Background
Methods
Rotavirus hospitalizations; observational study
Statistical analysis
Model design
Model parameters
Parameter | Value (95% CI) | Distribution | Data source | Method | ||
---|---|---|---|---|---|---|
Total population | Ineligible population | Eligible population | ||||
Birth cohort (%)
| 182,662 | 168,215 (92.1%) | 14,448 (7.9%) | - | Published results on birth cohort size and prevalence of high risk conditions | |
RV incidence
| ||||||
<1 year | 18,075 (11,768; 22,932) | Calculated | Calculated | Pert | Community-based cohort study [47] | Incidence based on simulations from original study data updated to 2011 population size, see Mangen et al. for details [45] Distribution among eligible and ineligible based on relative size of each group in birth cohort |
1 to 4 years | 42,218 (24,711; 56,272) | |||||
5 to 64 years | 147,997 (41,573;282,866) | |||||
5 to 9 years | 6.2% of 5 to 64 years | Based on age-distribution of cases 5 to 64 years in original study data | ||||
10 to 14 years | 2.9% of 5–64 years | |||||
GP visits 0 to 1 years | 21.2% (12.8; 26.5) | Calculated | Calculated | Pert | GP based cohort study [48] | Percentage of all RV cases, based on simulations from original GP study data, see Mangen et al. for details [45]. Distribution among eligible and ineligible based on relative size of each group in birth cohort |
GP visits 1 to 4 years | 18.7% (16.4; 19.9) | |||||
GP visits 5 to 14 years | 4.0% (1.8; 4.7) | |||||
Hospitalization (95% CI) | Calculated | 3,884 (3,244; 4,524) | 491 (357; 626) | Pert | RoHo-study | Weighted incidence estimation based on original study data, see Bruijning-Verhagen et al. for details [33]. |
Nosocomial (95% CI) | Calculated | 227 (162; 293) | 269 (172; 365) | Pert | RoHo-study | Weighted incidence estimation based on original study data, see Bruijning-Verhagen et al. for details [33] |
Mortality rate (per 1,000 RV hospitalizations) | Calculated | 0.00 (0.00; 0.04) | 0 81 (0.36; 1.46) | Triangular | RoHo study, External dataset Sophia Children’s hospital | Observed mortality cases from both sources were combined for weighted mortality rate estimation |
Age distribution of RV hospitalizations and fatal cases | Additional file 1: Table S2 | RoHo study | ||||
Utilities RV gastroenteritis
|
QALY Loss
| |||||
Mild (RV episode without medical care) | 0.0011/0.002a
| Published data | ||||
Moderate (GP visit) | 0.0022/0.004a
| |||||
Severe (Hospitalization) | 0.0022/0.004a
| |||||
Nosocomial | Calculated | Calculated | Calculated | RoHo Study | Based on severity distribution of nosocomial cases observed in RoHo-study | |
Mortality | Calculated | 80.7 minus patient’s age | Simulated, whereby assuming a life expectancy of 1; 20; 41.3 minus patient’s age with probability of 1/3 eachb
| Uniform | Statistics Netherlands [46], Expert opinion | For ineligible: Based on average life expectancy in the Netherlands. For eligible: Based on expert panel† |
Direct healthcare costs (Euro)
| ||||||
Gastroenteritis episodes without medical care | 0 | Fixed | ||||
Standard GP visits | 29 | Guidelines for health-economic evaluations [39] | Standard Cost Prices. See Mangen et al. for details [45] | |||
Home visit GP | 45 | |||||
GP consultation by phone | 15 | |||||
Prescriptions | 40 | See Mangen et al. [45] | ||||
Laboratory costs | 73 | |||||
Hospitalization | Calculated | 2,179 (2,027;2,330) | 2,550 (2,508; 3,606) | Pert | RoHo study | Weighted estimates from original study data, see Additional file 1
|
Nosocomial | Calculated | 1,995 (1,242; 2,748) | 2,129 (1,203; 3,055) | |||
Direct non-healthcare costs
| ||||||
RV episode without medical care | Additional diapers | Uniform | Assumption | See Mangen et al. [45] | ||
GP visits | Additional diapers and travel costs | Guidelines for health-economic evaluations [39] | ||||
Hospitalization | Travel costs | Pert | ||||
Nosocomial | ||||||
Indirect non-healthcare costs
c
| ||||||
Costs per hour work loss (euro) | 31.11 | Fixed | See Mangen et al. [45] | |||
Hours of work loss for RV episode without medical care | 0.93; 1.36; 0.84 for ages 0 to 4; 5 to 9 and 10 to 14 years respectively | Uniform | Dependent of patient-age. See Mangen et al. [45] | |||
Hours of work loss GP visits | 1.35; 1.98; 1.23 for ages 0 to 4; 5 to 9 and 10 to 14 years respectively | Uniform | ||||
Hours of work loss Hospitalization | 37.32 | hospital based observational study [51] | ||||
Hours of work loss Nosocomial | 24.58 | Based on the findings from Friesema et al. [52] for children up to 18, adjusted for excess duration of hospitalization among nosocomial in RoHo study (2.7 versus 2.9 days) | ||||
Vaccine efficacy
| Table 2
| |||||
Herd-immunity
|
Universal RV vaccination
|
Targeted RV vaccination
| ||||
30% (0% to 46%) | - | Triangular | Published data | |||
Vaccination costs
| ||||||
RV1 | 60; 75; 90 | 80; 100; 120 | Previous CEA [10] For Eligible: Assumption | Assumed tender Price | ||
RV5 | 60; 75; 90 | 80; 100; 120 | ||||
Startup costs first year | 218,440 | - | ||||
Application costs | 6.44 | See Mangen et al. [45] | ||||
Administration costs | 1.64 |
Vaccine efficacya
| Method | Source | ||||
---|---|---|---|---|---|---|
RV1 | Mild (RV episode without medical care) | Moderate (GP visit) | Severe (Hospitalization)b
| Nosocomialc
| ||
After first dose | Calculated | Calculated | 89.8% (8.9 to 99.8) | Calculated | (Calculated from) Published data Efficacy for mild and moderate cases after first season calculated from efficacy ratios for mild, moderate, severe during first season | [53] |
First season (after second dose) | 71.7% (50.4 to 83.9) | 91.8% (84.0 to 96.3) | 100% (81.8 to 100) | |||
Second season | 50.5% (24.3 to 67.7) | 76.2% (63.0 to 85.0) | 92.2% (65.6 to 99.1) | |||
Third-fifth season | Calculated | Calculated | Calculated | Efficacy during third to fifth season calculated as linear decline equal to reduction between first and second season | ||
RV5
| ||||||
After first dose | Calculated | Calculated | 88% (65 to 97) | Calculated | (Calculated from) Published data Efficacy after first dose and between first and second dose for mild and moderate cases calculated from efficacy ratios for mild, moderate, severe during first season | [57] |
After second dose | Calculated | Calculated | 88% (69 to 96) | |||
First season (after third dose) | 65.1% (54.1 to 73.5) | 72.0% (63.2 to 78.9) | 94.8% (89.4 to 97.8) | (Calculated from) Published data | ||
Second season | 49.8% (27.0 to 65.4) | 58.5% (40.1 to 71.7) | 90.8% (76.9 to 97.1) | |||
Third season | Calculated | Calculated | 100.0% (27.9 to 100) | Efficacy during third season for mild and moderate cases calculated from efficacy ratios for mild, moderate, severe during second season | [55] | |
Fourth-fifth season | Calculated | Calculated | Calculated | Efficacy during third to fifth season calculated as linear decline equal to reduction between first and second season |
Cost-effectiveness analysis
Results
Rotavirus hospitalizations; observational study
Prevalence |
P-valueb
| RRb
| ||||||
---|---|---|---|---|---|---|---|---|
Observational study | Weighted estimates national RV hospitalizations (95% CI) | General infant populationa
| ||||||
High Risk Conditions | % | N | % | N | % | N | ||
GA < 36 weeks | 8.9 | 83 | 6.8 (5.1; 8.5) | 347 ( 243; 451) | 4.3 | 7617 | 0.005 |
1.7 (1.2; 2.8)
|
LBW | 11.1 | 104 | 8.8 (6.6; 11.1) | 462 (309; 615) | 6.0 | 10545 | 0.014 |
1.6 (1.1; 2.3)
|
Congenital pathology | 12.4 | 116 | 6.2 (4.9; 7.4) | 309 (244; 374) | 1.5 | 2719 | <0.0001 |
4.4 (3.4; 5.4)
|
Healthy (N = 657)
|
High risk conditions
| |||||||
GA <36 weeks (N = 83)
|
LBW (N = 104)
|
Congenital pathology (N = 116)
| ||||||
Outcome and healthcare utilization
|
N (%)
|
N (%)
|
RR (95% CI)
|
N (%)
|
RR (95% CI)
|
N (%)
|
RR (95% CI)
| |
ICU admission | 4 (0.6%) | 4 (4.8%) |
7.9 (2.0; 31.1)
| 3 (2.9%) |
4.7 (1.1; 20.9)
| 3 (2.6%) |
4.2 (1.0; 18.7)
| |
RV related death (number,%) | 0 | 0 | 0 | 2 (1.7%) |
NA
| |||
Mean difference (95% CI)
|
Mean difference (95% CI)
|
Mean difference (95% CI)
| ||||||
LOS (mean, SD) | 3.6 (2.1) | 5.2 (4.7) |
+1.6 (0.1; 3.0)
| 5.1 (4.5) |
+1.5 (0.3; 2.7)
| 6.6 (4.2) |
+3.0 (1.9; 4.1)
| |
Healthcare costs (mean, SD) | 2,203 (2,113) | 3,001 (3,407) |
+798 (28; 1,568)
| 2,851 (3,206) |
+648 (−2; 1,297)
| 3,737 (3,500) |
+1,533 (867; 2,199)
|
RV mortality
RV epidemiology and vaccination effects
RV disease burden (95% CI)a
| RV disease costsa(€ million) | Vaccination costs (€ million) | |||||
---|---|---|---|---|---|---|---|
Disease episodes (x1000) | Hospitalizationsb
| Fatal cases | QALY’s lost (undiscounted) | Direct healthcare costs (undiscounted) | Societal costs (undiscounted) | (undiscounted) | |
No vaccination
| 74.1(57.8; 90.0) | 4,870 (4,310; 5,430) | 6.5 (3.2; 11.0) | 257 (136; 422) | 11.9 (10.5; 13.3) | 18.2 (16.2; 20.3) | - |
Targeted RV vaccination
| |||||||
RV1 | 67.3 (51.3; 82.4) | 4,370 (3,890; 4,870) | 0.7(0.2; 1.6) | 119 (79; 177) | 10.5 (9.3; 11.8) | 16.4 (14.6; 18.2) | 1.5 |
Percent reduction | 8% | 10% | 89% | 54% | 12% | 10% | |
RV5 | 67.4 (51.5; 82.7) | 4,384 (3,892; 4,870) | 0.8 (0.3; 1.7) | 121 (80; 184) | 10.6 (9.4; 11.8) | 16.4 (14.6; 18.2) | 1.6 |
Percent reduction | 8% | 10% | 88% | 53% | 11% | 10% | |
Universal RV vaccination
| |||||||
RV1 | 40.6 (30.1; 51.2) | 1,370 (1,150; 1,650) | 0.4 (0.2; 0.8) | 60 (42; 81) | 3.4 (2 8; 4 1) | 5.9 (5.0; 6.9) | 15.2 |
Percent reduction | 45% | 72% | 94% | 77% | 71% | 67% | |
RV5 | 42.6 (31.7; 53.6) | 1,440 (1,210; 1,710) | 0.5(0.2; 0.9) | 66 (45; 91) | 3.6 (3.1; 4.3) | 6.3 (5.3; 7.3) | 16.7 |
Percent reduction | 43% | 70% | 92% | 75% | 70% | 65% |
Targeted versus no vaccination | Universal versus no vaccination | Universal versus targeted vaccination | |
---|---|---|---|
Costs (€)
a
| |||
per case avoided | 21 | 174 | 191 |
per life year saved | 2,400 | 96,600 | 894,000 |
per fatal case | 0.03b
| 1.03b
| 21.60b
|
per QALY gained | 2,600 | 60,200 | 162,000 |