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Monoclonal antibody for reducing the risk of respiratory syncytial virus infection in children

  1. Tea Andabaka1,*,
  2. Jason W Nickerson2,
  3. Maria Ximena Rojas-Reyes3,
  4. Juan David Rueda4,
  5. Vesna Bacic Vrca5,
  6. Bruno Barsic6

Editorial Group: Cochrane Acute Respiratory Infections Group

Published Online: 30 APR 2013

Assessed as up-to-date: 8 AUG 2012

DOI: 10.1002/14651858.CD006602.pub4


How to Cite

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 of Systematic Reviews 2013, Issue 4. Art. No.: CD006602. DOI: 10.1002/14651858.CD006602.pub4.

Author Information

  1. 1

    Ewopharma Ltd, Zagreb, Croatia

  2. 2

    Institute of Population Health, Ottawa, Ontario, Canada

  3. 3

    Pontificia Universidad Javeriana, Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Bogota, DC, Colombia

  4. 4

    Pontificia Universidad Javeriana, Departamento de Cirugía, Bogota, Cundinamarca, Colombia

  5. 5

    University Hospital Dubrava, Department of Hospital Pharmacy, Zagreb, Croatia

  6. 6

    University of Zagreb, School of Medicine, Hospital for Infectious Diseases, Department of Intensive Care, Zagreb, Croatia

*Tea Andabaka, Ewopharma Ltd, Zadarska 80 / 2, Zagreb, 10000, Croatia. Tea.Andabaka@gmail.com.

Publication History

  1. Publication Status: New
  2. Published Online: 30 APR 2013

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Characteristics of included studies [ordered by study ID]
Abarca 2009

MethodsStudy design: 2-year study, using different methodologies. The first year of this study was a phase I/II, multicentre, open-label, dose-escalation study. The second year (consecutive RSV season) was a randomized (1:1), double-blind study

Dates of study: late winter 2004 in the United States (year 1) and May to June 2005 (year 2). Dates for recruitment during year one in the Southern Hemisphere are not given

Locations: year 1 - USA (9 sites), Chile (4 sites) and Brazil (3 sites). Year 2 - 6 sites in South America (4 in Chile and 2 in Brazil)


ParticipantsSeason 1:

217 children with:

1) a gestational age between 32 and 35 weeks and were ≤ 6 months of chronological age; or

2) were ≤ 24 months of age and had CLD of prematurity requiring treatment with stable or decreasing doses of diuretics, steroids, or bronchodilators within the previous 6 months

Children were excluded if they had any of the following: hospitalization at the time of entry (unless discharge was expected within 3 days of study entry); birth hospitalization of > 6 weeks’ duration (for children without CLD) or birth hospitalization > 12 weeks’ duration (for children with CLD); chronic oxygen therapy or mechanical ventilation at the time of study entry (including continuous positive airway pressure); congenital heart disease; evidence of infection with hepatitis A, B or C virus; known renal impairment; hepatic dysfunction; chronic seizure disorder; immunodeficiency or human immunodeficiency virus infection or mother with known infection; laboratory findings in blood obtained within 7 days before study entry for blood urea nitrogen or creatinine > 1.5 times the upper limit of normal for age; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal for age; haemoglobin < 9.5 G/dL, white blood cell count < 4000 cells/mm3, or platelet count < 120,000 cells/mm3; acute illness or progressive clinical disorder; active infection, including acute RSV infection; previous reaction to immunoglobulin intravenous (IVIG), blood products, or other foreign proteins; treatment with palivizumab; current or previous (within 120 days) treatment with immunoglobulin products (e.g. RSV-IVIG) or any investigational agents; current participation in any investigational study; or previous participation in any investigational study using RSV vaccines or monoclonal antibodies

Season 2:

136 children (66 in motavizumab group and 70 in palivizumab group) who received ≥ 3 doses of motavizumab (3 or 15 mg/kg) in the previous RSV season and were ≤ 24 months of age at enrolment


InterventionsDuring season 1, children received between 2 and 5 doses of motavizumab (3 or 15 mg/kg) at 30-day intervals, depending on when during the RSV season a child was enrolled

During season 2, children were randomized to receive intramuscular injections of motavizumab (15 mg/kg) or palivizumab (15 mg/kg) every 30 days for a total of 4 to 5 doses


OutcomesPrimary outcomes: adverse events and serious adverse events (assessed for severity and potential relationship to study drug)

Children were followed for AEs and SAEs from the first study injection through 30 days after the final dose


NotesThe data extracted for our analysis includes only data from the second year, when the study was randomized and double-blind


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskStudy has 2 phases: first phase was open-label, with motavizumab and no comparison group. In the second consecutive RSV season children were randomly assigned 1:1 to receive motavizumab or palivizumab. The randomization schedule was stratified by site with a block size of 4 (p. 268)

Allocation concealment (selection bias)Unclear riskDuring the second RSV season, treatment assignments were double-blind. Only the independent monitor and the study pharmacist had access to information that identified a patient's treatment allocation. Method of allocation concealment remains unclear (p. 268)

Incomplete outcome data (attrition bias)
All outcomes
High riskIn season 1, 217 children were enrolled. Of these 217, 136 children participated in the next season. Of the 136 children, 131 (96.3%) completed the second season of the study. Reasons for attrition are given within season 2, though for attrition between season 1 and season 2 are not. Despite only 131/136 participants completing the study, data on all 136 participants are reported in Table 2

Selective reporting (reporting bias)Low riskAll outcomes reported in the methods are also reported in the results section. Adverse events were described on an as-reported basis, with clear criteria for defining adverse events, severe adverse events, etc.

Other biasUnclear riskThis study was sponsored by MedImmune. One of MedImmune employees assisted with data analysis and several study authors received research grants or were employees/consultants of MedImmune (p. 267, 272)

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskTreatment assignments were double-blind. Does not state how the treatments were delivered. Only the independent monitor and the study pharmacist had access to information that identified a patient's treatment allocation (p. 268)

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskThis is an adverse events study, where the first phase was open-label. Details of monitoring regime are reported for season 1 and season 2, though it is unclear whether assessors had knowledge of which intervention participants received

Bentley 2011

MethodsCost-utility analysis, payer's perspective, decision analytic model, lifetime follow-up, GBP, UK


ParticipantsInfants with CLD, and preterm infants born at less than 29, 29 to 32, and 33 to 35 weeks gestational age


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: QALYs, mortality benefits included, risk of sequelae included

Summary measures: incremental cost per QALY


NotesThis is an abstract of a presentation at a conference. Authors IF, KG and KB are employed at Abbott. This study suggests that the use of palivizumab is cost-effective in the UK


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Carbonell-Estrany 2010

MethodsStudy design: randomized (1:1), double-blind, palivizumab-controlled, phase III, non-inferiority trial

Dates of study: November 2004 and May 2006 during 2 RSV seasons in the northern hemisphere and 1 season in the southern hemisphere

Locations: 347 sites in 24 countries


Participants6635 preterm children (3329 to motavizumab group and 3306 to palivizumab group) with a gestational age ≤ 35 weeks who were either:

1) ≤ 24 months of age with chronic lung disease (CLD) that required medical management within 6 months before randomization, or

2) ≤ 6 months of age at enrolment

Exclusion criteria were: hospitalization at randomization (unless discharge was anticipated within 10 days); mechanical ventilation or other mechanical support; life expectancy < 6 months; active RSV infection; known renal, hepatic, chronic seizure, unstable neurologic or haemodynamically significant congenital heart disorders; immunodeficiency; use of palivizumab or RSV intravenous immunoglobulin < 3 months before randomization or anticipated use during the study; receipt of RSV vaccine; and participation in any other investigational study


InterventionsChildren received motavizumab (15 mg/kg) or palivizumab (15 mg/kg) applied as intramuscular injections at 30-day intervals for the total of 5 doses


OutcomesPrimary outcomes: hospitalization or death due to RSV

Primary efficacy outcome was met when a child had a positive RSV test and was hospitalised for respiratory symptoms or had a new onset of RSV-positive lower respiratory illness with worsening respiratory status while already in the hospital or when a death caused by RSV occurred

Secondary outcomes: all-cause and RSV-specific outpatient medically attended lower respiratory tract infection (MALRI), frequency and incidence of medically attended otitis media (OM), frequency of prescribed antibiotics for LRI and OM, adverse events and serious adverse events (graded for severity and causality), development of anti motavizumab antibodies, motavizumab serum concentrations

Children were involved during only 1 season and were followed up for 150 days after randomization


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskChildren were randomly assigned 1:1 by using an interactive voice-response system to receive motavizumab or palivizumab. Randomisation was stratified by site and diagnosis of protocol-defined CLD (p. e36)

Allocation concealment (selection bias)Low riskAll personnel at all sites were blind to study treatment. Motavizumab and palivizumab were provided in identical vials in coded kits (p. e36)

Incomplete outcome data (attrition bias)
All outcomes
Low riskAttrition rates in both groups were same (1.8%) and reasons for attrition were provided. The ITT population included all randomly assigned patients. The safety population included all patients who received any study medication and had any safety follow-up (p. e37)

Selective reporting (reporting bias)High risk6635 participants from 347 sites in 24 countries. RSV-specific outpatient MALRI was assessed only in children from 133 sites (p. e38). This likely represents the sample size calculation on page e37, though it is unclear how these sites were selected, possibly introducing bias toward sites with better outcomes data. Standard deviations for continuous data (days) are not reported (p. e46)

Other biasHigh riskThis study was sponsored by MedImmune. All authors were compensated by or employees of MedImmune (p. e35).

Differences in laboratory methods used to test for the presence of RSV in this study were cited by the FDA as a significant methodological concern which may have favoured motavizumab over palivizumab in this study. This was cited as one of the reasons for rejecting the licensing approval for motavizumab

Blinding of participants and personnel (performance bias)
All outcomes
Low riskInjections were provided in identical vials in coded kits. All personnel at all sites were blind to study treatment (p. e36)

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAll personnel at all sites were blind to study treatment (p. e36)

Chirico 2009

MethodsCost-utility and cost-effectiveness analysis, payer's perspective, decision analytic model, lifetime follow-up, 3% discount rate, 2007 EUR, Italy


ParticipantsPreterm infants of different gestational ages (GA) (less than 33 weeks, and 33 to 35 weeks), with or without bronchopulmonary dysplasia (BPD)


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization due to RSV infection (ordinary ward or ICU), mortality benefits included, risk of recurrent wheezing included, LYGs and QALYs

Summary measures: incremental cost per QALY, incremental cost per LYG


NotesAuthor U.S. is employed at Abbott. This paper was supported by a non-binding contribution provided by Abbott. This study suggests that palivizumab prophylaxis is cost-effective


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Chiroli 2005

MethodsCost-effectiveness analysis, payer's perspective, decision analytic model, 1-year follow-up, no discounting, 2004 EUR, Italy


ParticipantsChildren with haemodynamically significant congenital heart disease (CHD)


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization due to RSV infection, ICU stay, mortality benefits included, risk of sequelae not included, LYGs

Summary measures: incremental cost per LYG


NotesAuthor SC is employed at Abbott. This study supports the cost-effectiveness of palivizumab prophylaxis


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

ElHassan 2006

MethodsCost-utility analysis, societal perspective, decision analytic model, 8 years follow-up, 3% discount rate, 2002 USD, USA


ParticipantsPreterm infants without chronic lung disease (CLD) born at 26 to 32 weeks' gestation


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization due to RSV infection, mortality benefits not included, risk of asthma included

Summary measures: incremental cost per QALY


NotesNo conflict of interest declared. This study supports implementing more restrictive guidelines for palivizumab prophylaxis


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Embleton 2007

MethodsCost-effectiveness analysis, societal perspective, 1-year follow-up, no discounting, 2005 GBP, UK


ParticipantsPreterm infants with less than 32 weeks gestational age without BPD, or preterm infants with BPD


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization, mortality benefits not included, risk of wheezing or asthma not included

Summary measures: incremental cost per hospitalization averted


NotesNot funded by the industry. This study does not support the cost-effectiveness of palivizumab prophylaxis


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Feltes 2003

MethodsStudy design: randomized (1:1), double-blind, placebo-controlled, multicentre trial

Dates of study: 4 consecutive RSV seasons from 1998 through 2002

Locations: 76 – USA (47 sites), Canada (6 sites), Sweden (3 sites), Germany (4 sites), Poland (6 sites), France (4 sites) and UK (6 sites)


Participants1287 children (639 to palivizumab group and 648 to placebo group) with congenital heart disease (CHD) who:

1) were ≤ 24 months old at the time of random assignment;

2) had documented haemodynamically significant CHD determined by the investigator; and

3) had unoperated or partially corrected CHD

Children were not eligible if they had unstable cardiac or respiratory status, including cardiac defects so severe that survival was not expected or for which cardiac transplantation was planned or anticipated; were hospitalised, unless discharge was anticipated within 21 days; anticipated cardiac surgery within 2 weeks of random assignment; required mechanical ventilation, extracorporeal membrane oxygenation, continuous positive airway pressure, or other mechanical respiratory or cardiac support; had associated noncardiac anomalies or end-organ dysfunction resulting in anticipated survival of < 6 months or unstable abnormalities of end-organ function

Additional exclusion criteria were known HIV infection; acute RSV or other acute infection or illness; previous receipt of palivizumab or other monoclonal antibody; receipt of investigational agents within the previous 3 months (other than investigational agents commonly used during cardiac surgery or the immediate postoperative period, i.e. nitric oxide); current participation in other investigational protocols of drugs or biological agents; or receipt of intravenous immune globulin (IVIG), including RSV-IVIG, within 3 months before random assignment or anticipated use of IVIG, RSV-IVIG, or open-label palivizumab during the study period. Children with uncomplicated small atrial or ventricular septal defects or patent ductus arteriosus were excluded

Children with the following anatomic diagnoses were included in the cyanotic stratum: pulmonary atresia with ventricular septal defect, pulmonary atresia with intact septum, tetralogy of Fallot, single ventricle including hypoplastic left or right heart, tricuspid atresia, double-outlet right ventricle with transposed great arteries, Ebstein anomaly, or D-transposition of the great arteries with/without ventricular septal defect, with/without pulmonary stenosis. The remaining children were stratified to the “other” (acyanotic) stratum


InterventionsChildren received palivizumab (15 mg/kg) or an equal volume of placebo by intramuscular injection every 30 days for a total of 5 doses


OutcomesPrimary outcome: incidence of RSV hospitalization, including primary RSV hospitalisations and nosocomial RSV hospitalisations

A primary RSV hospitalization was defined as a hospitalization for an acute cardiorespiratory illness in which the RSV antigen test was positive within 48 hours before or after admission. Deaths occurring outside the hospital that could be demonstrated to be associated with RSV were also considered as primary RSV hospitalization end points. A nosocomial RSV hospitalization was one in which hospitalised patients had an objective measure of worsening cardiorespiratory status reported as a serious adverse event and the RSV antigen test was positive

Secondary outcomes: total RSV hospital days, RSV hospital days with increased supplemental oxygen, incidence and total days of RSV-associated intensive care, incidence and total days of RSV-associated mechanical ventilation, serum palivizumab concentration, the palivizumab through concentrations before second and fifth doses, adverse events and serious adverse events (assessed for severity and potential relation to study drug)

Children participated during only 1 season and were followed for 150 days after random assignment (30 days after the last scheduled study injection)


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom assignment was based on a computer-generated sequence, and was stratified by site to reduce the effect of practice discrepancies and anatomic cardiac lesion. Randomisation was performed centrally with the use of an interactive voice response system (p. 533)

Allocation concealment (selection bias)Low riskChildren were randomly assigned 1:1 to receive palivizumab or an equal volume of identically appearing placebo. Palivizumab and placebo were supplied in coded vials and dispensed in a syringe that did not identify the contents. Randomisation was performed centrally using an interactive voice response system (p. 533)

Incomplete outcome data (attrition bias)
All outcomes
Low risk95.6% of participants in the palivizumab group and 95.5% in the placebo group completed the study, and 93% of participants in the palivizumab group and 91.8% in the placebo group received all 5 injections. All randomly assigned patients were included in the safety and efficacy analyses, and patients who received at least 1 dose of study drug were included in the analyses of serum palivizumab concentrations (p. 534)

Selective reporting (reporting bias)High riskAll primary and secondary outcomes and safety/adverse events data were included in report of results. Adverse events were categorised, and graded by a blinded investigator for potential relation to study drug (p. 534). Standard deviations for continuous data (days) are not reported (p. 536)

Other biasUnclear riskThis study was supported by MedImmune, several MedImmune employees contributed to this study (p. 532, 538)

Blinding of participants and personnel (performance bias)
All outcomes
Low riskPalivizumab and placebo were identically appearing, supplied in coded vials and dispensed in a syringe that did not identify the contents (p. 533)

Blinding of outcome assessment (detection bias)
All outcomes
Low riskThis was a double-blind study with good randomization protocols. Adverse events were categorised, and graded by a blinded investigator for potential relation to study drug (p. 534)

Feltes 2011

MethodsStudy design: randomized (1:1), multinational, double-blind, palivizumab-controlled, phase II trial

Dates of study: 2 RSV seasons (2005 to 2006, and 2007 to 2008)

Locations: 34 sites in season 1 (North America, 51; European Union, 56; and rest of the world, 27) and 100 sites in season 2 (North America, 37; European Union, 48; and rest of the world, 15)


Participants1236 children (624 to motavizumab group and 612 to palivizumab group) aged ≤ 24 months who had:

1) Documented haemodynamically significant CHD defined as uncorrected or palliated cyanotic CHD or acyanotic CHD associated with documented pulmonary hypertension (systolic pulmonary arterial pressure ≥ 40 mm Hg) and/or a requirement for daily medication to manage congestive heart failure

Patients not eligible for enrolment included those with unstable cardiac or respiratory status, including severe cardiac defects with unanticipated survival or with anticipated cardiac transplantation; hospitalization, unless discharge was anticipated within 21 days; cardiac surgery anticipated within 2 weeks of randomization; any requirement for mechanical ventilation, extracorporeal membrane oxygenation, continuous positive airway pressure, or other mechanical respiratory or cardiac support; any associated noncardiac anomalies or end organ dysfunction resulting in anticipated survival of < 6 months or unstable abnormalities of end organ function; acute respiratory illness, or other acute infection or illness (patients with respiratory symptoms were tested for RSV before randomization and were excluded if they were positive); chronic seizure or neurologic disorder; immunodeficiency; mother with human immunodeficiency virus (HIV) infection (unless the child was negative for HIV infection); known allergy to any immunoglobulin products; receipt of any polyclonal antibody or palivizumab within 3 months before randomization; use of any investigational agents other than those commonly used during cardiac surgery or the immediate postoperative period; or current participation in any other investigational protocols

Children with cyanotic CHD included those with the most commonly encountered cyanotic cardiac lesions. Children who did not have one of the designated diagnoses to be included in the cyanotic stratum were classified as 'other' anticipating that this group would largely comprise children with acyanotic CHD lesions


InterventionsChildren received motavizumab (15 mg/kg) or palivizumab (15 mg/kg) applied as intramuscular injections at 30-day intervals for a total of 5 doses


OutcomesPrimary outcomes: adverse events and serious adverse events (assessed for severity and relationship to study drug)

Secondary outcomes: incidence of RSV hospitalization, RSV outpatient medically attended lower respiratory tract infection (for patients in season 2 only)

RSV hospitalization was defined as hospitalization for cardiac/respiratory symptoms accompanied by a positive RSV test or a new onset of RSV-positive lower respiratory illness with worsening respiratory status while already in the hospital or death caused by RSV. RSV outpatient MALRI was an outpatient medically attended event diagnosed as a lower respiratory illness accompanied by a positive RSV test. Each patient participated during a single RSV season and was followed for 150 days after random assignment (30 days after the last dose of study drug)


NotesInclusion and exclusion criteria for patients in this study are consistent with criteria in Feltes 2003


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskPatients were randomly assigned 1:1 using an interactive voice-response system. Randomisation was stratified by site and the presence or absence of cyanotic CHD (p. 187)

Allocation concealment (selection bias)Low riskMotavizumab and palivizumab were provided in identical vials in coded kits. Randomisation was performed centrally. All study personnel were blinded to treatment assignments (p. 187)

Incomplete outcome data (attrition bias)
All outcomes
Low riskComparable attrition rates in both groups. Reasons for attrition given in supplemental material. The ITT population included all randomized patients. The safety population included all patients who received any study medication and had any safety follow-up (p. 187)

Selective reporting (reporting bias)High riskAdverse events were determined on an as-encountered basis, and assessed for severity and relationship to study drug by the blinded site investigators (p. 187). Secondary outcomes reported in the methods are also reported in the results section. RSV outpatient MALRIs were assessed for patients in season 2 only, with no explanations provided, and without reporting the total number of randomized patients in the subset

Other biasUnclear riskThis study was sponsored by MedImmune (p. 186). MedImmune was involved in study design; collection, analysis and interpretation of data; and writing of the manuscript. Several authors are employees/consultants/speakers of MedImmune

Blinding of participants and personnel (performance bias)
All outcomes
Low riskMotavizumab and palivizumab were delivered in identical vials in coded kits. All study personnel were blinded to treatment assignments (p. 187)

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskStudy was not powered as a stand-alone efficacy study, though it reports efficacy data (p. 189). The authors note that despite this, their results were consistent with previous studies, thus the actual impact of the study being underpowered may be minimal

Fernandez 2010

MethodsStudy design: phase II, randomized (1:1:1), double-blind, cross-over study

Dates of study: 1 RSV season (April 2006 through February 2007)

Locations: 18 – Chile (7 sites), New Zealand (5 sites) and Australia (6 sites)


Participants260 children (83 to M/P treatment group, 84 to P/M treatment group, and 93 to motavizumab only group) born preterm who:

1) had gestational age ≤ 35 weeks and the chronological age was ≤ 6 months at the time of entry into the study; or

2) if they were ≤ 24 months of age at the time of entry into the study and had a diagnosis of CLD of prematurity requiring medical management within 6 months before randomization

Eligible children had to be in good health at the time of study entry. They could not be hospitalised (unless discharge was expected within 10 days); be receiving chronic oxygen therapy or any ventilatory support; have significant congenital heart disease; have evidence of infection with hepatitis A, B, or C virus or HIV; have any acute illness, including acute RSV infection; known renal impairment, hepatic dysfunction, chronic seizure disorder or immunodeficiency; have suspected serious allergic or immune-mediated events in association with prior receipt of immunoglobulins, blood products or other foreign proteins; have received within the past 120 days or currently be receiving immunoglobulin products, palivizumab or any investigational agent


InterventionsChildren received motavizumab (15 mg/kg) or palivizumab (15 mg/kg) applied as intramuscular injections at 30-day intervals for a total of 5 doses in the following way:

1) 2 doses of motavizumab followed by 3 doses of palivizumab – M/P treatment group

2) 2 doses of palivizumab followed by 3 doses of motavizumab – P/M treatment group

3) 5 doses of motavizumab only – control


OutcomesPrimary outcomes: adverse events, serious adverse events and laboratory evaluations

AEs were assessed for severity, relationship to study treatment, and whether the event met criteria as an SAE

Secondary outcomes: anti drug antibodies and serum trough concentrations of motavizumab and palivizumab

Children were monitored for AEs and SAEs from the time of randomization through study day 150 (30 days after the final planned dose)


NotesThis is a cross-over study whereby participants received either motavizumab/palivizumab, palivizumab/motavizumab or motavizumab only, with cross-over occurring after dose 2, out of a total of 5 doses. The data extracted for our analysis include only data after the first 2 doses, before the cross-over occurred


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskChildren were randomly assigned 1:1:1 (stratified by site) using an automated randomization system (p. 2)

Allocation concealment (selection bias)Unclear riskThis was a randomized, double-blind study (p. 2). Method of allocation concealment remains unclear; no information is provided

Incomplete outcome data (attrition bias)
All outcomes
Low risk94.6% of subjects received all 5 doses of study drug and 92.7% subjects completed the study. Reasons for attrition are given (p. 5). The safety population included all randomized subjects who received study drug and had any safety follow-up (p. 4)

Selective reporting (reporting bias)Low riskAll outcomes reported in the methods are also reported in the results section. Adverse events were determined on an as-encountered basis and assessed by the investigator for severity, relationship to study drug and whether it met criteria as an SAE (p. 3)

Other biasUnclear riskThis study was sponsored by MedImmune (p. 12). All authors received research grants/funding or were employees of MedImmune. MedImmune was involved in study design, and analysis and interpretation of data

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskDetails on blinding of participants and personnel are not available

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskDetails on blinding of participants and personnel are not available

Garcia-Altes 2010

MethodsCost-effectiveness analysis, payer's perspective, decision analytic model, 1-year and an alternative lifetime follow-up, 3% discount rate, 2008 EUR, Spain


ParticipantsPreterm children less than 2 years old with and without chronic lung disease, children less than 2 years old with chronic lung disease and children less than 5 years old with congenital heart disease


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization rate, mortality benefits included, risk of sequelae not included, ICU stay

Summary measures: incremental cost per hospitalization averted, incremental cost per LYG


NotesNot funded by the industry. Administration of palivizumab is not cost-effective in these populations, neither for hospitalisations averted nor for LYGs. Paper is written in Spanish


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Hampp 2011

MethodsCost-effectiveness analysis, payer's perspective, decision analytic model, no discounting, 2010 USD, Florida, USA


ParticipantsChildren up to 2 years of age with: CLD only, CHD only, CLD and prematurity (≤ 32 weeks gestation), CHD and prematurity, CHD and CLD, any of these indications, none of these indications and premature infants up to 6 months of age


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: incidence rate of hospitalization due to RSV infection, absolute risk reduction, mortality benefits not included, risk of wheezing or asthma not included

Summary measures: incremental cost per RSV hospitalization avoided


NotesNo conflict if interest reported. This study suggests that recommendations for the use of palivizumab should be reconsidered, because the cost of prophylaxis far exceeded the economic benefit of prevented hospitalisations in any risk group


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Harris 2011

MethodsCost-effectiveness analysis, societal perspective, decision analytic model, no discounting, 2007 CAD, Canada


ParticipantsChildren less than 2 years old with haemodynamically significant CHD, born at 36 weeks gestation


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: risk of admission to hospital, days in hospital, mortality benefits included, risk of sequelae not included

Summary measures: incremental cost to prevent one day of hospitalization


NotesAuthor DGH received an honorarium of less than CAD 1000 from Abbott Laboratories. This study suggests that palivizumab is not cost-effective


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Hascoet 2008

MethodsCost-effectiveness analysis, societal and payer's perspective, decision analytic model, lifetime follow-up, 3% discount rate, 2006 EUR, France


ParticipantsPreterm infants born at 32 weeks of gestational age or less, with BPD or CHD


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: mortality benefits included, risk of sequelae included, hospitalization due to RSV infection

Summary measures: incremental cost per LYG, cost per hospitalization averted


NotesAuthor HB is employed at Abbott. This study suggests that palivizumab prophylaxis is cost-effective. Paper is written in French


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

IMpact-RSV 1998

MethodsStudy design: multicentre, randomized, double-blind, placebo-controlled, phase III trial

Dates of study: 1996 to 1997 RSV season

Locations: 139 - USA (119 sites), UK (11 sites) and Canada (9 sites)


Participants1502 children (1002 in palivizumab group and 500 in placebo group) who were either:

1) 35 weeks gestation or less and 6 months of age or younger; or

2) 24 months old or younger and had a clinical diagnosis of BPD requiring ongoing medical treatment (i.e. supplemental oxygen, steroids, bronchodilators or diuretics within the past 6 months)

Children were excluded if they had any of the following: hospitalization at the time of entry that was anticipated to last more than 30 days; mechanical ventilation at the time of entry; life expectancy less than 6 months; active or recent RSV infection; known hepatic or renal dysfunction, seizure disorder, immunodeficiency, allergy to IgG products; receipt of RSV immune globulin within the past 3 months; or previous receipt of palivizumab, other monoclonal antibodies, RSV vaccines or other investigational agents. Children with congenital heart disease were excluded, except for those with a patent ductus arteriosus or a septal defect that was uncomplicated and haemodynamically insignificant

Attrition: 16 participants due to death (n = 7), withdrawal of consent (n = 4) or loss to follow-up (n = 5)


InterventionsChildren received palivizumab (15 mg/kg) or an equivalent volume of placebo applied as intramuscular injections every 30 days for a total of 5 doses


OutcomesPrimary outcome: hospitalization with confirmed RSV infection

Children were considered to have reached the primary outcome if:

1) they were hospitalised for a respiratory illness and the RSV antigen test of respiratory secretions was positive; or

2) if children already hospitalised for reasons other than RSV illness had a positive RSV test, and had a minimum LRI score of 3 and at least 1 point higher compared with their last health visit

Secondary outcomes: total RSV hospital days, RSV hospital days with increased supplemental oxygen, RSV hospital days with moderate/severe lower respiratory tract illness, incidence and total days of intensive care and mechanical ventilation, incidence of non-RSV hospitalization, incidence of otitis media, adverse events (assessed for severity and potential relationship to study drug)

Children were followed for 150 days from randomization (30 days after the last scheduled injection)


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomisation (2 treatment to 1 control) was performed centrally using an interactive voice randomization system (p. 532)

Allocation concealment (selection bias)Low riskParticipants were centrally randomized to receive palivizumab or an equal volume of identically appearing placebo. Palivizumab and placebo were supplied as powder in coded vials and dispensed in a syringe that did not identify the contents (p. 532)

Incomplete outcome data (attrition bias)
All outcomes
Low risk99% of children completed the protocol follow-up, 94% of placebo group and 92% of palivizumab group received all 5 injections. All randomized patients were included in the safety and efficacy analyses (p. 532, 533)

Selective reporting (reporting bias)High riskPrimary and secondary endpoints listed in the methods on page 532 are reported in results section on pages 533 to 534. Adverse events were defined as they happened, in both groups, and reported on page 534. Standard deviations for continuous data (days) are not reported (p. 533, 534)

Other biasUnclear riskEmployees of MedImmune contributed to the study and assisted in preparation of the manuscript (p. 537)

Blinding of participants and personnel (performance bias)
All outcomes
Low riskParticipants were centrally randomized to receive palivizumab or an equal volume of identically appearing placebo (p. 532)

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAdverse events were judged by the blinded investigator to be related or not to the study drug (p. 534)

LRI score was completed on all patients, regardless and all patients were followed for 150 days (30 days after the last immunisation), regardless of the amount of study drug they received (p. 532)

Joffe 1999

MethodsCost-effectiveness analysis, societal perspective, decision analytic model, 3% discount rate, 1995 USD, California, USA


ParticipantsPreterm infants discharged from the neonatal intensive care unit within 12 months prior to RSV season (8 risk groups)


InterventionsPalivizumab prophylaxis compared to RSV-IVIG prophylaxis and no prophylaxis


OutcomesEffectiveness outcomes: number needed to treat to prevent 1 RSV hospitalization, mortality benefits included, risk of sequelae not included

Summary measures: incremental cost per hospitalization averted, incremental cost per LYG


NotesNo conflict of interest declared. This study suggests more restrictive recommendations for the use of palivizumab


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Kang 2009

MethodsCost-effectiveness analysis, payer's and societal perspective, decision analytic model, lifetime follow-up, 5% discount rate, KW, Korea


ParticipantsChildren with congenital heart disease


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: number of RSV hospitalisations and deaths avoided

Summary measures: incremental cost per LYG


NotesThis is an abstract of a presentation at a conference. This study suggests that the use of palivizumab is cost-effective


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Lanctot 2008

MethodsCost-effectiveness and cost-utility analysis, payer's and societal perspective, decision analytic model, lifetime follow-up, 5% discount rate, 2007 CAD, Canada


ParticipantsPreterm infants born at 32 to 35 weeks of gestational age without chronic lung disease


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization due to RSV infection (general ward or ICU), risk of asthma and recurrent wheezing included, mortality benefits included, LYGs, QALYs

Summary measures: incremental cost per LYG, incremental cost per QALY


NotesAbbott provided financial support for this analysis. This study suggests that palivizumab prophylaxis is cost-effective from both perspectives, in patients with 2 or more risk factors


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Lazaro y de Mercado 2006

MethodsCost-effectiveness and cost-utility analysis, payer's and societal perspective, decision analytic model, lifetime follow-up, 3% discount rate, 2006 EUR, Spain


ParticipantsPreterm infants born at 32 to 35 weeks' gestational age with 2 or more risk factors described by the Spanish Neonatology Society


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: life expectancy, mortality benefits included, hospitalization rate, risk of recurrent wheezing included, number needed to treat

Summary measures: incremental cost per LYG, incremental cost per QALY


NotesFunded by the industry. This study suggests that palivizumab is a cost-effective alternative for the prophylaxis of RSV in preterm children with 2 or more risk factors. Paper is written in Spanish


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Lazaro y de Mercado 2007

MethodsCost-effectiveness and cost-utility analysis, payer's and societal perspective, decision analytic model, lifetime follow-up, 3.5% discount rate, 2006 EUR, Spain


ParticipantsPreterm infants born at 35 weeks of gestational age or less and 6 months of age or younger, or 24 months old or younger and with a clinical diagnosis of BPD requiring ongoing medical treatment


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: life expectancy, mortality benefits included, hospitalization rate, risk of recurrent wheezing included, number needed to treat

Summary measures: incremental cost per LYG, incremental cost per QALY


NotesNo conflict of interest declared. However, for the economic evaluation performed on the same topic by the same authors in 2006, the authors received a grant from Abbott. This study suggests that palivizumab is a cost-effective alternative for the prophylaxis of RSV in preterm children with 2 or more risk factors. Paper is written in Spanish


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Lofland 2000

MethodsCost-effectiveness analysis, payer’s perspective, decision analytic model, 1-year follow-up, no discounting, 1999 USD, USA


ParticipantsPreterm infants (≤ 35 weeks of gestational age) and children with BPD


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization due to RSV infection, mortality benefits not included, risk of sequelae not included

Summary measures: incremental cost per RSV hospitalization avoided


NotesPaper was supported by a grant from MedImmune, Inc., Gaithersburg. This study gives ICER ranges for different palivizumab prophylaxis costs, and leaves the conclusions about the cost-effectiveness up to the readers


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Mayen-Herrera 2011

MethodsCost-utility analysis, payer's perspective, decision analytic model, 3% discount rate, MXN, Mexico


ParticipantsPreterm infants born at less than 29 weeks of gestational age


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: QALYs

Summary measures: incremental cost per QALY


NotesThis is an abstract of a presentation at a conference. Author EMH is employed at Abbott. This study suggests that palivizumab prophylaxis is cost-effective


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Neovius 2011

MethodsCost-utility and cost-effectiveness analysis, societal perspective, decision analytic Markov model, lifetime follow-up, 3% discount rate, 2009 SEK, Sweden


ParticipantsPreterm infants born at less than 29 weeks of gestation


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization due to RSV infection, risk of asthma included, mortality benefits included

Summary measures: incremental cost per QALY, incremental cost per LYG


NotesAuthors KB and KS are employed at Abbott. Study was funded by Abbott Scandinavia. Palivizumab was found to be cost-effective, based on a willingness-to-pay of SEK 500,000 per QALY


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Nuijten 2007

MethodsCost-effectiveness and cost-utility analysis, payer's and societal perspective, decision analytic model, lifetime follow-up, 3.5% discount rate, 2003 GBP, UK


ParticipantsPreterm infants born at 35 weeks of gestation or less, children with BPD (≤ 2 years) and children with CHD (≤ 2 years)


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: mortality benefits included, risk of sequelae included, hospitalization rate, life expectancy, utilities

Summary measures: incremental cost per LYG, incremental cost per QALY


NotesFunded by the industry. This study suggests that palivizumab prophylaxis may be a cost-effective option against severe RSV infections in the UK versus no prophylaxis


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Nuijten 2009a

MethodsCost-utility and cost-effectiveness analysis, societal perspective, decision analytic model, lifetime follow-up, no discounting, 2006 EUR, Netherlands


ParticipantsPreterm infants and infants with BPD (as one subgroup) and children with CHD (as another subgroup)


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization due to RSV infection, risk of asthma and recurrent wheezing included, mortality benefits included, life expectancy, utilities

Summary measures: incremental cost per QALY, incremental cost per LYG


NotesAuthor WW is employed at Abbott. Author MN was paid by Abbott to conduct this analysis. This study suggests that palivizumab prophylaxis is cost-effective


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Nuijten 2009b

MethodsCost-utility and cost-effectiveness analysis, societal and payer’s perspective, decision analytic model, lifetime follow-up, 5% discount rate, 2006 EUR, Germany


ParticipantsInfants with haemodynamically significant congenital heart disease


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization due to RSV infection, risk of asthma and recurrent wheezing included, mortality benefits included, utilities

Summary measures: incremental cost per QALY, incremental cost per LYG


NotesAuthor WW is employed at Abbott. Author MN was paid by Abbott to conduct this analysis. This study suggests that palivizumab prophylaxis is cost-effective


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Nuijten 2010

MethodsCost-effectiveness and cost-utility analysis, payer's and societal perspective, decision analytic model, lifetime follow-up, 3% discount rate, 2006 EUR, Spain


ParticipantsPreterm children born at or before 32 weeks of gestational age who were less than 6 months old at the onset of RSV season


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: mortality benefits included, risk of sequelae included, hospitalization rate, life expectancy, utilities

Summary measures: incremental cost per LYG, incremental cost per QALY


NotesFunded by the industry. This study suggests that palivizumab may be a cost-effective prophylactic option against severe RSV infections in Spain compared to no prophylaxis


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Ravasio 2006

MethodsCost-effectiveness and cost-utility analysis, payer's perspective, decision analytic model, 14 years follow-up, 3% discount rate, EUR, Italy


ParticipantsPreterm infants of less than 33 weeks, or 33 to 35 weeks of gestation, with and without BPD


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: mortality benefits included, hospitalization rate, risk of asthma included

Summary measures: incremental cost per LYG, incremental cost per QALY


NotesFunded by the industry. This study suggests that palivizumab is cost-effective in prevention of RSV infection in preterm infants. Paper is written in Italian


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Raya Ortega 2006

MethodsCost-effectiveness analysis, payer's perspective, decision analytic model, 1-year follow-up, no discounting, 2006 EUR, Spain


ParticipantsPreterm infants born at 32 to 35 weeks of gestation


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization rate

Summary measures: incremental cost per hospitalization avoided


NotesNot funded by the industry. This study suggests that palivizumab prophylaxis is not cost-effective. Paper is written in Spanish


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Resch 2008

MethodsCost-effectiveness and cost-utility analysis, payer's and societal perspective, decision analytic model, lifetime follow-up, 5% discount rate, 2006 EUR, Austria


ParticipantsPreterm infants born at 35 weeks of gestation or less, children with BPD and children with CHD


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization, mortality benefits included, life expectancy, risk of asthma included

Summary measures: incremental cost per LYG, incremental cost per QALY


NotesAuthor WW is employed at Abbott. Palivizumab was cost-effective compared to no prophylaxis in high-risk infants in Austria


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Resch 2012

MethodsCost-effectiveness and cost-utility analysis, payer's and societal perspective, decision analytic model, lifetime follow-up, 5% discount rate, 2010 EUR, Austria


ParticipantsPreterm infants born at 36 weeks of gestation or less, children with BPD and children with CHD


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: LYG, QALY, mortality benefits included, risk of sequelae included

Summary measures: incremental cost per LYG, incremental cost per QALY


NotesConflicts of interest are not clearly stated. Author SS is employed at Abbott. Study suggests that palivizumab is cost-effective in prevention of RSV disease in high-risk infants. This study incorporated changes in medication costs and new country-specific epidemiologic data, as compared to Resch 2008


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Rietveld 2010

MethodsCost-effectiveness analysis, societal perspective, decision analytic model, 1-year follow-up, no discounting, 2000 EUR, Netherlands


ParticipantsPreterm infants born at 28 weeks of gestation or less, with birth weight ≤ 2500 g, having BPD and aged 0 months at the beginning of the season (October)


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization rate, mortality benefits not included, risk of sequelae not included

Summary measures: cost per hospitalization averted


NotesNot funded by the industry. This study recommends a restrictive immunisation policy, immunizing only the children with BPD in high-risk months


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Roeckl-Wiedmann 2003

MethodsCost-effectiveness analysis, societal perspective, decision analytic model, 1-year follow-up, no discounting, EUR, Germany


ParticipantsPreterm infants of male gender born at ≤ 35 weeks of gestational age, with siblings in daycare, discharge between October and December, and with or without CLD. Economic evaluation is nested in the Munich RSV study.


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization rate, mortality benefits included, risk of sequelae not included

Summary measures: cost per hospitalization averted


NotesFunded by the industry. This study suggests restrictive use of palivizumab prophylaxis in preterm infants with CLD in their risk combination


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Salinas-Escudero 2012

MethodsCost-effectiveness and cost-utility analysis, payer's perspective, decision analytic model, 18 years follow-up, 3% discount rate, 2009 USD, Mexico


ParticipantsPreterm infants without CLD or CHD, born at less than 29, or at 29 to 32 weeks of gestational age, and up to 6 months old at the start of the RSV season, or born during the season


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: LYG, QALY, risk of asthma included, mortality benefits included

Summary measures: incremental cost per LYG, incremental cost per QALY


NotesThe authors received support of Abbott Laboratories in Mexico. This study suggests that palivizumab is a cost-effective alternative for preterm infants ≤ 32 weeks of gestational age (wGA) in Mexico


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Smart 2010

MethodsCost-effectiveness and cost-utility analysis, payer's and societal perspective, decision analytic model, lifetime follow-up, 5% discount rate, 2010 CAD, Canada


ParticipantsPreterm infants born at 32 to 35 weeks' gestational age


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization rate, mortality benefits included, with and without risk of sequelae included, life expectancy

Summary measures: incremental cost per LYG, incremental cost per QALY


NotesNot funded by the industry. Palivizumab was cost-effective compared to no prophylaxis in high-risk infants in Canada. Methodology was based on Lanctot 2008 study


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Subramanian 1998

MethodsStudy design: randomized (2:1), double-blind, placebo-controlled, phase I/II, multicentre, dose-escalation trial

Dates of study: 1995 to 1996 RSV season

Locations: 10 sites (locations not specified)


Participants62 patients (42 to palivizumab group and 20 to placebo group) who:

1) were born at ≤ 35 weeks of gestation and were ≤ 6 months of age; or

2) had bronchopulmonary dysplasia and were ≤ 24 months of age

Infants were excluded if they had any of the following: mechanical ventilation at the time of enrolment; life expectancy < 1 year; known renal impairment, hepatic dysfunction, persistent seizure disorder or immunodeficiency; blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase or bilirubin > 1.5 times the upper limit of normal for age; haemoglobin < 9.0 g/dl; white blood cell count < 2000 cells/mm3; platelet count < 110,000 cells/mm3; abnormal serum IgG, IgM and IgA values, positive hepatitis B surface antigen, hepatitis C antibody or HIV antibody (unless provided to be not infected with HIV); supplemental oxygen requirement of > 30% FiO2 or > 1.5 litres/min; any acute illness or progressive clinical disorder, including acute RSV infection; previous reaction to intravenous immunoglobulin, blood products or other foreign proteins; treatment with intravenous immunoglobulin or other immunoglobulin products within the past 2 months; treatment with other investigational agents or participation in any investigational study of RSV agents; or expectation that the patient would not be able to be followed for the duration of the study


InterventionsChildren received 3, 10 or 15 mg/kg of palivizumab intravenously, or an equal volume of placebo applied as intravenous infusion every 30 days (- 3 to + 7 days) for up to 5 doses


OutcomesPrimary outcomes: adverse events (assessed for severity, seriousness and relationship to study drug)

Secondary outcomes: frequency and severity of RSV infection

Infants who were assessed by the family or the patient’s physician as having a respiratory infection or who had 2 or more of the following new respiratory symptoms (coryza, fever, cough, wheezing, intercostal retractions or nasal flaring) or who had exacerbation of existing respiratory conditions were evaluated for evidence of RSV infection (RSV antigen). When a child was hospitalised for RSV illness, the child was evaluated daily until discharge

Patients were followed for 150 days (30 days after the last infusion)


NotesThe data extracted for our analysis includes only data for 15 mg/kg dosing regimen


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation (1 placebo: 2 MEDI-493 within each dosage) was done centrally. Insufficient information about sequence generation process is given (p. 111)

Allocation concealment (selection bias)Low riskThe study drug (palivizumab or placebo) was dispensed from the pharmacy in a syringe enclosed in a plastic bag that did not contain the drug assignment on the label (p. 111, 112)

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll randomized patients who received study drug were included in analyses. Overall 91.9% patients completed the study. Reasons for attrition are given (p. 112)

Selective reporting (reporting bias)Low riskAll outcomes reported in the methods are also reported in the results section. LRI score was used; adverse events were reported on as-encountered basis and assessed by the blinded investigator for relationship to study drug (p. 111)

Other biasUnclear riskSeveral authors of this study are MedImmune employees (p. 110)

Blinding of participants and personnel (performance bias)
All outcomes
Low riskStudy drug assignment and the investigators were blinded. Study drugs were dispensed from the pharmacy in a syringe enclosed in a plastic bag that did not contain the drug assignment on the label. The safety monitoring committee had the power to unblind the study group assignment if needed, but didn't do it during their review (p. 111, 112)

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcomes were assessed by the blinded investigator. The treatment assignment was unblinded by the medical monitor for 1 child who died who was assigned to the placebo group (p. 111, 112)

Tam 2009

MethodsCost-effectiveness and cost-utility analysis, payer's and societal perspective, decision analytic model, lifetime follow-up, 5% discount rate, 2007 CAD, Canada


ParticipantsInfants less than 1 year of age on Baffin Island


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization rate, mortality benefits included, risk of sequelae not included, life expectancy, utilities

Summary measures: incremental cost per LYG, incremental cost per QALY


NotesFunded by the industry. Palivizumab was cost-effective in infants less than 1 year of age residing in the Eastern Canadian Arctic. However, palivizumab was not cost-effective for infants of all ages residing in Iqaluit


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Vogel 2002

MethodsCost-effectiveness analysis, societal perspective, decision analytic model, no discounting, 2000 NZD, New Zealand


ParticipantsPreterm infants < 32 weeks' gestational age


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization rate, mortality benefits not included, risk of sequelae not included, number needed to treat

Summary measures: cost per hospitalization averted


NotesFunded by the industry. This study does not indicate cost savings associated with the use of palivizumab for any subgroup


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Wang 2011

MethodsCost-utility analysis, payer's perspective, decision analytic model, lifetime follow-up, 3.5% discount rate, 2006 GBP, UK


ParticipantsPreterm infants ≤ 35 weeks gestational age. Subgroup analyses in four categories: CLD, CLD/CHD, acyanotic CHD and cyanotic CHD


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: odds ratios for age, gestational age, gender, CHD, CLD, sibling at school, multiple births, smoking exposure, overcrowding, parental education of high school or less, mortality benefits included, with and without risk of sequelae included

Summary measures: incremental cost per QALY


NotesNot funded by the industry. This study suggests that palivizumab is not cost-effective


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Weiner 2012

MethodsCost-utility analysis, societal perspective, decision analytic model, lifetime follow-up, 3% discount rate, 2010 USD, USA


ParticipantsPreterm infants without CLD or CHD divided in 4 subgroups; data presented for infants born at less than 32 weeks of gestation and with 6 months of chronological age or less


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: QALYs, utilities, mortality benefits included, risk of sequelae not included

Summary measures: incremental cost per QALY


NotesFunded by the industry. This study suggests that palivizumab prophylaxis is highly cost-effective


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Yount 2004

MethodsCost-effectiveness and cost-utility analysis,  payer's perspective, decision analytic model, lifetime follow-up, 3% discount rate, 2002 USD, USA


ParticipantsChildren with congenital hearth disease ≤ 2 years old


InterventionsPalivizumab prophylaxis compared to no prophylaxis


OutcomesEffectiveness outcomes: hospitalization rate, life expectancy, mortality benefits included, risk of sequelae included

Summary measures: incremental cost per LYG, incremental cost per QALY


NotesNot funded by the industry. Routine use of palivizumab in young children with haemodynamically significant CHD needs to be evaluated further


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Allocation concealment (selection bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Selective reporting (reporting bias)Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Other biasUnclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee Appendix 6 for assessment of risk of bias in economic evaluations

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Banerji 2009This is a partial economic evaluation study

Buckley 2010This is a partial economic evaluation study

Chan 2003This is a partial economic evaluation study

Clark 2000This is a partial economic evaluation study

Datar 2012This is a partial economic evaluation study

Farina 2002This is a partial economic evaluation study

Korbal 2003This is a retrospective analysis, not a randomized controlled trial

Krilov 2010This is a partial economic evaluation study

Lapena Lopez 2003This is a partial economic evaluation study

Lee 2001This is a partial economic evaluation study

Marchetti 1999This is a partial economic evaluation study

Marques 2010This is a partial economic evaluation study

Martinez 2002This is a trial with a historical control, not a randomized controlled trial

McCormick 2002This is a partial economic evaluation study

Meberg 2006This is a partial economic evaluation study

Meissner 1999Product SB 209763 is not palivizumab. It is another kind of intramuscular monoclonal antibody against respiratory syncytial virus (RSV) that failed to prove efficacy in preventing severe RSV disease

Numa 2000This is neither a cost-effectiveness nor a cost-utility analysis

Parmigiani 2001This is not a randomized controlled trial

Rackham 2005This is a partial economic evaluation study

Reeve 2006This is a partial economic evaluation study

Rodriguez 2008This is a partial economic evaluation study

Shireman 2002This is neither a cost-effectiveness nor a cost-utility analysis

Stevens 2000This economic evaluation analyses RSV-IVIG and palivizumab together. Results of these analyses represent combined effect of both prophylaxis. There is no comparison of palivizumab prophylaxis alone with placebo, no prophylaxis or other prophylaxis

Strutton 2003This is a systematic review of economic evaluations and not a primary analysis

Takeuchi 2002This is not a randomized controlled trial

Vann 2007This is a partial economic evaluation study

Wang 2008The technology assessment performed in Wang 2008 was later updated and reported in Wang 2011

Wegner 2004This is a partial economic evaluation study

Wendel 2010This is a partial economic evaluation study

 
Characteristics of studies awaiting assessment [ordered by study ID]
NCT00233064

MethodsStudy design: phase IV, randomized, double-blind, dose comparison trial

Date of first enrolment: October 2005

Target sample size: 417

Recruitment status: completed in November 2007

Locations: sites in USA

Sponsor: MedImmune LLC

ParticipantsInclusion criteria:

  1. Medically stable child with chronic lung disease of prematurity who is ≤ 24 months of age at randomization or child with premature birth (gestational age ≤ 35 weeks or less) and who is 6 months of age or younger at randomization
  2. Written informed consent obtained from the patient's parent(s) or legal guardian(s)
  3. The child must be able to complete the follow-up visit 4 to 6 months after the last dose of study drug


Exclusion criteria:

  1. Hospitalisation at the time of randomization (unless discharge is anticipated within 3 weeks)
  2. Be receiving mechanical ventilation at the time of study entry (including CPAP)
  3. Congenital heart disease (children with uncomplicated CHD (e.g. PDA, small septal defect) and children with complicated CHD who are currently anatomically and haemodynamically normal can be enrolled)
  4. Mother with HIV infection (unless the child has been proven to be not infected)
  5. Life expectancy < 6 months
  6. Known allergy to Ig products
  7. Acute respiratory or other acute infection or illness
  8. Previous reaction to IVIG, blood products, or other foreign proteins
  9. Receipt of lyophilised palivizumab, RSV-IVIG, or other RSV-specific monoclonal antibody, or any other polyclonal antibody (for example, hepatitis B IG, IVIG, VZIG) within 3 months prior to randomization
  10. Any previous receipt of MEDI-524
  11. Participation in other investigational drug product studies

InterventionsChildren received 15 mg/kg of liquid palivizumab, or 15 mg/kg of lyophilised palivizumab administered intramuscularly every 30 days for a total of 5 injections

OutcomesPrimary outcome: number and percentage of participants with immune reactivity

Children were followed for 240 to 300 days

Notes

NCT00240929

MethodsStudy design: phase II, randomized, double-blind, dose comparison, cross-over trial

Date of first enrolment: September 2002

Target sample size: 150

Recruitment status: completed in April 2003

Locations: 20 sites in the USA

Sponsor: MedImmune LLC

ParticipantsInclusion criteria:

  1. The child must have been born at less than or equal to 35 weeks gestation and be less than or equal to 6 months of age at the time of randomization (child must be randomized on or before their 6-month birthday)
  2. The child's parent or legal guardian must provide written informed consent
  3. The child must be able to complete the follow-up visits on study days 30 and 60 within the protocol specified windows (± 2 days)
  4. Parent/legal guardian of patient has available telephone access


Exclusion criteria:

  1. Hospitalised
  2. Birth hospitalization > 6 weeks duration
  3. Receiving mechanical ventilation at the time of study entry (including CPAP)
  4. Bronchopulmonary dysplasia (BPD), defined as history of prematurity and associated chronic lung disease with oxygen requirement for > 28 days
  5. Congenital heart disease (CHD) (children with medically or surgically corrected (closed) patent ductus arteriosus and no other CHD may be enrolled)
  6. Known renal impairment, hepatic dysfunction, chronic seizure disorder or immunodeficiency
  7. Any of the following laboratory findings in blood obtained within 7 days prior to study entry: BUN or creatinine > 1.5 the upper limit of normal for age, AST (SGOT) or ALT (SGPT) > 1.5 the upper limit of normal for age, haemoglobin < 9.0 gm/dL, white blood cell count < 4000 cells/mm3, platelet count < 110,000 cells/mm3
  8. Acute illness or progressive clinical disorder
  9. History of recent difficult venous access
  10. Active infection, including acute RSV infection
  11. Previous reaction to IVIG, blood products or other foreign proteins
  12. Received within the past 120 days or currently receiving IVIG, other immunoglobulin products or any investigational agents
  13. Have ever received palivizumab
  14. Currently participating in any investigational study
  15. Previously participated in any investigational study of RSV vaccines or monoclonal antibodies

InterventionsChildren received sequence A (single dose of the liquid formulation on study day 0 and a single dose of the lyophilised formulation on study day 30), or sequence B (single dose of the lyophilised formulation on study day 0 and single dose of the liquid formulation on study day 30)

OutcomesPrimary outcomes: adverse events and palivizumab concentrations in serum

Secondary outcomes: adverse events and serious adverse events

Children were followed for 30 days after each injection

Notes

NTR1023

MethodsStudy design: randomized, double-blind, placebo-controlled trial

Date of first enrolment: 1 October 2007

Target sample size: 452

Recruitment status: completed

Locations: sites in Netherlands

ParticipantsInclusion criteria:

  1. Gestational age 32 to 35 weeks


Exclusion criteria:

  1. Severe congenital anomaly
  2. Congenital heart disease
  3. Down syndrome

InterventionsChildren received monthly injection of placebo or palivizumab 15 mg/kg during the winter season

OutcomesPrimary outcome: number of wheezing days during the first year of life

Secondary outcomes: health-related quality of life at age 1, 3 and 6 years, and asthmatic symptoms at age 3 and 6 years measured by questionnaires

Notes

 
Comparison 1. Palivizumab versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Hospitalisation for RSV infection32831Risk Ratio (M-H, Fixed, 95% CI)0.49 [0.37, 0.64]

 2 All-cause mortality32831Risk Ratio (M-H, Fixed, 95% CI)0.69 [0.42, 1.15]

 3 Total RSV hospital days per 100 children22789Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Admission to ICU22789Risk Ratio (M-H, Fixed, 95% CI)0.50 [0.30, 0.81]

 5 Days in the ICU per 100 children22789Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Mechanical ventilation for RSV infection22789Risk Ratio (M-H, Random, 95% CI)1.10 [0.20, 6.09]

 7 Days of mechanical ventilation per 100 children22789Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Days of supplemental oxygen therapy per 100 children22789Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Number of children reporting any AE11287Risk Ratio (M-H, Fixed, 95% CI)0.99 [0.97, 1.01]

 10 Number of children reporting related AE32831Risk Ratio (M-H, Fixed, 95% CI)1.09 [0.85, 1.38]

 11 Number of children reporting any SAE11287Risk Ratio (M-H, Fixed, 95% CI)0.88 [0.80, 0.96]

 12 Number of children reporting related SAE11287Risk Ratio (M-H, Fixed, 95% CI)0.14 [0.01, 2.80]

 
Comparison 2. Palivizumab versus motavizumab

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Hospitalisation for RSV infection27870Risk Ratio (M-H, Fixed, 95% CI)1.36 [0.97, 1.90]

 2 RSV-specific outpatient MALRI23026Risk Ratio (M-H, Fixed, 95% CI)1.98 [1.25, 3.13]

 3 All-cause mortality48265Risk Ratio (M-H, Fixed, 95% CI)0.74 [0.38, 1.43]

 4 Total RSV hospital days per 100 children27870Mean Difference (IV, Fixed, 95% CI)24.95 [-21.59, 71.49]

 5 Admission to ICU27870Risk Ratio (M-H, Fixed, 95% CI)1.68 [0.89, 3.19]

 6 Days in the ICU per 100 children27870Mean Difference (IV, Fixed, 95% CI)21.34 [-13.69, 56.37]

 7 Mechanical ventilation for RSV infection27870Risk Ratio (M-H, Fixed, 95% CI)3.79 [1.26, 11.42]

 8 Days of mechanical ventilation per 100 children27870Mean Difference (IV, Fixed, 95% CI)16.06 [-16.60, 48.72]

 9 Supplemental oxygen therapy for RSV infection27870Risk Ratio (M-H, Fixed, 95% CI)1.49 [0.98, 2.26]

 10 Days of supplemental oxygen therapy per 100 children27870Mean Difference (IV, Fixed, 95% CI)28.42 [-13.64, 70.48]

 11 Number of children reporting any AE48238Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.99, 1.02]

 12 Number of children reporting related AE31625Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.73, 1.32]

 13 Number of children reporting any SAE48238Risk Ratio (M-H, Fixed, 95% CI)1.04 [0.96, 1.13]

 14 Number of children reporting related SAE31625Risk Ratio (M-H, Fixed, 95% CI)0.88 [0.32, 2.43]

 
Summary of findings for the main comparison. Palivizumab compared to placebo for high risk of severe respiratory syncytial virus infection

Palivizumab compared to placebo for high riskof severe respiratory syncytial virus infection

Patient or population: patients at high risk of severe respiratory syncytial virus infection
Settings: hospital
Intervention: palivizumab
Comparison: placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

PlaceboPalivizumab

Hospitalisation for RSV infectionStudy populationRR 0.49
(0.37 to 0.64)
2831
(3 studies)
⊕⊕⊕⊕
high

101 per 100050 per 1000
(37 to 65)

Moderate

100 per 100049 per 1000
(37 to 64)

All-cause mortalityStudy populationRR 0.69
(0.42 to 1.15)
2831
(3 studies)
⊕⊕⊕⊝
moderate1

28 per 100019 per 1000
(12 to 32)

Moderate

42 per 100029 per 1000
(18 to 48)

Total RSV hospital days per 100 childrenSee commentSee commentNot estimable2789
(2 studies)
⊕⊕⊕⊝
moderate2
Data on standard deviations missing; meta-analysis not possible.

Admission to ICUStudy populationRR 0.5
(0.3 to 0.81)
2789
(2 studies)
⊕⊕⊕⊕
high

34 per 100017 per 1000
(10 to 28)

Moderate

34 per 100017 per 1000
(10 to 28)

Mechanical ventilation for RSV infectionStudy populationRR 1.1
(0.2 to 6.09)
2789
(2 studies)
⊕⊝⊝⊝
very low1,3

13 per 100014 per 1000
(3 to 80)

Moderate

12 per 100013 per 1000
(2 to 73)

Supplemental oxygen therapy for RSV infectionStudy populationNot estimable0
(0)
See commentNumbers not reported in any of the three studies

See commentSee comment

Moderate


Number of children reporting any SAEStudy populationRR 0.88
(0.8 to 0.96)
1287
(1 study)
⊕⊕⊕⊕
high

631 per 1000555 per 1000
(505 to 606)

Moderate

631 per 1000555 per 1000
(505 to 606)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; ICU: intensive care unit; RR: risk ratio; RSV: respiratory syncytial virus; SAE: serious adverse event

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1No statistical significance in results and very wide 95% CIs around estimates of effect.
2Data on standard deviations missing in both studies.
3Substantial heterogeneity across the two studies; point estimates of effect on opposite sides.
 
Summary of findings 2. Palivizumab compared to motavizumab for high risk of severe respiratory syncytial virus infection

Palivizumab compared to motavizumab for high riskof severe respiratory syncytial virus infection

Patient or population: patients at high risk of severe respiratory syncytial virus infection
Settings: hospital
Intervention: palivizumab
Comparison: motavizumab

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

MotavizumabPalivizumab

Hospitalisation for RSV infectionStudy populationRR 1.36
(0.97 to 1.9)
7870
(2 studies)
⊕⊕⊕⊝
moderate1

15 per 100020 per 1000
(14 to 28)

Moderate

17 per 100023 per 1000
(16 to 32)

All-cause mortalityStudy populationRR 0.74
(0.38 to 1.43)
8265
(4 studies)
⊕⊕⊕⊝
moderate1

5 per 10004 per 1000
(2 to 7)

Moderate

15 per 100011 per 1000
(6 to 21)

Total RSV hospital days per 100 childrenThe mean total RSV hospital days per 100 children in the intervention groups was
24.95 higher
(21.59 lower to 71.49 higher)
7870
(2 studies)
⊕⊕⊝⊝
low2,3

Admission to ICUStudy populationRR 1.68
(0.89 to 3.19)
7870
(2 studies)
⊕⊕⊕⊝
moderate1

4 per 10006 per 1000
(3 to 12)

Moderate

6 per 100010 per 1000
(5 to 19)

Mechanical ventilation for RSV infectionStudy populationRR 3.79
(1.26 to 11.42)
7870
(2 studies)
⊕⊕⊕⊕
high

1 per 10004 per 1000
(1 to 12)

Moderate

2 per 10008 per 1000
(3 to 23)

Supplemental oxygen therapy for RSV infectionStudy populationRR 1.49
(0.98 to 2.26)
7870
(2 studies)
⊕⊕⊕⊝
moderate1

9 per 100014 per 1000
(9 to 21)

Moderate

12 per 100018 per 1000
(12 to 27)

Number of children reporting any SAEStudy populationRR 1.04
(0.96 to 1.13)
8238
(4 studies)
⊕⊕⊕⊕
high

191 per 1000199 per 1000
(183 to 216)

Moderate

119 per 1000124 per 1000
(114 to 134)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval;ICU: intensive care unit; RR: risk ratio; RSV : respiratory syncytial virus; SAE : serious adverse event

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1No statistical significance in results and very wide 95% CI around pooled estimate of effect.
2The 95% CI includes no effect and confidence limits are very wide.
3Data on standard deviations missing in Carbonell-Estrany 2010.
 
Table 1. Characteristics of included economic evaluations

Study IDCountryStudy designPopulationEconomic outcomesIntervention1 (doses)PerspectivePrice yearTime horizon

Bentley 2011UKCUAInfants with CLD, preterm infants < 29 wGA, 29 to 32 wGA, and 33 to 35 wGAICER

(per QALY)
PalivizumabPayer'sGBPLifetime

Chirico 2009ItalyCUA

CEA
Preterm infants born at < 33 wGA, and 33 to 35 wGA, with and without BPDICER

(per QALY and LYG)
Palivizumab (5 doses at 15 mg/kg)Payer's2007 EURLifetime

Chiroli 2005ItalyCEAChildren with haemodynamically significant CHDICER

(per LYG)
Palivizumab (5 doses at 15 mg/kg)Payer's2004 EUR1 year

ElHassan 2006USACUAPreterm infants born at 26 to 32 wGA without CLDICER

(per QALY)
Palivizumab (5 doses at 15 mg/kg)Societal2002 USD8 years

Embleton 2007UKCEAPreterm infants born at < 32 wGA without BPD and with BPDICER

(per hospitalization averted)
Palivizumab (5 doses at 15 mg/kg)Societal2005 GBP1 year

Garcia-Altes 2010SpainCEAPreterm children < 2 years old with and without CLD, children < 2 years old with CLD, and children < 5 years old with CHDICER

(per hospitalization avoided and LYG)
Palivizumab (3 doses at 15 mg/kg)Payer's2008 EUR1 year

Lifetime

Hampp 2011USACEAChildren < 2 years old with different combinations of risk factors (8 subgroups)ICER

(per hospitalization avoided)
Palivizumab (6 doses, 50 to 200 mg vials used)Payer's2010 USDNot stated

Harris 2011CanadaCEAChildren < 2 years old, born at 36 wGA, with haemodynamically significant CHDICER

(per 1 day of hospitalization prevented)
Palivizumab (4.5 doses at 15 mg/kg)Societal2007 CADNot stated

Hascoet 2008FranceCEAPreterm infants born at ≤ 32 wGA with BPD or CHD (2 subgroups)ICER

(per LYG and hospitalization averted)
Palivizumab (4.87 and 4.93 doses at 15 mg/kg)Societal

Payer's
2006 EURLifetime

Joffe 1999USACEAPreterm infants discharged within 12 months prior to RSV season (8 risk groups)ICER

(per hospitalization averted and LYG)
Palivizumab (4 doses at 15 mg/kg)Societal1995 USDNot stated

Kang 2009KoreaCEAChildren with CHDICER

(per LYG)
Palivizumab (5 doses)Payer's

Societal
KWLifetime

Lanctot 2008CanadaCUAPreterm infants born at 32 to 35 wGA without CLDICER

(per LYG and QALY)
Palivizumab (5.39 doses at 15 mg/kg)Payer's

Societal
2007 CADLifetime

Lazaro y de Mercado 2006SpainCEA

CUA
Preterm infants born at 32 to 35 wGA with 2 or more risk factorsICER

(per LYG and QALY)
Palivizumab (3.88 doses at 15 mg/kg)Societal

Payer's
2006 EURLifetime

Lazaro y de Mercado 2007SpainCEA

CUA
Preterm infants born at ≤ 35 wGA and 6 months of age or younger, or ≤ 24 months old and with BPD requiring treatmentICER

(per LYG and QALY)
Palivizumab (4.1 doses at 15 mg/kg)Societal

Payer's
2006 EURLifetime

Lofland 2000USACEAPreterm infants born at ≤ 35 wGA and children with BPDICER

(per hospitalization avoided)
Palivizumab (5 doses at 15 mg/kg)Payer's1999 USD1 year

Mayen-Herrera 2011MexicoCUAPreterm infants < 29 wGAICER

(per QALY)
Palivizumab (5 doses at 15 mg/kg)Payer'sMXNNot stated

Neovius 2011SwedenCUA

CEA
Preterm infants born at < 29 wGAICER

(per QALY and LYG)
Palivizumab (5 doses at 15 mg/kg)Societal2009 SEKLifetime

Nuijten 2007UKCEA

CUA
Preterm infants born at ≤ 35 wGA, children with BPD (≤ 2 years) and children with CHD (≤ 2 years)ICER

(per LYG and QALY)
Palivizumab (4.87 doses at 15 mg/kg)Societal

Payer's
2003 GBPLifetime

Nuijten 2009aNetherlandsCUA

CEA
Preterm infants, preterm children, children with BPD and children with CHDICER

(per QALY and LYG)
Palivizumab (4.87 and 4.93 doses at 15 mg/kg)Societal2006 EURLifetime

Nuijten 2009bGermanyCUA

CEA
Children with haemodynamically significant CHDICER

(per QALY and LYG)
Palivizumab (4.93 doses at 15 mg/kg)Societal

Payer's
2006 EURLifetime

Nuijten 2010SpainCEA

CUA
Children born at ≤ 32 wGA who were < 6 months old at the onset of RSV seasonICER

(per LYG and QALY)
Palivizumab (4.1 doses at 15 mg/kg)Societal

Payer's
2006 EURLifetime

Ravasio 2006ItalyCEA

CUA
Preterm infants < 33 wGA, and 33 to 35 wGA, with and without BPDICER

(per LYG and QALY)
Palivizumab (5 doses at 15 mg/kg)Payer's2005 EUR14 years

Raya Ortega 2006SpainCEAPreterm infants born at 32 to 35 wGAICER

(per hospitalization avoided)
Palivizumab (3.8 doses at 15 mg/kg)Payer's2006 EUR1 year

Resch 2008AustriaCEA

CUA
Preterm infants born at ≤ 35 wGA, children with BPD and children with CHDICER

(per LYG and QALY)
Palivizumab (4.87 doses at 15 mg/kg)Societal

Payer's
2006 EURLifetime

Resch 2012AustriaCEA

CUA
Preterm infants ≤ 36 wGA, children with BPD and children with CHDICER

(per LYG and QALY)
Palivizumab (3.98 doses at 15 mg/kg)Payer's

Societal
2010 EURLifetime

Rietveld 2010NetherlandsCEAPreterm infants ≤ 28 wGA, birth weight ≤ 2500 g, having BPD, aged 0 months at the beginning of season (October)Cost per hospitalization avertedPalivizumabSocietal2000 EUR1 year

Roeckl-Wiedmann 2003GermanyCEAPreterm infants of male gender born at ≤ 35 wGA, with siblings in day care, discharge between October and December, and with or without CLDCost per hospitalization avertedPalivizumab (4 to 5 doses at 15 mg/kg)SocietalEUR1 year

Salinas-Escudero 2012MexicoCEA

CUA
Preterm infants < 29 wGA or 29 to 32 wGAICER

(per LYG and QALY)
Palivizumab (4.1 doses at 15 mg/kg)Payer's2009 USD18 years

Smart 2010CanadaCEA

CUA
Preterm infants born at 32 to 35 wGAICER

(per LYG and QALY)
Palivizumab (5.39 doses at 15 mg/kg)Societal

Payer's
2010 CADLifetime

Tam 2009CanadaCEA

CUA
Infants < 1 year of age from Baffin IslandICER

(per LYG and QALY)
Palivizumab (5 doses at 15 mg/kg)Societal

Payer's
2007 CADLifetime

Vogel 2002New ZealandCEAPreterm infants born at < 32 wGACost per hospitalization avertedPalivizumab (3 doses at 15 mg/kg)Societal2000 NZDNot stated

Wang 2011UKCUAPreterm infants born at ≤ 35 wGA or children with CLD and CHD; 4 subgroup analyses: CLD, CLD/CHD, acyanotic CHD, and cyanotic CHDICER

(per QALY)
Palivizumab (5 doses at 15 mg/kg)Payer's2006 GBPLifetime

Weiner 2012USACUAPreterm infants < 32 wGA and ≤ 6 months of age, without CLD or CHDICER

(per QALY)
Palivizumab (≤ 5 doses at 15 mg/kg, depending on month of birth)Societal2010 USDLifetime

Yount 2004USACUA

CEA
Children with CHD ≤ 2 years oldICER

(per LYG and QALY)
Palivizumab (5 doses at 15 mg/kg)Societal

Payer's
2002 USDLifetime

 BPD = bronchopulmonary dysplasia
CAD = Canadian dollar
CEA = cost-effectiveness analysis
CHD = congenital heart disease
CLD = chronic lung disease
CUA = cost-utility analysis
EUR = Euro
GBP = Great British pound
ICER = incremental cost-effectiveness ratio
KW = Korean won
LYG = life-year gained
MXN = Mexican peso
NZD = New Zealand dollar
QALY = quality-adjusted life-year
RSV = respiratory syncytial virus
SEK = Swedish krona
UK = United Kingdom
USA = United States of America
USD = United States dollar
wGA = weeks of gestational age
1Palivizumab prophylaxis was compared to no prophylaxis in all included economic evaluations.
 
Table 2. Economic impact of immunoprophylaxis given at neonatal period or within the first 6 months of life

Study IDFunded by industryIncremental effectivenessIncremental costDiscount rate (%)

Price year
ICER reportedICER present value at 2011 EUR

Infants born at35 weeks of gestation without other comorbidity

Payer's perspective

Chirico 2009Yes0.088 LYG

0.159 QALY
EUR 1376.503%

2007 EUR
Preterms < 33 wGA:

EUR 17,885.86/LYG

EUR 9380.00/QALY

Preterms 33 to 35 wGA:

EUR 28,417.08/LYG

EUR 14,937.32/QALY
Preterms < 33 wGA:

EUR 19,433.61/LYG         

EUR 10,191.70/QALY

Preterms 33 to 35 wGA:

EUR 30,876.15/LYG         

EUR 16,229.92/QALY

Hampp 2011No3.29% absolute risk reductionAny studied indication:

USD 4805
NA

2010 USD
USD 302,103/hosp. avertedEUR 252,885.00/hosp. averted

Lanctot 2008Yes0.137 LYG

0.198 QALY
Direct costs including asthma:

CAD 4140
5%

2007 CAD
Direct costs including asthma:

CAD 30,230/LYG

CAD 20,924/QALY
Direct costs including asthma:

EUR 22,738.62/LYG      

EUR 15,738.76/QALY

Nuijten 2007Yes0.14 LYG

0.19 QALY
GBP 28583.5%

2003 GBP
GBP 20,344/LYG

GBP 14,883/QALY
EUR 35,724.66/LYG

EUR 26,134.98/QALY

Nuijten 2010Yes-0.33 LYL

0.49 QALY
Direct costs:

EUR 6321

Direct costs with sequelae:

EUR 3205
3%

2006 EUR
Direct costs:

EUR 18,872/LYL

EUR 12,814/QALY

Direct costs with sequelae:

EUR 9570/LYL

EUR 6498/QALY
Direct costs:

EUR 21,147.66/LYL

EUR 14,359.16/QALY

Direct costs with sequelae:

EUR 10,723.99/LYL

EUR 7281.55/QALY 

Ravasio 2006YesPreterms < 33 wGA:

0.080 LYG

0.150 QALY

Preterms 33 to 35 wGA:

0.080 LYG

0.151 QALY
Preterms < 33 wGA:

EUR 1873.80

Preterms 33 to 35 wGA:

EUR 2834.99
3%

2005 EUR
Preterms < 33 wGA:

EUR 23,413.52/LYG

EUR 12,452.72/QALY

Preterms 33 to 35 wGA:

EUR 35,255.90/LYG

EUR 18,790.96/QALY
Preterms < 33 wGA:

EUR 26,439.11/LYG

EUR 14,061.91/QALY

Preterms 33 to 35 wGA:

EUR 39,811.81/LYG

EUR 21,219.20/QALY

Raya Ortega 2006NoHospitalisation avoided:

42 cases
EUR 2,860,367NA

2006 EUR
EUR 68,104/hosp. avoidedEUR 76,316.25/hosp. avoided

Resch 2008Yes0.10 LYG

0.14 QALY
Direct costs without asthma:

EUR 2955
5%

2006 EUR
Direct costs without asthma:

EUR 29,558/LYG

EUR 20,704/QALY
Direct costs without asthma:

EUR 32,938.16/LYG

EUR 23,071.65/QALY

Resch 2012YesPreterms ≤ 36 wGA:

0.09 LYG

0.13 QALY
Direct costs without wheezing:

EUR  3146
5%

2010 EUR
Direct costs without wheezing:

EUR 34,956/LYG

EUR 26,212/QALY
Direct costs without wheezing:

EUR 36,097.98/LYG

EUR 27,068.32/QALY

Salinas-Escudero 2012YesPreterms < 29 wGA and 29 to 32 wGA:

0.12 LYG

0.16 QALY
Preterms < 29 wGA:

USD 2871

Preterms 29 to 32 wGA:

USD 3400
3%

2009 USD
Preterms < 29 wGA:

USD 25,029/LYG

USD 17,532/QALY

Preterms 29 to 32 wGA:

USD 29,637/LYG

USD 20,760/QALY
Preterms < 29 wGA:

EUR 19,425.36/LYG

EUR 13,606.84/QALY

Preterms 29 to 32 wGA:

EUR 23,001.70/LYG

EUR 16,112.13/QALY

Smart 2010No0.137 LYG

0.198 QALY

(from Lanctot 2008
Not stated5%

2010 CAD
Direct costs including asthma:

CAD 20,814/QALY

Direct costs without asthma:

CAD 31,360/QALY
Direct costs including asthma:    

EUR 16,981.12/QALY

Direct costs without asthma:

EUR 25,585.08/QALY

Wang 2011No0.0072 QALYGBP 33153.5%

2006 GBP
Range:

GBP 78,000/QALY to

GBP 965,000/QALY
Range:

EUR 133,477.60/QALY to

EUR 1,651,357.46/QALY

Societal perspective

ElHassan 2006NoRange (min to max):

0.0018 QALY (32 wGA) to

0.0060 QALY (26 wGA)
Preterms 29 to 30 wGA:

USD 2449

Preterms 32 wGA:

USD 6330
3%

2002 USD
Preterms 29 to 30 wGA:

USD 675,780/QALY

Preterms 32 wGA:

USD 1,855,000/QALY
Preterms 29 to 30 wGA:

EUR 894,362.54/QALY

Preterms 32 wGA:

EUR 2,455,003.86/QALY

Embleton 2007NoNot statedPreterms < 32 wGA:

GBP 2550
NA

2005 GBP
Preterms < 32 wGA:

GBP 40,400/hosp. averted
Preterms < 32 wGA:      

EUR 72,780.17/hosp. averted

Lanctot 2008Yes0.137 LYG

0.198 QALY
Direct and indirect including asthma:

CAD 2578
5%

2007 CAD
Direct and indirect including asthma:

CAD 18,825/LYG

CAD 13,029/QALY
Direct and indirect including asthma:

EUR 14,159.92/LYG     

EUR 9800.25/QALY

Neovius 2011Yes0.102 QALY

0.073 LYG
SEK 20,0203%

2009 SEK
SEK 275,907/LYG

SEK 195,420/QALY
EUR 26,448.33/LYG

EUR 18,732.88/QALY

Nuijten 2010Yes-0.33 LYL

0.49 QALY
Indirect costs:

- EUR 3601

Total costs:

- EUR 396
3%

2006 EUR
Total costs:

Dominant
Total (direct and indirect) costs:

Dominant

Roeckl-Wiedmann 2003YesHospitalisation averted:

125 cases
EUR 3,161,000NA

2002 EUR
EUR 25,288/hosp. avertedEUR 29,199.27/hosp. averted

Vogel 2002YesHospitalisation averted:

29 infants
NZD 1,090,000NA

2000 NZD
NZD 37,000/hosp. avertedEUR 24,617.27/hosp. averted

Weiner 2012YesPreterms < 32 wGA:

0.046 QALY
Total costs:

 - USD 2339
3%

2010 USD
DominantDominant

Infants with bronchopulmonary dysplasia (BPD) or chronic lung disease (CLD)

Payer's perspective

Chirico 2009Yes0.088 LYG

0.159 QALY
EUR 1376.503%

2007 EUR
EUR 4332.29/LYG

EUR 2731.81/QALY
EUR 4707.18/LYG

EUR 2968.21/QALY

Lofland 2000Yes5% lower incidence of hospitalizationNot statedNA

1999 USD
USD 79,706/hosp. avertedEUR 104,456.40/hosp. averted

Ravasio 2006Yes0.122 LYG

0.231 QALY
EUR 677.363%

2005 EUR
EUR 5537.03/LYG

EUR 2937.84/QALY
EUR 6252.55/LYG

EUR 3317.48/QALY

Wang 2011No0.052 QALYGBP 33153.5%

2006 GBP
Range:

GBP 10,000/QALY to

GBP 66,000/QALY
Range:

EUR 17,112.51/QALY to

EUR 112,942.58/QALY

Societal perspective

Embleton 2007NoNot statedGBP 2663NA

2005 GBP
GBP 54,800/hosp. avertedEUR 98,721.62/hosp. averted

Hascoet 2008Yes0.18 LYG

Hospitalisations: not clear
EUR 49053%

2006 EUR
EUR 27,255/LYGEUR 29,511.31/LYG

Nuijten 2009aYes0.42 QALY

0.37 LYG
Direct costs including asthma:

EUR 5369

Direct and indirect including asthma:

EUR 3007
NA

2006 EUR
Direct costs including asthma:

EUR 12,728/QALY

EUR 14,701/LYG

Direct and indirect including asthma:

EUR 7130/QALY
Direct costs including asthma:

EUR 13,901.85/QALY

EUR 16,056.81/LYG

Direct and indirect including asthma:

EUR 7787.57/QALY

Rietveld 2010NoHospitalisation risk difference:

0.1 to 4.2
Range:

EUR 550 to EUR 955
NA

2000 EUR
Range:

EUR 13,190/hosp. averted to

EUR 833,695/hosp. averted
Range:

EUR 16,481.18/hosp. averted to

EUR 1,041,719.41/hosp. averted

Roeckl-Wiedmann 2003YesHospitalisation averted:

296 cases
EUR 1,965,000NA

2002 EUR
EUR 6639/hosp. avertedEUR 7665.85/hosp. averted

Infants with congenital heart disease (CHD)

Payer's perspective

Wang 2011NoAcyanotic CHD:

0.0670 QALY

Cyanotic CHD:

0.0226 QALY
Acyanotic CHD:

GBP 3285

Cyanotic CHD:

3609
3.5%

2006 GBP
Acyanotic CHD (range):

GBP 100,000/QALY to

GBP 266,000/QALY

Cyanotic CHD (range):

GBP 230,000/QALY to

GBP 596,000/QALY
Acyanotic CHD (range):

EUR 171,125.13/QALY to

EUR 455,192.83/QALY

Cyanotic CHD (range):

EUR 393,587.79/QALY to

EUR 1,019,905.75/QALY

Societal perspective

Hascoet 2008Yes0.26 LYG

Hospitalisations: not clear
EUR 54053%

2006 EUR
EUR 20,788/LYG

Hospitalisations: not clear
EUR 22,508.93/LYG

Nuijten 2009aYes1.39 QALY

1.36 LYG
Direct costs including asthma:

EUR 5926

Direct and indirect including asthma:

EUR 2670
NA

2006 EUR
Direct costs including asthma:

EUR 4256/QALY

EUR 4353/LYG

Direct and indirect including asthma:

Dominant
Direct costs including asthma:

EUR 4648.51/QALY

EUR 4754.46/LYG

Direct and indirect including asthma:

Dominant

 CAD = Canadian dollar
EUR = Euro
ICER = incremental cost-effectiveness ratio
GBP = Great British pound
hosp. = hospitalization
LYL = life-year lost
LYG = life-year gained
NA = not applied
NZD = New Zealand dollar
QALY = quality-adjusted life-year
SEK = Swedish krona
wGA = weeks of gestational age
USD = United States dollar
 
Table 3. Economic impact of immunoprophylaxis given to children aged 6 months and older

Study IDFunded by industryIncremental effectivenessIncremental costDiscount rate (%)

Price year
ICER reportedICER present value at 2011 EUR

Children born at35 weeks of gestation without other comorbidity

Payer's perspective

Tam 2009YesChildren living in rural and urban areas (all areas):

0.13 QALY

Children living in high-risk areas:

0.36 QALY
Direct costs:

All areas: CAD 5057

High-risk areas: CAD 119
5%

2007 CAD
Direct costs:

All areas:

CAD 39,435/QALY

High-risk areas:

CAD 334/QALY
Direct costs:

All areas:

EUR 29,662.50/QALY

High-risk areas:

EUR 251.23/QALY

Wang 2011No0.0072 QALYGBP 32633.5%

2006 GBP
Range:

GBP 383,000/QALY to

GBP 54,436,000/QALY
Range:

EUR 655,409.23/QALY to

EUR 93,153,673.29/QALY

Societal perspective

Tam 2009YesChildren living in rural and urban areas (all areas):

0.13 QALY

Children living in high-risk areas:

0.36 QALY
Direct and indirect costs:

All areas: CAD 4753

High-risk areas: - CAD 730
5%

2007 CAD
Direct and indirect costs:

All areas:

CAD 37,070/QALY

High-risk areas:

Dominant
Direct and indirect costs:

All areas:

EUR 27,883.58/QALY

High-risk areas:

Dominant

Children with congenital heart disease (CHD)

Payer's perspective

Chiroli 2005Yes0.5 LYGEUR 3394.16NA

2004 EUR
EUR 7186/LYGEUR 8276.82/LYG

Hampp 2011No1.65% absolute risk reductionAny studied indication:

USD 4805
NA

2010 USD
USD 823,868/hosp. avertedEUR 689,645.11/hosp. averted

Nuijten 2007YesCyanotic CHD:

0.25 LYG

0.26 QALY

Acyanotic CHD:

0.74 LYG

0.78 QALY
Cyanotic CHD:

GBP 3904

Acyanotic CHD:

GBP 2733
3.5%

2003 GBP
Cyanotic CHD:

GBP 15,575/LYG

GBP 14,816/QALY

Acyanotic CHD:

GBP 3688/LYG

GBP 3512/QALY
Cyanotic CHD:

EUR 27,350.15/LYG

EUR 26,017.33/QALY

Acyanotic CHD:

EUR 6476.24/LYG

EUR 6167.17/QALY

Nuijten 2009bYes0.38 QALY

0.36 LYG
Payer's perspective:

EUR 6364
5%

2006 EUR
Payer's perspective:

EUR 16,673/QALY

EUR 17,700/LYG
Payer's perspective:

EUR 18,166.72/QALY

EUR 19,285.73/LYG

Resch 2008Yes0.36 LYG

0.38 QALY
Direct costs without asthma:

EUR 4349

Direct costs including asthma:

EUR 3724
5%

2006 EUR
Direct costs without asthma:

EUR 12,091/LYG

EUR 11,390/QALY

Direct costs including asthma:

EUR 10,355/LYG

EUR 9754/QALY
Direct costs without asthma:

EUR 13,473.69/LYG

EUR 12,692.53/QALY

Direct costs including asthma:

EUR 11,539.17/LYG

EUR 10,869.44/QALY

Resch 2012Yes0.36 LYG

0.38 QALY
Direct costs without wheezing:

EUR 3224
5%

2010 EUR
Direct costs without wheezing:

EUR 8956/LYG

EUR 8484/QALY
Direct costs without wheezing:

EUR 9248.58/LYG

EUR 8761.16/QALY

Wang 2011NoAcyanotic CHD:

0.0670 QALY

Cyanotic CHD:

0.0226 QALY
Acyanotic CHD:

GBP 3285

Cyanotic CHD:

GBP 3609
3.5%

2006 GBP
Acyanotic CHD (range):

GBP 523,000/QALY to

GBP 14,545,000/QALY

Cyanotic CHD (range):

GBP 1,127,000/QALY to

GBP 30,203,000/QALY
Acyanotic CHD (range):

EUR 894,984.41/QALY to

EUR 24,890,149.50/QALY

Cyanotic CHD (range):

EUR 1,928,580.16/QALY to

EUR 51,684,921.64/QALY

Yount 2004No203.33 LYG

QALY: not stated
USD 20,415,7533%

2002 USD
USD 100,338/LYG

USD 114,337/QALY
EUR 132,792.55/LYG   

EUR 151,319.56/QALY

Societal perspective

Harris 2011No1 day of hospitalization avertedCAD 8292NA

2007 CAD
CAD 15,514/day of hosp. avertedEUR 11,669.43/day of hosp. averted

Nuijten 2009bYes0.38 QALY

0.36 LYG
Societal perspective:

EUR 3637
5%

2006 EUR
Societal perspective:

EUR 9529/QALY

EUR 10,116/LYG
Societal perspective:

EUR 10,382.69/QALY

EUR 11,022.28/LYG

Children with bronchopulmonary dysplasia (BPD) or chronic lung disease (CLD)

Payer's perspective

Hampp 2011No1.03% absolute risk reductionAny studied indication:

USD 4805
NA

2010 USD
USD 1,322,422/hosp. avertedEUR 1,106,975.71/hosp. averted

Nuijten 2007Yes0.11 LYG

0.15 QALY
GBP 31223.5%

2003 GBP
GBP 28,569/LYG

GBP 20,953/QALY
EUR 50,168.00/LYG

EUR 36,794.08/QALY

Resch 2008Yes0.08 LYG

0.11 QALY
Direct costs without asthma:

EUR 3527
5%

2006 EUR
Direct costs without asthma:

EUR 45,369/LYG

EUR 31,867/QALY
Direct costs without asthma:

EUR 50,557.26/LYG

EUR 35,511.21/QALY

Resch 2012Yes0.09 LYG

0.13 QALY
Direct costs without wheezing:

EUR 3205
5%

2010 EUR
Direct costs without wheezing:

EUR 35,611/LYG

EUR 24,654/QALY
Direct costs without wheezing:

EUR 36,774.38/LYG

EUR 25,459.42/QALY

Wang 2011No0.052 QALYGBP 33153.5%

2006 GBP
Range:

GBP 29,000/QALY to

GBP 3,456,000/QALY
Range:

EUR 49,626.29/QALY to

EUR 5,914,084.34/QALY

 CAD = Canadian dollar
CHD = congenital heart disease
EUR = Euro
GBP = Great British pound
hosp. = hospitalization
ICER = incremental cost-effectiveness ratio
hosp. = hospitalization
LYG = life-year gained
NA = not applied
QALY = quality-adjusted life-year
USD = United States dollar
 
Table 4. Economic impact of immunoprophylaxis given to high-risk infants and children up to five years of age (born preterm, with or without bronchopulmonary dysplasia, or with congenital heart disease)

Study IDFunded by industryIncremental effectivenessIncremental costDiscount rate (%)

Price year
ICER reportedICER present value at 2011 EUR

Payer's perspective

Garcia-Altes 2010NoHospitalisation averted:

0.058

LYG: not stated
Not stated3%

2008 EUR
Range:

EUR 17,337/hosp. averted to

EUR 68,380/hosp. averted

EUR 166,721/LYG to

EUR 147,656,881/LYG
Range:

EUR 18,160.68/hosp. averted to

EUR 71,628.73/hosp. averted

EUR 174,641.91/LYG to

EUR 154,672,059.42/LYG

Societal perspective

Joffe 1999NoNumber needed to treat:

7.4 to 152
USD 1618.14NA for hosp. averted

3% for LYG

1995 USD
Range:

USD 12,000/hosp. averted to

USD 420,000/hosp. averted

USD 33,000/LYG to

USD 1,200,000/LYG
Exchange rate to Euros not available for 1995

Lazaro y de Mercado 2007Not clear0.13 LYG

0.18 QALY
Direct and indirect costs:

EUR 726
3.5%

2006 EUR
EUR 5583/LYG

EUR 4095/QALY
EUR 6256.22/LYG

EUR 4588.79/QALY

 EUR = Euro
hosp. = hospitalization
ICER = incremental cost-effectiveness ratio
LYG = life-year gained
NA = not applied
QALY = quality-adjusted life-year
USD = United States dollar