#### Volume 12, Number 10—October 2006

*Research*

# Health Benefits, Risks, and Cost-Effectiveness of Influenza Vaccination of Children

## Table A1

Variable | Most likely estimate | Range for sensitivity analysis | Source | Type of distribution | Distribution parameter 1 | Distribution parameter 2 | |
---|---|---|---|---|---|---|---|

Influenza illness attack rate (annual) | (1–10) | ||||||

6–23 mo | 0.157 | 0.02–0.35 | β^{1}
| 2.2 | 11.8 | ||

2 y | 0.155 | 0.02–0.35 | Derived^{2}
| ||||

3–4 y | 0.155 | 0.02–0.35 | Derived | ||||

5–11 y | 0.08 | 0.01–0.18 | Derived | ||||

12–17 y | 0.06 | 0.01–0.14 | Derived | ||||

Probability of an outpatient visit for child with influenza illness^{3}
| (5,11,12)4 | ||||||

6–23 mo | 0.5 | 0.17–0.83 | β | 3.3 | 3.5 | ||

2 y | 0.47 | 0.15–0.81 | β | 3.29 | 3.71 | ||

3–4 y | 0.43 | 0.12–0.78 | β | 3.01 | 3.99 | ||

5–11 y | 0.28 | 0.11–0.5 | β | 5.6 | 14.4 | ||

12–17 y | 0.24 | 0.06–0.5 | β | 2.88 | 19.12 | ||

Probability of otitis media for a child with medically attended influenza illness | (13–16), expert panel | ||||||

6–23 mo | 0.63 | 0.33–0.8 | β | 6.3 | 3.7 | ||

2 y | 0.58 | 0.27–0.8 | β | 5.22 | 3.78 | ||

3–4 y | 0.39 | 0.17–0.6 | β | 6.24 | 9.76 | ||

5–11 y | 0.23 | 0.05–0.5 | β | 2.53 | 8.47 | ||

12–17 y | 0.15 | 0.01–0.4 | β | 1.5 | 8.5 | ||

Probability of nonhospitalized pneumonia or other outpatient complication for child with medically attended influenza illness^{5}
| (11,12); expert panel | ||||||

6–23 mo | 0.2 | 0.04–0.5 | β | 2.6 | 10.4 | ||

2 y | 0.15 | 0.02–0.4 | β | 1.95 | 11.05 | ||

3–4 y | 0.15 | 0.02–0.4 | β | 1.95 | 11.05 | ||

5–11 y | 0.11 | 0.02–0.3 | β | 2.2 | 17.8 | ||

12–17 y | 0.08 | 0.01–0.2 | β | 2.16 | 24.84 | ||

Hospitalizations for pneumonia or other respiratory conditions due to influenza per 10,000 children not at high risk^{6}
| (7,11,17); W. Thompson, pers. comm.) | ||||||

6–23 mo | 28.3 | 1.9–80.0 | β | 5.5 | 244.5 | ||

2 y | 17.1 | 0–56.8 | β | 3.4 | 246.6 | ||

3–4 y | 8.0 | 0–35.4 | β | 1.6 | 248.4 | ||

5–11 y | 3.1 | 0–16.0 | β | 7.95 | 1,492.1 | ||

12–17 y | 3.1 | 0–14.9 | β | 10.5 | 1,489.5 | ||

Probability of long-term sequelae after influenza-related hospitalization^{2}
| 0.01 | 0.001–0.03 | Expert panel | β | 1.3 | 11.7 | |

Probability of death during influenza-related hospitalization | 0.0009 | 0–0.002 | (18)4 | β | 1.7 | 18.3 | |

Vaccine effectiveness in preventing influenza illness9 | |||||||

IIV | 0.69 | 0.4–0.9 | (19)4 | β | 7.59 | 3.41 | |

LAIV | 0.838 | 0.6–0.96 | (20)4 | β | 16.76 | 3.24 | |

Probability of medically attended vaccination-related adverse events | |||||||

Injection site reaction | |||||||

6–23 mo | 0.008 | 0.002–0.017 | (8) | β | 4.0 | 46.0 | |

2 y | 0.003 | Derived^{10}
| |||||

3–4 y | 0.002 | Derived | |||||

5–11 y | 0.001 | Derived | |||||

12–17 y | 0.0003 | Derived | |||||

Systemic reaction (fever)11 | |||||||

6–23 mo | 0.013 | 0.001–0.025 | (20) | β | 5.2 | 194.8 | |

2 y | 0.011 | Derived | |||||

3–4 y | 0.009 | Derived | |||||

5–11 y | 0.004 | Derived | |||||

12–17 y | 0.003 | Derived | |||||

Anaphylaxis | 0.00000025 | 0–0.000001 | Expert panel | β^{12}
| 0.5 | 19.5 | |

Guillain-Barré syndrome | 0.000001 | 0–0.00001 | Expert panel | Triangular | 0.000001 (most likely) | 0 (min), 0.000002 (max) | |

Influenza-related costs | |||||||

OTC medications^{13}
| $3 | (21,22); J. Finkelstein, pers. comm.; expert panel | |||||

Physician visit for uncomplicated influenza^{14}
| $27 | $0–$180 | Marketscan database15 | Lognormal^{16}
| 32 | 27 | |

Physician visit for otitis media | |||||||

6–3 mo | $78 | $23–$197 | Marketscan database^{17}
| Lognormal | 98 | 78 | |

2–4 y | $83 | $23–$200 | Marketscan database^{17}
| Lognormal | 100 | 83 | |

5–17 y | $94 | $31–$245 | Marketscan database^{17}
| Lognormal | 117 | 94 | |

Physician visit for nonhospitalized pneumonia | |||||||

6–23 mo | $179 | $62–$715 | Marketscan database^{17}
| Lognormal | 252 | 179 | |

2–4 y | $88 | $27–$333 | Marketscan database^{17}
| Lognormal | 130 | 88 | |

5–17 y | $109 | $34–$503 | Marketscan database^{17}
| Lognormal | 187 | 109 | |

Hospitalization^{18}
| |||||||

6–23 mo | $4,306 | $1,307–$34,473 | Marketscan database^{17}
| Lognormal | 13194 | 4306 | |

3–4 y | $4,180 | $1,292–$32,030 | Marketscan database^{17}
| Lognormal | 10000 | 4180 | |

5–17 y | $5,135 | $1,373–$42,990 | Marketscan database^{17}
| Lognormal | 14956 | 5135 | |

Long-term sequelae following influenza-related hospitalization^{19}
| $625,000 | $0–$1,000,000 | (23) | ||||

Vaccination costs | |||||||

Per dose, IIV^{20} (children <3 y)
| $9.56^{21}
| 1×–4× base case | (21) | ||||

Per dose, IIV (children >3 y) | $6.86^{21}
| 1×–4× base case | (21) | ||||

Per dose, LAIV^{20}
| $12.89^{22}
| $10–$25 | (24,25) | ||||

Administration (0–2 visits)^{23}
| $25 | $10–$40 | (26) | ||||

Parent time costs^{24}
| $32 | $0–$62 | (27), expert panel | ||||

Total vaccination costs | $30–$110 | ||||||

6–23 mo | $79 | ||||||

2 y | $66 | ||||||

3–4 y | $59 | ||||||

5–11 y | $49 | ||||||

12–17 y | $49 | ||||||

Vaccination-related adverse events | |||||||

Physician visit for injection site reaction^{25}
| $61 | $30–$-683 | Marketscan database^{26}
| Lognormal^{16}
| 202 | 61 | |

Anaphylaxis^{27}
| $2,699 | $52–$13,754 | Marketscan database^{28}
| Lognormal^{16}
| 4527 | 2699 | |

Guillain-Barré syndrome^{29}
| $23,359 | $6,663–$78,912 | Marketscan database^{28}
| Lognormal^{16}
| 32196 | 23359 | |

Quality adjustments^{30,31} (disutility associated with an event)
| |||||||

Episode of influenza | 0.005 | 0.002–0.009 | (27)
| β | 7.35 | 1492.65 | |

Otitis media | 0.042 | 0.023–0.065 | (28)
| β | 14.56 | 335.44 | |

Nonhospitalized complications (pneumonia) | 0.046 | 0.027–0.071 | (28) | β | 16.21 | 333.8 | |

Hospitalization, pneumonia | 0.076 | 0.054–0.100 | (28) | β | 37.85 | 462.15 | |

Anaphylaxis | 0.02 | 0.006–0.041 | (27) | β | 4.53 | 225.47 | |

Guillain-Barré syndrome | 0.141 | 0.092–0.199 | (27) | β | 22.53 | 137.47
IIV, inactivated influenza vaccine; LAIV, live, attenuated influenza vaccine; OTC, over the counter. |

IIV, inactivated influenza vaccine; LAIV, live, attenuated influenza vaccine; OTC, over the counter.^{1}Distributions for transition probabilities were assigned using most likely values and ranges identified in the literature and/or expert panel. For these parameters, primary data were not available and beta distributions were assigned to match the values identified in the table.^{2}Distributions for age groups other than 6–23 mo are based on the 6- to 23-mo distribution multiplied by the ratio of the most likely estimates for the age group in question to children 6–23 mo (e.g., the distribution for 2 y is calculated by multiplying the distribution for 6–23 mo by 0.155/0.157).^{3}Estimates for healthy children are shown in Table. Probabilities are estimated to be twice as high for children at high risk for influenza-related complications.^{4}Range for sensitivity analysis determined by expert opinion.^{5}Estimates for healthy children shown in Table. Probabilities are estimated to be up to 5 times as high for children at high risk for influenza-related complications. Base case estimates for children at high risk are 1.6 times as high as for healthy children.^{6}Children at high risk are estimated to be hospitalized at 3–6 times the rate of healthy children.^{7}Probability from distribution divided by 10.^{8}Probability from distribution divided by 100.^{9}Assumes vaccine is poorly matched with circulating virus 1 in 10 years (i.e., vaccine effectiveness is assumed to be 0 in years with a poor match).^{10}Distributions for age groups other than 6–23 mo are based on the 6- to 23-mo distribution multiplied by the ratio of the most likely estimates for the age group in question to children ages 6–23 mo (e.g., the distribution for 2 years is calculated by multiplying the distribution for 6–23 mo by 0.003/0.008).^{11}Definitions and follow-up for incidence of fever following vaccination vary by study. Rates are 2× higher for high-risk subgroups.^{12}Probability from distribution divided by 100,000.^{13}Vary by age, calculated by costing out recommended dose of acetaminophen for average weight in each age group.^{14}Only a proportion of children with influenza illness are assumed to make a physician visit. ICD-9 codes: 487 and 487.0.^{15}1993–1997 Marketscan database, The Medstat Group, Ann Arbor, MI, USA.^{16}Lognormal distributions are approximated using the mean and median in Treeage. In this table, parameter 1 is the mean and parameter 2 is the median for each distribution.^{17}2001-2003 Marketscan database, The Medstat Group, Ann Arbor, MI.^{18}ICD-9 codes: 460-466, 471-474, 477, 478, 480-483, 490-496, 506-508, 510, 511, 514, 518, 519. 2001-2003 Marketscan database.^{19}Includes costs of lifetime care and special education.^{20}Assumed 2 doses will be required for children <5 years receiving their first influenza vaccination.^{21}Vaccine dose costs are based on 2004 CDC negotiated prices. Cost for children <3 years assumes thimerosal-free vaccine is used.^{22}Based on 2004 CDC negotiated price.^{23}Common Procedural Terminology (CPT) codes: 99211, 90471. Physician costs for vaccine administration at existing visit is $10.37 (90471); $19.95 for vaccine administration requiring a separate visit (99211).^{24}Each physician visit is assumed to take 2 hours of parent time valued at an average hourly wage rate of $15.54.^{25}5- minute visit, CPT code 99211.^{26} 2001–2003 Marketscan database.^{27}ICD-9 codes: 999.4, 995.0, 995.6x.^{28}2001-2003 Marketscan database.^{29}ICD-9 code: 357.0.^{30}Quality adjustments are included in the model as a one-time decrement in utility for each temporary health state. For example, an episode of influenza results in a one-time loss of 0.005 quality-adjusted life years (QALYs). Utility losses were calculated by dividing the discounted time-traded off by the respondent’s discounted life expectancy.^{31}Average life span used to calculate total QALYs lost due to life-long sequelae and death was 77.9–78.2 y, depending on child’s current age. See Table A1 References in Appendix.