Introduction
Methods
Updated rotavirus disease burden
Rotavirus community incidence
Parameter | Total population | Non-target group | Target group | Distribution | Data source | Method |
---|---|---|---|---|---|---|
Birth cohort n (%) | 171,387 | 157,847 (92.1%) | 13,540 (7.9%) | Fixed | Birth cohort size 2016. Prevalence of high-risk conditions, same as in Bruijning et al. [11] | |
Rotavirus incidence |
Most likely value (minimum–maximum)
| |||||
Population: < 1 year | 15,188 (10,161-21,597) | Calculated | Pert | Incidence based on simulations from original study data (for details see [17]), scaled to the years 2013–2017. Distribution among non-target and target groups based on relative size of each category in birth cohort | ||
Population: 1–4 years | 35,756 (21,805-54,972) | |||||
Population: 5–14 yearsa | 7897 (1426-26,004) | |||||
GP visits < 1 year | 21.5% (12.8–29.1%) | Pert | GP-based cohort study [13] | Percentage of rotavirus cases based on simulations from original study data (for details see [17]) | ||
GP visits 1–4 years | 18.5% (16.3–20.8%) | |||||
GP visits 5–14 years | 6.4% (4.8–7.3%) | |||||
Community-acquired (CA) hospitalization | 2024 (1789 – 2256) | 82.8% (82.7– 82.9%) of total | Calculated (total minus non-target) | Pert | Incidence based on original study data (for details see [11]) and scaled to the years 2013–2016. Distribution over non-target and target groups and over CA and nosocomial cases based on active AGE surveillance in 2014–2016 | |
Nosocomial infections per CA case | Calculated | 0.21 (0.206–0.213) | 0.89 (0.88–0.90) | Pert | RIVAR AGE surveillance [18] | |
Mortality rate/1000 hospitalizations | Calculated | 0.00 (0.00; 0.04) | 0 81 (0.36; 1.46) | Pert | RoHo study [14]; External dataset Sophia Children’s hospital | For details see [11] |
Age distribution of hospitalizations and fatal cases | RoHo study [14]; | Same as [11] | ||||
Intussusception (IS) incidence | ||||||
Vaccine-induced IS risk | 1/50,000 vaccinated children | Fixed | ||||
Complicated (with intestinal resection) | 4.8% of induced IS cases | Fixed | [36] | Calculated from [36]: 56 with resection out of 1176 IS cases in infants < 12 months | ||
Utilities rotavirus AGE | QALY loss | |||||
Mild (no medical care) | 0.0011 | Fixed | GP study in Canada [48] | |||
Moderate (GP visit only) | 0.0022 | Fixed | GP study in Canada [48] | |||
Severe (hospitalization) | 0.0034 | Fixed | Emergency-department study in UK [20] | |||
Nosocomial | Calculated | Calculated | Calculated | RoHo study [14] | Based on severity distribution, same as in [10] | |
Rotavirus fatal cases | Calculated | 81.5 minus patient age at rotavirus infection | Simulated, assuming LE of 1; 20; 41.3 minus patient’s age with probability of 1/3 each | Uniform | For non-target group, based on average LE in the Netherlands. For target group, same as Bruijning et al. [11] | |
Utilities intussception | QALY loss | |||||
Uncomplicated IS | 0.0037 | Fixed | Based on Reyes et al. [37] | |||
Complicated IS | 0.0111 | Fixed | Assumption | Assuming three times more severe than uncomplicated IS; see Additional file 1 | ||
Healthcare costs rotavirus AGE | ||||||
No medical care | €0 | Fixed | ||||
Standard GP visit (€/unit) | €33 | Dutch reference prices [22] | If GP attendance; home visit: Pert (0; 0.1; 0.1), standard GP visit: Pert (0.9; 0.9; 1.0), and GP telephone consultation: Pert (0; 0.97; 0.97); same as in [11, 17] Average cost/episode including antibiotics, oral rehydration solutions, and other prescribed drugs/GP consultation (home or standard GP visit) | |||
GP home visit (€/unit) | €50 | |||||
GP telephone consultation (€/unit) | €17 | |||||
Drug costs incl. Prescription fee (€/unit) | €43 | |||||
Laboratory costs (€/unit) | €78 | Expert elicitation | 10% with laboratory test [52] | |||
Ambulance (€/unit) | €618.6 | Fixed | Dutch reference price [22]; hospital-based observational study [50] | 1% of hospitalized cases transported by ambulance [50] | ||
Rotavirus hospitalization (€/hospitalization) | Calculated | €2417 (2248–2584) | €2828 (2782–4000) | Pert | RoHo study [11] | Weighted estimates from original study data (see additional file in [11]) |
Nosocomial rotavirus (€/hospitalization) | Calculated | €2413 (1378–3048) | €2361 (1334–3388) | |||
Uncomplicated IS (€/hospitalization) | €1423 | Fixed | Average LOS for Dutch IS cases = 2.11 days + costs of diagnostics (i.e., abdominal X-ray, ultrasonography) | |||
Complicated IS (€/hospitalization) | €6759 | Fixed | Assumption | 3× LOS for uncomplicated IS, whereof 1 day in ICU, and additional procedures (i.e., ileocecal resection, abdominal X-ray, ultrasonography). See Additional file 1 | ||
Patient and family costs for rotavirus AGEb | ||||||
Without medical care | Additional diapers | Uniform | Assumption | |||
Requiring GP visit | Additional diapers and travel costs | Pert | Assumptions and guidelines for health economic evaluation [22] | |||
Hospitalization | Travel costs | |||||
Nosocomial rotavirus | Not applicable | |||||
Productivity losses caregiver | ||||||
Cost per hour paid work loss | €32 | |||||
Hours of paid work loss per episode:
| ||||||
Without medical care | 1 day (~ 8 h) in 5% of episodes | Beta | RotaFam (see Additional file 1) | For children > 10 years of age work loss estimates were reduced by 50% | ||
Requiring GP visit | 0.5–2 days in 25% of episodes | Beta; uniform | RotaFam (see Additional file 1) | |||
Hospitalization | 26.40 | Based on [50] | For details see [17] | |||
Nosocomial AGE | 24.58 | Based on [50] | For details see [11] | |||
Uncomplicated IS | 4.93 | Fixed | Based on LOS and applying average caregiver employment of 16.4 h/week (similar to Mangen et al. [38])d | |||
Complicated IS | 14.79 | Fixed | ||||
Vaccine coverage | Universal vaccination | Targeted vaccination | ||||
Vaccine coverage | 86.2% | 86.2% | Fixed | Discrete choice experiment [28] | ||
Vaccine efficacy | Pert | |||||
Herd protection | See Table 2 | Not applicable | Fixed | Published estimates, see Table 2 | Only for universal vaccination scenarios | |
Vaccination costs | ||||||
Vaccine costs/infantsc | €75 | €135.32 | Fixed | |||
Application and administration costs | €12.36 | €12.36 | Fixed | [30] | ||
Start-up cost first year | €233,760 | Fixed | [17] |
Rotavirus hospitalizations
Other parameter updates
Intussusception
Model
Cost-effectiveness and risk-benefit analyses
Sensitivity and scenario analyses
Results
Disease and cost burden | AGE episodes (× 1000) | Hospitalizationsa (× 1000) | Fatal cases | Vaccine- induced IS | QALYs lostb | Life years lostb | Net societal costsb (mio €) | |
No vaccination | 1251 (903–1627) | 54 (48–60) | 110 (59–175) | NA | 2597 (1681–3727) | 1309 (471–2372) | 180 (153–218) | |
Targeted vaccination | 1208 (871–1573) | 46 (41–51) | 12 (5–23) | 4.61 | 1458 (1057–1890) | 195 (18–463) | 163 (139–199) | |
Universal vaccination | 586 (407–789) | 14 (12–16) | 7 (4–11) | 58.40 | 689 (477–923) | 105 (5–245) | 278 (268–294) | |
Incremental results from vaccination | Averted AGE episodes (× 1000) | Averted hospitalizations (× 1000) | Averted fatal cases | Additional IS | Incremental QALYs gained | Incremental life years gained | ∆ net societal costs (in mio €)c | ICER €/QALY gained |
Targeted vaccination vs no vaccination | ||||||||
Absolute change | 433 (32–55) | 8 (7–9) | 99 (54–153) | 4.61 | 1139 (426–2022) | 1114 (399–2004) | -−17c (−21 to –13.6)c | Cost-saving (cost-saving − cost-saving) |
Percent reduction | 3.4% (2.9–4.0%) | 14.7% (13.9–15.3%) | 89.8% (86.7–92.2%) | NA | 42.7% (23.0–57.7%) | 85.6% (72.3–97.2%) | 9.4% (8.0–11.0%) | NA |
Universal vaccination vs no vaccination | ||||||||
Absolute change | 664 (482–864) | 40 (35–45) | 103 (56–165) | 58.40 | 1907 (1114–2915) | 1204 (428–2191) | 98 (74–116.4) | 51,277 (29,259–94,686) |
Percent reduction | 53.2% (48.1–58.4%) | 74.4% (71.9-76.5%) | 93.9% (92.7–94.8%) | NA | 72.9% (63.0–81.1%) | 92.1% (82.5–99.3%) | NA | NA |
Universal vaccination vs targeted vaccinationd | ||||||||
Absolute change | 622 (451–810) | 32 (28–36) | 4 (1–12) | 53.79 | 769 (561–1003) | 90 (9–239) | 115 (94–131) | 149,282 (101,101–220,113) |
Percent reduction | 51.5% (46.5–56.7%) | 70% (67.4–72.3%) | 39.5% (26.9–53.4%) | NA | 52.8% (47.6–58.8%) | 48.2% (25.4–88.6%) | NA | NA |
Induced IS: prevented fatal cases | Induced IS: prevented hospitalized cases | Induced complicated IS: prevented fatal cases | Induced complicated IS: prevented hospitalized cases | |
---|---|---|---|---|
All children | ||||
Targeted vaccination | 1:21 (1:12–1:33) | 1:1707 (1:1494–1:1920) | 1:445 (1:244–1:691) | 1:35,564 (1:31,126–1:39,995) |
Universal vaccination | 1:1.8 (1:1.0–1:2.8) | 1:685 (1:603–1:767) | 1:37 (1:20–1:59) | 1:14,267 (1:12,566–1:15,974) |
Targeted group | ||||
Targeted vaccination | 1:21 (1:12–1:33) | 1:1707 (1:1494–1:1920) | 1:445 (1:244–1:691) | 1:35,564 (1:31,126–1:39,995) |
Universal vaccination | 1:22 (1:12–1:34) | 1:2012 (1:1773–1:2252) | 1:455 (1:250–1:706) | 1:41,913 (1:36,942–1:46,921) |
Healthy children | ||||
Targeted vaccination | NA | NA | NA | NA |
Universal vaccination | 1:0.05 (1:0.00–1:0.16) | 1:571 (1:503–1:639) | 1:1.0 (1:0.03–1:3.24) | 1:11,896 (1:10,475–1:13,319) |