analysis showed that palivizumab represents a cost-effective means of prophylaxis against severe RSV infection requiring hospitalisation in infants with haemodynamically significant CHD. Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by approximately 50% compared with placebo. We compared the efficacy and safety of motavizumab, an investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies, with palivizumab.
                This randomized, double-blind, multinational, phase 3, noninferiority trial assessed safety and RSV hospitalization in 6635 preterm infants aged <or=6 months at enrollment or children aged <or=24 months with chronic lung disease of prematurity who received 15 mg/kg palivizumab or motavizumab monthly. Secondary end points included outpatient medically attended lower respiratory tract infections (MALRIs), RSV-specific LRIs, otitis media, antibiotic use, development of antimotavizumab antibodies, and motavizumab serum concentrations.
                Motavizumab recipients had a 26% relative reduction in RSV hospitalization compared with palivizumab recipients, achieving noninferiority. Motavizumab was superior to palivizumab for reduction of RSV-specific outpatient MALRIs (50% relative reduction). Overall, adverse events (AEs) were not significantly different between groups. Cutaneous events were reported in 2 percentage points more motavizumab recipients (7.2% vs 5.1%); most were mild, but 0.3% resulted in dosing discontinuation. Antidrug antibodies (ADA) were detected in 1.8% of motavizumab recipients. Patients with anti-drug antibody reported 6 RSV events and 17 cutaneous events.
                Children receiving prophylaxis with motavizumab or palivizumab had low rates of RSV hospitalization; motavizumab recipients experienced 50% fewer RSV MALRIs than palivizumab recipients. AEs were similar in both groups, although cutaneous AEs were higher for motavizumab recipients. Motavizumab may offer an improved alternative in prophylaxis for serious RSV disease in infants and children at high risk. Prophylactic therapy with palivizumab, a humanized monoclonal antibody, has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in preterm infants. The cost-effectiveness of this therapy has not been evaluated from the provider's perspective using cost data.
                The objectives of this study were to determine the cost per RSV infection episode avoided by using prophylactic palivizumab therapy in a high-risk infant population and to determine whether certain subgroups of infants derived greater benefit from prophylactic therapy.
                A decision-analytic model simulating an RSV infection episode was developed to evaluate the cost-effectiveness of palivizumab prophylaxis from the perspective of the health care system (provider). Data to populate the model were gathered from the medical literature (identified through a MEDLINE search of studies on the incidence of RSV infection) and the IMpact-RSV clinical trial. Data included incidence of RSV infection and the associated health care resource use and costs. Costs to the provider were determined using a university-affiliated hospital cost-accounting system. Cost-effectiveness ratios were calculated over a range of RSV infection incidence rates in a control population. Sensitivity analyses were performed for the cost of palivizumab therapy, the cost of RSV-related hospitalization, and the number of emergency department, physician office, and home health care visits. For the subgroup analysis, infants were classified by gestational age (<32 and > or = 32 weeks) and stratified by severity of chronic lung disease.
                The cost per additional RSV infection episode avoided ranged from dollars 0 (cost savings) to dollars 39,591 for palivizumab prophylaxis costs of dollars 2500 and from dollars 2702 to dollars 79,706 for palivizumab prophylaxis costs of dollars 4500. The model was insensitive to changes in the number of emergency department, physician office, and home health care visits. The difference in RSV incidence between the treatment and control groups was greater among infants > or = 32 weeks' gestational age than among infants <32 weeks' gestational age. onclusions: The incremental cost-effectiveness of palivizumab compared with no prophylactic therapy was sensitive to changes in the incidence of RSV infection in control infants, the average cost of RSV hospitalization, and the cost of palivizumab. Clinicians may use this information along with additional factors to determine whether palivizumab is cost-effective in their clinical setting and geographic area. To assess the cost effectiveness of palivizumab for prevention of severe respiratory syncytial virus (RSV) disease in high-risk infants in Spain, incorporating country-specific observational hospitalisation data.
                An existing decision tree model, designed using data from a large international clinical trial of palivizumab versus no prophylaxis, was updated to include Spanish observational hospitalisation data. The analysis was performed for preterm children born at or before 32 weeks gestational age, who are at high risk of developing severe RSV disease requiring hospitalisation. Data sources included published literature, official price/tariff lists and national population statistics. The primary perspective of the study was that of the Spanish National Health Service in 2006.
                The base-case analysis included the direct medical costs associated with palivizumab prophylaxis and hospital care for RSV infections. Use of palivizumab produces an undiscounted incremental cost-effectiveness ratio (ICER) of euro6,142 per quality-adjusted life-year (QALY), and a discounted ICER of euro12,814/QALY.
                Palivizumab provides a cost-effective method of prophylaxis against severe RSV disease requiring hospitalisation among preterm infants in Spain. To evaluate the costs and benefits of two new agents, respiratory syncytial virus immune globulin (RSVIG) and palivizumab, to prevent respiratory syncytial virus (RSV) infection among premature infants discharged from the neonatal intensive care unit (NICU) before the start of the RSV season. Method. Decision analysis was used to compare the projected societal cost-effectiveness of three strategies-RSVIG, palivizumab, and no prophylaxis-among a hypothetical cohort of premature infants. Probabilities and costs of hospitalization were derived from a cohort of 1721 premature infants discharged from six Kaiser Permanente-Northern California NICUs. Efficacies of prophylaxis were based on published trials. Costs of prophylaxis were derived from published sources. Mortality among infants hospitalized for RSV was assumed to be 1.2%. Future benefits were discounted at 3%.
                Palivizumab was both more effective and less costly than RSVIG. Cost-effectiveness varied widely by subgroup. Palivizumab appeared most cost-effective for infants whose gestational age was </=32 weeks, who required >/=28 days of oxygen in the NICU, and who were discharged from the NICU from September through November. In this subgroup, palivizumab was predicted to cost $12,000 per hospitalization averted (after taking into account savings from prevention of RSV admissions) or $33,000 per life-year saved, and the number needed to treat to avoid one hospitalization was estimated at 7.4. However, for all other subgroups, ratios ranged from $39,000 to $420,000 per hospitalization averted or $110,000 to $1,200,000 per life-year saved, and the number needed to treat extended from 15 to 152. The results were sensitive to varying assumptions about the cost and efficacy of prophylaxis, as well as the probability of hospitalization, but were less sensitive to the cost of hospitalization.
                In our model, the cost of prophylaxis against RSV for most subgroups of preterm infants was high relative to the benefits realized. Lower costs might permit the benefits of prophylaxis to be extended to additional groups of preterm infants. To evaluate the cost-effectiveness of palivizumab as respiratory syncytial virus prophylaxis in premature infants without chronic lung disease and to evaluate the impact on cost-effectiveness of a potential reduction in risk of asthma following respiratory syncytial virus infection among infants receiving palivizumab.
                Two decision analytic models were designed, one with and the other without accounting for increased risk of asthma following respiratory syncytial virus infection.
                A hypothetical community or university hospital.
                Hypothetical cohorts of infants without chronic lung disease born at 26 to 32 weeks' gestation.
                Palivizumab prophylaxis vs no prophylaxis.
                Expected costs and incremental cost-effectiveness ratio expressed as cost per quality-adjusted life-year.
                The expected costs were higher for palivizumab prophylaxis as compared with no prophylaxis. The incremental cost-effectiveness ratios were high for all gestations and are not considered cost-effective by today's standards (<$200 000 per quality-adjusted life-year). Both models were sensitive to variation in the cost of palivizumab. The model that included asthma was sensitive to variation in quality of life for children with asthma. In instances where asthma was considered severe with profound worsening in quality of life compared with life without asthma, some infants had an incremental cost per quality-adjusted life-year that was less than $200 000.
                Our model supports implementing more restrictive guidelines for palivizumab prophylaxis. Palivizumab was cost-effective for some infants in an analysis that accounted for increased risk of severe asthma following respiratory syncytial virus infection. To assess the cost-effectiveness of palivizumab, a monoclonal antibody against respiratory syncytial virus (RSV), in infants at high risk for severe RSV lower respiratory tract infection, such as premature infants, infants with bronchopulmonary dysplasia, and those with congenital heart disease, based on long-term epidemiologic data from Austria.
                A decision-tree model was used, and the analysis was based on a lifetime follow-up investigating cost-effectiveness of palivizumab versus no RSV infection prevention. The primary perspective of the study was that of the healthcare system, the second that of society. Cost and effects were discounted by 5%. The base case analysis included only direct medical costs, and a scenario analysis included various indirect costs.
                Analyses were based on epidemiologic data on a total of 1579 children hospitalized because of RSV lower respiratory tract infection during 16 seasons. The incremental cost-effectiveness ratio for the first outcome measure (life years gained) amounted to discounted costs of €34,956 (for all preterm infants), €35,056 (for < 33 weeks' gestational age [wGA] infants), €35,233 (for 33-35 wGA infants), €35,611 (for infants with bronchopulmonary dysplasia), and €8956 (for infants with congenital heart disease). Use of palivizumab compared with no prophylaxis had an incremental cost-utility ratio of €26,212, €26,292, €24,392, €24,654, and €8484, respectively, per quality-adjusted life years. Results from the society perspective were more cost-effective in all study populations. An additional scenario analysis with 7 injections for the 33 to 35 wGA group revealed cost-effectiveness as well.
                Our results based on nationwide long-term epidemiologic data suggest that palivizumab is cost-effective in prevention of RSV disease in high-risk infants. Prophylactic therapy with palivizumab, a humanized monoclonal antibody, has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in preterm infants, including those in the 32-35 weeks' gestational age (GA) subgroup. The cost-effectiveness of this therapy in Canada is unknown.
                To evaluate the cost-effectiveness of palivizumab as respiratory syncytial virus prophylaxis in premature infants born at 32-35 weeks' GA. Design: A decision analytic model was designed to compare both direct and indirect medical costs and benefits of prophylaxis in this subgroup of premature infants. Sensitivity analyses were performed to ascertain the robustness of the model for five point estimates: mortality rate, discounting rates, health-utility values, degree of vial-sharing and administration costs. A probabilistic sensitivity analysis (PSA) was also conducted.
                Canadian publicly funded health-care system (Ministry of Health payer perspective) for base-case analysis. Societal perspective, accounting for future lost productivity, was adopted for a secondary analysis. Participants: Canadian infants born at 32-35 weeks' GA without chronic lung disease. Interventions: Palivizumab prophylaxis versus no prophylaxis. Main outcome measures: Expected costs and incremental cost-effectiveness ratio expressed as cost per life-year gained (LYG) and quality-adjusted life-year (QALY) using 2007 Canadian dollars. Results: The expected costs were higher for palivizumab prophylaxis as compared with no prophylaxis. The incremental cost-effectiveness ratio (ICER) for the base-case scenario was $20 924 per QALY after discounting, which is considered cost-effective in Canada. When the uncertainty of the input parameter assumptions was tested through sensitivity analyses assessing several data sources for five key parameters, no substantial differences were found from the base-case results. The PSA indicated a 0.99 probability that the ICER for palivizumab was less than $50 000/QALY. Sub-analyses that varied the number of risk factors found that for infants with two or more risk factors, or at least moderate risk, palivizumab had incremental costs per QALY that indicated moderate-to-strong evidence for adoption (range: $808-81 331, per QALY).
                Palivizumab was cost-effective and the authors' model supports prophylaxis for infants born at 32-35 weeks' GA, particularly those with more than two risk factors or at least a moderate level of risk according to a risk scoring tool. Children with hemodynamically significant congenital heart disease (CHD) are at risk for serious respiratory syncytial virus (RSV) disease. This study was designed to assess the safety and tolerability of motavizumab versus palivizumab in children with CHD and was not powered for efficacy. Patients (n = 1236) aged ≤24 mo were randomized to receive five monthly doses (15 mg/kg) of motavizumab or palivizumab during the RSV season. Adverse events (AEs) and serious AEs (SAEs) were recorded through 30 d after the last dose. RSV hospitalizations and RSV outpatient medically attended lower respiratory tract infections (MALRI; season 2) were summarized. Approximately 93 and 50% of patients reported an AE or SAE, respectively. Skin events occurred in 19.3% of motavizumab recipients and 16.2% of palivizumab recipients. Rates of hospitalizations and RSV MALRI were similar between treatment groups [relative risk (RR): 0.75; 95% CI, 0.34-1.59 and RR: 0.49; 95% CI, 0.10-1.99, respectively; both p > 0.05]. Motavizumab and palivizumab had similar safety profiles in children with hemodynamically significantly CHD; with the exception of skin events which were increased in motavizumab recipients. Safety and efficacy were consistent with another study comparing motavizumab with palivizumab in premature infants without CHD. To evaluate the efficiency (cost-effectiveness) of palivizumab in preventing severe respiratory syncytial virus (RSV) infection in premature infants with a gestational age of 32-35 weeks (GA 32-35) and two or more risk factors (RF) in Spain.
                Design: decision tree model using data from the scientific literature and the FLIP I and FLIP II studies (cohort of 326 infants with GA 32-35 and two or more RF who received palivizumab) sponsored by the Spanish Society of Neonatology. Main effectiveness measure: quality-adjusted life years (QALY) gained. Perspectives: the national health service (NHS), which includes direct costs (administration of palivizumab and hospital admissions), and the societal perspective, which also includes indirect costs (the child's future lost productivity). Discount: 3 % annually for effectiveness and indirect costs. Sensitivity analysis: construction of 37 scenarios modifying variables related to effectiveness and costs.
                Prophylaxis with palivizumab in premature infants with GA 32-35 and two or more RF produced an incremental cost-effectiveness ratio (ICER) of 13,849 euro/QALY from the NHS perspective, and an ICER of 4,605 euro/QALY from the societal perspective. In the sensitivity analysis, from the NHS perspective the ICER ranged from 5,351 euro/QALY (most favorable scenario) to 23,276 euro/QALY (least favorable scenario).
                Palivizumab is a cost-effective therapy as prophylaxis against RSV in infants with GA 32-35 and two or more RF. Its use is efficient from the NHS perspective, since the cost of a QALY, even in the least favorable scenarios, is lower than the threshold of 30,000 Euro/QALY considered socially acceptable in Spain. The aim of this study was to assess the cost-utility of palivizumab versus no prophylaxis in the prevention of respiratory syncytial virus infection among high-risk preterm infants.
                We used and adapted a pre-existent model in which two cohorts of patients received palivizumab or no prophylaxis. The patients were followed for their expected lifetimes. The economic evaluation was conducted from the perspective of the Italian National Health Service. We considered Life-Years Gained (LYGs), Quality-Adjusted Life-Years (QALYs) and direct medical costs (pharmacological treatment, hospitalization, recurrences for wheezing, etc.). LYGs and QALYs were based on the results of a double blind cohort study with prospective follow-up and direct medical costs were based on Italian treatment patterns. Benefits and costs were discounted at 3%. Costs were assessed in 2007 Euros. Sensitivity and threshold analysis on key clinical and economic parameters were performed.
                For the two cohorts, the expected life-years (per patient) with palivizumab versus no prophylaxis were 29.842 and 29.754 years, respectively. Quality-adjusted life years (per patient) with palivizumab were 29.202, and for no prophylaxis were 29.043. The expected cost (per patient) was euro 6,244.20 with palivizumab and euro 4,867.70 with no prophylaxis. We calculated for palivizumab versus no prophylaxis the incremental cost per LYG and per QALY gained. It was euro 15,568.65 and euro 8,676.74, respectively.
                This study suggests that, compared with no prophylaxis, palivizumab is cost-effective in the prevention of respiratory syncytial virus infection among high risk preterm infants. Respiratory syncytial virus is the most common cause of bronchiolitis, a lower respiratory tract infection occurring in infancy. It is responsible for several rehospitalizations, substantial morbidity and occasional deaths in the UK every year. Palivizumab is a recombinant monoclonal antibody that has been shown to reduce hospitalizations in infected infants. It is licensed for high-risk infants, primarily those born pre-term or with chronic pulmonary or cardiac conditions. Palivizumab is expensive, but several economic analyses have determined highly discrepant costs. This article reviews the limitations of the available efficacy and economic data, and highlights problems in interpretation and extrapolation. We also present the results of a cost-effectiveness analysis relevant to populations of high-risk infants in the UK. The aim of this study was to estimate the cost-effectiveness of palivizumab, a monoclonal antibody against severe respiratory syncytial virus infection, in high-risk infants in Austria.
                A decision tree model was developed to determine cost-effectiveness in infants born prematurely (<or=35 weeks' gestational age), those with bronchopulmonary dysplasia (BPD), and children with congenital heart disease (CHD). The primary perspective of the analysis was that of the compulsory health insurance fund. The societal perspective was also considered.
                From the health insurance fund perspective, including the costs associated with asthma, the incremental cost-effectiveness ratio (cost per quality-adjusted life year [QALY] gained) without discounting was estimated to be euro 4484 (2006 euros) in preterm infants, euro 6719 in children with BPD, and euro 2668 in the CHD population. When discounted, these figures increased to euro 14,439, euro 21,672, and euro 9754, respectively. The results from the societal perspective were substantially more cost-effective in all populations. The undiscounted cost per QALY was euro 1435 in preterm infants, euro 4881 in children with BPD, and euro 251 in the CHD group. Discounted figures were euro 4623, euro 15,741, and euro 917, respectively. Sensitivity analyses confirmed the robustness of the model, and scenario analyses found that the inclusion of indirect costs led to further improvement in the cost-effectiveness outcomes for palivizumab.
                Use of palivizumab was cost-effective compared with no prophylaxis in high-risk infants and children in Austria. The study evaluated the incremental cost-effectiveness ratio (ICER) of the prophylaxis of palivizumab, for the reduction of complications associated to the respiratory syncytial virus in preterm patients in Mexico.
                A decision tree was developed in preterm groups [<29 and 29-32 weeks of gestational age (wGA)], by using epidemiological and cost local data; the effectiveness was obtained with a systematic review. Patients were evaluated according to their life expectancy. Mexican Health System perspective was used. Effectiveness measures employed were LYG and QALYs. The costs are reported in USD 2009.
                ICERs per LYG resulted on values of USD $25,029 and USD $29,637 for <29 wGA and 29-32 wGA respectively, whereas ICERs per QALYs obtained in the model accounted for USD $17,532 and USD $20,760.
                Palivizumab prophylaxis for preterm newborn patients ≤32 weeks of age resulted in a cost-effective alternative. To establish the preterm infant hospitalization risks from respiratory syncytial virus (RSV) in New Zealand and the net cost per hospitalization averted by palivizumab.
                The 437 infants born < 32 weeks' gestation in 1997 and treated at five major neonatal units were identified. Subsequent admissions during the next 2 years for bronchiolitis, pneumonia and croup were tracked, and information collected on RSV tests performed. Data on the length of stay and hospital costs were used to calculate the potential net cost per hospitalization averted associated with the use of palivizumab and the number needed to treat (NNT) to prevent one hospitalization.
                Estimated RSV readmission risk before 1 year corrected age in infants < 32 weeks' gestation discharged home on oxygen, and those " 28 weeks' gestation, or between 29 and 31 weeks' gestation with or without chronic lung disease was 42%, 23%, 19%, 10% and 8%, respectively. The NNT with palivizumab to prevent one hospitalization ranged from six to 26 across subgroups. Mean (range) net cost per hospitalization averted was 60,000 New Zealand dollars ($28,000-$166,700). In no subgroup would prophylaxis result in net cost saving. Prophylaxis for all NZ infants " 28 weeks' gestation would cost approximately $1,090,000 net and prevent 29 hospitalizations annually, being equivalent to $37,000 net per hospitalization averted, with eight infants treated to prevent one hospitalization. Alternative assumptions about cost and efficacy failed to alter these findings.
                If value is placed on preventing morbidity, the priority groups for palivizumab prophylaxis are preterm infants discharged home on oxygen, followed by preterm infants of 28 weeks' gestation or less. Canadian, Inuit, full term infants have the highest rate of respiratory syncytial virus (RSV) infection globally, which results in substantial costs associated hospitalisation.
                Decision-analytical techniques were used to estimate the incremental cost-effectiveness ratio (ICER) for palivizumab compared to no prophylaxis for Inuit infants of all gestational age. The time horizon was that of life-time follow-up, and costs and effectiveness were discounted at 5% per year. Costs (2007 CAD$) for palivizumab, hospitalisation (including medical evacuation, intensive care unit [ICU]), physician visits, and transportation were calculated based on the Canadian payer's perspective. Benefits on decreasing RSV hospitalisation were expressed as quality-adjusted life-years (QALYs). One-way and probabilistic sensitivity analysis (PSA) were conducted, varying: mortality rates, utilities, length of stay in hospital and ICU.
                For all of Baffin Island infants (<1 year), the ICER was $39,435/QALY. However, when infants were grouped by age and area of residence, those residing in Iqaluit (<1 year) had an ICER of $152,145/QALY, while those residing in rural areas (outside of Iqaluit) had an ICER of $24,750/QALY. Prophylaxis was a dominant strategy (cost saving) for rural infants under 6 months of age, with the PSA demonstrating that it was dominant 98% of the time.
                The ICERs suggested that palivizumab is a cost-effective option for the prevention of RSV for Inuit infants on Baffin Island compared to no prophylaxis. Palivizumab is highly cost effective in Arctic infants <1 year of age specifically residing outside of Iqaluit and is a dominant strategy for those under 6 months of age in rural areas. However, palivizumab is not cost effective compared to no treatment for infants of all ages residing in Iqaluit. Acquisition costs of palivizumab have increased in Canada since 2007. This analysis aims to re-evaluate the cost effectiveness of palivizumab in Canada for premature infants born between 32 and 35 weeks' gestational age using updated 2010 healthcare costs compared to those used in a 2007 decision analytic model.
                New costs (CAN$) were acquired from the same Health Canada and Ontario Ministry of Health sources that were utilized in the previously published 2007 model. Palivizumab prices were acquired from Abbott Laboratories Ltd., current as of August 2010.
                Incremental cost-effectiveness ratios (ICERs) rose by $742, going from $30,618/QALY to $31,360/QALY. ICER changes increased from a range of $801,297 to $820,701 for infants with zero risk factors to a decrease from $808 to $192 for infants with four or more risk factors.
                Palivizumab ICERs remained fairly stable from 2007 to 2010. The original recommendation stating that palivizumab is cost effective in infants born between 32 and 35 weeks' GA with two or more risk factors, or who are at moderate-to-high risk based on a risk assessment model, does not change. Analyses founded on evolving country-specific variables are needed in order to accurately reassess the cost effectiveness of interventions as costs change worldwide.
                There are a limited number of publications reporting mortality in premature Canadian infants with RSV as a primary outcome. In addition, conclusions drawn from this analysis are country-specific and limited to premature infants dwelling in Canada. Medicaid infants are at high risk of severe respiratory syncytial virus (RSV) disease. The study objective was to estimate the cost-effectiveness of palivizumab in a Medicaid population.
                A societal cost-utility analysis was conducted of prophylaxis with palivizumab vs no prophylaxis among four groups of premature infants: (1) <32 weeks gestational age (wGA) and ≤ 6 months chronologic age (CA); (2) 32-34 wGA, ≤ 3 months CA with 2009 American Academy of Pediatrics (AAP) risk factors (RF); (3) 32-35 wGA, ≤ 6 months CA with 2006 AAP RF; and (4) 32-35 wGA, ≤ 6 months CA with ≤ 1 RF. Full dosing of palivizumab was assumed throughout the RSV season (consistent with the FDA-approved label). All costs were in 2010 US dollars. The societal public payer spend for palivizumab was estimated using Medicaid reimbursement methodologies for the top 10 palivizumab-using states in 2010 minus mandatory manufacturer rebates. This study reports the incremental cost-effectiveness ratios (ICERs) in cost per quality-adjusted life-year (QALY) gained. Sensitivity and probabilistic analyses were also conducted.
                Palivizumab saved costs and improved QALYs among infants <32 wGA. Palivizumab was cost-effective in infants 32-34 wGA with 2009 AAP RF ($16,037 per QALY) and in infants 32-35 wGA with 2006 AAP RF ($38,244 per QALY). The ICER for infants 32-35 wGA with ≤ 1 RF was $281,892 per QALY. Influential variables in the sensitivity analysis included the background rate of RSV hospitalization, the cost of palivizumab, and the efficacy of palivizumab. KEY LIMITATIONS: These results are not generalizable to commercially insured infants or infants outside of the US.
                This is the first cost-utility analysis of palivizumab in a Medicaid population. Palivizumab, when dosed consistent with the FDA-approved labeling, was either cost-saving or cost-effective among current guideline-eligible infants in the Medicaid population. Palivizumab did not demonstrate cost-effectiveness in 32-35 wGA infants with ≤ 1 RF. To show if surfactant applied in different social-sanitary realities as prophylaxis of respiratory distress syndrome (RDS) is equally useful and able to reduce mortality and incidence of 3-4 radiological grade RDS.
                Two neonatal intensive care units (NICU) in Italy, one NICU in Bulgaria and one NICU in Romania were involved in a randomized controlled clinical trial of prophylaxis vs rescue treatment of RDS. Babies with gestational age 26-30 wks were randomized before birth to prophylaxis in the delivery-room with 200 mg/kg of porcine surfactant (prophylaxis) or to routine assistance (control). Subsequently the babies developing RDS requiring mechanical ventilation and fraction of inspired oxygen (FiO2) > or = 0.4 to maintain PaO2 about 50 mmHg were allowed to be treated rescue with 200 mg/kg of the same surfactant. To reach end-points of reducing mortality by 40% and incidence of radiological grade 3-4 RDS a total number of 174 patients were required.
                Due to logistic, practical and social-political problems the study was interrupted after enrollment of 93 babies (61 in Italy and 32 in Bulgaria). The Romanian centre did not start the study because it was impossible in the scheduled times to equip it for mechanical ventilation of the newborn infants. Analysis done on an intention to treat basis did not show significant reductions of mortality and 3-4 radiological grade RDS, even if there was a trend towards a reduction in the babies given prophylaxis. A significantly lower number of babies given prophylaxis required a subsequent rescue treatment compared to controls (p < 0.001). There was no difference in other complications such as intraventricular haemorrhage, air-leak syndromes and infections between prophylaxis and control infants. As regards pulmonary gas exchange, the PaO2/FiO2 ratio was significantly improved in the babies given prophylaxis for the first 12 hours of life vs the controls.
                Even if the study was terminated before term, the analysis of the data shows that prophylaxis with surfactant is equally effective in different social-clinical conditions to improve pulmonary gas-exchange, especially in the first critical hours of life of premature babies. : Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children. Motavizumab is an investigational humanized monoclonal antibody for RSV prophylaxis.
                : A dose-escalation study was conducted followed by assessment of safety, tolerability, serum concentrations, and immunogenicity during a second consecutive RSV season. In season 1, premature infants aged < or =6 months or children < or =24 months with chronic lung disease of prematurity received monthly motavizumab (3 or 15 mg/kg). In season 2, children who received > or =3 motavizumab doses in season 1 were randomized to receive monthly motavizumab or palivizumab 15 mg/kg.
                : Of 217 children enrolled in season 1, 211 (97.2%) received motavizumab 15 mg/kg and 205 (94.5%) patients completed the study through 90 days after the final dose. In season 2, 136 children were randomized to receive motavizumab (n = 66) or palivizumab (n = 70). The most commonly reported related adverse event was transient injection site erythema. In season 1, mean trough motavizumab concentrations were 7.9 and 50.2 microg/mL after the 3- and 15-mg/kg doses, respectively. Trough concentrations increased with repeated motavizumab dosing; a similar pattern was seen in season 2. Antimotavizumab reactivity occurred infrequently (3.3%) in season 1. In season 2, no treatment group-specific antidrug antibody was detected through 90 to 120 days after dosing with either product.
                : The pharmacokinetic profile of motavizumab was similar to that of other IgG1 antibodies. Increased adverse reactions or immunogenicity were not observed during and after a second season of treatment with motavizumab. Safety findings from these studies supported the continued development of motavizumab. To compare the hospital course and clinical outcome of preterm infants with respiratory distress syndrome treated with surfactant and managed with high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CV) as their primary mode of ventilator support.
                A prospective randomized clinical trial.
                Three community-based level III neonatal intensive care units.
                A total of 125 neonates who were 35 weeks or less estimated gestation requiring intubation and assisted ventilation for respiratory distress syndrome with arterial to alveolar oxygen ratio less than .50.
                Patients were randomized to continue CV (61 patients) or be changed to HFOV (64 patients) after exogenous surfactant administration (100 mg/kg). HFOV was used in a strategy to promote lung recruitment and maintain lung volume. Protocol respiratory care guidelines were followed; otherwise routine care was provided by each neonatal intensive care unit.
                No differences were noted in demographic features between the two study groups. The study population birth weight was 1.51 +/- .47 kg (mean +/- SD), gestational age was 30.9 +/- 2.5 weeks, and study entry age was 2 to 3 hours. Patients randomized to HFOV demonstrated the following significant findings compared with CV-treated patients: vasopressor support was less intensive; surfactant redosing was not as frequent; oxygenation improved more rapidly and remained higher during the first 7 days; fewer infants required prolonged supplemental oxygen or ventilator support; treatment failure was reduced; more patients survived without chronic lung disease at 30 days; need for continuous supplemental oxygen at discharge was less; frequency of necrotizing enterocolitis illness was lower; there were fewer abnormal hearing tests; and hospital costs were decreased. No differences were seen between the two study groups in the frequency or severity of patent ductus arteriosus, air leak, retinopathy of prematurity, or intraventricular hemorrhage. Length of hospital stay and survival to discharge were similar for HFOV- and CV-treated infants.
                When used early with a lung recruitment strategy, HFOV after surfactant replacement resulted in clinical outcomes consistent with a reduction in both acute and chronic lung injury. Benefit was evident for preterm infants both less than or equal to 1 kg and more than 1 kg. In addition, early HFOV treatment may have had a more global effect on patient health throughout the hospitalization, resulting in reduced morbidity and decreased health care cost.
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.