CONTEXT:

Palivizumab prophylaxis is used as passive immunization for respiratory syncytial virus (RSV). However, because of its high cost, the value of this intervention is unclear.

OBJECTIVE:

To systematically review the cost-effectiveness of palivizumab prophylaxis compared with no prophylaxis in infants <24 months of age.

DATA SOURCES:

Medline, Embase, and Cochrane Library up to August 2018.

STUDY SELECTION:

Two reviewers independently screened results to include economic evaluations conducted between 2000 and 2018 from Organization for Economic Cooperation and Development countries.

DATA EXTRACTION:

Two reviewers independently extracted outcomes. Quality appraisal was completed by using the Joanna Briggs Institute checklist. Costs were adjusted to 2017 US dollars.

RESULTS:

We identified 28 economic evaluations (20 cost-utility analyses and 8 cost-effectiveness analyses); most were from the United States (n = 6) and Canada (n = 5). Study quality was high; 23 studies met >80% of the Joanna Briggs Institute criteria. Palivizumab prophylaxis ranged from a dominant strategy to having an incremental cost-effectiveness ratio of $2 526 203 per quality-adjusted life-year (QALY) depending on study perspective and targeted population. From the payer perspective, the incremental cost-effectiveness ratio for preterm infants (29–35 weeks’ gestational age) was between $5188 and $791 265 per QALY, with 90% of estimates <$50 000 per QALY. Influential parameters were RSV hospitalization reduction rates, palivizumab cost, and discount rate.

LIMITATIONS:

Model design heterogeneity, model parameters, and study settings were barriers to definitive conclusions on palivizumab’s economic value.

CONCLUSIONS:

Palivizumab as RSV prophylaxis was considered cost-effective in prematurely born infants, infants with lung complications, and infants from remote communities.

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in infants and young children worldwide.1 It is a ubiquitous virus that nearly 100% of infants will contract within 2 years after birth.2,4 RSV is a seasonal respiratory infection that is a significant cause of morbidity and mortality, with the virus estimated to cause up to 90% of pediatric bronchiolitis hospitalizations and up to 50% of pediatric hospitalizations for pneumonia.1,5 Risk factors for severe RSV in infants include preterm birth, congenital heart disease (CHD), bronchopulmonary dysplasia (BPD) or chronic lung disease (CLD), cystic fibrosis, Down syndrome, and a weakened immune system.6,8 

Although there is currently no vaccine available to prevent RSV infection, since 1998, passive prophylaxis has been available with palivizumab.9 Palivizumab is a humanized murine monoclonal antibody administered monthly as an intramuscular injection and has shown a significant reduction in the overall rate of hospitalization due to RSV infection.10 However, because of its high acquisition costs, there has been considerable debate surrounding the cost-effectiveness of this intervention. Since 2000, the cost-effectiveness of palivizumab has been summarized in 8 reviews, of which half were completed >10 years ago.11,14 In a recent study in 2013, Andabaka et al15 reported that the economic evaluation results are inconsistent across studies, ranging from highly cost-effective to not cost-effective depending on the scenario. Our objective for this study was to provide an update on the cost-effectiveness of palivizumab passive immunization for the prevention of RSV in infants and children up to 24 months of age and, when possible, to stratify results by at-risk populations to inform policy decisions for these groups. We conducted a systematic scientific-literature review for economic evaluations conducted in high-income countries from the Organization for Economic Cooperation and Development (OECD) to limit heterogeneity in population baseline health, health care systems, and quality of care and included studies conducted after 2000. With this review, we provide a much-needed update to support health-policy decision-making for palivizumab prophylaxis, with particular emphasis on cost-effectiveness results according to gestational age at birth for preterm infants, which has historically been an area of clinical and policy uncertainty.11,16,17 

We conducted our systematic review by following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.18 The search strategy was developed with a Public Health Agency of Canada librarian. We conducted a scientific literature search for English- and French-language studies published in 3 electronic databases: Medline and Epub Ahead of Print and Medline In-Process & Other Non-Indexed Citations (Ovid interface), Embase (Ovid interface), and the Cochrane Library, which included the Health Technology Assessment Database, the National Health Service (NHS) Economic Evaluation Database, and the Database of Abstracts of Reviews of Effects. In our search, we used medical-subject headings and text words related to the following concepts: respiratory syncytial virus, palivizumab, economic evaluations, and cost-effectiveness. The primary search strategy was developed in Medline and adapted to other databases to account for database-specific vocabulary and functionality. A complete list of search terms and the full search strategy for Medline are summarized in Supplemental Table 4. We manually searched the reference lists from relevant articles and systematic reviews.

The protocol and eligibility criteria for studies are published on PROSPERO (identifier CRD42018104977). We included full economic evaluations (eg, cost-benefit analysis, cost-effectiveness analysis, and cost-utility analysis) in which palivizumab prophylaxis for RSV was compared with any comparator (eg, no prophylaxis) for infants up to 24 months of age on the basis of current guidelines from Canada’s National Advisory Committee on Immunization.19 We included economic evaluations that were conducted in OECD countries between 2000 and present and reported outcomes related to an incremental ratio of cost per unit (eg, cost per quality-adjusted life-year [QALY], cost per case averted, cost per life-year gained [LYG], and cost-benefit ratio). We excluded cost-minimization studies, cost-of-illness studies, and budget-impact analyses. We excluded studies conducted outside of OECD countries, studies published in a language other than English or French, and studies published before 2000.

Screening, data extraction, and quality appraisal were completed in duplicate (by S.M. and A.S.). All levels of screening were completed using DistillerSR (Evidence Partners, Ottawa, Canada). Conflicts were discussed and resolved through consensus. Data extraction was guided by Consolidated Health Economics Evaluation and Reporting Standards statement.20 We collected study characteristics (publication year, country, study design, study perspective, time horizon, discounting, primary and secondary outcomes, use of cost-effectiveness thresholds, and funding sources), study population characteristics (age range, gestational age, health conditions, and setting), key parameters (RSV incidence and/or hospitalization rates, mortality rates, sequelae, cost of palivizumab, and number of doses), and results (base-case incremental cost-effectiveness ratios [ICERs], scenario analyses, type of sensitivity analysis, and influential parameters). The quality of included studies was assessed by using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Economic Evaluations.21 We classified a study as high quality if it met >80% of the JBI checklist criteria.22 

We descriptively summarized the study characteristics and population characteristics. Cost-effectiveness outcomes were adjusted to 2017 US dollars (USDs) by using purchasing power parity rates from the OECD23 and US inflation rates from the US Department of Labor. Unadjusted and adjusted ICERs were summarized. We conducted subgroup analyses to summarize the cost-effectiveness for studies conducted from remote regions of the Canadian Arctic and studies in which cost-effectiveness was reported in costs per QALY for preterm infants. For studies that included preterm infants, we stratified on the basis of gestational age at birth (weeks) and plotted this against the adjusted ICERs to visually identify the spread of ICER estimates and possible trends related to gestational age. The number of estimates and the proportion of them being cost-effective at various thresholds were summarized. A meta-analysis of cost-effectiveness was inappropriate because of the heterogeneity of the study setting, model designs, parameters used, population, and perspective taken in the studies.

Our systematic literature search identified 237 deduplicated records, of which 30 met our eligibility criteria and were included in our review (Fig 1).14,24,52 Conclusions of 2 studies31,51 were updated by using more recent data,32,39 which excluded them from our review’s analysis and conclusions. The 28 studies included were published between 2000 and 2018, with most conducted in the United States (n = 6), Canada (n = 5), Netherlands (n = 3), United Kingdom (n = 3), and Spain (n = 3). The rest of the studies were conducted in Austria (n = 2), Germany (n = 2), Italy (n = 1), Mexico (n = 1), New Zealand (n = 1), and Sweden (n = 1). Study characteristics are summarized in Table 1.

FIGURE 1

Literature search and study selection.

FIGURE 1

Literature search and study selection.

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TABLE 1

Study Characteristics

Author, yCountryPerspectiveType of AnalysisOutcome MeasurePopulationTime HorizonDiscount RateIndustry Funding
Banerji et al24 2016 Canada Payer CEA Cost per HA Term infants 6 mo N/A Abbott and MedImmune, LLC (grants) 
Bentley et al35 2013 United Kingdom Payer CUA Cost per QALY Preterm infants with CHD, and CLD Lifetime 3.5% AbbVie 
Blanken et al46 2018 Netherlands Societal CUA Cost per QALY Preterm infants 1 y N/A Unknown: grants for investigator-initiated studies from MedImmune and AbbVie, including the MAKI trial, from which data for this CEA were derived 
Chirico et al47 2009 Italy Payer CUA Cost per QALY Preterm infants with BPD Lifetime 3% Abbott 
Elhassan et al44 2006 United States Societal CUA; CBA Cost per QALY Preterm infants without CLD 8 y 3% None 
Hampp et al48 2011 United States Payer CEA Cost per HA Preterm and term infants (both with and without CHD and CLD) NR NR None 
Harris et al49 2011 Canada Societal CEA; CBA Cost per day of HA Infants with CHD 5 ya NR Unknown: honorarium (<$1000) from Abbott Laboratories 
Hascoet et al50 2008 France Societal (BC) and payer CEA; CBA Cost per LYG Preterm infants with CHD or BPD Lifetime 3% Abbott France 
Lofland et al45 2000 United States Payer CEA Cost per RSV infection avoided Preterm infants with CLD 6 mo N/A MedImmune, LLC 
Mahadevia et al52 2012 United States Societal CUA Cost per QALY Preterm infants Lifetime 3% MedImmune, LLC 
McGirr et al25 2017 Canada Payer CUA Cost per QALY Term infants with cystic fibrosis Lifetime 5% None 
Neovius et al26 2011 Sweden Societal CUA Cost per QALY Preterm infants Lifetime 3% Abbott Scandinavia 
Nuijten et al30 2009 Germany Societal (BC) and payer CUA Cost per QALY Infants with CHD Lifetime 5% Abbott 
Nuijten et al29 2009 Netherlands Payer (BC) and societal CUA Cost per QALY Preterm infants with BPD and CHD Lifetime 4%, 1.5%b Abbott GmbH & Co KG (Ludwigshafen, Germany) 
Nuijten et al28 2010 Spain Payer (BC) and societal CUA Cost per QALY Preterm infants Lifetime 3% Abbott GmbH & Co KG (Ludwigshafen, Germany) 
Nuijten et al27 2007 United Kingdom Payer (BC) and societal CUA Cost per QALY; cost per HA Preterm infants with BPD and CHD Lifetime 3.5% Abbott GmbH & Co KG (Ludwigshafen, Germany) 
Resch et al31,32 2008, 2012 Austria Payer (BC) and societal CUA Cost per QALY Preterm infants with BPD and CHD Lifetime 5% None 
Rietveld et al33 2010 Netherlands Societal CEA Cost per HA Preterm infants with BPD 1 y N/A None 
Roeckl-Wiedmann et al34 2003 Germany Societal CEA Cost per HA Preterm infants with risk factors 1 y N/A Abbott Laboratories, Germany 
Salinas-Escudero et al36 2012 Mexico Payer CUA Cost per QALY Preterm infants Lifetime 3% Abbott Laboratories of Mexico 
Sanchez-Luna et al37 2017 Spain Payer (BC) and societal CUA Cost per QALY Preterm infants with risk factors 6 y 3% None 
Schmidt et al38 2017 Spain Societal CUA Cost per QALY Infants with CHD Lifetime 3% AbbVie (grant) 
Smart et al39,51 2010 Canada Payer (BC) and societal CUA Cost per QALY Preterm infants with risk factors Lifetime 5% Unknown: financial and other relationships with Abbott but not funded for this study 
Tam et al40 2009 Canada Payer (BC) and societal CUA Cost per QALY NR Lifetime 5% Abbott Laboratories and Abbott International (grant) 
Vogel et al41 2002 New Zealand Societal CEA; CBA Cost per case averted Preterm infants with CLD 3 ya NR Abbott (grant) 
Wang et al14 2008 United Kingdom Payer (BC) and societal CUA Cost per QALY Preterm infants with BPD, CHD, or CLD; term infants with risk factors Lifetime 3.5% None 
Weiner et al42 2012 United States Societal CUA Cost per QALY Preterm infants with risk factors Lifetime 3% MedImmune, LLC 
Yount et al43 2004 United States Societal CUA; CBA Cost per QALY Infants with CHD Lifetime 3% None 
Author, yCountryPerspectiveType of AnalysisOutcome MeasurePopulationTime HorizonDiscount RateIndustry Funding
Banerji et al24 2016 Canada Payer CEA Cost per HA Term infants 6 mo N/A Abbott and MedImmune, LLC (grants) 
Bentley et al35 2013 United Kingdom Payer CUA Cost per QALY Preterm infants with CHD, and CLD Lifetime 3.5% AbbVie 
Blanken et al46 2018 Netherlands Societal CUA Cost per QALY Preterm infants 1 y N/A Unknown: grants for investigator-initiated studies from MedImmune and AbbVie, including the MAKI trial, from which data for this CEA were derived 
Chirico et al47 2009 Italy Payer CUA Cost per QALY Preterm infants with BPD Lifetime 3% Abbott 
Elhassan et al44 2006 United States Societal CUA; CBA Cost per QALY Preterm infants without CLD 8 y 3% None 
Hampp et al48 2011 United States Payer CEA Cost per HA Preterm and term infants (both with and without CHD and CLD) NR NR None 
Harris et al49 2011 Canada Societal CEA; CBA Cost per day of HA Infants with CHD 5 ya NR Unknown: honorarium (<$1000) from Abbott Laboratories 
Hascoet et al50 2008 France Societal (BC) and payer CEA; CBA Cost per LYG Preterm infants with CHD or BPD Lifetime 3% Abbott France 
Lofland et al45 2000 United States Payer CEA Cost per RSV infection avoided Preterm infants with CLD 6 mo N/A MedImmune, LLC 
Mahadevia et al52 2012 United States Societal CUA Cost per QALY Preterm infants Lifetime 3% MedImmune, LLC 
McGirr et al25 2017 Canada Payer CUA Cost per QALY Term infants with cystic fibrosis Lifetime 5% None 
Neovius et al26 2011 Sweden Societal CUA Cost per QALY Preterm infants Lifetime 3% Abbott Scandinavia 
Nuijten et al30 2009 Germany Societal (BC) and payer CUA Cost per QALY Infants with CHD Lifetime 5% Abbott 
Nuijten et al29 2009 Netherlands Payer (BC) and societal CUA Cost per QALY Preterm infants with BPD and CHD Lifetime 4%, 1.5%b Abbott GmbH & Co KG (Ludwigshafen, Germany) 
Nuijten et al28 2010 Spain Payer (BC) and societal CUA Cost per QALY Preterm infants Lifetime 3% Abbott GmbH & Co KG (Ludwigshafen, Germany) 
Nuijten et al27 2007 United Kingdom Payer (BC) and societal CUA Cost per QALY; cost per HA Preterm infants with BPD and CHD Lifetime 3.5% Abbott GmbH & Co KG (Ludwigshafen, Germany) 
Resch et al31,32 2008, 2012 Austria Payer (BC) and societal CUA Cost per QALY Preterm infants with BPD and CHD Lifetime 5% None 
Rietveld et al33 2010 Netherlands Societal CEA Cost per HA Preterm infants with BPD 1 y N/A None 
Roeckl-Wiedmann et al34 2003 Germany Societal CEA Cost per HA Preterm infants with risk factors 1 y N/A Abbott Laboratories, Germany 
Salinas-Escudero et al36 2012 Mexico Payer CUA Cost per QALY Preterm infants Lifetime 3% Abbott Laboratories of Mexico 
Sanchez-Luna et al37 2017 Spain Payer (BC) and societal CUA Cost per QALY Preterm infants with risk factors 6 y 3% None 
Schmidt et al38 2017 Spain Societal CUA Cost per QALY Infants with CHD Lifetime 3% AbbVie (grant) 
Smart et al39,51 2010 Canada Payer (BC) and societal CUA Cost per QALY Preterm infants with risk factors Lifetime 5% Unknown: financial and other relationships with Abbott but not funded for this study 
Tam et al40 2009 Canada Payer (BC) and societal CUA Cost per QALY NR Lifetime 5% Abbott Laboratories and Abbott International (grant) 
Vogel et al41 2002 New Zealand Societal CEA; CBA Cost per case averted Preterm infants with CLD 3 ya NR Abbott (grant) 
Wang et al14 2008 United Kingdom Payer (BC) and societal CUA Cost per QALY Preterm infants with BPD, CHD, or CLD; term infants with risk factors Lifetime 3.5% None 
Weiner et al42 2012 United States Societal CUA Cost per QALY Preterm infants with risk factors Lifetime 3% MedImmune, LLC 
Yount et al43 2004 United States Societal CUA; CBA Cost per QALY Infants with CHD Lifetime 3% None 

BC, base case; CBA, cost-benefit analysis; CEA, cost-effectiveness analysis; CUA, cost-utility analysis; NR, not reported; N/A, not applicable.

a

Not clearly reported; assumed on the basis of data used for cohorts.

b

Four percent for economic outcomes and 1.5% for clinical outcomes.

Most studies (83%) met >80% of the JBI quality appraisal checklist criteria (Supplemental Table 5). The 2 checklist items that were least met were whether the study results included all issues of concerns to users (39%) and whether all relevant costs and outcomes were identified (75%). Overall, studies included in this review were considered relatively high quality (Fig 2).

FIGURE 2

Quality appraisal results.

FIGURE 2

Quality appraisal results.

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In 14 studies, the subject's chronological age was explicitly reported to be <24 months, whereas in the other 14 studies, it was assumed that the cost-effectiveness of palivizumab was assessed in infants <24 months of age on the basis of their respective country guidelines on palivizumab use. High-risk infant populations were often studied, and, in some cases, overlapped: preterm infants (≤35 weeks’ gestational age [wGA]) (n = 19), BPD or CLD (n = 13), CHD (n = 11), and other risk factors (n = 6).

Base-case analyses were almost equally conducted from a societal perspective (n = 13) or health care–payer perspective (n = 15). In 8 of the 15 payer-perspective studies, additional analyses were performed from a societal perspective. Time horizon ranged from 6 months to lifetime; a time horizon was not reported in 1 study.48 (Table 1) Discount rates ranged between 3% and 5%; in 5 studies, the authors did not discount because of a limited time horizon,24,33,34,45,46 and a discount rate was not reported in 3 studies.41,48,49 The majority of studies were industry sponsored (n = 17; 61%). Cost-effectiveness was mostly reported as cost per QALY (n = 20) and cost per hospitalization averted (HA) (n = 5). For the remainder of this review, we described results using adjusted ICERs (2017 USDs); original unadjusted ICERs are summarized in Table 2.

TABLE 2

Study Outcomes

Author, yCountry or Original Currency, yICER (Original)ICER (Adjusted), 2017 USDOutcome MeasureResults (Context)Type of Sensitivity AnalysisStudy Conclusions
Banerji et al24 2016 CAD 2011 4633 4073 Cost per HA Scenario B, Nunavut without Iqaluita Deterministic Palivizumab was cost-effective in the Kitikmeot and Kivalliq regions and in Nunavik. Scenario B (compared with Scenario A) was more cost-effective in all regions except the Kitikmeot region. 
  14 545 12 787  Scenario B, Nunavuta   
  15 601 13 716  Scenario B, Nunavika   
  22 954 20 180  Scenario A, Kivalliq regiona   
  28 580 25 126  Scenario A, Nunavut without Iqaluita   
  30 230 26 577  Scenario A, Nunavika   
  41 404 36 401  Scenario A, Nunavuta   
  105 259 92 539  Scenario B, Qikiqtaaluk region without Iqaluita   
  133 407 117 286  Scenario B, Qikiqtaaluk regiona   
  166 600 146 468  Scenario A, Qikiqtaaluk region without Iqaluita   
  211 444 185 893  Scenario A, Qikiqtaaluk regiona   
  326 441 286 993  Scenario B, NWTa   
  545 115 479 242  Scenario A, NWTa   
  Dominant Dominant  Scenario A, Kitikmeot regiona   
  Dominant Dominant  Scenario B, Kitikmeot regiona   
  Dominant Dominant  Scenario B, Kivalliq regiona   
Bentley et al35 2013 GBP 2010 3845 6165 Cost per QALY gained Preterm infants (<29 wGA) Deterministic; probabilistic Prophylactic palivizumab represents an economically viable use of NHS resources for infants (aged <24 mo) with CHD, infants (aged <24 mo) with CLD, preterm infants born at ≤32 wGA, and preterm infants born 33–35 wGA when additional risk factors are considered. 
  19 168 30 734  Infants with CLD   
  30 205 48 430     
  33 216 53 258  Infants with CHD   
  99 056 158 824  Preterm infants (33–35 wGA)   
Blanken et al46 2018 Netherlands 2015 214 748 272 654 Cost per QALY gained Preterm (32–35 wGA) Deterministic; probabilistic — 
Chirico et al47 2009 Italy 2007 2732 3984 Cost per QALY gained BPD Deterministic Compared with no prophylaxis, palivizumab is cost-effective in the prevention of RSV infection among high-risk preterm infants. 
  8677 12 653  Preterm (<35 wGA, mix) with BPD   
  9380 13 679  Preterm (<33 wGA)   
  14 937 21 783  Preterm (33–35 wGA)   
Elhassan et al44 2006 USD 2002 103 053 140 341 Cost per QALY gained Base case, preterm (26 wGA), targeted use policy Deterministic Our model supports implementing more restrictive guidelines for palivizumab prophylaxis. Palivizumab was cost-effective for some infants in an analysis used to account for increased risk of severe asthma after RSV infection. We found evidence that long-term health consequences of RSV are central to the determination of the cost-effectiveness of the intervention. 
  216 830 295 287  Base case, preterm (28 wGA), targeted use policy   
  280 083 381 427  Base case, preterm (29–30 wGA), targeted use policy   
  675 780 920 300  Base case, preterm (29–30 wGA)   
  830 152 1 130 530  Base case, preterm (26 wGA)   
  1 212 497 1 651 220  Base case, preterm (31 wGA)   
  1 295 781 1 764 639  Base case, preterm (27 wGA)   
  1 500 351 2 043 230  Base case, preterm (28 wGA)   
  1 855 000 2 526 203  Base case, preterm (32 wGA)   
Hampp et al48 2011 USD 2010 302 103 339 852 Cost per HA Preterm (<32 wGA) Deterministic; probabilistic The cost of immunoprophylaxis with palivizumab far exceeded the economic benefit of preventing hospitalizations, even in infants at highest risk for RSV infection. 
  361 727 406 926  Preterm (<32 wGA) and CHD   
  368 048 414 037  Preterm (<32 wGA) and CLD   
  522 490 587 777  Term, CLD, and CHD   
  823 868 926 813  Term and CHD only   
  920 033 1 034 994  Any risk factor (indication)   
  1 322 422 1 487 663  Term and CLD only   
  2 138 870 2 406 129  No risk factor (indication)   
Harris et al49 2011 CAD 2007 8292 8077 Cost to treat 1 child per RSV season Base case Deterministic With our study, we contribute to the growing body of literature in which it is suggested that palivizumab is not cost-effective in children <2 y old with hemodynamically significant CHD. 
  15 513 15 111 Cost to prevent 1 d of hospitalization Base case   
Hascoet et al50 2008 France 2006 10 172 13 798 Cost per LYG Preterm (<32 wGA), with BPD (health care) Deterministic; probabilistic Prophylaxis with palivizumab for RSV in premature children with BPD or hemodynamically significant CHD can be considered cost-effective in France. 
  20 788 28 198  Preterm (<32 wGA), with cardiopathy (societal)   
  27 255 36 971  Preterm (<32 wGA), with BPD (societal)   
Lofland et al45 2000 USD 2000 1008 1434 Cost per RSV-infection episode avoided Base case, preterm (NR wGA), 81% reduction incidence of RSV infection (5% vs 26%) Deterministic The incremental cost per RSV-infection episode avoided ranged from $0 (cost savings) to $39 591 for palivizumab prophylaxis costs of $2500 and from $2702 to $79 706 for palivizumab prophylaxis costs of $4500. Clinicians may use this information to help determine if prophylactic palivizumab therapy is cost-effective in their clinical practice setting. 
  39 591 56 313  Preterm (NR wGA), 50% reduction incidence of RSV infection (5% vs 10%)   
  Dominant Dominant  Preterm (NR wGA), 83% reduction incidence of RSV infection (5% vs 28%)   
Mahadevia et al52 2012 USD 2010 44 774 50 369 Cost per QALY gained Group 2, preterm (32–35 wGA) with risk factorsb Deterministic Palivizumab remained cost-effective for guideline-eligible high-risk infants across both public and private sectors. Guideline-eligible infants included infants of <32 wGA, 32–34 wGA with 2009 AAP risk factors, and 32–35 wGA with 2006 AAP risk factors. Palivizumab was not cost-effective in infants of 32–35 wGA with 1 risk factor. 
  79 477 89 408  Group 3, preterm (32–35 wGA) with risk factorsb   
  464 476 522 514  Group 4, preterm (32–35 wGA) with risk factorsb   
  Dominant Dominant  Group 1, preterm (<32 wGA)b   
McGirr et al25 2017 CAD 2013 157 332 135 207 Cost per QALY gained High-risk CF <2 y (high risk for severe RSV disease) Deterministic Palivizumab is not cost-effective in Canada by commonly used thresholds. However, given the rarity of CF and the relatively small budget impact, consideration may be given. 
  652 560 560 792  All CF < 2 y   
Neovius et al26 2011 SEK 2009 148 293 19 000 Cost per QALY gained Preterm (<29 wGA), adding wheezing to asthma Deterministic; probabilistic On the basis of a willingness-to-pay threshold of 500 000 SEK per QALY, palivizumab was found to be cost-effective compared with no prophylaxis for infants born at <29 wk if severe RSV infection was assumed to increase subsequent asthma or mortality risk. 
  195 420 25 038  Base case, preterm (<29 wGA)   
  383 825 49 178  Preterm (<29 wGA), excluding indirect effect on asthma   
  492 430 63 093  Preterm (<29 wGA), excluding indirect effect on mortality   
  8 856 829 1 134 793  Preterm (<29 wGA), excluding the indirect effect of mortality and asthma   
Nuijten et al30 2009_DEU Germany 2006 2221 3180 Cost per QALY gained Base case, Cardiac Study parameters, societal Deterministic; probabilistic This analysis revealed that palivizumab represents a cost-effective means of prophylaxis against severe RSV infection requiring hospitalization in infants with hemodynamically significant CHD. 
  9528 13 643  Base case, Cardiac Study parameters, including asthma, payer   
  9529 13 644  Base case, societal   
  11 126 15 931  Base case, Cardiac Study parameters, excluding asthma, payer   
  16 673 23 874  Base case, direct medical costs (including asthma), payer   
  18 266 26 155  Base case, direct medical costs (excluding asthma), payer   
  123 439 176 749  Base case, excluding mortality, societal   
Nuijten et al29 2009_NLD Netherlands 2006 7067 9837 Cost per QALY gained Base case: CHD Deterministic; probabilistic 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. 
  11 336 15 779  Base case: preterm (<35 wGA, mix), with BPD (total costs, societal)   
  18 563 25 838  Preterm (<35 wGA, mix)   
  20 236 28 167  Base case: preterm (<35 wGA, mix), with BPD   
  23 461 32 655  Subpopulations with BPD    
  Dominant Dominant  Base case: CHD (total costs, societal)   
Nuijten and Wittenberg28 2010 Spain 2006 6498 10 715 Cost per QALY gained Base case, preterm (<32 wGA), inclusion of costs of sequelae treatment Deterministic; probabilistic Palivizumab provides a cost-effective method of prophylaxis against severe RSV disease among preterm infants in Spain. 
  12 814 21 130  Base case, preterm (<32 wGA)   
  Dominant Dominant  Base case, preterm (<32 wGA), societal perspective   
Nuijten et al27 2007 GBP 2003 6664 12 733 Cost per QALY gained CHD Deterministic; probabilistic This study reveals that palivizumab prophylaxis against severe RSV infection in children at high risk may be cost-effective from the NHS perspective 
  11 494 21 962  Base case, preterm (<35 wGA), with indirect costs (societal)   
  14 883 28 438  Preterm (<35 wGA)   
  16 720 31 948  Base case, preterm (<35 wGA), with BPD   
  20 953 40 036  BPD only   
Resch et al31,32 2008, 2012 Austria 2010 3045 4071 Cost per QALY gained Base case, CHD, including recurrent wheezing treatment, societal Deterministic Our results, which are based on nationwide long-term epidemiological data, reveal that palivizumab is cost-effective in the prevention of RSV disease in high-risk infants. 
  7818 10 452  Base case, CHD, including recurrent wheezing treatment   
  8484 11 343  Base case, CHD   
  15 800 21 124  Base case, for all preterm (<35 wGA, mix), including recurrent wheezing treatment, societal   
  15 992 21 380  Base case, preterm (33–35 wGA), including recurrent wheezing treatment, societal   
  17 554 23 469  Base case, BPD, including recurrent wheezing treatment, societal   
  18 133 24 243  Base case, preterm (<33 wGA), including recurrent wheezing treatment, societal   
  21 669 28 970  Base case, for all preterm (<35 wGA, mix), including recurrent wheezing treatment   
  21 862 29 228  Base case, preterm (33–35 wGA), including recurrent wheezing treatment   
  22 515 30 101  Base case, BPD, including recurrent wheezing treatment   
  23 833 31 863  Base case, preterm (<33 wGA), including recurrent wheezing treatment   
  24 392 32 611  Base case, preterm (33–35 wGA)   
  24 654 32 961  Base case, BPD   
  26 212 35 044  Base case, for all preterm (<35 wGA, mix)   
  26 292 35 151  Base case, preterm (<33 wGA)   
Rietveld et al33 2010 Netherlands 2000 13 190 21 066 Cost per HA Male infant, preterm (<28 wGA), birth wt <2500 g, with BPD (December) Deterministic Every mo, costs per HA were higher for children without BPD and children with higher gestational ages. Incremental costs per HA were always high. Passive immunization was always most cost-effective in December. A restrictive immunization policy requiring immunization of only children with BPD in high-risk months is therefore recommended. The costs of passive immunization would have to be considerably reduced to achieve cost-effectiveness. 
  30 795 49 184  Male infant, preterm (<28 wGA), birth wt <2500 g, with BPD (January)   
  31 055 49 599  Male infant, preterm (<28 wGA), birth wt <2500 g, with BPD (November)   
  47 145 75 297  Male infant, preterm (<28 wGA), birth wt <2500 g, with BPD (February)   
  105 120 167 892  Male infant, preterm (<28 wGA), birth wt <2500 g, with BPD (March)   
  395 860 632 245  Male infant, preterm (<28 wGA), birth wt <2500 g, with BPD (April)   
  833 695 1 331 529  Male infant, preterm (<28 wGA), birth wt <2500 g, with BPD (October)   
Roeckl-Wiedmann et al34 2003 Germany 2000 6639 10 011 Cost per HA Group A, preterm (<35 wGA)c Deterministic Because of the findings of our cost-effectiveness analysis, we would recommend a restricted use of palivizumab prophylaxis in premature infants with CLD in their risk combination. The results of this cost-effectiveness analysis do not justify the widespread use of palivizumab among preterm infants. Palivizumab was most cost-effective among male infants with CLD who had siblings visiting day care groups and who were discharged between October and December. 
  25 288 38 134  Group B, preterm (<35 wGA), with risk factorsc   
  52 838 79 678  Group C, preterm (<35 wGA), with risk factorsc   
  204 684 308 658  Group D, preterm (<35 wGA), with risk factorsc   
Salinas-Escudero et al36 2012 USD 2009 4539 5188 Cost per QALY gained Partial coverage, preterm (<29 wGA) Deterministic; probabilistic Palivizumab prophylaxis for preterm newborn patients born at ≤32 wk resulted in a cost-effective alternative. When evaluating the ICER per QALY and LYG against the USD $50 000 threshold, all age groups within the prophylaxis group are cost-effective. 
  7294 8337  Partial coverage, preterm (29–32 wGA)   
  17 532 20 038  Full coverage, preterm (<29 wGA)   
  20 760 23 728  Full coverage, preterm (29–32 wGA)   
Sanchez-Luna et al37 2017 Spain 2016 11 550 17 792 Cost per QALY gained Subgroup A (payer)d Deterministic; probabilistic Of 1000 Monte Carlo simulations, 85.7% of the cases presented an ICUR <€30 000 per QALY. Palivizumab is efficient for preventing RSV infections in preterm infants 32 1/7 to 35 0/7 wGA in Spain, including specific high-risk subgroups. 
  14 177 21 839  Subgroup B (payer)d   
  17 153 26 424  Base case (societal), preterm (32–35 wGA)   
  18 938 29 173  Subgroup C (payer)d   
  19 698 30 344  Base case (payer), preterm (32–35 wGA)   
Schmidt et al38 2017 Spain 2016 15 748 24 259 Cost per QALY gained Base case Deterministic; probabilistic PSA revealed that the probability of palivizumab prophylaxis being cost-effective at a €30 000-per-QALY threshold was 92.7%. The ICER remained below this threshold for most extreme-scenario analyses. Palivizumab prophylaxis was shown to be a cost-effective health care intervention according to the commonly accepted standards of cost-effectiveness in Spain (ICER below the threshold of €30 000 per QALY). 
Smart et al39,51 2010 CAD 2010 192 177 Cost per QALY gained Preterm (32–35 wGA), ≥4 risk factors Deterministic; probabilistic 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 wGA with ≥2 risk factors or in infants who are at a moderate to high risk on the basis of a risk-assessment model, does not change. 
  5274 4859  Preterm (32–35 wGA), risk-scoring tool, high risk (65–100 score)   
  20 814 19 175  Base case, preterm (32–35 wGA), including asthma   
  26 701 24 598  Preterm (32–35 wGA), 3 risk factors   
  31 360 28 890  Base case, preterm (32–35 wGA), excluding asthma   
  34 438 31 726  Preterm (32–35 wGA), risk-scoring tool, medium risk (49–64 score)   
  48 495 44 675  Base case, preterm (32–35 wGA), mortality rate (1.2%)   
  50 434 46 462  Base case, preterm (32–35 wGA), mortality rate (1.0%)   
  82 732 76 216  Preterm (32–35 wGA), 2 risk factors   
  146 218 134 701  Preterm (32–35 wGA), 1 risk factor   
  183 561 169 103  Preterm (32–35 wGA), risk-scoring tool, low risk (0–48 score)   
  820 701 756 060  Preterm (32–35 wGA), 0 risk factors (preterm only)   
Tam et al40 2009 CAD 2007 334 325 Cost per QALY gained High risk area (defined as having hospitalization rates over 500/1000 live births) and <1 y Deterministic; probabilistic Palivizumab is a cost-effective option for the prevention of RSV for Inuit infants on Baffin Island, is highly cost-effective in Arctic infants <1 y of age specifically residing outside of Iqaluit, and is a dominant strategy for those <6 mo of age in remote areas. However, palivizumab is not cost-effective compared with no treatment of infants of all ages residing in Iqaluit. 
  7822 7619  Infants from Baffin Island <6 mo, societal   
  10 190 9926  Infants from Baffin Island <6 mo   
  22 383 21 803  Outside of Iqaluit (remote areas) <1 y, societal   
  24 750 24 109  Outside of Iqaluit (remote areas) <1 y   
  37 070 36 110  All infants from Baffin Island <1 y, societal   
  39 435 38 414  All infants from Baffin Island <1 y   
  100 872 98 260  Residing in Iqaluit <6 mo, societal   
  103 235 100 561  Residing in Iqaluit <6 mo   
  149 782 145 903  Residing in Iqaluit <1 y, societal   
  152 145 148 205  Residing in Iqaluit <1 y   
  Dominant Dominant  Infants in remote areas <6 mo   
  Dominant Dominant  High-risk areas, <6 mo   
  Dominant Dominant  High-risk areas, <1 y, societal   
  Dominant Dominant  Infants in remote areas <6 mo, societal   
  Dominant Dominant  High-risk areas, <6 mo, societal   
Vogel et al41 2002 NZD 2000 28 700 28 265 Cost per case averted Preterm (32–35 wGA), with CLD, discharged from the hospital on oxygen Deterministic If value is placed on preventing morbidity, the priority groups for palivizumab prophylaxis are preterm infants discharged from the hospital on oxygen followed by preterm infants of ≤28 wk gestation. 
  32 000 31 515  Preterm (≤28 wGA), no CLD   
  60 000 59 091  Total cohort, preterm (32–35 wGA), with CLD, societal   
  65 000 64 016  Preterm (≤28 wGA), with CLD   
  98 000 96 516  Preterm (29–31 wGA), no CLD   
  166 700 164 176  Preterm (29–31 wGA), with CLD   
Wang et al14 2008 GBP 2006 51 800 90 261 Cost per HA Preterm infants (<35 wGA) and children without CLD Deterministic According to this model, prophylaxis with palivizumab is not a cost-effective strategy for preterm infants and children with CHD compared with no prophylaxis from both an NHS perspective and a societal perspective. These findings are robust to probabilistic and other sensitivity analyses. Prophylaxis with palivizumab is also not a cost-effective strategy for preterm infants or infants with CLD who have no other risk factors. Subgroup analyses revealed that prophylaxis with palivizumab for children with CLD may be cost-effective at a willingness-to-pay threshold of £30 000 per QALY. 
  63 800 111 171 Cost per QALY gained Preterm infants (<35 wGA) and children with CLD   
  66 900 116 573  Preterm infants (<35 wGA) and children with CLD (societal)   
  67 600 117 792 Cost per HA Preterm infants (<35 wGA) and children with CLD   
  78 600 136 960  CHD   
  79 800 139 051 Cost per QALY gained CHD   
  83 200 144 975  CHD (societal)   
  454 100 791 265  Preterm infants (<35 wGA) and children without CLD   
  475 600 828 728  Preterm infants (<35 wGA) and children without CLD (societal)   
Weiner et al42 2012 USD 2010 16 037 18 041 Cost per QALY gained Base-case group 2, preterm (32–34 wGA), with risk factorse Deterministic; probabilistic Palivizumab, when dosed consistently with the FDA-approved labeling, was either cost saving or cost-effective among current guideline-eligible infants in the Medicaid population. Palivizumab did not reveal cost-effectiveness in infants of 32–35 wGA with ≤1 risk factor. 
  38 244 43 023  Base-case group 3, preterm (32–35 wGA), with risk factorse   
  281 892 317 115  Base-case group 4, preterm (32–35 wGA), with risk factorse   
  Dominant Dominant  Base-case group 1, preterm (<32 wGA)e   
Yount and Mahle43 2004 USD 2002 114 337 155 708 Cost per QALY gained Base case, term, CHD Deterministic The cost of palivizumab prophylaxis was high relative to benefits realized. Given the large No. CHD patients who might be considered candidates for RSV prophylaxis (>6000 patients per y in the United States), routine use of palivizumab in young children with CHD needs to be evaluated further. 
Author, yCountry or Original Currency, yICER (Original)ICER (Adjusted), 2017 USDOutcome MeasureResults (Context)Type of Sensitivity AnalysisStudy Conclusions
Banerji et al24 2016 CAD 2011 4633 4073 Cost per HA Scenario B, Nunavut without Iqaluita Deterministic Palivizumab was cost-effective in the Kitikmeot and Kivalliq regions and in Nunavik. Scenario B (compared with Scenario A) was more cost-effective in all regions except the Kitikmeot region. 
  14 545 12 787  Scenario B, Nunavuta   
  15 601 13 716  Scenario B, Nunavika   
  22 954 20 180  Scenario A, Kivalliq regiona   
  28 580 25 126  Scenario A, Nunavut without Iqaluita   
  30 230 26 577  Scenario A, Nunavika   
  41 404 36 401  Scenario A, Nunavuta   
  105 259 92 539  Scenario B, Qikiqtaaluk region without Iqaluita   
  133 407 117 286  Scenario B, Qikiqtaaluk regiona   
  166 600 146 468  Scenario A, Qikiqtaaluk region without Iqaluita   
  211 444 185 893  Scenario A, Qikiqtaaluk regiona   
  326 441 286 993  Scenario B, NWTa   
  545 115 479 242  Scenario A, NWTa   
  Dominant Dominant  Scenario A, Kitikmeot regiona   
  Dominant Dominant  Scenario B, Kitikmeot regiona   
  Dominant Dominant  Scenario B, Kivalliq regiona   
Bentley et al35 2013 GBP 2010 3845 6165 Cost per QALY gained Preterm infants (<29 wGA) Deterministic; probabilistic Prophylactic palivizumab represents an economically viable use of NHS resources for infants (aged <24 mo) with CHD, infants (aged <24 mo) with CLD, preterm infants born at ≤32 wGA, and preterm infants born 33–35 wGA when additional risk factors are considered. 
  19 168 30 734  Infants with CLD   
  30 205 48 430     
  33 216 53 258  Infants with CHD   
  99 056 158 824  Preterm infants (33–35 wGA)   
Blanken et al46 2018 Netherlands 2015 214 748 272 654 Cost per QALY gained Preterm (32–35 wGA) Deterministic; probabilistic — 
Chirico et al47 2009 Italy 2007 2732 3984 Cost per QALY gained BPD Deterministic Compared with no prophylaxis, palivizumab is cost-effective in the prevention of RSV infection among high-risk preterm infants. 
  8677 12 653  Preterm (<35 wGA, mix) with BPD   
  9380 13 679  Preterm (<33 wGA)   
  14 937 21 783  Preterm (33–35 wGA)   
Elhassan et al44 2006 USD 2002 103 053 140 341 Cost per QALY gained Base case, preterm (26 wGA), targeted use policy Deterministic Our model supports implementing more restrictive guidelines for palivizumab prophylaxis. Palivizumab was cost-effective for some infants in an analysis used to account for increased risk of severe asthma after RSV infection. We found evidence that long-term health consequences of RSV are central to the determination of the cost-effectiveness of the intervention. 
  216 830 295 287  Base case, preterm (28 wGA), targeted use policy   
  280 083 381 427  Base case, preterm (29–30 wGA), targeted use policy   
  675 780 920 300  Base case, preterm (29–30 wGA)   
  830 152 1 130 530  Base case, preterm (26 wGA)   
  1 212 497 1 651 220  Base case, preterm (31 wGA)   
  1 295 781 1 764 639  Base case, preterm (27 wGA)   
  1 500 351 2 043 230  Base case, preterm (28 wGA)   
  1 855 000 2 526 203  Base case, preterm (32 wGA)   
Hampp et al48 2011 USD 2010 302 103 339 852 Cost per HA Preterm (<32 wGA) Deterministic; probabilistic The cost of immunoprophylaxis with palivizumab far exceeded the economic benefit of preventing hospitalizations, even in infants at highest risk for RSV infection. 
  361 727 406 926  Preterm (<32 wGA) and CHD   
  368 048 414 037  Preterm (<32 wGA) and CLD   
  522 490 587 777  Term, CLD, and CHD   
  823 868 926 813  Term and CHD only   
  920 033 1 034 994  Any risk factor (indication)   
  1 322 422 1 487 663  Term and CLD only   
  2 138 870 2 406 129  No risk factor (indication)   
Harris et al49 2011 CAD 2007 8292 8077 Cost to treat 1 child per RSV season Base case Deterministic With our study, we contribute to the growing body of literature in which it is suggested that palivizumab is not cost-effective in children <2 y old with hemodynamically significant CHD. 
  15 513 15 111 Cost to prevent 1 d of hospitalization Base case   
Hascoet et al50 2008 France 2006 10 172 13 798 Cost per LYG Preterm (<32 wGA), with BPD (health care) Deterministic; probabilistic Prophylaxis with palivizumab for RSV in premature children with BPD or hemodynamically significant CHD can be considered cost-effective in France. 
  20 788 28 198  Preterm (<32 wGA), with cardiopathy (societal)   
  27 255 36 971  Preterm (<32 wGA), with BPD (societal)   
Lofland et al45 2000 USD 2000 1008 1434 Cost per RSV-infection episode avoided Base case, preterm (NR wGA), 81% reduction incidence of RSV infection (5% vs 26%) Deterministic The incremental cost per RSV-infection episode avoided ranged from $0 (cost savings) to $39 591 for palivizumab prophylaxis costs of $2500 and from $2702 to $79 706 for palivizumab prophylaxis costs of $4500. Clinicians may use this information to help determine if prophylactic palivizumab therapy is cost-effective in their clinical practice setting. 
  39 591 56 313  Preterm (NR wGA), 50% reduction incidence of RSV infection (5% vs 10%)   
  Dominant Dominant  Preterm (NR wGA), 83% reduction incidence of RSV infection (5% vs 28%)   
Mahadevia et al52 2012 USD 2010 44 774 50 369 Cost per QALY gained Group 2, preterm (32–35 wGA) with risk factorsb Deterministic Palivizumab remained cost-effective for guideline-eligible high-risk infants across both public and private sectors. Guideline-eligible infants included infants of <32 wGA, 32–34 wGA with 2009 AAP risk factors, and 32–35 wGA with 2006 AAP risk factors. Palivizumab was not cost-effective in infants of 32–35 wGA with 1 risk factor. 
  79 477 89 408  Group 3, preterm (32–35 wGA) with risk factorsb   
  464 476 522 514  Group 4, preterm (32–35 wGA) with risk factorsb   
  Dominant Dominant  Group 1, preterm (<32 wGA)b   
McGirr et al25 2017 CAD 2013 157 332 135 207 Cost per QALY gained High-risk CF <2 y (high risk for severe RSV disease) Deterministic Palivizumab is not cost-effective in Canada by commonly used thresholds. However, given the rarity of CF and the relatively small budget impact, consideration may be given. 
  652 560 560 792  All CF < 2 y   
Neovius et al26 2011 SEK 2009 148 293 19 000 Cost per QALY gained Preterm (<29 wGA), adding wheezing to asthma Deterministic; probabilistic On the basis of a willingness-to-pay threshold of 500 000 SEK per QALY, palivizumab was found to be cost-effective compared with no prophylaxis for infants born at <29 wk if severe RSV infection was assumed to increase subsequent asthma or mortality risk. 
  195 420 25 038  Base case, preterm (<29 wGA)   
  383 825 49 178  Preterm (<29 wGA), excluding indirect effect on asthma   
  492 430 63 093  Preterm (<29 wGA), excluding indirect effect on mortality   
  8 856 829 1 134 793  Preterm (<29 wGA), excluding the indirect effect of mortality and asthma   
Nuijten et al30 2009_DEU Germany 2006 2221 3180 Cost per QALY gained Base case, Cardiac Study parameters, societal Deterministic; probabilistic This analysis revealed that palivizumab represents a cost-effective means of prophylaxis against severe RSV infection requiring hospitalization in infants with hemodynamically significant CHD. 
  9528 13 643  Base case, Cardiac Study parameters, including asthma, payer   
  9529 13 644  Base case, societal   
  11 126 15 931  Base case, Cardiac Study parameters, excluding asthma, payer   
  16 673 23 874  Base case, direct medical costs (including asthma), payer   
  18 266 26 155  Base case, direct medical costs (excluding asthma), payer   
  123 439 176 749  Base case, excluding mortality, societal   
Nuijten et al29 2009_NLD Netherlands 2006 7067 9837 Cost per QALY gained Base case: CHD Deterministic; probabilistic 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. 
  11 336 15 779  Base case: preterm (<35 wGA, mix), with BPD (total costs, societal)   
  18 563 25 838  Preterm (<35 wGA, mix)   
  20 236 28 167  Base case: preterm (<35 wGA, mix), with BPD   
  23 461 32 655  Subpopulations with BPD    
  Dominant Dominant  Base case: CHD (total costs, societal)   
Nuijten and Wittenberg28 2010 Spain 2006 6498 10 715 Cost per QALY gained Base case, preterm (<32 wGA), inclusion of costs of sequelae treatment Deterministic; probabilistic Palivizumab provides a cost-effective method of prophylaxis against severe RSV disease among preterm infants in Spain. 
  12 814 21 130  Base case, preterm (<32 wGA)   
  Dominant Dominant  Base case, preterm (<32 wGA), societal perspective   
Nuijten et al27 2007 GBP 2003 6664 12 733 Cost per QALY gained CHD Deterministic; probabilistic This study reveals that palivizumab prophylaxis against severe RSV infection in children at high risk may be cost-effective from the NHS perspective 
  11 494 21 962  Base case, preterm (<35 wGA), with indirect costs (societal)   
  14 883 28 438  Preterm (<35 wGA)   
  16 720 31 948  Base case, preterm (<35 wGA), with BPD   
  20 953 40 036  BPD only   
Resch et al31,32 2008, 2012 Austria 2010 3045 4071 Cost per QALY gained Base case, CHD, including recurrent wheezing treatment, societal Deterministic Our results, which are based on nationwide long-term epidemiological data, reveal that palivizumab is cost-effective in the prevention of RSV disease in high-risk infants. 
  7818 10 452  Base case, CHD, including recurrent wheezing treatment   
  8484 11 343  Base case, CHD   
  15 800 21 124  Base case, for all preterm (<35 wGA, mix), including recurrent wheezing treatment, societal   
  15 992 21 380  Base case, preterm (33–35 wGA), including recurrent wheezing treatment, societal   
  17 554 23 469  Base case, BPD, including recurrent wheezing treatment, societal   
  18 133 24 243  Base case, preterm (<33 wGA), including recurrent wheezing treatment, societal   
  21 669 28 970  Base case, for all preterm (<35 wGA, mix), including recurrent wheezing treatment   
  21 862 29 228  Base case, preterm (33–35 wGA), including recurrent wheezing treatment   
  22 515 30 101  Base case, BPD, including recurrent wheezing treatment   
  23 833 31 863  Base case, preterm (<33 wGA), including recurrent wheezing treatment   
  24 392 32 611  Base case, preterm (33–35 wGA)   
  24 654 32 961  Base case, BPD   
  26 212 35 044  Base case, for all preterm (<35 wGA, mix)   
  26 292 35 151  Base case, preterm (<33 wGA)   
Rietveld et al33 2010 Netherlands 2000 13 190 21 066 Cost per HA Male infant, preterm (<28 wGA), birth wt <2500 g, with BPD (December) Deterministic Every mo, costs per HA were higher for children without BPD and children with higher gestational ages. Incremental costs per HA were always high. Passive immunization was always most cost-effective in December. A restrictive immunization policy requiring immunization of only children with BPD in high-risk months is therefore recommended. The costs of passive immunization would have to be considerably reduced to achieve cost-effectiveness. 
  30 795 49 184  Male infant, preterm (<28 wGA), birth wt <2500 g, with BPD (January)   
  31 055 49 599  Male infant, preterm (<28 wGA), birth wt <2500 g, with BPD (November)   
  47 145 75 297  Male infant, preterm (<28 wGA), birth wt <2500 g, with BPD (February)   
  105 120 167 892  Male infant, preterm (<28 wGA), birth wt <2500 g, with BPD (March)   
  395 860 632 245  Male infant, preterm (<28 wGA), birth wt <2500 g, with BPD (April)   
  833 695 1 331 529  Male infant, preterm (<28 wGA), birth wt <2500 g, with BPD (October)   
Roeckl-Wiedmann et al34 2003 Germany 2000 6639 10 011 Cost per HA Group A, preterm (<35 wGA)c Deterministic Because of the findings of our cost-effectiveness analysis, we would recommend a restricted use of palivizumab prophylaxis in premature infants with CLD in their risk combination. The results of this cost-effectiveness analysis do not justify the widespread use of palivizumab among preterm infants. Palivizumab was most cost-effective among male infants with CLD who had siblings visiting day care groups and who were discharged between October and December. 
  25 288 38 134  Group B, preterm (<35 wGA), with risk factorsc   
  52 838 79 678  Group C, preterm (<35 wGA), with risk factorsc   
  204 684 308 658  Group D, preterm (<35 wGA), with risk factorsc   
Salinas-Escudero et al36 2012 USD 2009 4539 5188 Cost per QALY gained Partial coverage, preterm (<29 wGA) Deterministic; probabilistic Palivizumab prophylaxis for preterm newborn patients born at ≤32 wk resulted in a cost-effective alternative. When evaluating the ICER per QALY and LYG against the USD $50 000 threshold, all age groups within the prophylaxis group are cost-effective. 
  7294 8337  Partial coverage, preterm (29–32 wGA)   
  17 532 20 038  Full coverage, preterm (<29 wGA)   
  20 760 23 728  Full coverage, preterm (29–32 wGA)   
Sanchez-Luna et al37 2017 Spain 2016 11 550 17 792 Cost per QALY gained Subgroup A (payer)d Deterministic; probabilistic Of 1000 Monte Carlo simulations, 85.7% of the cases presented an ICUR <€30 000 per QALY. Palivizumab is efficient for preventing RSV infections in preterm infants 32 1/7 to 35 0/7 wGA in Spain, including specific high-risk subgroups. 
  14 177 21 839  Subgroup B (payer)d   
  17 153 26 424  Base case (societal), preterm (32–35 wGA)   
  18 938 29 173  Subgroup C (payer)d   
  19 698 30 344  Base case (payer), preterm (32–35 wGA)   
Schmidt et al38 2017 Spain 2016 15 748 24 259 Cost per QALY gained Base case Deterministic; probabilistic PSA revealed that the probability of palivizumab prophylaxis being cost-effective at a €30 000-per-QALY threshold was 92.7%. The ICER remained below this threshold for most extreme-scenario analyses. Palivizumab prophylaxis was shown to be a cost-effective health care intervention according to the commonly accepted standards of cost-effectiveness in Spain (ICER below the threshold of €30 000 per QALY). 
Smart et al39,51 2010 CAD 2010 192 177 Cost per QALY gained Preterm (32–35 wGA), ≥4 risk factors Deterministic; probabilistic 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 wGA with ≥2 risk factors or in infants who are at a moderate to high risk on the basis of a risk-assessment model, does not change. 
  5274 4859  Preterm (32–35 wGA), risk-scoring tool, high risk (65–100 score)   
  20 814 19 175  Base case, preterm (32–35 wGA), including asthma   
  26 701 24 598  Preterm (32–35 wGA), 3 risk factors   
  31 360 28 890  Base case, preterm (32–35 wGA), excluding asthma   
  34 438 31 726  Preterm (32–35 wGA), risk-scoring tool, medium risk (49–64 score)   
  48 495 44 675  Base case, preterm (32–35 wGA), mortality rate (1.2%)   
  50 434 46 462  Base case, preterm (32–35 wGA), mortality rate (1.0%)   
  82 732 76 216  Preterm (32–35 wGA), 2 risk factors   
  146 218 134 701  Preterm (32–35 wGA), 1 risk factor   
  183 561 169 103  Preterm (32–35 wGA), risk-scoring tool, low risk (0–48 score)   
  820 701 756 060  Preterm (32–35 wGA), 0 risk factors (preterm only)   
Tam et al40 2009 CAD 2007 334 325 Cost per QALY gained High risk area (defined as having hospitalization rates over 500/1000 live births) and <1 y Deterministic; probabilistic Palivizumab is a cost-effective option for the prevention of RSV for Inuit infants on Baffin Island, is highly cost-effective in Arctic infants <1 y of age specifically residing outside of Iqaluit, and is a dominant strategy for those <6 mo of age in remote areas. However, palivizumab is not cost-effective compared with no treatment of infants of all ages residing in Iqaluit. 
  7822 7619  Infants from Baffin Island <6 mo, societal   
  10 190 9926  Infants from Baffin Island <6 mo   
  22 383 21 803  Outside of Iqaluit (remote areas) <1 y, societal   
  24 750 24 109  Outside of Iqaluit (remote areas) <1 y   
  37 070 36 110  All infants from Baffin Island <1 y, societal   
  39 435 38 414  All infants from Baffin Island <1 y   
  100 872 98 260  Residing in Iqaluit <6 mo, societal   
  103 235 100 561  Residing in Iqaluit <6 mo   
  149 782 145 903  Residing in Iqaluit <1 y, societal   
  152 145 148 205  Residing in Iqaluit <1 y   
  Dominant Dominant  Infants in remote areas <6 mo   
  Dominant Dominant  High-risk areas, <6 mo   
  Dominant Dominant  High-risk areas, <1 y, societal   
  Dominant Dominant  Infants in remote areas <6 mo, societal   
  Dominant Dominant  High-risk areas, <6 mo, societal   
Vogel et al41 2002 NZD 2000 28 700 28 265 Cost per case averted Preterm (32–35 wGA), with CLD, discharged from the hospital on oxygen Deterministic If value is placed on preventing morbidity, the priority groups for palivizumab prophylaxis are preterm infants discharged from the hospital on oxygen followed by preterm infants of ≤28 wk gestation. 
  32 000 31 515  Preterm (≤28 wGA), no CLD   
  60 000 59 091  Total cohort, preterm (32–35 wGA), with CLD, societal   
  65 000 64 016  Preterm (≤28 wGA), with CLD   
  98 000 96 516  Preterm (29–31 wGA), no CLD   
  166 700 164 176  Preterm (29–31 wGA), with CLD   
Wang et al14 2008 GBP 2006 51 800 90 261 Cost per HA Preterm infants (<35 wGA) and children without CLD Deterministic According to this model, prophylaxis with palivizumab is not a cost-effective strategy for preterm infants and children with CHD compared with no prophylaxis from both an NHS perspective and a societal perspective. These findings are robust to probabilistic and other sensitivity analyses. Prophylaxis with palivizumab is also not a cost-effective strategy for preterm infants or infants with CLD who have no other risk factors. Subgroup analyses revealed that prophylaxis with palivizumab for children with CLD may be cost-effective at a willingness-to-pay threshold of £30 000 per QALY. 
  63 800 111 171 Cost per QALY gained Preterm infants (<35 wGA) and children with CLD   
  66 900 116 573  Preterm infants (<35 wGA) and children with CLD (societal)   
  67 600 117 792 Cost per HA Preterm infants (<35 wGA) and children with CLD   
  78 600 136 960  CHD   
  79 800 139 051 Cost per QALY gained CHD   
  83 200 144 975  CHD (societal)   
  454 100 791 265  Preterm infants (<35 wGA) and children without CLD   
  475 600 828 728  Preterm infants (<35 wGA) and children without CLD (societal)   
Weiner et al42 2012 USD 2010 16 037 18 041 Cost per QALY gained Base-case group 2, preterm (32–34 wGA), with risk factorse Deterministic; probabilistic Palivizumab, when dosed consistently with the FDA-approved labeling, was either cost saving or cost-effective among current guideline-eligible infants in the Medicaid population. Palivizumab did not reveal cost-effectiveness in infants of 32–35 wGA with ≤1 risk factor. 
  38 244 43 023  Base-case group 3, preterm (32–35 wGA), with risk factorse   
  281 892 317 115  Base-case group 4, preterm (32–35 wGA), with risk factorse   
  Dominant Dominant  Base-case group 1, preterm (<32 wGA)e   
Yount and Mahle43 2004 USD 2002 114 337 155 708 Cost per QALY gained Base case, term, CHD Deterministic The cost of palivizumab prophylaxis was high relative to benefits realized. Given the large No. CHD patients who might be considered candidates for RSV prophylaxis (>6000 patients per y in the United States), routine use of palivizumab in young children with CHD needs to be evaluated further. 

CAD, Canadian dollar; CF, Cystic fibrosis; FDA, Food and Drug Administration; GBP, Great Britain pound; ICUR, Incremental cost-utility ratio; NR, not reported; NWT, Northwest Territories; NZD, New Zealand dollar; PSA, Probabilistic sensitivity analysis; SEK, Swedish krona; —, not applicable.

a

Scenario A24: universal palivizumab prophylaxis for all healthy term infants who were <6 mo of age as of January 1, 2009, was compared with no prophylaxis; Scenario B: palivizumab prophylaxis for infants up to 5 mo of age only (for 6 mo of protection) was compared with no prophylaxis.

b

Group 152: <32 wGA and <6 mo chronological age; group 2: 32–34 wGA and ≤3 mo chronological age, with 2009 AAP risk factors; group 3: 32–35 wGA and ≤6 mo chronological age, with 2006 AAP risk factors; group 4: 32–35 wGA and ≤6 mo chronological age, with ≤1 risk factor.

c

Group A34: Male infants, siblings in day care, discharged between October and December, CLD; group B: male infants, siblings in day care, discharged between October and December; group C: male infants, siblings in day care; group D: male infants.

d

Subgroup A: preterm (32–35 wGA), with risk factors (2 major, 2 minor); Subgroup B: preterm (32–35 wGA), with risk factors (2 major, 1 minor); Subgroup C: preterm (32–35 wGA), with risk factors (2 major risk factors)

e

Base-case group 142: <32 wGA and ≤6 mo chronological age; base-case group 2: 32–34 wGA and ≤3 mo chronological age, with 2009 AAP risk factors (ie, having siblings <5 y of age and/or attending day care); base-case group 3: 32–35 wGA and ≤6 mo chronological age, with 2006 AAP risk factors (any 2 of the following: exposure to environmental air pollutants, congenital abnormalities of the airways, severe neuromuscular disease, school-aged siblings, and day care attendance); base-case group 4: 32–35 wGA and ≤6 mo chronological age, with ≤1 risk factor.

For studies in which cost-effectiveness was reported in cost per QALY units, we summarized the number of estimates, the ICER ranges, and the proportion of estimates under selected thresholds of $50 000 to $200 000 per QALY, stratified by population subgroups and study perspective in Table 3. From a health care–payer perspective, there were 22 varying cost-effectiveness estimates for preterm infants, ranging between $5188 and $791 265 per QALY.* The subgroups with the next highest estimates were preterm infants with risk factors (n = 14),25,37,39,40 in which the ICER was between $177 and $169 103 per QALY; infants with CHD (n = 10),14,27,29,30,32,35 in which the ICER was between $9837 and $139 051 per QALY; and infants with BPD or CLD (n = 6),27,29,32,35,47 in which the ICER was between $3984 and $40 036 per QALY. At a threshold of $100 000 per QALY, 86% of estimates for preterm infants, 86% of estimates for preterm infants with risk factors, 90% of estimates for infants with CHD, and 100% of estimates for infants with BPD or CLD were considered cost-effective. Other risk factors considered in preterm infants included chronological age at the beginning of the RSV season, school-aged siblings, day care attendance, smoking during pregnancy, male sex, and cystic fibrosis (in term infants only).25,37,39,42,52 From a societal perspective, palivizumab prophylaxis was considered a dominant strategy (ie, the strategy provided additional clinical benefit and was cost saving) in some instances for preterm infants,28,42,52 term infants (with and without other risk factors),40 and infants with CHD.29 

TABLE 3

Summary of Cost-effectiveness Estimates by Health Condition and Perspective

Health Conditions
BPD or CLDCHDHealthyPretermPreterm With BPD or CLDPreterm With Risk FactorsOther Risk Factorsa
Payer perspective        
 No. estimates 10 22 14 
 ICER (minimum) 3984 9837 Dominant 5188 12 653 177 Dominant 
 ICER (maximum) 40 036 139 051 148 205 791 265 111 171 169 103 560 792 
 Proportion of estimates’ CE <$50 000 per QALY 1.00 0.80 0.67 0.86 0.75 0.79 0.50 
 Proportion of estimates’ CE <$100 000 per QALY 1.00 0.90 0.67 0.86 0.75 0.86 0.50 
 Proportion of estimates’ CE <$200 000 per QALY 1.00 1.00 1.00 0.91 1.00 1.00 0.75 
Societal perspective        
 No. estimates 23 
 ICER (minimum) 23 469 Dominant Dominant Dominant 15 779 18 041 Dominant 
 ICER (maximum) 23 469 176.749 145 903 2 526 203 116 573 522 514 Dominant 
 Proportion of estimates’ CE <$50 000 per QALY 1.00 0.63 0.67 0.43 0.67 0.33 1.00 
 Proportion of estimates’ CE <$100 000 per QALY 1.00 0.63 0.83 0.48 0.67 0.67 1.00 
 Proportion of estimates’ CE <$200 000 per QALY 1.00 1.00 1.00 0.52 1.00 0.67 1.00 
Health Conditions
BPD or CLDCHDHealthyPretermPreterm With BPD or CLDPreterm With Risk FactorsOther Risk Factorsa
Payer perspective        
 No. estimates 10 22 14 
 ICER (minimum) 3984 9837 Dominant 5188 12 653 177 Dominant 
 ICER (maximum) 40 036 139 051 148 205 791 265 111 171 169 103 560 792 
 Proportion of estimates’ CE <$50 000 per QALY 1.00 0.80 0.67 0.86 0.75 0.79 0.50 
 Proportion of estimates’ CE <$100 000 per QALY 1.00 0.90 0.67 0.86 0.75 0.86 0.50 
 Proportion of estimates’ CE <$200 000 per QALY 1.00 1.00 1.00 0.91 1.00 1.00 0.75 
Societal perspective        
 No. estimates 23 
 ICER (minimum) 23 469 Dominant Dominant Dominant 15 779 18 041 Dominant 
 ICER (maximum) 23 469 176.749 145 903 2 526 203 116 573 522 514 Dominant 
 Proportion of estimates’ CE <$50 000 per QALY 1.00 0.63 0.67 0.43 0.67 0.33 1.00 
 Proportion of estimates’ CE <$100 000 per QALY 1.00 0.63 0.83 0.48 0.67 0.67 1.00 
 Proportion of estimates’ CE <$200 000 per QALY 1.00 1.00 1.00 0.52 1.00 0.67 1.00 

All ICERs are reported in 2017 USDs per QALY. CE, cost-effective.

a

Cystic fibrosis, major risk factors (chronological age <10 wk at beginning of RSV season [being born during first 10 wk of the season], school-aged siblings, and day care attendance), and minor risk factors (mother smoking during pregnancy and male sex).

There were 5 studies in which cost-effectiveness was reported in cost per HA,14,24,33,34,48 of which 2 were industry funded.24,34 In the study by Banerji et al,24 the authors studied healthy term infants from a payer perspective in different regions of the Canadian Arctic and compared 2 scenarios of palivizumab prophylaxis for infants who were <6 months of age. The ICER for palivizumab prophylaxis ranged from being dominant (in specific Arctic regions) to $479 242 per HA in the Northwest Territories.24 Also from the payer perspective, Hampp et al48 assessed cost-effectiveness in preterm infants (<32 wGA) and term infants with CHD, CLD, and combinations of all 3 risk factors in a Florida setting. The ICERs were between $339 852 (preterm infants) and $2 406 129 per HA (healthy term infants without CLD or CHD).48 

From a societal perspective, the study by Rietveld et al33 in 2010 from southwest Netherlands studied preterm infants (<28 wGA) with additional risk factors (male sex, birth weight <2500 g, and BPD). The ICER ranged between $21 066 and $1 331 529 per HA depending on the month of the prophylaxis. The most cost-effective month for palivizumab prophylaxis (lowest ICER) was December, whereas the least cost-effective month was October. In this study, the authors recommended a restricted immunization policy on the basis of their results.33 Roeckl-Wiedmann et al34 conducted a study in 2003 from southern Germany on preterm infants (<35 wGA) with additional risk factors. ICERs ranged between $10 011 and $308 658 per HA for preterm infants with CLD and preterm infants with risk factors (male sex, no CLD, and no siblings in school), respectively. In this study, the authors also recommended a restricted use of palivizumab in preterm infants with CLD.34 

Authors of 4 studies reported cost-effectiveness of palivizumab prophylaxis in other units: cost to prevent 1 day of hospitalization,49 cost per LYG,50 cost per case averted,41 and cost per RSV infection episode avoided.45 In 3 of 4 studies, authors conducted analyses from a societal perspective.41,49,50 Harris et al49 conducted an economic evaluation on term infants with CHD in western Canada. The base-case ICER was $15 111 per 1 day of hospitalization prevented.49 Hascoet et al50 studied preterm infants (<32 wGA) with BPD or significant CHD in France. The base-case ICER was $36 971 per LYG and $28 198 per LYG for preterm infants with BPD and preterm infants with cardiopathy (CHD), respectively. The authors of this study used a cost-effectiveness threshold (unadjusted) of 45 000 Euros per LYG and considered prophylaxis cost-effective for both subgroups in France.50 In New Zealand, Vogel et al41 studied preterm infants (<28 and 29–31 wGA) and infants with CLD. The ICER ranged between $28 265 per case avoided for preterm infants discharged from the hospital on oxygen and $164 176 per case avoided for preterm (29–31 wGA) infants with CLD. The authors concluded that the intervention was more cost-effective for preterm infants discharged from the hospital on oxygen followed by preterm infants of ≤28 weeks’ gestation.41 Lastly, Lofland et al45 studied preterm infants with CLD in the United States. Their model used a reduction in incidence of RSV infection instead of a hospitalization reduction approach, ranging from a 50% ($56 313 per RSV infection episode avoided) to 83% reduction, in which palivizumab prophylaxis was considered a dominant strategy (ie, cost savings).45 

The cost-effectiveness of palivizumab prophylaxis compared with no palivizumab prophylaxis ranged from being a dominant strategy to $2 526 203 per QALY in preterm infants. Because studies estimated cost-effectiveness for varying ranges of wGA, we were unable to group all estimates into predefined intervals. For example, we did not group <29 wGA estimates under the <32 wGA estimates because we could not infer or reasonably assume the breakdown of the wGA in each preterm group. From the payer perspective, the ICER for palivizumab prophylaxis for infants born at <29 wGA (n = 3) ranged between $5188 and $20 038 per QALY.35,36 For infants born at 29 to 32 wGA, the ICER (n = 3) ranged between $8337 and $48 430 per QALY.35,36 At <32 wGA and <33 wGA, 2 estimates ($10 715–$21 130 per QALY)28 and 3 estimates ($13 679–$35 151 per QALY) were identified, respectively.32,47 In the 32- to 35-wGA range (includes 2 estimates at 32–35 wGA and 4 estimates at 33–35 wGA), there were 6 ICER estimates for preterm infants ($21 783–$756 060 per QALY)32,35,37,39,47 and 14 ICER estimates for preterm infants with additional risk factors ($177–$169 103 per QALY).37,39 For preterm infants born at <35 wGA, there were 5 estimates between $25 838 and $791 265 per QALY.14,27,29,32 All preterm infants with BPD or CLD were estimated in this <35-wGA group, in which the 4 estimates were between $12 653 and $111 171 per QALY.14,27,29,47 

From a societal perspective, estimates of preterm infants born at 26 to 28 wGA were entirely extracted from Elhassan et al,44 with ICERs between $140 341 and $2 043 230 per QALY. For preterm infants born at <29 wGA, there were 5 ICER estimates between $19 000 and $1 134 793 per QALY.26 The cost-effectiveness of palivizumab from a societal perspective varied across studies for preterm infants born between 29 and 35 wGA, with ICER estimates between $381 427 and $920 300 per QALY (29–30 wGA),44 being a dominant strategy (ie, cost savings and provides clinical benefits for <32 wGA),28,42,52 $26 424 and $272 654 per QALY (32–35 wGA),37,46 and $21 124 and $828 728 per QALY (<35 wGA).14,32 In preterm infants (<35 wGA) with lung complications, 3 studies reported separate ICER estimates between $15 779 and $116 573 per QALY.14,27,29 Six estimates were reported for preterm infants with risk factors between $18 401 and $522 514 per QALY ($18 401–$50 369 per QALY for two 32–34-wGA estimates and $43 023–$522 514 per QALY for four 32–35-wGA estimates).42,52 

We stratified and plotted the ICERs for palivizumab prophylaxis expressed in cost per QALY in preterm infants by wGA in Fig 3; we presented 57 of 72 ICER estimates, stratified by study perspective, that were estimated <$200 000 per QALY. In Fig 3, 51 of the 57 (89%) ICER estimates for preterm infants (with or without other RSV risk factors) were below the $100 000-per-QALY threshold. Of the 15 ICER estimates excluded from Fig 3, 8 (ie, more than half) were from a single study by Elhassan et al,44 whereas the rest were single estimates from other studies.14,26,35,39,42,46,52 

FIGURE 3

Cost-effectiveness of palivizumab in preterm infants in which the ICER was <$200 000 per QALY. The total number of estimates in the scatterplot (n = 57). ICERs >$200 000 per QALY were not captured in this figure (n = 15): From the payer perspective, the following were excluded: preterm (<35 wGA): $791 265 per QALY14 and preterm (32–35 wGA): $756 060 per QALY.39 From the societal perspective, the following were excluded: preterm (26 wGA): $1 130 530 per QALY,44 preterm (27 wGA): $1 764 639 per QALY,44 preterm (28 wGA): $2 043 230 per QALY,44 preterm (28 wGA): $295 287 per QALY,44 preterm (<29wGA): $1 134 793 per QALY,26 preterm (29–30 wGA): $920 300 per QALY,44 preterm (29–30 wGA): $381 427 per QALY,44 preterm (31 wGA): $1 651 220 per QALY,44 preterm (32 wGA): $2 526 203 per QALY,44 preterm (32–35 wGA): $272 654 per QALY,46 preterm (<35 wGA): $828 728 per QALY,14 and preterm (32–35 wGA) with RFs: $522 514 per QALY52 and $317 115 per QALY.42 RF, risk factor.

FIGURE 3

Cost-effectiveness of palivizumab in preterm infants in which the ICER was <$200 000 per QALY. The total number of estimates in the scatterplot (n = 57). ICERs >$200 000 per QALY were not captured in this figure (n = 15): From the payer perspective, the following were excluded: preterm (<35 wGA): $791 265 per QALY14 and preterm (32–35 wGA): $756 060 per QALY.39 From the societal perspective, the following were excluded: preterm (26 wGA): $1 130 530 per QALY,44 preterm (27 wGA): $1 764 639 per QALY,44 preterm (28 wGA): $2 043 230 per QALY,44 preterm (28 wGA): $295 287 per QALY,44 preterm (<29wGA): $1 134 793 per QALY,26 preterm (29–30 wGA): $920 300 per QALY,44 preterm (29–30 wGA): $381 427 per QALY,44 preterm (31 wGA): $1 651 220 per QALY,44 preterm (32 wGA): $2 526 203 per QALY,44 preterm (32–35 wGA): $272 654 per QALY,46 preterm (<35 wGA): $828 728 per QALY,14 and preterm (32–35 wGA) with RFs: $522 514 per QALY52 and $317 115 per QALY.42 RF, risk factor.

Close modal

Authors of 2 studies investigated the cost-effectiveness of palivizumab prophylaxis in Arctic (remote) regions of Canada.24,40 In the study by Tam et al,40 palivizumab was cost-effective from a health care–payer perspective for all infants from Baffin Island who were <1 year of age ($38 414 per QALY) or <6 months of age ($9926 per QALY), infants <1 year of age and from high risk areas for RSV ($325 per QALY), infants <1 year of age from remote areas ($24 109 per QALY), infants <6 months of age from remote areas (dominant), and infants <6 months of age from high risk areas for RSV (dominant). However, when compared with a $100 000-per-QALY threshold, it was not cost-effective for infants <6 months or for infants <1 year of age residing in Iqaluit.40 Similarly, Banerji et al24 concluded that their proposed palivizumab programs would be cost-effective in some but not all Arctic regions. The authors of both studies attributed the likelihood of these results to the higher hospitalization rates and transportations costs associated with hospitalization from remote areas to hospitals.24,40 

Reduction in RSV hospitalization used in models ranged between 39% for infants with CLD in the United Kingdom35 and 96% in healthy infants in a Canadian Arctic setting.24 Mortality was reported in 19 studies, ranging between 1%40,50 and 8.11%32 for various infant populations. The number of palivizumab doses per season was between an average of 3.88 doses in a 5-month season in Spain37 and 6 doses in a 6-month RSV season.24 Authors of most studies evaluated cost-effectiveness assuming 5 palivizumab doses per RSV seasons (n = 17), whereas the authors of 3 studies did not report the dose schedule.35,46,48 The cost of a 100-mg vial of palivizumab in 2017 USDs was between $904 (from a UK study)35 and $1866 (from a US study).44 

The most influential parameters reported across the 28 studies were the following: RSV hospitalization rates (43%), cost of palivizumab (36%),§ discount rate (32%),26,30,32,35,36,38 and efficacy of palivizumab (29%).33,35,41,42,46,48,52 Other parameters that were influential in multiple studies included the following: mortality rate reduction, incidence of RSV (and/or sequelae), drug wastage resulting from vial usage, utility values (quality of life), and dosage scheme.

In our systematic review, we identified 28 relevant economic evaluations from OECD countries assessing the cost-effectiveness of palivizumab prophylaxis compared with no prophylaxis. The greatest number of cost-effectiveness estimates came from preterm infants, which was expected given their higher risk for RSV.6,8 The majority of estimates for infants with or without additional risk factors (eg, BPD and CHD) were below the $100 000-per-QALY threshold. The only exception to this was the estimates for preterm infants from the societal perspective, in which only 48% of the estimates were <$100 000 per QALY. This exception was likely a result of a large group of estimates (n = 8; 35% of subgroup) extracted from 1 study, with estimates between $295 287 and $2 526 203 per QALY.44 Possible reasons for the higher ICERs in this study may include: using the highest adjusted cost for a 100-mg vial of palivizumab at $1866, following infants only up to 8 years of age, and, as suggested by the authors, overestimating the quality of life (utility) for subsequent asthma onset. Separate sensitivity analyses reducing the palivizumab cost by 25% and reducing the health-state utility value of asthma afforded ICERs <$200 000 per QALY and <$100 000 per QALY, respectively.44 

On the basis of our review, the cost-effectiveness of palivizumab prophylaxis varies depending on the population and setting. To facilitate comparisons and summarize our findings, we adjusted all ICERs to 2017 USDs per QALY and stratified them on the basis of gestational age at birth and risk factors for RSV in Fig 3. For term and preterm infants with BPD or CLD, the ICER was <$50 000 per QALY in 9 of the 10 estimates from a payer perspective. All other subgroups of infants (term, preterm, and with CHD or other risk factors) resulted in inconsistent results for palivizumab prophylaxis, with the intervention being dominant at times and having an ICER up to $791 265 per QALY in other scenarios. When stratifying for preterm births by wGA, we noticed lacking evidence for infants born at <28 wGA, especially from the payer perspective. No specific trend was depicted between the wGA and the ICER, overall or stratified by perspective. However, we should note that although preterm estimates were available across 26 to 35 wGA, estimates for preterm infants with additional risk factors or BPD or CLD were limited to 33 to 35 wGA. Generally, one would expect ICERs from a societal perspective to be lower than those from a payer perspective, but on the basis of our review, this trend does not exist for 2 potential reasons: (1) payer and societal perspective estimates were coming from different studies and (2) there was heterogeneity in model designs and differences between setting-specific costs and RSV epidemiology.

Because palivizumab prophylaxis was determined to be cost-effective in some settings but not cost-effective in others, we summarized the most frequently reported influential parameters affecting the ICER, which were the RSV hospitalization rates and cost of palivizumab used. Reduction in RSV hospitalization varied drastically between 39% and 96% depending on the population of interest and the source of the data. The cost of a 100-mg vial of palivizumab also ranged between $904 and $1866 (2017 USDs). The influential nature of both parameters was expected given that reduction in RSV and RSV hospitalization is essential to reduction in costs and future sequelae, whereas the costs of palivizumab is directly related to the ICER. However, it was interesting to note that vial usage and dosage scheme only affected the ICER in 427,28,38,41 and 3 studies,37,41,47 respectively. In studies where drug wastage through vial usage was addressed, ICERs fluctuated up to 50% depending on the assumed vial usage. In a New Zealand study, assuming no vial sharing (the entire 100-mg vial is used per injection) increased costs up to 50%,41 whereas authors of a study from Spain reported a lower ICER when 50-mg vials were used instead of 100-mg vials.28 It has been suggested in the literature and by physicians that vial-usage efficiency can be achieved for palivizumab.53 Authors of many studies did not assess scenarios in which the vial usage became more efficient or the number of assumed doses was reduced, which remains a question that can be addressed in future studies.

The cost-effectiveness of palivizumab prophylaxis has been explored in multiple reviews in the past 2 decades,11,12,14 but only 4 have been published between 2010 and 2013.15,54,56 Our results and conclusions are consistent with those in other reviews and are most comparable with the systematic review by Smart et al54 published in 2010 in which the authors reported ICERs (in 2009 Canadian dollars) for palivizumab prophylaxis varying between being dominant and $3 365 768 per QALY depending on the study population, outcomes, and model parameters. We added onto this review by capturing studies from 2010 to mid-2018 but limited our scope to OECD countries and adjusted for inflation differences by using the purchasing power parity rates from the OECD. In their reviews, Andabaka et al15 and Prescott et al56 similarly concluded that cost-effectiveness of palivizumab was inconsistent. Hussman et al55 conducted a review on RSV prophylaxis overall and included studies in which palivizumab and other interventions (eg, respiratory syncytial virus immune globulin intravenous) were compared. To our knowledge, our review is the first to provide an update on the cost-effectiveness of palivizumab prophylaxis compared with no prophylaxis since the 2014 American Academy of Pediatrics (AAP) guideline update.57 

Our review has several limitations. Differences in model designs, RSV hospitalization rates used, disease progress, study perspectives, and settings prevented us from providing definitive conclusions on the value of this intervention. We attempted to summarize the cost-effectiveness of this intervention from 2000 to 2018 but acknowledge that changes in AAP recommendations in the United States (and decision-makers in other respective countries) over time can affect model design and input data. Lastly, our review may be subject to publication and language bias because we did not search the gray literature or include articles not in English or French.

Despite these limitations, with our review, we provide a comprehensive summary of the cost-effectiveness of palivizumab prophylaxis from OECD countries to inform decision-makers of the estimated value of this intervention in term infants, preterm infants, and infants at high risk for RSV (eg, CHD and BPD or CLD). We extracted all base-case results and scenario analyses to create Fig 3, which gives a sense of the number of studies (and estimates) that fall under specific cost-effectiveness thresholds from both payer and societal perspectives. We standardized all estimates to 2017 USDs, which allowed us to group, stratify, and compare the cost-effectiveness estimates in costs per QALY. These adjusted ICERs should be useful for program decision-makers because costs can be significantly underestimated if not appropriately inflated.

Palivizumab prophylaxis for RSV can be considered cost-effective in certain subgroups of infants according to predefined cost-effectiveness thresholds but varied depending on study setting, population of interest, risk factors, and input parameters. From a payer perspective, palivizumab was found to be relatively cost-effective in infants with BPD or CLD, infants with CHD, term infants from specific remote communities, and preterm infants with and without lung complications. Authors of future studies should take into account all influential parameters presented in this review, especially concerns regarding vial usage and dosage because these can drastically reduce the costs associated with the intervention and impact the model outcomes.

Mr Mac contributed to conceptualization of the study, critically appraising the scientific literature, analysis, and drafting and revising the manuscript; Ms Sumner contributed to conceptualization of the study, critically appraising the scientific literature, and analysis; Mr Duchesne-Belanger contributed to critically appraising the scientific literature; Dr Stirling contributed to conceptualization of the study and review of the manuscript; Dr Tunis contributed to conceptualization of the study, review of the manuscript, and supervision of the study; Dr Sander contributed to conceptualization of the study, critically appraising the scientific literature, critical revision of the manuscript, and supervision of the study; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

This review has been registered with PROSPERO (https://www.crd.york.ac.uk/prospero) (identifier CRD42018104977).

FUNDING: Supported by the Public Health Agency of Canada.

*

Refs 14,2729,32,36,37,39,47 

Refs 14,2629,​31,​32,​3537,​39,​42,​44,​47,​51,​52.

Refs 24,​27,​29,​30,​3335,​39,​40,​42,​48,​52.

§

Refs 25,30,33,34,42,44,45,48,49,52.

We thank Public Health Agency of Canada librarian Lynda Gamble for her assistance in developing the search strategy and managing results.

     
  • BPD

    bronchopulmonary dysplasia

  •  
  • CHD

    congenital heart disease

  •  
  • CLD

    chronic lung disease

  •  
  • HA

    hospitalization averted

  •  
  • ICER

    incremental cost-effectiveness ratio

  •  
  • JBI

    Joanna Briggs Institute

  •  
  • LYG

    life-year gained

  •  
  • NHS

    National Health Service

  •  
  • OECD

    Organization for Economic Cooperation and Development

  •  
  • QALY

    quality-adjusted life-year

  •  
  • RSV

    respiratory syncytial virus

  •  
  • USD

    US dollar

  •  
  • wGA

    weeks’ gestational age

1
Meates-Dennis
M
.
Bronchiolitis.
Arch Dis Child Educ Pract Ed
.
2005
;
90
(
4
):
ep81
ep86
2
Collins
CL
,
Pollard
AJ
.
Respiratory syncytial virus infections in children and adults.
J Infect
.
2002
;
45
(
1
):
10
17
[PubMed]
3
Glezen
WP
,
Paredes
A
,
Allison
JE
,
Taber
LH
,
Frank
AL
.
Risk of respiratory syncytial virus infection for infants from low-income families in relationship to age, sex, ethnic group, and maternal antibody level.
J Pediatr
.
1981
;
98
(
5
):
708
715
[PubMed]
4
Hall
CB
.
Respiratory syncytial virus and parainfluenza virus.
N Engl J Med
.
2001
;
344
(
25
):
1917
1928
[PubMed]
5
Paes
BA
,
Mitchell
I
,
Banerji
A
,
Lanctôt
KL
,
Langley
JM
.
A decade of respiratory syncytial virus epidemiology and prophylaxis: translating evidence into everyday clinical practice.
Can Respir J
.
2011
;
18
(
2
):
e10
e19
[PubMed]
6
Simoes
EA
.
Respiratory syncytial virus infection.
Lancet
.
1999
;
354
(
9181
):
847
852
[PubMed]
7
Sánchez-Solis
M
,
Gartner
S
,
Bosch-Gimenez
V
,
Garcia-Marcos
L
.
Is palivizumab effective as a prophylaxis of respiratory syncytial virus infections in cystic fibrosis patients? A meta-analysis.
Allergol Immunopathol (Madr)
.
2015
;
43
(
3
):
298
303
[PubMed]
8
Wang
EE
,
Law
BJ
,
Stephens
D
.
Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) prospective study of risk factors and outcomes in patients hospitalized with respiratory syncytial viral lower respiratory tract infection.
J Pediatr
.
1995
;
126
(
2
):
212
219
[PubMed]
9
American Academy of Pediatrics
. Palivizumab granted licensure for prophylaxis of RSV disease. AAP News. October 1, 1998. Available at: www.aappublications.org/content/14/10/10.3. Accessed December 19, 2018
10
The IMpact-RSV Study Group
.
Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. The IMpact-RSV Study Group.
Pediatrics
.
1998
;
102
(
3, pt 1
):
531
537
11
Embleton
ND
,
Harkensee
C
,
Mckean
MC
.
Palivizumab for preterm infants. Is it worth it?
Arch Dis Child Fetal Neonatal Ed
.
2005
;
90
(
4
):
F286
F289
[PubMed]
12
Fenton
C
,
Scott
LJ
,
Plosker
GL
.
Palivizumab: a review of its use as prophylaxis for serious respiratory syncytial virus infection.
Paediatr Drugs
.
2004
;
6
(
3
):
177
197
[PubMed]
13
Harkensee
C
,
Brodlie
M
,
Embleton
ND
,
Mckean
M
.
Passive immunisation of preterm infants with palivizumab against RSV infection.
J Infect
.
2006
;
52
(
1
):
2
8
[PubMed]
14
Wang
D
,
Cummins
C
,
Bayliss
S
,
Sandercock
J
,
Burls
A
.
Immunoprophylaxis against respiratory syncytial virus (RSV) with palivizumab in children: a systematic review and economic evaluation.
Health Technol Assess
.
2008
;
12
(
36
):
iii
, ix–x, 1–86
[PubMed]
15
Andabaka
T
,
Nickerson
JW
,
Rojas-Reyes
MX
,
Rueda
JD
,
Bacic Vrca
V
,
Barsic
B
.
Monoclonal antibody for reducing the risk of respiratory syncytial virus infection in children.
Cochrane Database Syst Rev
.
2013
;(
4
):
CD006602
[PubMed]
16
Byington
CL
,
Munoz
FM
.
Palivizumab prophylaxis for healthy preterm infants: more data supporting American Academy of Pediatrics guidelines.
Pediatrics
.
2016
;
138
(
2
):
e20161494
17
Chabra
S
.
Precise gestational age definitions needed for palivizumab prophylaxis in preterm infants.
Am J Respir Crit Care Med
.
2018
;
197
(
5
):
680
[PubMed]
18
Moher
D
,
Liberati
A
,
Tetzlaff
J
,
Altman
DG
;
PRISMA Group
.
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
PLoS Med
.
2009
;
6
(
7
):
e1000097
[PubMed]
19
National Advisory Committee on Immunization
.
Statement on the recommended use of monoclonal anti-RSV antibody (palivizumab) [in French].
Can Commun Dis Rep
.
2003
;
29
:
1
15
20
Husereau
D
,
Drummond
M
,
Petrou
S
, et al;
ISPOR Health Economic Evaluation Publication Guidelines-CHEERS Good Reporting Practices Task Force
.
Consolidated Health Economic Evaluation Reporting Standards (CHEERS)–explanation and elaboration: a report of the ISPOR Health Economic Evaluation Publication Guidelines Good Reporting Practices Task Force.
Value Health
.
2013
;
16
(
2
):
231
250
[PubMed]
21
Gomersall
JS
,
Jadotte
YT
,
Xue
Y
,
Lockwood
S
,
Riddle
D
,
Preda
A
.
Conducting systematic reviews of economic evaluations.
Int J Evid-Based Healthc
.
2015
;
13
(
3
):
170
178
[PubMed]
22
Patel
H
,
Sander
B
,
Nelder
MP
.
Long-term sequelae of West Nile virus-related illness: a systematic review.
Lancet Infect Dis
.
2015
;
15
(
8
):
951
959
[PubMed]
23
Organization for Economic Cooperation and Development
. Purchasing power parities (PPP) (indicator). Available at: . Accessed December 19, 2018
24
Banerji
A
,
Panzov
V
,
Young
M
, et al
.
Hospital admissions for lower respiratory tract infections among infants in the Canadian Arctic: a cohort study.
CMAJ Open
.
2016
;
4
(
4
):
E615
E622
[PubMed]
25
McGirr
AA
,
Schwartz
KL
,
Allen
U
,
Solomon
M
,
Sander
B
.
The cost-effectiveness of palivizumab in infants with cystic fibrosis in the Canadian setting: a decision analysis model.
Hum Vaccin Immunother
.
2017
;
13
(
3
):
599
606
[PubMed]
26
Neovius
K
,
Buesch
K
,
Sandström
K
,
Neovius
M
.
Cost-effectiveness analysis of palivizumab as respiratory syncytial virus prophylaxis in preterm infants in Sweden.
Acta Paediatr
.
2011
;
100
(
10
):
1306
1314
[PubMed]
27
Nuijten
MJC
,
Wittenberg
W
,
Lebmeier
M
.
Cost effectiveness of palivizumab for respiratory syncytial virus prophylaxis in high-risk children: a UK analysis.
Pharmacoeconomics
.
2007
;
25
(
1
):
55
71
[PubMed]
28
Nuijten
MJ
,
Wittenberg
W
.
Cost effectiveness of palivizumab in Spain: an analysis using observational data.
Eur J Health Econ
.
2010
;
11
(
1
):
105
115
[PubMed]
29
Nuijten
M
,
Lebmeier
M
,
Wittenberg
W
.
Cost effectiveness of palivizumab for RSV prevention in high-risk children in the Netherlands.
J Med Econ
.
2009
;
12
(
4
):
291
300
[PubMed]
30
Nuijten
M
,
Lebmeier
M
,
Wittenberg
W
.
Cost effectiveness of palivizumab in children with congenital heart disease in Germany.
J Med Econ
.
2009
;
12
(
4
):
301
308
[PubMed]
31
Resch
B
,
Gusenleitner
W
,
Nuijten
MJ
,
Lebmeier
M
,
Wittenberg
W
.
Cost-effectiveness of palivizumab against respiratory syncytial viral infection in high-risk children in Austria.
Clin Ther
.
2008
;
30
(
4
):
749
760
[PubMed]
32
Resch
B
,
Sommer
C
,
Nuijten
MJ
, et al
.
Cost-effectiveness of palivizumab for respiratory syncytial virus infection in high-risk children, based on long-term epidemiologic data from Austria.
Pediatr Infect Dis J
.
2012
;
31
(
1
):
e1
e8
[PubMed]
33
Rietveld
E
,
Steyerberg
EW
,
Polder
JJ
, et al
.
Passive immunisation against respiratory syncytial virus: a cost-effectiveness analysis.
Arch Dis Child
.
2010
;
95
(
7
):
493
498
[PubMed]
34
Roeckl-Wiedmann
I
,
Liese
JG
,
Grill
E
,
Fischer
B
,
Carr
D
,
Belohradsky
BH
.
Economic evaluation of possible prevention of RSV-related hospitalizations in premature infants in Germany.
Eur J Pediatr
.
2003
;
162
(
4
):
237
244
[PubMed]
35
Bentley
A
,
Filipovic
I
,
Gooch
K
,
Büsch
K
.
A cost-effectiveness analysis of respiratory syncytial virus (RSV) prophylaxis in infants in the United Kingdom.
Health Econ Rev
.
2013
;
3
(
1
):
18
[PubMed]
36
Salinas-Escudero
G
,
Martínez-Valverde
S
,
Reyes-López
A
, et al
.
Cost-effectiveness analysis of the use of palivizumab in the prophylaxis of preterm patients in Mexico.
Salud Publica Mex
.
2012
;
54
(
1
):
47
59
[PubMed]
37
Sanchez-Luna
M
,
Burgos-Pol
R
,
Oyagüez
I
, et al
.
Cost-utility analysis of palivizumab for respiratory syncytial virus infection prophylaxis in preterm infants: update based on the clinical evidence in Spain.
BMC Infect Dis
.
2017
;
17
(
1
):
687
[PubMed]
38
Schmidt
R
,
Majer
I
,
García Román
N
,
Rivas Basterra
A
,
Grubb
E
,
Medrano López
C
.
Palivizumab in the prevention of severe respiratory syncytial virus infection in children with congenital heart disease; a novel cost-utility modeling study reflecting evidence-based clinical pathways in Spain.
Health Econ Rev
.
2017
;
7
(
1
):
47
[PubMed]
39
Smart
KA
,
Paes
BA
,
Lanctôt
KL
.
Changing costs and the impact on RSV prophylaxis.
J Med Econ
.
2010
;
13
(
4
):
705
708
[PubMed]
40
Tam
DY
,
Banerji
A
,
Paes
BA
,
Hui
C
,
Tarride
JE
,
Lanctôt
KL
.
The cost effectiveness of palivizumab in term Inuit infants in the Eastern Canadian Arctic.
J Med Econ
.
2009
;
12
(
4
):
361
370
[PubMed]
41
Vogel
AM
,
McKinlay
MJ
,
Ashton
T
, et al
.
Cost-effectiveness of palivizumab in New Zealand.
J Paediatr Child Health
.
2002
;
38
(
4
):
352
357
[PubMed]
42
Weiner
LB
,
Masaquel
AS
,
Polak
MJ
,
Mahadevia
PJ
.
Cost-effectiveness analysis of palivizumab among pre-term infant populations covered by Medicaid in the United States.
J Med Econ
.
2012
;
15
(
5
):
997
1018
[PubMed]
43
Yount
LE
,
Mahle
WT
.
Economic analysis of palivizumab in infants with congenital heart disease.
Pediatrics
.
2004
;
114
(
6
):
1606
1611
[PubMed]
44
Elhassan
NO
,
Sorbero
ME
,
Hall
CB
,
Stevens
TP
,
Dick
AW
.
Cost-effectiveness analysis of palivizumab in premature infants without chronic lung disease.
Arch Pediatr Adolesc Med
.
2006
;
160
(
10
):
1070
1076
[PubMed]
45
Lofland
JH
,
O’Connor
JP
,
Chatterton
ML
, et al
.
Palivizumab for respiratory syncytial virus prophylaxis in high-risk infants: a cost-effectiveness analysis.
Clin Ther
.
2000
;
22
(
11
):
1357
1369
[PubMed]
46
Blanken
MO
,
Frederix
GW
,
Nibbelke
EE
, et al;
Dutch RSV Neonatal Network
.
Cost-effectiveness of rule-based immunoprophylaxis against respiratory syncytial virus infections in preterm infants.
Eur J Pediatr
.
2018
;
177
(
1
):
133
144
[PubMed]
47
Chirico
G
,
Ravasio
R
,
Sbarigia
U
.
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.
Ital J Pediatr
.
2009
;
35
(
1
):
4
[PubMed]
48
Hampp
C
,
Kauf
TL
,
Saidi
AS
,
Winterstein
AG
.
Cost-effectiveness of respiratory syncytial virus prophylaxis in various indications.
Arch Pediatr Adolesc Med
.
2011
;
165
(
6
):
498
505
[PubMed]
49
Harris
KC
,
Anis
AH
,
Crosby
MC
,
Cender
LM
,
Potts
JE
,
Human
DG
.
Economic evaluation of palivizumab in children with congenital heart disease: a Canadian perspective.
Can J Cardiol
.
2011
;
27
(
4
):
523.e11
523.e15
[PubMed]
50
Hascoet
JM
,
Fagnani
F
,
Charlemagne
A
,
Vieux
R
,
Rozé
JC
,
Bendjenana
H
.
Methodological aspects of economic evaluation in pediatrics: illustration by RSV infection prophylaxis in the French setting [in French].
Arch Pediatr
.
2008
;
15
(
12
):
1739
1748
[PubMed]
51
Lanctôt
KL
,
Masoud
ST
,
Paes
BA
, et al
.
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.
Curr Med Res Opin
.
2008
;
24
(
11
):
3223
3237
[PubMed]
52
Mahadevia
PJ
,
Masaquel
AS
,
Polak
MJ
,
Weiner
LB
.
Cost utility of palivizumab prophylaxis among pre-term infants in the United States: a national policy perspective.
J Med Econ
.
2012
;
15
(
5
):
987
996
[PubMed]
53
Seeler
RA
,
Schatz
B
.
Palivizumab (Synagis)–cohorting babies to reduce waste.
Pediatrics
.
1999
;
104
(
5, pt 1
):
1170
1171
[PubMed]
54
Smart
KA
,
Lanctôt
KL
,
Paes
BA
.
The cost effectiveness of palivizumab: a systematic review of the evidence.
J Med Econ
.
2010
;
13
(
3
):
453
463
[PubMed]
55
Hussman
JM
,
Li
A
,
Paes
B
,
Lanctôt
KL
.
A review of cost-effectiveness of palivizumab for respiratory syncytial virus.
Expert Rev Pharmacoecon Outcomes Res
.
2012
;
12
(
5
):
553
567
[PubMed]
56
Prescott
WA
 Jr
,
Doloresco
F
,
Brown
J
,
Paladino
JA
.
Cost effectiveness of respiratory syncytial virus prophylaxis: a critical and systematic review.
Pharmacoeconomics
.
2010
;
28
(
4
):
279
293
[PubMed]
57
American Academy of Pediatrics Committee on Infectious Diseases
;
American Academy of Pediatrics Bronchiolitis Guidelines Committee
.
Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection [published correction appears in Pediatrics. 2014;134(6):1221].
Pediatrics
.
2014
;
134
(
2
):
415
420
[PubMed]

Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

Supplementary data