Cost-effectiveness of pediatric norovirus vaccination in daycare settings

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Cost-effectiveness; Norovirus; Vaccination.

Fig. A2.

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.

Fig. A3.

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.

Fig. A4.

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.

Fig. 1.

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 p_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 p_V and if the policy decision is to not vaccinate and follow the oSOC, then the fraction is denoted by p_oSOC. The fraction of infected individuals that develop symptoms is denoted p_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.

Fig. 2.

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 λ(t) and pass through a latent period (E₁ through E₃) before becoming symptomatically infected or asymptomatically infected (A₁ through A₃). 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 (F₁). Pathogens on the fomites decay, moving to F₂ 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 (V_a1 to V_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 Appendix Table A2.

Fig. 3.

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.

Fig. 4.

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.

Fig. 5.

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