0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Article |

Cost-effectiveness Analysis of Palivizumab in Premature Infants Without Chronic Lung Disease FREE

Nahed O. ElHassan; Melony E. S. Sorbero, MD, MPH; Caroline B. Hall, PhD, MS, MPH; Timothy P. Stevens, MD; Andrew W. Dick, MD, MPH
[+] Author Affiliations

Author Affiliations: Division of Neonatology, Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock (Dr ElHassan); RAND Corp, Pittsburgh, Pa (Drs Sorbero and Dick); and Divisions of Infectious Disease (Dr Hall) and Neonatology (Dr Stevens), Department of Pediatrics, Strong Children's Research Center, Rochester, NY.


Arch Pediatr Adolesc Med. 2006;160(10):1070-1076. doi:10.1001/archpedi.160.10.1070.
Text Size: A A A
Published online

Objectives  To evaluate the cost-effectiveness of palivizumab as respiratory syncytial virus prophylaxis in premature infants without chronic lung disease and to evaluate the impact on cost-effectiveness of a potential reduction in risk of asthma following respiratory syncytial virus infection among infants receiving palivizumab.

Design  Two decision analytic models were designed, one with and the other without accounting for increased risk of asthma following respiratory syncytial virus infection.

Setting  A hypothetical community or university hospital.

Participants  Hypothetical cohorts of infants without chronic lung disease born at 26 to 32 weeks' gestation.

Interventions  Palivizumab prophylaxis vs no prophylaxis.

Main Outcome Measures  Expected costs and incremental cost-effectiveness ratio expressed as cost per quality-adjusted life-year.

Results  The expected costs were higher for palivizumab prophylaxis as compared with no prophylaxis. The incremental cost-effectiveness ratios were high for all gestations and are not considered cost-effective by today's standards (<$200 000 per quality-adjusted life-year). Both models were sensitive to variation in the cost of palivizumab. The model that included asthma was sensitive to variation in quality of life for children with asthma. In instances where asthma was considered severe with profound worsening in quality of life compared with life without asthma, some infants had an incremental cost per quality-adjusted life-year that was less than $200 000.

Conclusions  Our model supports implementing more restrictive guidelines for palivizumab prophylaxis. Palivizumab was cost-effective for some infants in an analysis that accounted for increased risk of severe asthma following respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is the most important pathogen in lower respiratory tract infection in infants and young children.1 By age 2 years, approximately 80% to 90% of children experience at least 1 episode of RSV infection. Although the majority of RSV infections resolve uneventfully in otherwise healthy children, high-risk populations such as premature infants may develop severe and sometimes fatal lower respiratory tract infections.1 Long-term complications of RSV infections are unclear. Although there is an established association between RSV infection and recurrent wheezing, a cause-effect relationship has not been demonstrated.24 Palivizumab (Synagis; MedImmune, Inc, Gaithersburg, Md), a humanized monoclonal antibody, is effective in reducing the risk of hospitalization secondary to RSV infection.5 The American Academy of Pediatrics (AAP), Elk Grove Village, Ill, developed guidelines6 for the use of palivizumab for RSV prophylaxis in 1998 and revised these guidelines in 2003.7 In part owing to cost concerns, the AAP policy recommended the use of palivizumab only in infants at highest risk for severe RSV infection. A number of economic analyses of RSV intravenous immunoglobulin and palivizumab have been performed in the United States and in other countries.820 Multiple economic analyses of palivizumab performed outside of the United States concluded that the use of the prophylaxis is not cost-effective,1719 but analyses performed in the United States have generated mixed results.814,16,20 A systematic review15 of economic analyses of RSV intravenous immunoglobulin and palivizumab found a significant difference in results by funding source (P = .002); all of the 4 studies with pharmaceutical funding reported that the prophylaxis was either cost-effective or cost-saving for a high-risk infant population whereas none of the 8 studies without pharmaceutical funding reported similar findings.15 None of these analyses considered potential long-term sequelae, ie, the possible increased risk of asthma following RSV infection in infancy and its impact on quality of life.21

The objectives of this study were to evaluate the cost-effectiveness of palivizumab as RSV prophylaxis in premature infants without chronic lung disease and to evaluate the impact on cost-effectiveness of a potential reduction in risk of asthma following RSV infection among infants receiving palivizumab. To our knowledge, our model is the first to study the cost-effectiveness of RSV prophylaxis by specific gestational age, to evaluate the implication of the possible increased risk of asthma with RSV infection, and to integrate measures of morbidity (quality-adjusted life-years).

MODEL SETTING AND ASSUMPTIONS

This study was an economic evaluation using decision analytic modeling. The DATA 3.5 for Healthcare software package (TreeAge Software, Williamstown, Mass) was used to combine data from secondary data sources, including publications and government documents, and to simulate costs and outcomes for the intervention.

A hypothetical cohort of premature infants born at 26 to 32 weeks' gestation was assumed to be discharged from the neonatal intensive care unit at 36 weeks' postconceptional age based on unpublished data from the University of Rochester Medical Center, Rochester, NY (T.P.S., 2003). We assumed that an infant had an equal probability of being discharged from the neonatal intensive care unit at different months of the year. Each infant's weight at the time of discharge was assumed to be 2000 g (10% of the growth curve for an infant at 36 weeks' postconceptional age).22 Because the association between RSV infection and asthma remains unclear, we completed 2 sets of analyses, one with and the other without asthma included in the models. The models including asthma used time-dependent Markov processes to allow the risk of asthma to vary with the age of the cohort.23 Analyses were conducted from the societal perspective24 and therefore included all of the relevant costs and outcomes regardless of to whom they accrued. A separate decision analytic model was constructed for each gestational age. Sensitivity analyses were performed to test the robustness of the results.

The model combined published data on the risk of RSV hospitalization by gestational age, the seasonal pattern of RSV hospitalization, the efficacy of palivizumab in reducing the risk of RSV hospitalization, national costs of RSV hospitalizations, costs of palivizumab injection visits, costs of emergency department visits, drug costs, and costs of work hours missed by parents for visits and hospitalization. In the base-case analysis with asthma, the model also included the risk of asthma, reduction in quality of life due to asthma, and national estimates of the cost of asthma for a child with the disease. There is no current evidence that palivizumab reduces the probability of death in infants; therefore, we did not include risk of death secondary to RSV hospitalization in the models.6,7

Analyses without asthma had a time horizon of 1 year's postconception age because palivizumab has not been shown to affect other long-term health outcomes; these were cost-benefit analyses. Cost-effectiveness analyses were performed on the models that included asthma. The model with asthma had a time horizon of 8 years in the base-case analysis and was varied up to 10 years in sensitivity analyses to reflect the length of increased risk of asthma following RSV bronchiolitis.2527 Future benefits and costs were discounted at 3% annually. The use of RSV prophylaxis was evaluated using the incremental cost-effectiveness ratio (ICER), defined as the additional costs associated with the use of palivizumab divided by the additional quality-adjusted life-years associated with its use. Based on recent recommendations,28 we considered an ICER of less than $200 000 per quality-adjusted life-year to be cost-effective.

NONCOST PARAMETERS

The values of noncost parameters included in the model are shown in Table 1. The table shows base-case values and ranges of values used for sensitivity analyses.

Table Graphic Jump LocationTable 1. Point Estimates for Noncost Variables
Probability of RSV Hospitalization by Gestational Age

We calculated the probability of RSV hospitalization by specific gestational age and month of neonatal intensive care unit discharge29,30 by using gestational age–specific RSV hospitalization rates and the seasonal pattern of respiratory hospitalization. We used gestational age–specific risks (ie, at ≤26, 27-28, 29-30, and 31-32 weeks' gestation) of RSV hospitalization as reported by Stevens et al30 in the only study to provide detailed gestational age–specific risks. We applied a monthly adjustment factor based on the seasonal relationship between hospitalization owing to respiratory illness and month of neonatal intensive care unit discharge reported by Cunningham et al.29 The probability of RSV hospitalization was varied across the range of risk reported in the literature5,2935 for premature infants in sensitivity analyses.

We calculated the gestational age–specific estimates of the efficacy of palivizumab in reducing risk of RSV hospitalization among infants without chronic lung disease using data from the IMpact-RSV study,5 the only randomized trial of palivizumab. The probability of RSV hospitalization for the no-prophylaxis group was calculated as the probability of hospitalization without prophylaxis multiplied by (1 − efficacy). In the sensitivity analysis, we allowed the efficacy of palivizumab to improve to 95% to determine whether prophylaxis would be cost-effective with very high efficacy rates.

Length of RSV Hospitalization

From reported values, an average length of stay of 6.8 days30,34,36,37 for RSV hospitalization was included in our base-case analysis. The entire range of values reported in the literature was considered in sensitivity analyses.

Probability of Asthma and Length of Increased Risk of Asthma following RSV Bronchiolitis

We based our estimates of the increased risk of asthma on data by Sigurs et al26,27 in the only study to prospectively evaluate the risk of asthma among children who had been hospitalized with RSV bronchiolitis as infants relative to controls (data shown in Table 1). A linear extrapolation was performed to calculate the risk of asthma at ages not included in these articles by Sigurs and colleagues. In the sensitivity analysis, we considered the range of values of increased risk of asthma following RSV bronchiolitis reported in retrospective studies.3846

Quality of Life With and Without Asthma

Quality of life data have been increasingly used to evaluate the benefits of health care options. In this approach, patients' preferences for a condition are multiplied by the duration spent with the condition to generate a quality-adjusted life-year. Quality-of-life estimates for children with symptomatic asthma (0.89)47 and the absolute difference in quality of life with and without asthma (0.03)48 were obtained from articles and measured using the Health Utility Index. In sensitivity analyses, the quality of life with asthma was varied by 1 SD.47

MODEL COSTS

The costs included in the model are shown in Table 2. Costs are reported in 2002 US dollars and estimates were updated with relevant portions of the Consumer Price Index51,52,54 as necessary.

Table Graphic Jump LocationTable 2. Point Estimates of Cost Variables
Drug Costs

The current recommended palivizumab dosage is 15-mg/kg intramuscular injections once per month for a total of 5 doses during the RSV season, which is November through March. The costs of 50-mg and 100-mg vials of palivizumab were derived from published wholesale prices.49 Once reconstituted, the shelf life of palivizumab is estimated at 6 hours21; hence, drug wastage was accounted for in the base-case analysis.

We predicted the weight that a 2000-g infant would attain at each recommended palivizumab injection visit using standard growth curves22 to calculate the total amount and the cost of the drug. Assumptions about drug wastage and costs were varied in sensitivity analyses.

Costs of Drug Injection

Palivizumab injections were assumed to take place during office visits coded as “established patient, intermediate,” and the cost of these visits was assigned the lowest reimbursement rate by local private insurers.50 The total administration costs were obtained by multiplying the cost of each visit by the number of recommended palivizumab injections, calculated as described in our previous article.56

Hospitalization Costs

Stang et al16 estimated the cost of an infant hospitalized with RSV infection using a National Inpatient Sample. The 95% confidence interval ($8000-$10 520) of the estimate was used in our sensitivity analyses.

Emergency Department Visit Costs

We assumed that infants hospitalized with RSV infection were admitted through the emergency department with a visit coded as being of moderate severity. The cost of an emergency department visit of moderate severity was obtained from local estimates in Rochester, NY. Medicare reimbursement rates were not used owing to this being a pediatric population.

Nonmedical Costs

We assumed that 1 parent lost an average of 8 hours of work per day during RSV hospitalization as well an average of 3 hours of work per day for palivizumab injection visits and emergency department visits. The national costs of time lost from work were based on US Bureau of Labor Statistics data.53

Costs of Asthma

Estimates of per capita costs of asthma for persons younger than 18 years were taken from the study by Weiss et al.55 These estimates included the costs of inpatient and outpatient hospital services, emergency department visits, office-based physician services, and pharmaceuticals as well as time lost from work.

TARGETED USE POLICY

In addition to the 2 scenarios and 1-way sensitivity analyses described earlier, we generated estimates for a targeted best-case scenario for the use of palivizumab prophylaxis. The current AAP recommendations for the use of palivizumab result in treating many infants who are at low risk for RSV hospitalization, leading us to conduct additional simulations modifying the current recommendations to seek more cost-effective alternatives using the following parameters: no drug wastage; application of prophylaxis restricted to only the infant's first RSV season; younger chronological age cutoffs, ie, those infants assumed to be discharged from September through March; and infants born at 27 weeks' gestation or earlier if discharged before the RSV season and infants born at 30 weeks' gestation or earlier if discharged during the RSV season.

COST-BENEFIT ANALYSIS ASSUMING NO CAUSAL RELATIONSHIP WITH ASTHMA

The results for the different gestational ages are summarized in Table 3. The results for infants born at 29 and 30 weeks' gestation are reported together since the estimates of the cost and probabilities are identical for infants born at these gestational ages.

Table Graphic Jump LocationTable 3. Expected and Incremental Costs per Quality-Adjusted Life-Year for Gestational Ages

Irrespective of the gestational age at birth, we found that the added costs of prophylaxis are greater than the savings from reduced hospitalizations. The expected costs for the prophylaxis group are greatest for infants born at 28 weeks' gestation ($8000 in the model with no increased risk of asthma). Thereafter, the expected costs decrease markedly.

COST-EFFECTIVENESS ANALYSIS ASSUMING A CAUSAL RELATIONSHIP WITH ASTHMA

The ICERs for the different gestational ages are summarized in Table 3. The ICERs are higher than $200 000 per quality-adjusted life-year for all gestations and reach a maximum of $1 855 000 per quality-adjusted life-year for infants born at 32 weeks' gestation when palivizumab is used in accordance with AAP recommendations.

SENSITIVITY ANALYSES

The results of the most significant sensitivity analyses are summarized in Table 4 for the models without increased risk of asthma and in Table 5 for the models with increased risk of asthma. These analyses were shown for 5 different gestational ages to display the trend of varying a specific quantity in the model on ICERs and incremental expected costs. In the model without asthma, the use of RSV prophylaxis did not result in cost savings for any of the sensitivity analyses performed. The model that included asthma was sensitive to varying the quality of life for children with asthma and costs of palivizumab vials. When the quality of life with asthma was reduced to 0.8, the ICER was approximately $200 000 per quality-adjusted life-year for infants born at 26 and 29 to 30 weeks' gestation (Table 5). Reductions in palivizumab costs to 25% of their current values result in an ICER less than $100 000 per quality-adjusted life-year for infants born at 26 and 29 weeks' gestation.

Table Graphic Jump LocationTable 4. One-way Sensitivity Analysis in the Model Without Increased Risk of Asthma
Table Graphic Jump LocationTable 5. Sensitivity Analysis in the Model With Increased Risk of Asthma
TARGETED USE POLICY

The alterations included in the targeted policy dramatically improved the ICER for the use of palivizumab, with the ICER ranging from $103 053 per quality-adjusted life-year for infants born at 26 weeks' gestation to $280 083 per quality-adjusted life-year for infants born at 29 and 30 weeks' gestation. With the targeted policy, the ICER is less than $200 000 per quality-adjusted life-year for infants born at 26 or 27 weeks' gestation.

This decision analytic model compared the costs and effects of palivizumab prophylaxis for RSV and no prophylaxis for a hypothetical cohort of premature infants without chronic lung disease. Our results show that palivizumab prophylaxis is not cost-effective for these infants. Under the first scenario in which we assumed that RSV had no effect on asthma rates, we found that for all gestational ages, the increased costs associated with the use of prophylaxis were greater than the cost savings from reduced hospitalizations and other costs. The decrease in expected costs for infants born at more than 28 weeks' gestation reflects the AAP policy for RSV prophylaxis: infants born at 29 to 32 weeks' gestation receive palivizumab if they are younger than 6 months at the start of the RSV season, and infants born at 26 to 28 weeks' gestation receive prophylaxis if they are younger than 12 months at the start of the RSV season, ie, infants born at 26 to 28 weeks' gestation generally received a higher total number of palivizumab injections and, thereafter, a higher cost of RSV prophylaxis than infants born at 29 to 32 weeks' gestation.6,7 With the second scenario in which we included the health effects associated with the potential increase in asthma rates among children with RSV infections, we found that the ICERs are greater than $200 000 per quality-adjusted life-year for all gestational ages. Our model was most sensitive to variation in the quality of life with asthma, with ICERs less than $200 000 per quality-adjusted life-year for some gestational ages (infants born at 26 and 29 to 30 weeks' gestation) when the quality of life with asthma was reduced to 0.80, and to variation in the cost of palivizumab, with ICERs less than $100 000 per quality-adjusted life-year for some gestational ages (infants born at 26 and 29 weeks' gestation) when palivizumab costs were only 25% of their current values. The cost-effectiveness of the current guideline for RSV prophylaxis does not compare favorably with many accepted interventions,57 numerous vaccinations for children,58,59 or other health care for premature infants.60

Our analyses reveal 2 main explanations for these findings. First, the use of palivizumab results in substantially increased expected costs. Second, the use of palivizumab results in very small increases in expected quality-adjusted life-years for 3 reasons: (1) there is no evidence of, nor did we model, a mortality benefit to the use of the prophylaxis; (2) there is no evidence of long-term improvement in the quality of life associated with its use; and (3) if there is an improvement in quality-adjusted life-years owing to a reduced prevalence of asthma, the value of the improvement is likely to be small. These explanations for the relatively small potential long-term quality of life effects suggest that the overall welfare effects of the prophylaxis strategy will be driven by the cost consequences. Given the current costs of palivizumab, the reduction in other medical and nonmedical costs is simply not great enough to offset the drug costs. Our formulation of a targeted use policy, however, would be considered cost-effective for more restricted use among infants born at 26 or 27 weeks' gestation, but it is based on the assumption that drug wastage could be eliminated.

Our study has several limitations. First, the cost and length of hospitalization was assumed to be equal for all gestational ages. This assumption will bias our base-case model findings toward improved cost-effectiveness in the more premature infants and worse cost-effectiveness in the less premature infants. Second, the costs of asthma were based on data collected during 1985 to 1994. Finally, 1 assumption was made in our base-case analysis that deliberately biased our results toward improved cost-effectiveness of RSV prophylaxis. We assumed that the weights of the infant at the time of discharge and the time of injections are at 10% of the growth curve. This assumption will markedly reduce the cost of prophylaxis for different gestational ages.

In conclusion, our model is the first to our knowledge to study the cost-effectiveness of RSV prophylaxis by specific gestational age, to evaluate the implication of the possible increased risk of asthma on the economic analysis of RSV prophylaxis, and to integrate measures of morbidity (quality of life). We found that the current AAP recommendations for the use of palivizumab as RSV prophylaxis in premature infants without chronic lung disease are not cost-effective by today's standards. Our analyses support the implementation of more restrictive guidelines for RSV prophylaxis for these infants. Additional studies are needed to identify the best way to target RSV prophylaxis guidelines to enhance the cost-effectiveness of palivizumab. We found evidence that long-term health consequences of RSV are central to the determination of the cost-effectiveness of the intervention. In analyses where asthma following RSV infection was considered severe with profound worsening in quality of life (0.8) compared with quality of life without asthma (0.92), palivizumab was marginally cost-effective only for infants born at 26, 29, or 30 weeks' gestation.

Correspondence: Melony E. S. Sorbero, PhD, MS, MPH, RAND Corp, 4570 Fifth Ave, Suite 600, Pittsburgh, PA 15213 (msorbero@rand.org).

Accepted for Publication: June 22, 2006.

Author Contributions:Study concept and design: ElHassan, Sorbero, Hall, Stevens, and Dick. Acquisition of data: ElHassan, Sorbero, and Stevens. Analysis and interpretation of data: ElHassan, Sorbero, Hall, Stevens, and Dick. Drafting of the manuscript: ElHassan, Sorbero, Hall, and Stevens. Critical revision of the manuscript for important intellectual content: ElHassan, Hall, and Dick. Statistical analysis: ElHassan and Dick. Administrative, technical, and material support: ElHassan and Sorbero. Study supervision: Hall and Dick.

Acknowledgment: We acknowledge Kenneth McConnochie, MD, MPH, and Kristine Palmer, MD, for their help in reviewing the manuscript.

Hall  CBFeign  RDedCherry  JDedDemmler  GJedKaplan  Sed Respiratory syncytial virus Textbook of Pediatric Infectious Diseases. 5th ed Philadelphia, Pa WB Saunders Co2003;
Sly  PDHibbert  ME Childhood asthma following hospitalization with acute viral bronchiolitis in infancy Pediatr Pulmonol 1989;7153- 158
PubMed Link to Article
Twiggs  JTLarson  LAO’Connell  EJIlstrup  DM Respiratory syncytial virus infection: ten-year follow-up Clin Pediatr (Phila) 1981;20187- 190
PubMed Link to Article
Long  CEMcBride  JTHall  CBPickering  LKed Sequelae of respiratory syncytial virus infections: a role for intervention studies Am J Respir Crit Care Med 1995;1511678- 1681
PubMed Link to Article
IMpact-RSV Study Group, Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants Pediatrics 1998;102531- 537
PubMed Link to Article
American Academy of Pediatrics Committee on Infectious Diseases and Committee on Fetus and Newborn, Prevention of respiratory syncytial virus infections: indications for the use of palivizumab and update on the use of RSV-IGIV Pediatrics 1998;1021211- 1216
PubMed Link to Article
American Academy of Pediatrics, Respiratory syncytial virus Red Book: 2003 Report of the Committee on Infectious Diseases. 26th ed Elk Grove Village, Ill American Academy of Pediatrics2003;
Storch  GA Humanized monoclonal antibody for prevention of respiratory syncytial virus infection Pediatrics 1998;102648- 651
PubMed Link to Article
Joffe  SRay  GTEscobar  GJBlack  SBLieu  TA Cost-effectiveness of respiratory syncytial virus prophylaxis among preterm infants Pediatrics 1999;104419- 427
PubMed Link to Article
Marchetti  ALau  HMagar  RWang  LDevercelli  G Impact of palivizumab on expected costs of respiratory syncytial virus infection in preterm infants: potential for savings Clin Ther 1999;21752- 766
PubMed Link to Article
Lofland  JHTouch  SMO’Connor  JP  et al.  Palivizumab for respiratory syncytial virus prophylaxis in high-risk infants: a cost-effectiveness analysis Clin Ther 2000;221357- 1369
PubMed Link to Article
Barton  LLGrant  KLLemen  RJ Respiratory syncytial virus immune globulin: decisions and costs Pediatr Pulmonol 2001;3220- 28
PubMed Link to Article
Schrand  LMElliott  JMRoss  MBBell  EFMutnick  AH A cost-benefit analysis of RSV prophylaxis in high-risk infants Ann Pharmacother 2001;351186- 1193
PubMed Link to Article
Shireman  TIBraman  KS Impact and cost-effectiveness of respiratory syncytial virus prophylaxis for Kansas Medicaid's high-risk children Arch Pediatr Adolesc Med 2002;1561251- 1255
PubMed Link to Article
Kamal-Bahl  SDoshi  JCampbell  J Economic analyses of respiratory syncytial virus immunoprophylaxis in high-risk infants: a systematic review Arch Pediatr Adolesc Med 2002;1561034- 1041
PubMed Link to Article
Stang  PBrandenburg  NCarter  B The economic burden of respiratory syncytial virus-associated bronchiolitis hospitalizations Arch Pediatr Adolesc Med 2001;15595- 96
PubMed Link to Article
Vogel  AMMcKinlay  MJAshton  T  et al.  Cost-effectiveness of palivizumab in New Zealand J Paediatr Child Health 2002;38352- 357
PubMed Link to Article
Numa  A Outcome of respiratory syncytial virus infection and a cost-benefit analysis of prophylaxis J Paediatr Child Health 2000;36422- 427
PubMed Link to Article
Farina  DRodriguez  SPBauer  G  et al.  Respiratory syncytial virus prophylaxis: cost-effective analysis in Argentina Pediatr Infect Dis J 2002;21287- 291
PubMed Link to Article
Moler  FWBrown  RWFaix  RGGilsdorf  JR Comments on palivizumab (Synagis) Pediatrics 1999;103495- 497
PubMed Link to Article
Sanchez  PJ Immunoprophylaxis for respiratory syncytial virus Pediatr Infect Dis J 2002;21473- 478
PubMed Link to Article
Battaglia  FCLubchenco  LO A practical classification of newborn infants by weight and gestational age J Pediatr 1967;71159- 163
PubMed Link to Article
Keeler  ESloan  FAed Decision trees and Markov models in cost-effectiveness research Valuing Health Care: Costs, Benefits, and Effectiveness of Pharmaceuticals and Other Medical Technologies. New York, NY Cambridge University Press1998;
Luce  BRManning  WGSiegel  JELipscomb  JGold  MRedSiegel  JEedRussell  LBedWeinstein  MCed Estimating costs in cost-effectiveness analysis Cost-Effectiveness in Health and Medicine. New York, NY Oxford University Press1996;
Pullan  CRHey  EN Wheezing, asthma, and pulmonary dysfunction 10 years after infection with respiratory syncytial virus in infancy BMJ 1982;2841665- 1669
PubMed Link to Article
Sigurs  NBjarnarson  RSigurbergsson  FKjellman  BBjorksten  B Asthma and immunoglobulin E antibodies after respiratory syncytial virus bronchiolitis: a prospective cohort study with matched controls Pediatrics 1995;95500- 505
PubMed
Sigurs  NBjarnason  RSigurbergsson  FKjellman  B Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7 Am J Respir Crit Care Med 2000;1611501- 1507
PubMed Link to Article
Ubel  PAHirth  RAChernew  MEFendrick  AM What is the price of life and why doesn't it increase at the rate of inflation? Arch Intern Med 2003;1631637- 1641
PubMed Link to Article
Cunningham  CKMcMillan  JAGross  SJ Rehospitalization for respiratory illness in infants of less than 32 weeks' gestation Pediatrics 1991;88527- 532
PubMed
Stevens  TPSinkin  RAHall  CBManiscalco  WMMcConnochie  KM Respiratory syncytial virus and premature infants at 32 weeks' gestation or earlier: hospitalization and economic implications of prophylaxis Arch Pediatr Adolesc Med 2000;15455- 61
PubMed
PREVENT Study Group, Reduction of respiratory syncytial virus hospitalization among premature infants and infants with bronchopulmonary dysplasia using respiratory syncytial virus immune globulin prophylaxis Pediatrics 1997;9993- 99
PubMed Link to Article
O’Shea  TMSevick  MAGivner  LB Costs and benefits of respiratory syncytial virus immunoglobulin to prevent hospitalization for lower respiratory tract illness in very low birth weight infants Pediatr Infect Dis J 1998;17587- 593
PubMed Link to Article
Shay  DKHolman  RCNewman  RDLiu  LLStout  JWAnderson  LJ Bronchiolitis-associated hospitalizations among US children, 1980-1996 JAMA 1999;2821440- 1446
PubMed Link to Article
Joffe  SEscobar  GJBlack  SBArmstrong  MALieu  TA Rehospitalization for respiratory syncytial virus among premature infants Pediatrics 1999;104894- 899
PubMed Link to Article
Boyce  TGMellen  BGMitchel  EFWright  PFGriffin  MR Rates of hospitalization for respiratory syncytial virus infection among children in Medicaid J Pediatr 2000;137865- 870
PubMed Link to Article
Howard  TSHoffman  LHStang  PESimoes  EAF Respiratory syncytial virus pneumonia in the hospital setting: length of stay, charges, and mortality J Pediatr 2000;137227- 232
PubMed Link to Article
Romero  JR Palivizumab prophylaxis of respiratory syncytial virus disease from 1998 to 2002: results from four years of palivizumab usage Pediatr Infect Dis J 2003;22S46- S54
PubMed
Kneyber  MCJSteyerberg  EWde Groot  RMoll  HA Long-term effects of respiratory syncytial virus (RSV) bronchiolitis in infants and young children: a quantitative review Acta Paediatr 2000;89654- 660
PubMed Link to Article
Sims  DGDownham  MAGardner  PSWebb  JKWeightman  D Study of 8-year old children with a history of respiratory syncytial virus bronchiolitis in infancy BMJ 1978;111- 14
PubMed Link to Article
McConnochie  KMRoghmann  KJ Bronchiolitis as a possible cause of wheezing in childhood: new evidence Pediatrics 1984;741- 10
PubMed
Mok  JYQSimpson  H Outcome for acute bronchitis, bronchiolitis, and pneumonia in infancy Arch Dis Child 1984;59306- 309
PubMed Link to Article
Carlsen  KHLarsen  SBjerve  OLeegaard  J Acute bronchiolitis: predisposing factors and characterization of infants at risk Pediatr Pulmonol 1987;3153- 160
PubMed Link to Article
Murray  MWebb  MSCO’Callaghan  CSwarbrick  ASMilner  AD Respiratory status and allergy after bronchiolitis Arch Dis Child 1992;67482- 487
PubMed Link to Article
Osundwa  VMDawod  STEhlayel  M Recurrent wheezing in children with respiratory syncytial virus (RSV) bronchiolitis in Qatar Eur J Pediatr 1993;1521001- 1003
PubMed Link to Article
Noble  VMurray  MWebb  MSCAlexander  JSwarbrick  ASMilner  AD Respiratory status and allergy nine to 10 years after acute bronchiolitis Arch Dis Child 1997;76315- 319
PubMed Link to Article
Stein  RTSherrill  DMorgan  WJ  et al.  Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years Lancet 1999;354541- 545
PubMed Link to Article
Juniper  EFGuyatt  GHFeeney  DHGriffith  LEFerrie  PJ Minimum skills required by children to complete health-related quality of life instruments for asthma: comparison of measurement properties Eur Respir J 1997;102285- 2294
PubMed Link to Article
Gold  MFranks  PErickson  P Assessing the health of the nation: the predictive validity of a preference-based measure and self-rated health Med Care 1996;34163- 177
PubMed Link to Article
Medical Economics Co;; Thomson Healthcare, Drug Topics Red Book.  Montvale, NJ Medical Economics Co Inc2002;
American Hospital Directory, Current data sources http://www.ahd.com/data_sources.htmlAccessed November 3, 2003
Bureau of Labor Statistics, US Department of Labor, Consumer Price Index: December 1998 ftp://ftp.bls.gov/pub/news.release/History/cpi.011499.newsAccessed November 4, 2003
Bureau of Labor Statistics, US Department of Labor, Consumer Price Index: December 2002 http://www.bls.govAccessed November 4, 2003
Bureau of Labor Statistics, US Department of Labor, National compensation survey: occupational wages in the United States, July 2002 http://www.bls.gov/ncs/ocs/compub.htm#NationalAccessed November 3, 2003
Bureau of Labor Statistics, US Department of Labor, Consumer Price Index: December 1994 ftp://ftp.bls.gov/pub/news.release/History/cpi.011195.newsAccessed March 27, 2002
Weiss  KBSullivan  SDLyttle  CS Trends in the cost of illness for asthma in the United States, 1985-1994 J Allergy Clin Immunol 2000;106493- 499
PubMed Link to Article
Elhassan  NOStevens  TPSorbero  MESDick  AWGuillet  RHall  CB Guidelines for palivizumab prophylaxis: are they based on infant's risk of hospitalization for respiratory syncytial viral disease? Pediatr Infect Dis J 2003;22939- 942
PubMed Link to Article
Tengs  TOAdams  MEPliskin  JS  et al.  Five-hundred life-saving interventions and their cost-effectiveness Risk Anal 1995;15369- 390
PubMed Link to Article
Bloom  BSHillman  ALFendrick  AMSchwartz  JS A reappraisal of Hepatitis B virus vaccination strategies using cost-effectiveness analysis Ann Intern Med 1993;118298- 306
PubMed Link to Article
Lieu  TARay  GTBlack  SB  et al.  Projected cost-effectiveness of pneumococcal conjugate vaccination of healthy infants and young children JAMA 2000;2831460- 1468
PubMed Link to Article
Zupancic  JAFRichardson  DKO’Brien  BJEichenwald  ECWeinstein  MC Cost-effectiveness analysis of predischarge monitoring for apnea of prematurity Pediatrics 2003;111146- 152
PubMed Link to Article

Figures

Tables

Table Graphic Jump LocationTable 1. Point Estimates for Noncost Variables
Table Graphic Jump LocationTable 2. Point Estimates of Cost Variables
Table Graphic Jump LocationTable 3. Expected and Incremental Costs per Quality-Adjusted Life-Year for Gestational Ages
Table Graphic Jump LocationTable 4. One-way Sensitivity Analysis in the Model Without Increased Risk of Asthma
Table Graphic Jump LocationTable 5. Sensitivity Analysis in the Model With Increased Risk of Asthma

References

Hall  CBFeign  RDedCherry  JDedDemmler  GJedKaplan  Sed Respiratory syncytial virus Textbook of Pediatric Infectious Diseases. 5th ed Philadelphia, Pa WB Saunders Co2003;
Sly  PDHibbert  ME Childhood asthma following hospitalization with acute viral bronchiolitis in infancy Pediatr Pulmonol 1989;7153- 158
PubMed Link to Article
Twiggs  JTLarson  LAO’Connell  EJIlstrup  DM Respiratory syncytial virus infection: ten-year follow-up Clin Pediatr (Phila) 1981;20187- 190
PubMed Link to Article
Long  CEMcBride  JTHall  CBPickering  LKed Sequelae of respiratory syncytial virus infections: a role for intervention studies Am J Respir Crit Care Med 1995;1511678- 1681
PubMed Link to Article
IMpact-RSV Study Group, Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants Pediatrics 1998;102531- 537
PubMed Link to Article
American Academy of Pediatrics Committee on Infectious Diseases and Committee on Fetus and Newborn, Prevention of respiratory syncytial virus infections: indications for the use of palivizumab and update on the use of RSV-IGIV Pediatrics 1998;1021211- 1216
PubMed Link to Article
American Academy of Pediatrics, Respiratory syncytial virus Red Book: 2003 Report of the Committee on Infectious Diseases. 26th ed Elk Grove Village, Ill American Academy of Pediatrics2003;
Storch  GA Humanized monoclonal antibody for prevention of respiratory syncytial virus infection Pediatrics 1998;102648- 651
PubMed Link to Article
Joffe  SRay  GTEscobar  GJBlack  SBLieu  TA Cost-effectiveness of respiratory syncytial virus prophylaxis among preterm infants Pediatrics 1999;104419- 427
PubMed Link to Article
Marchetti  ALau  HMagar  RWang  LDevercelli  G Impact of palivizumab on expected costs of respiratory syncytial virus infection in preterm infants: potential for savings Clin Ther 1999;21752- 766
PubMed Link to Article
Lofland  JHTouch  SMO’Connor  JP  et al.  Palivizumab for respiratory syncytial virus prophylaxis in high-risk infants: a cost-effectiveness analysis Clin Ther 2000;221357- 1369
PubMed Link to Article
Barton  LLGrant  KLLemen  RJ Respiratory syncytial virus immune globulin: decisions and costs Pediatr Pulmonol 2001;3220- 28
PubMed Link to Article
Schrand  LMElliott  JMRoss  MBBell  EFMutnick  AH A cost-benefit analysis of RSV prophylaxis in high-risk infants Ann Pharmacother 2001;351186- 1193
PubMed Link to Article
Shireman  TIBraman  KS Impact and cost-effectiveness of respiratory syncytial virus prophylaxis for Kansas Medicaid's high-risk children Arch Pediatr Adolesc Med 2002;1561251- 1255
PubMed Link to Article
Kamal-Bahl  SDoshi  JCampbell  J Economic analyses of respiratory syncytial virus immunoprophylaxis in high-risk infants: a systematic review Arch Pediatr Adolesc Med 2002;1561034- 1041
PubMed Link to Article
Stang  PBrandenburg  NCarter  B The economic burden of respiratory syncytial virus-associated bronchiolitis hospitalizations Arch Pediatr Adolesc Med 2001;15595- 96
PubMed Link to Article
Vogel  AMMcKinlay  MJAshton  T  et al.  Cost-effectiveness of palivizumab in New Zealand J Paediatr Child Health 2002;38352- 357
PubMed Link to Article
Numa  A Outcome of respiratory syncytial virus infection and a cost-benefit analysis of prophylaxis J Paediatr Child Health 2000;36422- 427
PubMed Link to Article
Farina  DRodriguez  SPBauer  G  et al.  Respiratory syncytial virus prophylaxis: cost-effective analysis in Argentina Pediatr Infect Dis J 2002;21287- 291
PubMed Link to Article
Moler  FWBrown  RWFaix  RGGilsdorf  JR Comments on palivizumab (Synagis) Pediatrics 1999;103495- 497
PubMed Link to Article
Sanchez  PJ Immunoprophylaxis for respiratory syncytial virus Pediatr Infect Dis J 2002;21473- 478
PubMed Link to Article
Battaglia  FCLubchenco  LO A practical classification of newborn infants by weight and gestational age J Pediatr 1967;71159- 163
PubMed Link to Article
Keeler  ESloan  FAed Decision trees and Markov models in cost-effectiveness research Valuing Health Care: Costs, Benefits, and Effectiveness of Pharmaceuticals and Other Medical Technologies. New York, NY Cambridge University Press1998;
Luce  BRManning  WGSiegel  JELipscomb  JGold  MRedSiegel  JEedRussell  LBedWeinstein  MCed Estimating costs in cost-effectiveness analysis Cost-Effectiveness in Health and Medicine. New York, NY Oxford University Press1996;
Pullan  CRHey  EN Wheezing, asthma, and pulmonary dysfunction 10 years after infection with respiratory syncytial virus in infancy BMJ 1982;2841665- 1669
PubMed Link to Article
Sigurs  NBjarnarson  RSigurbergsson  FKjellman  BBjorksten  B Asthma and immunoglobulin E antibodies after respiratory syncytial virus bronchiolitis: a prospective cohort study with matched controls Pediatrics 1995;95500- 505
PubMed
Sigurs  NBjarnason  RSigurbergsson  FKjellman  B Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7 Am J Respir Crit Care Med 2000;1611501- 1507
PubMed Link to Article
Ubel  PAHirth  RAChernew  MEFendrick  AM What is the price of life and why doesn't it increase at the rate of inflation? Arch Intern Med 2003;1631637- 1641
PubMed Link to Article
Cunningham  CKMcMillan  JAGross  SJ Rehospitalization for respiratory illness in infants of less than 32 weeks' gestation Pediatrics 1991;88527- 532
PubMed
Stevens  TPSinkin  RAHall  CBManiscalco  WMMcConnochie  KM Respiratory syncytial virus and premature infants at 32 weeks' gestation or earlier: hospitalization and economic implications of prophylaxis Arch Pediatr Adolesc Med 2000;15455- 61
PubMed
PREVENT Study Group, Reduction of respiratory syncytial virus hospitalization among premature infants and infants with bronchopulmonary dysplasia using respiratory syncytial virus immune globulin prophylaxis Pediatrics 1997;9993- 99
PubMed Link to Article
O’Shea  TMSevick  MAGivner  LB Costs and benefits of respiratory syncytial virus immunoglobulin to prevent hospitalization for lower respiratory tract illness in very low birth weight infants Pediatr Infect Dis J 1998;17587- 593
PubMed Link to Article
Shay  DKHolman  RCNewman  RDLiu  LLStout  JWAnderson  LJ Bronchiolitis-associated hospitalizations among US children, 1980-1996 JAMA 1999;2821440- 1446
PubMed Link to Article
Joffe  SEscobar  GJBlack  SBArmstrong  MALieu  TA Rehospitalization for respiratory syncytial virus among premature infants Pediatrics 1999;104894- 899
PubMed Link to Article
Boyce  TGMellen  BGMitchel  EFWright  PFGriffin  MR Rates of hospitalization for respiratory syncytial virus infection among children in Medicaid J Pediatr 2000;137865- 870
PubMed Link to Article
Howard  TSHoffman  LHStang  PESimoes  EAF Respiratory syncytial virus pneumonia in the hospital setting: length of stay, charges, and mortality J Pediatr 2000;137227- 232
PubMed Link to Article
Romero  JR Palivizumab prophylaxis of respiratory syncytial virus disease from 1998 to 2002: results from four years of palivizumab usage Pediatr Infect Dis J 2003;22S46- S54
PubMed
Kneyber  MCJSteyerberg  EWde Groot  RMoll  HA Long-term effects of respiratory syncytial virus (RSV) bronchiolitis in infants and young children: a quantitative review Acta Paediatr 2000;89654- 660
PubMed Link to Article
Sims  DGDownham  MAGardner  PSWebb  JKWeightman  D Study of 8-year old children with a history of respiratory syncytial virus bronchiolitis in infancy BMJ 1978;111- 14
PubMed Link to Article
McConnochie  KMRoghmann  KJ Bronchiolitis as a possible cause of wheezing in childhood: new evidence Pediatrics 1984;741- 10
PubMed
Mok  JYQSimpson  H Outcome for acute bronchitis, bronchiolitis, and pneumonia in infancy Arch Dis Child 1984;59306- 309
PubMed Link to Article
Carlsen  KHLarsen  SBjerve  OLeegaard  J Acute bronchiolitis: predisposing factors and characterization of infants at risk Pediatr Pulmonol 1987;3153- 160
PubMed Link to Article
Murray  MWebb  MSCO’Callaghan  CSwarbrick  ASMilner  AD Respiratory status and allergy after bronchiolitis Arch Dis Child 1992;67482- 487
PubMed Link to Article
Osundwa  VMDawod  STEhlayel  M Recurrent wheezing in children with respiratory syncytial virus (RSV) bronchiolitis in Qatar Eur J Pediatr 1993;1521001- 1003
PubMed Link to Article
Noble  VMurray  MWebb  MSCAlexander  JSwarbrick  ASMilner  AD Respiratory status and allergy nine to 10 years after acute bronchiolitis Arch Dis Child 1997;76315- 319
PubMed Link to Article
Stein  RTSherrill  DMorgan  WJ  et al.  Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years Lancet 1999;354541- 545
PubMed Link to Article
Juniper  EFGuyatt  GHFeeney  DHGriffith  LEFerrie  PJ Minimum skills required by children to complete health-related quality of life instruments for asthma: comparison of measurement properties Eur Respir J 1997;102285- 2294
PubMed Link to Article
Gold  MFranks  PErickson  P Assessing the health of the nation: the predictive validity of a preference-based measure and self-rated health Med Care 1996;34163- 177
PubMed Link to Article
Medical Economics Co;; Thomson Healthcare, Drug Topics Red Book.  Montvale, NJ Medical Economics Co Inc2002;
American Hospital Directory, Current data sources http://www.ahd.com/data_sources.htmlAccessed November 3, 2003
Bureau of Labor Statistics, US Department of Labor, Consumer Price Index: December 1998 ftp://ftp.bls.gov/pub/news.release/History/cpi.011499.newsAccessed November 4, 2003
Bureau of Labor Statistics, US Department of Labor, Consumer Price Index: December 2002 http://www.bls.govAccessed November 4, 2003
Bureau of Labor Statistics, US Department of Labor, National compensation survey: occupational wages in the United States, July 2002 http://www.bls.gov/ncs/ocs/compub.htm#NationalAccessed November 3, 2003
Bureau of Labor Statistics, US Department of Labor, Consumer Price Index: December 1994 ftp://ftp.bls.gov/pub/news.release/History/cpi.011195.newsAccessed March 27, 2002
Weiss  KBSullivan  SDLyttle  CS Trends in the cost of illness for asthma in the United States, 1985-1994 J Allergy Clin Immunol 2000;106493- 499
PubMed Link to Article
Elhassan  NOStevens  TPSorbero  MESDick  AWGuillet  RHall  CB Guidelines for palivizumab prophylaxis: are they based on infant's risk of hospitalization for respiratory syncytial viral disease? Pediatr Infect Dis J 2003;22939- 942
PubMed Link to Article
Tengs  TOAdams  MEPliskin  JS  et al.  Five-hundred life-saving interventions and their cost-effectiveness Risk Anal 1995;15369- 390
PubMed Link to Article
Bloom  BSHillman  ALFendrick  AMSchwartz  JS A reappraisal of Hepatitis B virus vaccination strategies using cost-effectiveness analysis Ann Intern Med 1993;118298- 306
PubMed Link to Article
Lieu  TARay  GTBlack  SB  et al.  Projected cost-effectiveness of pneumococcal conjugate vaccination of healthy infants and young children JAMA 2000;2831460- 1468
PubMed Link to Article
Zupancic  JAFRichardson  DKO’Brien  BJEichenwald  ECWeinstein  MC Cost-effectiveness analysis of predischarge monitoring for apnea of prematurity Pediatrics 2003;111146- 152
PubMed Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 40

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
JAMAevidence.com