Noroviruses are the leading cause of acute gastroenteritis in the United States and outbreaks frequently occur in daycare settings. Results of norovirus vaccine trials have been promising, however there are open questions as to whether vaccination of daycare children would be cost-effective. We investigated the incremental cost-effectiveness of a hypothetical norovirus vaccination for children in daycare settings compared to no vaccination.

We conducted a model-based cost-effectiveness analysis using a disease transmission model of children attending daycare. Vaccination with a 90% coverage rate in addition to the observed standard of care (exclusion of symptomatic children from daycare) was compared to the observed standard of care. The main outcomes measures were infections and deaths averted, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER). Cost-effectiveness was analyzed from a societal perspective, including medical costs to children as well as productivity losses of parents, over a two-year time horizon. Data sources included outbreak surveillance data and published literature.

A 50% efficacious norovirus vaccine averts 571.83 norovirus cases and 0.003 norovirus-related deaths per 10,000 children compared to the observed standard of care. A $200 norovirus vaccine that is 50% efficacious has a net cost increase of $178.10 per child and 0.025 more QALYs, resulting in an ICER of $7,028/QALY. Based on the probabilistic sensitivity analysis, we estimated that a $200 vaccination with 50% efficacy was 94.0% likely to be cost-effective at a willingness-to-pay of $100,000/QALY threshold and 95.3% likely at a $150,000/QALY threshold.

Due to the large disease burden associated with norovirus, it is likely that vaccinating children in daycares could be cost-effective, even with modest vaccine efficacy and a high per-child cost of vaccination. Norovirus vaccination of children in daycare has a cost-effectiveness ratio similar to other commonly recommended childhood vaccines.

Noroviruses are the leading cause of acute gastroenteritis (AGE) in the United States. It is estimated that approximately 19 to 21 million AGE cases are attributable to norovirus annually, and these cases result in 1.7–1.9 million outpatient visits, 400,000 emergency department visits, and between 570 and 800 deaths annually [

In the United States in 2018, 4.7 million children aged 3–5 attended pre-school (daycare), representing about 39.1 percent of this population [

We aimed to determine the cost-effectiveness of norovirus vaccination of children in daycare in addition to the observed standard of practice (excluding symptomatic children from these settings) relative to the observed standard practice alone.

We used a dynamic transmission model of norovirus outbreaks in daycare settings to determine the impact of disease in terms of children’s health outcomes [

To determine the attack rate under the vaccination and no vaccination scenarios, we adapted a transmission model (Havumaki et al., 2021 [

Under the natural history model of norovirus, individuals start as susceptible (S), partially immune (P) or fully recovered and immune (R) depending on the level of acquired immunity, from previous exposure or their innate resistance. The force of infection depends on: 1) the number of symptomatic individuals (I) and asymptomatic individuals (A); 2) the level of environmental fomite pathogen contamination (F); and 3) human-to-human and fomiteto-human transmission rates. The model also considers social distancing or individual exclusion (X), in which symptomatic children are removed from the daycare setting, as part of both the oSOC and vaccination strategies. Symptomatic children spend between 1 hour and 1 day in the symptomatic compartment before moving to the individual exclusion (X) compartment. The parameters of the infectious disease model are provided in Havumaki et al. 2021 [

We consider the impact of vaccination on the transmission dynamics of norovirus in the daycare setting. Because we do not know precisely how many doses might be required for a norovirus vaccine, we do not make any assumptions about whether the vaccine would be 1 or 2 doses. Rather we only consider that the total cost and total efficacy of the complete administration of all dose(s). At the individual level, we assumed that, based on vaccine efficacy, either the vaccine completely protects the individual against symptomatic infection or the individual remains completely susceptible; i.e., the vaccine take (immunity) is all or nothing. Although some clinical trials for vaccines that prevent a norovirus infection are in late stages, data on the vaccine take, efficacy, and coverage are not available yet. At the population level, we considered two scenarios, one with a 50% and another with an 80% vaccine efficacy. These two estimates are from vaccine challenge studies that suggested vaccination reduces disease by approximately 50% among vaccinated individuals [

The model was adapted from a previously calibrated transmission model [

The model takes a societal perspective of cost. All costs were converted to a 2019 dollars using the gross domestic product implicit price deflator [

At baseline, we assumed a net cost of norovirus vaccine dose(s) and administration to be $200 based on existing costs of newer (HPV, Zoster, and rotavirus) vaccines [

We categorize the medical costs associated with a norovirus outbreak as medical (outpatient, inpatient, ED visit oral hydration therapy, over the counter drugs), and nonmedical (transportation costs, parent/caregiver time). Of children symptomatically infected with norovirus, patients utilize the healthcare system through outpatient office visits, emergency department visits, and hospitalization with age-based probabilities listed in [

In addition to cost outcomes, we consider the impact of norovirus infection on mortality and quality-of-life (QOL). We assigned event-specific quality-of-life weights from previously published studies of children age 18 months to 5-years of age [

Overall costs and QALYs from the two strategies of the oSOC and vaccination were compared using an incremental cost-effectiveness ratio (ICER) which examines the incremental cost of vaccination (compared to the oSOC) divided by the incremental QALYs gained from vaccination (compared to the oSOC) [

We performed a 1-way sensitivity analysis to estimate the effects of input assumptions (vaccine coverage, costs, event probabilities, and QOL weights) on ICERS. The transmission model is a stochastic model so we evaluated the model with respect to 2500 samples of the infectious disease model parameters (taken from Havumaki et al. 2021 [

The average-per-person cost was $29.82 for the oSOC while norovirus vaccination accrued costs of $207.02 and $200.08 on average per-person in the 50% and 80% efficacy scenarios when the cost of the vaccine was $200. No vaccination led to 0.052 QALYs lost per child due to norovirus while the vaccination scenarios averaged 0.027 and 0.013 QALYs lost due to norovirus in the 50% and 80% efficacy scenarios.

Using 1-way sensitivity analysis, we identified the 10 variables that had the largest effect on ICERs. The ICERs were most sensitive to the probability of norovirus introduction within the vaccination efficacy period, days in supportive care, and quality-of-life being in supportive care.

Because the probability of norovirus introduction was the most sensitive parameter in our analysis, we explored its full variability by conducting a detailed one-way sensitivity analysis.

Based on the probabilistic sensitivity analysis, we estimated that a $200 vaccination with 50% efficacy was 94.0% likely to be cost-effective at a WTP of $100,000/QALY threshold and 95.3% likely at a $150,000/QALY threshold (shown in

Due to the large disease burden associated with norovirus, it is likely that vaccinating children in daycares could be cost-effective, even with modest vaccine efficacy and a high per-child cost of vaccination. Even with a high price of $500 per child vaccinated and a modest efficacy of 50%, vaccination is cost-effective at a WTP threshold of $100,000 per additional QALY. Compared to the oSOC, vaccination incurs more costs, but also achieves more QALYs. Vaccination leads to a modest reduction in costs related to managing norovirus infections, but these reductions do not offset the increased costs of vaccination of children. However, even with modest efficacy, vaccination gains 253 QALYs per 10,000 children over the oSOC, leading vaccination to be cost-effective.

To our knowledge, this is the first study to evaluate the health and cost impact of norovirus vaccination of a pediatric population within daycares. Earlier studies suggest that pediatric populations (children under the age of 5) would be the most impactful target population for norovirus vaccination given children’s role in the transmission of norovirus [

These results are somewhat similar to rotavirus vaccination (another cause of acute gastroenteritis). One study found rotavirus vaccination had an ICER of about $200,000 per life-year saved [

The cost-effectiveness of norovirus vaccination is sensitive to the probability of introduction of norovirus into the daycare during the vaccination protection period. One-way sensitivity analyses showed that norovirus vaccination is still cost-effective using conventional thresholds in all scenarios if the probability of norovirus introduction into the daycare during the coverage period is at least 10%. Therefore, the duration of the vaccination protection period and the probability that norovirus would be introduced into a daycare during this period may be important factors to consider. In addition, the results were somewhat sensitive to quality-of-life measures for supportive care and outpatient visits which are the most common management options for symptomatic norovirus infections. The results of the probabilistic sensitivity analysis show that norovirus vaccination is more likely to be cost-effective at conventional thresholds than not, even with high cost and modest efficacy.

Our study has limitations. First, the norovirus outbreak model is calibrated to data that relies on self-reporting. These data may be under-reporting outbreaks which could potentially lead to attack rate, duration, and population size distributions that are not representative of all outbreaks in the U.S. Second, we do not include severe adverse events associated with vaccination, asymptomatic testing, daycare closures, or decontamination of daycares as part of the oSOC which could reduce the cost-effectiveness of vaccination. Third, we ignore the impact of secondary infections caused by infected children to others outside of the daycare. The findings from Steele et al. 2016 [

In conclusion, the use of vaccination against norovirus is likely to be cost-effective in children within daycares. Even with modest efficacy and a high cost, vaccination leads to an ICER/QALY value that is most likely cost-effective at conventional thresholds.

Funding

This study was funded by the Joint Initiative in Vaccine Economics, Phase 5, a cooperative agreement between the University of Michigan and the Centers for Diseases Control and Prevention (U01IP000965).

Disclaimer

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention (CDC).

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

With the following descriptions:

_{1}; _{2}; _{3} = Exposed to infection

_{1},_{2}; _{3} = Infected, asymptomatic

_{a} = Vaccinated, asymptomatic

_{t} = Excluded

_{1t}, _{2t} = Contaminated Fomite

The model is represented using continuous time through an ordinary differential equation model. However, when implementing the model, the proportion of individuals across disease states is updated at predefined timesteps (every 1/25 of a day).

To estimate the risk of norovirus introduction (at a level sufficient to cause an outbreak in the absence of vaccination), we used data from the United Kingdom estimating norovirus incidence using several methods and examining different age groups [

Initial condition values and uncertainty ranges.

Symbol | Description | Initial Value |
---|---|---|

T | Total population | Sampled from the NORS Dataset |

S | Susceptible | (1− |

_{1} to _{3} | Exposed | 0 children |

I | Symptomatically infected | 0 children |

_{1} to _{3} | Asymptomatically infected | 0 children |

R | Recovered | 0.2*T |

P | Partial immunity | r*T where r is randomly sampled from the Uniform(0,0.8) |

X | Excluded | 0 people |

_{1},_{2} | Contaminated fomite tracking compartments | 10 million pathogens (0–100 million) |

V | Partially immune due to vaccination |

The percentage starting with partial immunity is varied because there is not an established correlate of protection [

Input parameter values and ranges in the infectious disease model from Havumaki et al. (2021) [

Infectious disease model parameter | Symbol | Estimate/uncertainty ranges | Units | Reference |
---|---|---|---|---|

Outbreak transmission model parameters | ||||

Rate of transition through each latent state |
| 2.6 | days^{−1} | [ |

Proportion of latent individuals that do not become symptomatic |
| 0.3 | unitless | [ |

Transition rate from symptomatic (I) to asymptomatic (_{1}) |
| 0.8 | days^{−1} | [ |

Recovery rate |
| 0.2 | days^{−1} | [ |

Shedding rate for diseased (I, A, X) individuals |
_{I} | 0.2520 (0.000499–0.5000) | Pathogens /day | [ |

Rate of reduction in shedding, |
| 0.2 | unitless | [ |

Biphasic decay rate of norovirus in the environment |
| 0.763 (0.036 to 1.515) | days^{−1} | [ |

Reduction factor for asymptomatic shedding and transmission, (relative to symptomatic individuals) |
_{A} | −2.32 (−4.00 to −0.026) | unitless (sampled in log space) | [ |

Transmission rates | ||||

Human-to-human transmission rates |
_{HH} | infection/ time | [ | |

Fomite-to-human transmission rate derived by multiplying a scaling factor [0,2] |
_{FH} | 0 to 2_{HH} | unitless | Assumption |

Exclusion parameters | ||||

Transition rate from symptomatic (I) to excluded (X) |
| 1 to 24 | days^{−1} | Assumption |

We allow for a wide range of values which can increase or decrease rates relative to

Using 16.7 per 100 person-years as a base-case of incidence, if we assume that 50% of norovirus cases are from norovirus outbreaks in daycares, then we have that there are 8.35 new daycare outbreak cases per 100 person-years. Based on our model, we found that a norovirus outbreak leads to a 22.8% attack rate in the absence of vaccination and therefore the annual probability of introduction of norovirus at a sufficient level to cause an outbreak is 0.3662 (0.0835/0.228 = 36.62 persons per 100). This corresponds to rate of norovirus introduction at a sufficient level to cause an outbreak of 0.3662 and therefore a two-year probability of a norovirus introduction at a sufficient level to cause an outbreak is 0.5193. We define a norovirus outbreak in a daycare setting as at least one symptomatic case of norovirus within the daycare.

Phillips et al. [

Distributions were generally chosen as normal distributions with the mean chosen to represent the base case value and the standard deviation chosen so that the 95% of the time, the variable will cover the range. Most of the time, there was little risk the distribution simulated would give a value outside of a reasonable range (probabilities < 0, probabilities > 1, utilities < 0, utilities > 1, costs < 0). However, we did left truncate the distribution for emergency department visits at 0 as the range was wide enough it could lead to an appreciable risk of giving a value<0. We also used Beta distributions for the utilities and probabilities. These distributions were parameterized with the mean as the base case value and the standard deviation representing a quarter of the range in the one-way sensitivity analysis. We used Gamma distributions for costs, and they were parameterized with the mean as the base case value and the standard deviation representing a quarter of the range in the one-way sensitivity analysis. We selected a lognormal distribution for days for the length of infection symptoms so this time would not be <0.

Our analysis assumes that the period of effective protection is two-years. However, we also considered a scenario in which the vaccine’s effective protection is only one year, so that daycares would need to vaccinate twice within the two-year period. In this scenario, we assume that all vaccination costs (costs from administering and costs of the vaccine) are doubled relative to the two-year protection scenario. We found that the assumption did not affect the cost-effectiveness. In this case, the ICER for a $200 vaccination cost scenario was $14,380/QALY and $9,105/QALY when the vaccine efficacy was 50% and 80%, respectively. The resulting costs are provided in

Our analysis simulates a single introduction during the period of effective protection provided by the vaccine. These simulations show different attack rates under vaccination versus the oSOC. However, more than one outbreak could occur during the period. The key question is, how would infection outcomes be different between the vaccination and the oSOC during a second introduction? To get a sense of how those outcomes could be different during a second introduced outbreak, we look at the differences in the number of susceptible children at the end of the first introduction (and presumably the start of a second introduction), shown in

Differences of the number of susceptible children after a primary norovirus introduction under the observed standard of care (oSOC) and a vaccination program. For each vaccine efficacy scenario, we show a histogram showing the differences in number of susceptible children after an outbreak with a vaccination program in place versus the oSOC. Most of the time there are small differences in the number of susceptible children, however there are some simulated outbreaks for which these differences are larger.

One-way sensitivity analyses for the 80% vaccine efficacy scenarios when the net cost of vaccination is (a) $200 and (b) $500. QALY: quality-adjusted life-year. ICER: Incremental cost-effectiveness ratio.

In general, due to either the induced immunity from infection after recovery or residual protection from vaccination, the number of children remaining susceptible prior to a second introduction is very similar between vaccination and the oSOC. Therefore, it would be expected that the disease outcomes in a second introduction are unlikely to be substantially different between vaccination and the oSOC. We believe that omitting a second introduction is unlikely to substantially change the conclusions.

One-way sensitivity analyses for the 50% vaccine efficacy scenarios when the net cost of vaccination is (a) $200 and (b) $500. QALY: quality-adjusted life-year. ICER: Incremental cost-effectiveness ratio.

Difference in the recovered (R), susceptible (S), partially immune (P) compartments at the end of outbreak between the vaccination strategy (V) and the observed standard of care (oSOC) in terms of the absolute number of children in the daycare.

Vaccine efficacy | R_{oSOC}-R_{V} | P_{oSOC}-P_{V} | S_{oSOC}-S_{V} | ||||||
---|---|---|---|---|---|---|---|---|---|

Average | Min | Max | Average | Min | Max | Average | Min | Max | |

0.5 | 3.34 | −24 | 92 | −4.75 | −85 | 14 | 1.46 | −29 | 80 |

0.8 | 5.40 | −26 | 116 | −8.40 | −131 | 12 | 3.09 | −19 | 110 |

Difference in the recovered (R), susceptible (S), partially immune (P) compartments at the end of outbreak between the vaccination strategy (V) and the observed standard of care (oSOC) as a percentage of the number of children in the daycare.

Vaccine efficacy | R_{oSOC}-R_{V} (%) | P_{oSOC}-P_{V} (%) | S_{oSOC}-S_{V} (%) | ||||||
---|---|---|---|---|---|---|---|---|---|

Avg | Min | Max | Avg | Min | Max | Avg | Min | Max | |

0.5 | 3.3 | −21.6 | 80 | 4.5 | −70 | 14 | 1.2 | −43.3 | 38.1 |

0.8 | 5.4 | −18.9 | 80 | 8.1 | −75 | 11.8 | 2.9 | −22.4 | 52.9 |

We conducted a one-way sensitivity analysis on the proportion of latent individuals who do not become symptomatic. We varied this proportion from 10% to 50% while keeping all other model parameters in the infectious disease model constant. We found that, in all cases, the ICER was below $50,000/QALY and did not change our findings.

In the case where 10% of individuals do not become symptomatic, the attack rate in the absence of vaccination was 0.298 and the attack rate with a 50% effective vaccine was 0.154. In this case, vaccination led to an ICER of $1,426 in the case of a $100 vaccine that was 80% effective and an ICER of $13,433 in the case of a $500 vaccine that was 50% effective.

In the case where 50% of individuals do not become symptomatic, the attack rate in the absence of vaccination was 0.157 and the attack rate with a 50% effective vaccine was 0.082. The ICER was $3,256 in the case of a $100 vaccine that was 80% effective and the ICER was $26,402 in the case of a $500 vaccine that was 50% effective.

We use 0.8 as the utility weight for supportive care. This value came from [

Here, we provide additional details related to the health outcomes and their corresponding QALYs and costs under the base-case analysis and the sensitivity analyses.

Norovirus-related health outcomes averted per 10,000 children vaccinated.

Vaccine efficacy | Norovirus-related outcomes averted per 10,000 children | ||||
---|---|---|---|---|---|

Cases of norovirus | Outpatient visits | ED visits | Hospitalizations | Deaths | |

50% | 571.83 | 96.07 | 11.44 | 2.45 | 0.003 |

80% | 882.57 | 148.27 | 17.65 | 3.78 | 0.005 |

Costs related to the management of norovirus infection.

Vaccine efficacy | Infection-related costs per 10,000 children, $ | |||
---|---|---|---|---|

Outpatient visits | ED visits | Hospitalizations | Supportive care | |

No vaccination(oSOC) | 62,376 | 10,117 | 18,195 | 216,447 |

50% | 32,193 | 5,222 | 9,390 | 111,709 |

80% | 15,790 | 2,561 | 4,606 | 54,792 |

oSOC: observed standard of care.

Cost-effectiveness of norovirus vaccination compared with the oSOC in the different vaccination cost and efficacy scenarios, assuming a one-year coverage period.

Vaccine efficacy | Cost of vaccination, $ | Attack rate | Cost, $ | QALYs | QALYs lost due to norovirus | ICER, $/QALY | ||
---|---|---|---|---|---|---|---|---|

Medical | Non-medical | Total | ||||||

No Vaccination (oSOC) | - | 0.228 | 4.55 | 26.16 | 30.71 | 29.967 | 0.052 | NA |

50% | 100.00 | 0.117 | 179.91 | 37.92 | 217.83 | 29.993 | 0.027 | 7,384 |

200.00 | 0.117 | 357.21 | 37.92 | 395.13 | 29.993 | 0.027 | 14,380 | |

500.00 | 0.117 | 889.11 | 37.92 | 927.03 | 29.993 | 0.027 | 35,370 | |

80% | 100.00 | 0.058 | 178.72 | 31.04 | 209.75 | 30.006 | 0.013 | 4,475 |

200.00 | 0.058 | 356.02 | 31.04 | 387.05 | 30.006 | 0.013 | 9,105 | |

500.00 | 0.058 | 887.92 | 31.04 | 918.95 | 30.006 | 0.013 | 22,696 |

QALY: quality-adjusted life-year.

ICER: incremental cost-effectiveness ratio.

Future costs and QALYs are discounted. ICERs are reported based on unrounded costs and QALY estimates.

High-level decision tree of the decision to vaccinate children in daycare. After deciding whether or not to vaccinate the children in daycare, norovirus may be introduced into the daycare within the two-year period with probability _{I}. Then, given that norovirus was introduced into the daycare setting, the infectious disease model determines the fraction of children that become symptomatically infected with norovirus. The fraction of children that get infected depends on their vaccination status. In the case of vaccination, the fraction of children infected given the introduction of norovirus is denoted by _{V} and if the policy decision is to not vaccinate and follow the oSOC, then the fraction is denoted by _{oSOC}. The fraction of infected individuals that develop symptoms is denoted _{S}. From there, a fraction of symptomatically infected children will receive supportive care, various levels of medical care, or die. The final branches represent the highest level of care received.

Model schematic for a norovirus outbreak in a daycare setting. The black portion of the schematic shows norovirus outbreak in the absence of vaccination while the dark grey components of the schematic shows the disease transmission process under vaccination. In the no vaccination scenario, children begin in the susceptible pool (S) and become exposed according to the force of infection _{1} through _{3}) before becoming symptomatically infected or asymptomatically infected (_{1} through _{3}). We consider social distancing or individual exclusion, where children are removed from the daycare setting, which is represented by (X). During infection, children may shed pathogens onto environmental fomites (_{1}). Pathogens on the fomites decay, moving to _{2} which represents biphasic decay. Individuals may become immune following their infection. Individuals may also have innate resistance (R) or may be partially immune (P) at the start of the outbreak. Those starting in (R) do not become infected whereas those starting in (P) may become asymptomatically infected. Under a vaccination program, individuals for which the vaccination takes are provided partial immunity (V), although they may become asymptomatically infectious (_{a1} to _{a3}). Like those starting in (P), although these individuals cannot become symptomatically infected, they may contribute to the force of infection and shed on fomites. All parameters values are listed in

Sensitivity of the Base-case Incremental Cost-effectiveness ratio to key parameters ranked by importance and for the 50% efficacy and $200 cost scenario. NV: norovirus QALY: Quality-Adjusted Life-Year ICER: Incremental Cost-Effectiveness Ratio.

Sensitivity of the Incremental cost-effectiveness ratio to the probability that norovirus is introduced into the daycare in the two-year period. The base case probability is 51.9%. The dashed vertical line corresponds to a 2% probability that norovirus is introduced into the daycare setting within the two-year period. QALY: Quality-Adjusted Life-Year ICER: Incremental Cost-Effectiveness Ratio.

Probability of vaccination being cost-effective by willingness-to-pay threshold under various scenarios of vaccine cost and efficacy. QALY: Quality-Adjusted Life-Year.

Estimates for key economic model parameters. Costs were converted to a 2019 baseline.

Economic model parameter | Base case | Sensitivity analysis | Reference | |
---|---|---|---|---|

1-way analysis range | Distribution for probabilistic sensitivity analysis | |||

Norovirus-outbreak parameters | ||||

Two-year probability of introduction of norovirus into daycare facility | 0.5193 | 0.2004–0.9700 | Beta(2.8,2.6) | Assumption^{†} |

Probability estimates for healthcare utilization in the event of symptomatic infection | ||||

Outpatient office visit | 0.168 | 0.1008–0.2352 | Beta(20,98) | [ |

Emergency department visits | 0.02 | 0.01–0.03 | Beta(15,740) | [ |

Hospitalization | 0.00428 | 0.002568–0.005992 | Beta(24,5600) | [ |

Death | 0.000006 | 0.000003–0.000007 | Beta(35,5800000) | [ |

Quality-of-life (health utility weight) | ||||

Perfect health | 1.00 | [ | ||

Norovirus episode requiring supportive care | 0.80 | 0.7–0.9 | Beta(48,12) | [^{¶} |

Norovirus episode requiring health provider care | 0.69 | 0.55–0.82 | Beta(30,14) | [ |

Norovirus episode requiring emergency care | 0.425 | 0.33–0.52 | Beta(30,14) | [ |

Norovirus episode requiring hospitalization | 0.2 | 0.05–0.35 | Beta(5.3,21) | [ |

Death | 0.00 | [ | ||

Disutility from vaccination side effects | 0.001 | [ | ||

Vaccination costs | ||||

Cost of vaccination (administration and all doses) | $100, $200, $500 | Assumption | ||

Parental Time, hours | 1 | 0.5–1.1 | Gamma(43,0.023) | Assumption |

Fraction experiencing minor side effects | 0.046 | 0.026–0.066 | NA | [ |

Cost due to minor side effects (Children’s ibuprofen) | $3.25 | $1.63–4.88 | NA | [ |

Infection costs | ||||

Over-the-counter medications (per day) | $3.23 | $1.61–4.84 | Gamma(15,0.21) | [ |

Days^{§} | 2 | 1–3 | Lognormal(0.4, 0.8) | [ |

Outpatient visit, ages 0–4 | $93.89 | $86.24–101.53 | Normal(93.89,3.90) | [ |

Emergency department visit, physician | $42.12 | +/− 10% | Normal(42.12,2.15) | Medicare (physician) HCPCS 99,282 [ |

Emergency department visit, facility | $124.65 | +/− 10% | Normal(124.65,6.40) | Medicare (facility) APC 5022 [ |

Inpatient hospitalization, ages 0–4 | $3,312.09 | $3,304.98–3,619.19 | Normal(3312.33,156.98) | [ |

Productivity costs (Parents) | ||||

Market productivity, daily^{‡} | $141.64 | +/− 10% total | +/− Normal(1,0.05)% total | [ |

Non-market productivity, daily^{‡} | $78.66 | productivity | productivity | [ |

Numbers in parentheses for Uniform represent the minimum and maximum of the range. Numbers in parentheses for Normal represent the mean and standard deviations. Numbers in parentheses for Lognormal represent the mean and standard deviation of the distribution on a log scale. See

See

Productivity was estimated as an averaged of productivity for adults aged 25–44.

Days refers to the length of symptomatic infection. It is used to calculate total costs of over-the-counter medications with supportive care, as well as loss of quality-of-life associated with all infection outcomes.

See

Norovirus-related health outcomes per 10,000 children for the vaccine efficacy scenarios.

Vaccine efficacy | Norovirus-related outcomes per 10,000 children | ||||
---|---|---|---|---|---|

Cases | Outpatient visits | ED visits | Hospitalizations | Deaths | |

No Vaccination (oSOC) | 1181.71 | 198.53 | 23.63 | 5.06 | 0.007 |

50% | 609.88 | 102.46 | 12.29 | 2.61 | 0.004 |

80% | 299.14 | 50.25 | 5.98 | 1.28 | 0.002 |

oSOC: observed standard of care.

ED: emergency department.

Cost-effectiveness of norovirus vaccination compared with the oSOC in the different vaccination cost and efficacy scenarios.

Vaccine efficacy | Cost of vaccination, $ | Attack rate | Cost, $ | QALYs | QALYs lost due to norovirus | ICER, $/QALY | ||
---|---|---|---|---|---|---|---|---|

Medical | Non-Medical | Total | ||||||

No Vaccination (oSOC) | - | 0.228 | 4.42 | 25.40 | 29.82 | 29.967 | 0.052 | NA |

50% | 100.00 | 0.117 | 92.41 | 25.50 | 117.92 | 29.993 | 0.027 | 3,476 |

200.00 | 0.117 | 182.41 | 25.50 | 207.92 | 29.993 | 0.027 | 7,028 | |

500.00 | 0.117 | 452.41 | 25.50 | 477.92 | 29.993 | 0.027 | 17,629 | |

80% | 100.00 | 0.058 | 91.25 | 18.82 | 110.08 | 30.006 | 0.013 | 2,051 |

200.00 | 0.058 | 181.25 | 18.82 | 200.08 | 30.006 | 0.013 | 4,350 | |

500.00 | 0.058 | 451.25 | 18.82 | 470.08 | 30.006 | 0.013 | 11,249 |

QALY: quality-adjusted life-year.

ICER: incremental cost-effectiveness ratio.

Future costs and QALYs are discounted. ICERs are reported based on unrounded costs and QALY estimates.