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 | ONLINE FIRST

Effects of Adverse Events on the Projected Population Benefits and Cost-effectiveness of Using Live Attenuated Influenza Vaccine in Children Aged 6 Months to 4 Years FREE

Lisa A. Prosser, PhD; Martin I. Meltzer, PhD; Anthony Fiore, MD, MPH; Scott Epperson, MPH; Carolyn B. Bridges, MD; Virginia Hinrichsen, MS, MPH; Tracy A. Lieu, MD, MPH
[+] Author Affiliations

Author Affiliations: Child Health Evaluation and Research Unit, Division of Pediatrics, University of Michigan Health System, Ann Arbor (Dr Prosser); Center for Child Health Care Studies, Department of Population Medicine (Drs Prosser and Lieu and Ms Hinrichsen), Harvard Medical School and Harvard Pilgrim Health Care, Boston, Massachusetts; and Division of Emerging Infections and Surveillance Services, National Center for Preparedness Detection and Control of Infectious Diseases, and Coordinating Center for Infectious Diseases (Dr Meltzer), and Influenza Division (Drs Fiore and Bridges and Mr Epperson), Centers for Disease Control and Prevention, Atlanta, Georgia.


Arch Pediatr Adolesc Med. 2011;165(2):112-118. doi:10.1001/archpediatrics.2010.182.
Text Size: A A A
Published online

Live attenuated influenza vaccine (LAIV) is approved for children 2 years or older without a history of wheezing or asthma.13 A recent randomized controlled trial among children younger than 5 years of age found that intranasal LAIV was more effective in preventing laboratory-confirmed influenza compared with inactivated influenza vaccine (IIV), yet these data also suggested an increase in adverse events, such as wheezing, in children younger than 5 years of age who receive LAIV compared with IIV.1 Given that a possible increase in adverse events was of potential concern to providers and parents, we sought to evaluate the effect of these events on cost-effectiveness results. The objective of this study was to evaluate the cost-effectiveness of LAIV using new data on adverse events.

We used a previously validated simulation model, built using standard software (TreeAge Pro 2007 Software, release 1.2; TreeAge Software, Williamstown, Massachusetts), to estimate the effect of influenza vaccination on influenza-related health outcomes and costs among children.4 The decision tree evaluates 3 options: (1) no vaccination; (2) IIV; and (3) LAIV. A simplified schematic of the decision tree is shown in the Figure. Healthy children were divided into subgroups by age: 6 to 23 months, 2 years (24-35 months), and 3 to 4 years. We used a time frame of 1 year but also included the long-term effects of influenza and influenza vaccines (eg, death, long-term sequelae of influenza-related illness, and vaccine-related adverse effects). All effects lasting more than 1 year were discounted at 3% per year. We used a societal perspective. Event probabilities, by age and risk group, were derived from the published literature and were supplemented by expert opinion where data were limited or unavailable (Table 1 and eTable 1 and eTable 2). Additional details of the model structure are available in the eAppendix and have been published previously.4 Modifications to the model specific to this analysis are described later.

Place holder to copy figure label and caption
Figure.

Simplified schematic of influenza cost-effectiveness simulation model. *Injection site reaction for inactivated influenza vaccine only.

Graphic Jump Location
Table Graphic Jump LocationTable 1. Modeling Assumptions and Simulation Inputsa
VACCINATION-RELATED ADVERSE EVENTS

This analysis incorporated medically attended wheezing episodes and hospitalization following wheezing, in addition to 4 adverse events included in previous analyses (eAppendix)1,5,22,23,35 Trial data1 included a slight increase in all-cause hospitalization for LAIV compared with IIV, although these increases were not statistically significant; therefore, these probabilities were included in the current analysis as a parameter range that included zero.

COSTS

Costs included direct medical and opportunity costs (parent travel, waiting, and visit time)4 (Table 1 and eTable 1) The costing year of the analysis was 2006; all costs were adjusted to 2006 US dollars.36 Costs of influenza-related hospitalizations were updated to reflect new data available for costs of influenza-related hospitalizations in children.25

HEALTH OUTCOMES

The model projected 4 different outcomes that were averted through vaccination: influenza episodes, hospitalizations, deaths, and loss of quality-adjusted life-years (QALYs). A QALY attempts to measure a patient's physical health and well-being, including the ability to engage in “normal,” everyday activities. The QALYs lost to a disease or condition, therefore, measure the overall reduction in a patient's well-being, or health-related quality of life, due to an episode of disease and its consequences. We obtained QALY valuations for influenza-related and vaccination-related events from published studies conducted by us and from published data25,27,37,38 (Table 1). A value for the QALYs lost because of an episode of wheezing in a child was not available. We, therefore, used a published estimate of the QALYs lost because of wheezing in an adult experiencing an episode of acute asthma.34

ANALYSIS

The primary outcome measure was the incremental cost-effectiveness ratio in dollars per QALY saved for vaccination compared with no vaccination (eAppendix). Secondary measures included costs of vaccination and clinical influenza-related events averted per 1000 vaccinated children, dollars per influenza-related event avoided, dollars per hospitalization avoided, and dollars per death averted. One-way sensitivity analyses were conducted on all variables, in which the impact on the cost-effectiveness ratio was examined by altering each variable within the range of given values (Table 1). We also conducted a sensitivity analysis that examined the effect of increasing all-cause hospitalization following vaccination with LAIV (ie, a possible vaccine-related adverse effect). A probabilistic sensitivity analysis was also conducted (ie, a Monte Carlo analysis was conducted).

HEALTH BENEFITS, RISKS, AND COSTS

For lower-risk children aged 2 to 4 years, LAIV was projected to avert more episodes of influenza, influenza-related hospitalizations, and deaths than IIV per 1000 children vaccinated. However, adverse events were projected to be higher for LAIV than for IIV. All vaccination strategies had a net health benefit compared with no vaccination, as measured by QALYs gained. Costs of vaccination were projected to be higher for LAIV compared with IIV, reflecting both higher costs of the vaccine dose and higher probabilities of adverse events and associated costs for LAIV (Table 2).

Table Graphic Jump LocationTable 2. Health Benefits, Risks, and Costs of Influenza Vaccination for Lower-Risk Children Aged 6 Months to 4 Yearsa,b
COST-EFFECTIVENESS

For lower-risk children aged 2 and 3 to 4 years, vaccination with either IIV or LAIV resulted in a net cost both in terms of cost per influenza episode averted and cost per QALY saved (Table 2 and Table 3 and eTable 3). In 1-way sensitivity analyses, results were not sensitive to variables representing incidence, cost, or quality adjustment for wheezing following vaccination with LAIV (eFigure 1). Cost-effectiveness ratios were most sensitive to changes in the probability of influenza illness, probability of influenza-related hospitalizations, and total vaccination costs (eFigure 1). For a possible increase in the probability of all-cause hospitalization following vaccination with LAIV greater than 0.006, IIV would become the preferred strategy because LAIV would become more costly and save fewer QALYs (ie, LAIV is dominated by IIV) as this probability increased (eFigure 2 and eTable 4).

Table Graphic Jump LocationTable 3. Cost-effectiveness Ratios for Vaccination Using IIV and LAIV Compared With No Vaccination for Lower-Risk Children Aged 6 Months to 4 Years
MAJOR FINDINGS

Vaccinating lower-risk children using either LAIV or IIV did not generate cost savings but yielded cost-effectiveness ratios less than $40 000 per QALY gained for children aged 6 months to 4 years. For children in this age group, vaccination with LAIV yielded slightly more favorable mean cost-effectiveness ratios than IIV under a wide range of assumptions about the incidence of adverse events but confidence intervals for cost-effectiveness ratios were overlapping for the 2 vaccination strategies. We found the addition of wheezing-related adverse events had little impact on the cost-effectiveness of vaccination with LAIV (Table 3). Even after the inclusion of wheezing-related adverse events, vaccination with LAIV resulted in health benefits that outweighed vaccine adverse events as measured by QALYs.

COMMENTS

These findings are similar to results from a previous analysis using an earlier version of this simulation model.4 The current analysis revised the previous model to incorporate newly identified potential adverse events for LAIV, revised assumptions regarding the relative incidence of previously identified adverse events for LAIV and IIV, and new data on the costs of influenza-related hospitalizations for children. The key findings remain robust to the inclusion of new data on adverse events and hospitalization costs: cost-effectiveness ratios for vaccination of healthy children younger than 5 years are favorable compared with other well-accepted pediatric interventions. These results are also consistent with other published analyses of influenza vaccination in children that also demonstrated cost savings or cost-effective results for vaccination in similar age groups but that did not consider new adverse events.39

One potential limitation of this analysis is the exclusion of herd immunity effects. If these effects were considered, they would likely result in more favorable cost-effectiveness ratios for vaccination options. In addition, published data were not available for some key variables, such as quality adjustments for a wheezing episode and hospitalizations following vaccination, and our analysis used values from similar health states not associated with vaccination. The current analysis assumes that hospitalizations following vaccination have the same loss in quality of life associated with an influenza-related hospitalization. However, parents may place a greater value for the loss in quality of life due to a vaccination-related adverse event and that loss would not be fully captured herein.32

We used data on the loss in QALYs associated with wheezing events in adults because values for children were not available. This approach may underestimate the loss in quality of life associated with wheezing in children, because we have shown that respondents valued influenza health states in children as associated with a greater loss in quality of life (L.A.P., K. Payne, PhD, D. Rusinak, BA, P. Shi, MA, T. Uyeki, MD, MPH, M. Messonnier, PhD, “Value in Health,” unpublished data, December 2007); however, sensitivity analysis for this parameter did not demonstrate a substantial effect on results.

This analysis assumes that vaccine effectiveness does not vary by age whereas recent data have suggested that the relative effectiveness of LAIV compared with IIV may be greater in very young children.1 This would have some effect on cost-effectiveness ratios as demonstrated by 1-way sensitivity analyses that indicate that cost-effectiveness ratios could vary as much as 25% to 50% when using the upper and lower bounds of plausible ranges for vaccine effectiveness. However, given the substantial uncertainty associated with the base case estimates (Table 2 and Table 3), the main conclusion that the cost-effectiveness ratios for LAIV and IIV are not significantly different would likely hold even for the younger age groups. Future research should explore the variation of vaccine effectiveness by age on cost-effectiveness.

The cost-effectiveness of influenza vaccination for children remains favorable when considering new data for vaccine adverse effects. Cost-effectiveness ratios were comparable for LAIV and IIV for low-risk children aged 6 months to 4 years. Postlicensing safety studies of both LAIV and IIV in children should continue to monitor wheezing-related adverse advents, including all-cause hospitalization.

Correspondence: Lisa A. Prosser, PhD, Division of General Pediatrics, University of Michigan Health System, 300 N Ingalls St, Room 6E14, SPC 5456, Ann Arbor, MI 48109 (lisapros@med.umich.edu).

Accepted for Publication: August 3, 2010.

Author Contributions:Study concept and design: Prosser, Meltzer, Fiore, Bridges, and Lieu. Acquisition of data: Prosser, Meltzer, Epperson, Bridges, and Hinrichsen. Analysis and interpretation of data: Prosser, Meltzer, Fiore and Bridges. Drafting of the manuscript: Prosser, Meltzer, and Fiore. Critical revision of the manuscript for important intellectual content: Prosser, Meltzer, Fiore, Epperson, Bridges, Hinrichsen, and Lieu. Statistical analysis: Prosser and Meltzer. Obtained funding: Prosser, Fiore, Bridges, and Lieu. Administrative, technical, and material support: Epperson, Bridges, Hinrichsen, and Lieu. Study supervision: Prosser and Fiore.

Financial Disclosure: None reported.

Funding/Support: Funding for this study was provided by the Centers for Disease Control and Prevention (CDC) through the Harvard/CDC Joint Initiative in Vaccine Economics.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the CDC. This project was conceived and conducted primarily at the Department of Population Medicine (formerly the Department of Ambulatory Care & Prevention) at Harvard Medical School and Harvard Pilgrim Health Care.

Online-Only Material: The eAppendix, eFigures, and eTables are available at http://www.archpediatrics.com.

Belshe  RBEdwards  KMVesikari  T  et al. CAIV-T Comparative Efficacy Study Group, Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med 2007;356 (7) 685- 696
PubMed Link to Article
Ashkenazi  SVertruyen  AArístegui  J  et al. CAIV-T Study Group, Superior relative efficacy of live attenuated influenza vaccine compared with inactivated influenza vaccine in young children with recurrent respiratory tract infections. Pediatr Infect Dis J 2006;25 (10) 870- 879
PubMed Link to Article
Fleming  DMCrovari  PWahn  U  et al. CAIV-T Asthma Study Group, Comparison of the efficacy and safety of live attenuated cold-adapted influenza vaccine, trivalent, with trivalent inactivated influenza virus vaccine in children and adolescents with asthma. Pediatr Infect Dis J 2006;25 (10) 860- 869
PubMed Link to Article
Prosser  LABridges  CBUyeki  TM  et al.  Health benefits, risks, and cost-effectiveness of influenza vaccination of children. Emerg Infect Dis 2006;12 (10) 1548- 1558
PubMed Link to Article
Neuzil  KMDupont  WDWright  PFEdwards  KM Efficacy of inactivated and cold-adapted vaccines against influenza A infection, 1985 to 1990: the pediatric experience. Pediatr Infect Dis J 2001;20 (8) 733- 740
PubMed Link to Article
Fox  JPCooney  MKHall  CEFoy  HM Influenza virus infections in Seattle families, 1975-1979, II: pattern of infection in invaded households and relation of age and prior antibody to occurrence of infection and related illness. Am J Epidemiol 1982;116 (2) 228- 242
PubMed
Hall  CECooney  MKFox  JP The Seattle virus watch, IV: comparative epidemiologic observations of infections with influenza A and B viruses, 1965-1969, in families with young children. Am J Epidemiol 1973;98 (5) 365- 380
PubMed
Monto  ASSullivan  KM Acute respiratory illness in the community: frequency of illness and the agents involved. Epidemiol Infect 1993;110 (1) 145- 160
PubMed Link to Article
Neuzil  KMZhu  YGriffin  MR  et al.  Burden of interpandemic influenza in children younger than 5 years: a 25-year prospective study. J Infect Dis 2002;185 (2) 147- 152
PubMed Link to Article
Foy  HMHall  CECooney  MKAllan  IDFox  JP Influenza surveillance in the Pacific Northwest 1976-1980. Int J Epidemiol 1983;12 (3) 353- 356
PubMed Link to Article
Glezen  WPTaber  LHFrank  ALGruber  WCPiedra  PA Influenza virus infections in infants. Pediatr Infect Dis J 1997;16 (11) 1065- 1068
PubMed Link to Article
Monto  ASKoopman  JSLongini  IM  Jr Tecumseh study of illness, XIII: influenza infection and disease, 1976-1981. Am J Epidemiol 1985;121 (6) 811- 822
PubMed
Sullivan  KMMonto  ASLongini  IM  Jr Estimates of the US health impact of influenza. Am J Public Health 1993;83 (12) 1712- 1716
PubMed Link to Article
Taber  LHParedes  AGlezen  WPCouch  RB Infection with influenza A/Victoria virus in Houston families, 1976. J Hyg (Lond) 1981;86 (3) 303- 313
PubMed Link to Article
Neuzil  KMMellen  BGWright  PFMitchel  EF  JrGriffin  MR The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med 2000;342 (4) 225- 231
PubMed Link to Article
Neuzil  KMWright  PFMitchel  EF  JrGriffin  MR The burden of influenza illness in children with asthma and other chronic medical conditions. J Pediatr 2000;137 (6) 856- 864
PubMed Link to Article
Izurieta  HSThompson  WWKramarz  P  et al.  Influenza and the rates of hospitalization for respiratory disease among infants and young children. N Engl J Med 2000;342 (4) 232- 239
PubMed Link to Article
Thompson  WWShay  DKWeintraub  E  et al.  Influenza-associated hospitalizations in the United States. JAMA 2004;292 (11) 1333- 1340
PubMed Link to Article
Thompson  WWShay  DKWeintraub  E  et al.  Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 2003;289 (2) 179- 186
PubMed Link to Article
Nichol  KL The efficacy, effectiveness and cost-effectiveness of inactivated influenza virus vaccines. Vaccine 2003;21 (16) 1769- 1775
PubMed Link to Article
Finkelstein  JAStille  CSNordin  J  et al.  Reduction in antibiotic use among US children, 1996-2000. Pediatrics 2003;112 (3, pt 1) 620- 627
PubMed Link to Article
Belshe  RBEdwards  KMVesikari  T  et al. CAIV-T Comparative Efficacy Study Group, Live attenuated versus inactivated influenza vaccine in infants and young children: supplementary appendix. N Engl J Med 2007;356 (7) http://www.nejm.org/doi/suppl/10.1056/NEJMoa065368/suppl_file/nejm_belshe_685sa1.pdf. Accessed August 9, 2010
PubMed
Cvetkovich  TBaylor  M FDA briefing document for the Vaccines and Related Biological Products Advisory Committee (VRBPAC). http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4292B1-01.pdf. Published May 17, 2007. Accessed August 20, 2007
Physician's Desk Reference Staff, 2000 Redbook: Pharmacy's Fundamental Reference (Red Book Drug Topics).  Montvale, NJ Thomson PDR2000;
Keren  RZaoutis  TESaddlemire  SLuan  XQCoffin  SE Direct medical cost of influenza-related hospitalizations in children. Pediatrics 2006;118 (5) e1321- e1327
PubMed Link to Article
Morris  MTang  S Pediatric Service Utilization, Fees and Managed Care Arrangements: 2001 Report Based on 1999 Data.  Elk Grove Village, IL American Academy of Pediatrics2001;
Lieu  TABlack  SBRieser  NRay  PLewis  EMShinefield  HR The cost of childhood chickenpox: parents' perspective. Pediatr Infect Dis J 1994;13 (3) 173- 177
PubMed Link to Article
 Consumer price index. http://www.bls.gov/cpi. Accessed August 16, 2004
Physician's Desk Reference Staff, 2006 Redbook: Pharmacy's Fundamental Reference (Red Book Drug Topics)  Montvale, NJ Thomson PDR2006;
Prosser  LABridges  CBUyeki  TM  et al.  Values for preventing influenza-related morbidity and vaccine adverse events in children. Health Qual Life Outcomes 2005;318
PubMed Link to Article
Prosser  LARay  GTO’Brien  MKleinman  KSantoli  JLieu  TA Preferences and willingness to pay for health states prevented by pneumococcal conjugate vaccine. Pediatrics 2004;113 (2) 283- 290
PubMed Link to Article
Moy  MLFuhlbrigge  ALBlumenschein  K  et al.  Association between preference-based health-related quality of life and asthma severity. Ann Allergy Asthma Immunol 2004;92 (3) 329- 334
PubMed Link to Article
Belshe  RBGruber  WCMendelman  PM  et al.  Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine. J Pediatr 2000;136 (2) 168- 175
PubMed Link to Article
US Department of Labor Bureau of Labor Statistics, 2006 Consumer price index. http://www.bls.gov/cpi/. Accessed August 6, 2010
Huang  SMChen  CCChiu  PCCheng  MFLai  PHHsieh  KS Acute necrotizing encephalopathy of childhood associated with influenza type B virus infection in a 3-year-old girl. J Child Neurol 2004;19 (1) 64- 67
PubMed Link to Article
Morishima  TTogashi  TYokota  S  et al. Collaborative Study Group on Influenza-Associated Encephalopathy in Japan, Encephalitis and encephalopathy associated with an influenza epidemic in Japan. Clin Infect Dis 2002;35 (5) 512- 517
PubMed Link to Article
Savidan  EChevat  CMarsh  G Economic evidence of influenza vaccination in children. Health Policy 2008;86 (2-3) 142- 152
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure.

Simplified schematic of influenza cost-effectiveness simulation model. *Injection site reaction for inactivated influenza vaccine only.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Modeling Assumptions and Simulation Inputsa
Table Graphic Jump LocationTable 2. Health Benefits, Risks, and Costs of Influenza Vaccination for Lower-Risk Children Aged 6 Months to 4 Yearsa,b
Table Graphic Jump LocationTable 3. Cost-effectiveness Ratios for Vaccination Using IIV and LAIV Compared With No Vaccination for Lower-Risk Children Aged 6 Months to 4 Years

References

Belshe  RBEdwards  KMVesikari  T  et al. CAIV-T Comparative Efficacy Study Group, Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med 2007;356 (7) 685- 696
PubMed Link to Article
Ashkenazi  SVertruyen  AArístegui  J  et al. CAIV-T Study Group, Superior relative efficacy of live attenuated influenza vaccine compared with inactivated influenza vaccine in young children with recurrent respiratory tract infections. Pediatr Infect Dis J 2006;25 (10) 870- 879
PubMed Link to Article
Fleming  DMCrovari  PWahn  U  et al. CAIV-T Asthma Study Group, Comparison of the efficacy and safety of live attenuated cold-adapted influenza vaccine, trivalent, with trivalent inactivated influenza virus vaccine in children and adolescents with asthma. Pediatr Infect Dis J 2006;25 (10) 860- 869
PubMed Link to Article
Prosser  LABridges  CBUyeki  TM  et al.  Health benefits, risks, and cost-effectiveness of influenza vaccination of children. Emerg Infect Dis 2006;12 (10) 1548- 1558
PubMed Link to Article
Neuzil  KMDupont  WDWright  PFEdwards  KM Efficacy of inactivated and cold-adapted vaccines against influenza A infection, 1985 to 1990: the pediatric experience. Pediatr Infect Dis J 2001;20 (8) 733- 740
PubMed Link to Article
Fox  JPCooney  MKHall  CEFoy  HM Influenza virus infections in Seattle families, 1975-1979, II: pattern of infection in invaded households and relation of age and prior antibody to occurrence of infection and related illness. Am J Epidemiol 1982;116 (2) 228- 242
PubMed
Hall  CECooney  MKFox  JP The Seattle virus watch, IV: comparative epidemiologic observations of infections with influenza A and B viruses, 1965-1969, in families with young children. Am J Epidemiol 1973;98 (5) 365- 380
PubMed
Monto  ASSullivan  KM Acute respiratory illness in the community: frequency of illness and the agents involved. Epidemiol Infect 1993;110 (1) 145- 160
PubMed Link to Article
Neuzil  KMZhu  YGriffin  MR  et al.  Burden of interpandemic influenza in children younger than 5 years: a 25-year prospective study. J Infect Dis 2002;185 (2) 147- 152
PubMed Link to Article
Foy  HMHall  CECooney  MKAllan  IDFox  JP Influenza surveillance in the Pacific Northwest 1976-1980. Int J Epidemiol 1983;12 (3) 353- 356
PubMed Link to Article
Glezen  WPTaber  LHFrank  ALGruber  WCPiedra  PA Influenza virus infections in infants. Pediatr Infect Dis J 1997;16 (11) 1065- 1068
PubMed Link to Article
Monto  ASKoopman  JSLongini  IM  Jr Tecumseh study of illness, XIII: influenza infection and disease, 1976-1981. Am J Epidemiol 1985;121 (6) 811- 822
PubMed
Sullivan  KMMonto  ASLongini  IM  Jr Estimates of the US health impact of influenza. Am J Public Health 1993;83 (12) 1712- 1716
PubMed Link to Article
Taber  LHParedes  AGlezen  WPCouch  RB Infection with influenza A/Victoria virus in Houston families, 1976. J Hyg (Lond) 1981;86 (3) 303- 313
PubMed Link to Article
Neuzil  KMMellen  BGWright  PFMitchel  EF  JrGriffin  MR The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med 2000;342 (4) 225- 231
PubMed Link to Article
Neuzil  KMWright  PFMitchel  EF  JrGriffin  MR The burden of influenza illness in children with asthma and other chronic medical conditions. J Pediatr 2000;137 (6) 856- 864
PubMed Link to Article
Izurieta  HSThompson  WWKramarz  P  et al.  Influenza and the rates of hospitalization for respiratory disease among infants and young children. N Engl J Med 2000;342 (4) 232- 239
PubMed Link to Article
Thompson  WWShay  DKWeintraub  E  et al.  Influenza-associated hospitalizations in the United States. JAMA 2004;292 (11) 1333- 1340
PubMed Link to Article
Thompson  WWShay  DKWeintraub  E  et al.  Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 2003;289 (2) 179- 186
PubMed Link to Article
Nichol  KL The efficacy, effectiveness and cost-effectiveness of inactivated influenza virus vaccines. Vaccine 2003;21 (16) 1769- 1775
PubMed Link to Article
Finkelstein  JAStille  CSNordin  J  et al.  Reduction in antibiotic use among US children, 1996-2000. Pediatrics 2003;112 (3, pt 1) 620- 627
PubMed Link to Article
Belshe  RBEdwards  KMVesikari  T  et al. CAIV-T Comparative Efficacy Study Group, Live attenuated versus inactivated influenza vaccine in infants and young children: supplementary appendix. N Engl J Med 2007;356 (7) http://www.nejm.org/doi/suppl/10.1056/NEJMoa065368/suppl_file/nejm_belshe_685sa1.pdf. Accessed August 9, 2010
PubMed
Cvetkovich  TBaylor  M FDA briefing document for the Vaccines and Related Biological Products Advisory Committee (VRBPAC). http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4292B1-01.pdf. Published May 17, 2007. Accessed August 20, 2007
Physician's Desk Reference Staff, 2000 Redbook: Pharmacy's Fundamental Reference (Red Book Drug Topics).  Montvale, NJ Thomson PDR2000;
Keren  RZaoutis  TESaddlemire  SLuan  XQCoffin  SE Direct medical cost of influenza-related hospitalizations in children. Pediatrics 2006;118 (5) e1321- e1327
PubMed Link to Article
Morris  MTang  S Pediatric Service Utilization, Fees and Managed Care Arrangements: 2001 Report Based on 1999 Data.  Elk Grove Village, IL American Academy of Pediatrics2001;
Lieu  TABlack  SBRieser  NRay  PLewis  EMShinefield  HR The cost of childhood chickenpox: parents' perspective. Pediatr Infect Dis J 1994;13 (3) 173- 177
PubMed Link to Article
 Consumer price index. http://www.bls.gov/cpi. Accessed August 16, 2004
Physician's Desk Reference Staff, 2006 Redbook: Pharmacy's Fundamental Reference (Red Book Drug Topics)  Montvale, NJ Thomson PDR2006;
Prosser  LABridges  CBUyeki  TM  et al.  Values for preventing influenza-related morbidity and vaccine adverse events in children. Health Qual Life Outcomes 2005;318
PubMed Link to Article
Prosser  LARay  GTO’Brien  MKleinman  KSantoli  JLieu  TA Preferences and willingness to pay for health states prevented by pneumococcal conjugate vaccine. Pediatrics 2004;113 (2) 283- 290
PubMed Link to Article
Moy  MLFuhlbrigge  ALBlumenschein  K  et al.  Association between preference-based health-related quality of life and asthma severity. Ann Allergy Asthma Immunol 2004;92 (3) 329- 334
PubMed Link to Article
Belshe  RBGruber  WCMendelman  PM  et al.  Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine. J Pediatr 2000;136 (2) 168- 175
PubMed Link to Article
US Department of Labor Bureau of Labor Statistics, 2006 Consumer price index. http://www.bls.gov/cpi/. Accessed August 6, 2010
Huang  SMChen  CCChiu  PCCheng  MFLai  PHHsieh  KS Acute necrotizing encephalopathy of childhood associated with influenza type B virus infection in a 3-year-old girl. J Child Neurol 2004;19 (1) 64- 67
PubMed Link to Article
Morishima  TTogashi  TYokota  S  et al. Collaborative Study Group on Influenza-Associated Encephalopathy in Japan, Encephalitis and encephalopathy associated with an influenza epidemic in Japan. Clin Infect Dis 2002;35 (5) 512- 517
PubMed Link to Article
Savidan  EChevat  CMarsh  G Economic evidence of influenza vaccination in children. Health Policy 2008;86 (2-3) 142- 152
PubMed Link to Article

Correspondence

CME
Also 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.
Your answers have been saved for later.
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
Live Attenuated Influenza Vaccine and the Incidence of Wheezing Postvaccination
Posted on January 7, 2011
Christopher S. Ambrose, MD
MedImmune, LLC,
Conflict of Interest: None Declared
In their recent article, Prosser et al. examined the impact of vaccine-associated adverse events, particularly postvaccination wheezing, on the cost-effectiveness of vaccinating young children with live attenuated influenza vaccine (LAIV).1 The authors included LAIV- associated wheezing risks of 1.21, 0.37, and 0.16 per 100 vaccinated children aged 6-23 months, 24-35 months, and 36-59 months, respectively. LAIV is not approved for use in children 6-23 months of age because a small increase in postvaccination wheezing was observed between days 7 and 28 following the first vaccination in a large, randomized, controlled trial.2 However, the rationale for the authors' inclusion of LAIV- associated wheezing risks for children 24-35 and 36-59 months of age is not clearly addressed in the article. Although not explicitly stated, we believe that the LAIV-associated wheezing rates for recipients 24-35 and 36-59 months of age were included as hypothetical scenarios; if so, we agree that inclusion of these rates is appropriate to address the public health question raised. However, for the benefit of readers, the available data do not support an association between LAIV and an increased risk of wheezing postvaccination among children 24 months of age and older. In fact, in the overall cohort of children 24-59 months of age in the study by Belshe et al., 2.1% of LAIV recipients versus 2.5% of trivalent inactivated virus (TIV) recipients experienced medically significant wheezing through 42 days following vaccination.1, 3, 4 We realize that the authors demonstrated that the presence of a small increased risk of wheezing has little impact on LAIV cost-effectiveness. However, the presence or absence of a wheezing risk is relevant for parents and pediatric healthcare providers when evaluating influenza vaccine options.
Additionally, it is worth noting that Luce et al also evaluated the cost-effectiveness of LAIV and TIV among children 24-59 months of age using data from the randomized trial by Belshe et al. and identified net cost savings with LAIV compared with TIV.5
References
1. Prosser LA, Meltzer MI, Fiore A, et al. Effects of Adverse Events on the Projected Population Benefits and Cost-effectiveness of Using Live Attenuated Influenza Vaccine in Children Aged 6 Months to 4 Years. Arch Pediatr Adolesc Med. October 4 2010:archpediatrics.2010.2182.
2. Belshe RB, Edwards KM, Vesikari T, et al. Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med. Feb 15 2007;356(7):685-696.
3. Belshe RB, Ambrose C, Yi T. Safety and efficacy of live attenuated influenza vaccine in children 2-7 years of age. Vaccine. 2008;26S:D10-16.
4. FluMist®. Influenza Virus Vaccine Live, Intranasal, Full prescribing information. 2010.
5. Luce BR, Nichol KL, Belshe RB, et al. Cost-effectiveness of live attenuated influenza vaccine versus inactivated influenza vaccine among children aged 24-59 months in the United States. Vaccine. Jun 2 2008;26(23):2841-2848.

Conflict of Interest: Dr. Ambrose is an employee of MedImmune, LLC. Dr. Belshe has served as a consultant and/or member of a speaker's bureau for MedImmune, GlaxoSmithKline, and Novartis.
Submit a Comment

Multimedia

Effects of Adverse Events on the Projected Population Benefits and Cost-effectiveness of Using Live Attenuated Influenza Vaccine in Children Aged 6 Months to 4 Years
Arch Pediatr Adolesc Med.2011;165(2):112-118.eSupplement

eSupplement -Download PDF (63 KB). This file requires Adobe Reader®.

eAppendix

eTable 1. Expanded list of model inputs.

eTable 2. Number of additional physician visits required to administer requireddoses by age group.

eTable 3. Cost-effectiveness ratios, compared to no vaccination, for use ofinactivated and live attenuated influenza vaccination, mean (2.5% and 97.5%percentiles).

eTable 4. Sensitivity analysis for probability of hospitalization following vaccinationwith LAIV for lower-risk children aged 24-35 months compared to no vaccination.

eFigure 1. One-way sensitivity analyses on selected variables for lower-risk childrenaged 24-35 months, in $/QALY.

eFigure 2. Sensitivity analysis for probability of hospitalization following vaccinationwith LAIV for lower-risk children aged 24-35 months compared to no vaccination.

eReferences
Supplemental Content

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

Web of Science® Times Cited: 4

Related Content

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

Articles Related By Topic
Related Collections
PubMed Articles