Updated cost-effectiveness and risk-benefit analysis of two infant rotavirus vaccination strategies in a high-income, low-endemic setting

Bruijning-Verhagen, P.; van Dongen, J. A. P.; Verberk, J. D. M.; Pijnacker, R.; van Gaalen, R. D.; Klinkenberg, D.; de Melker, H. E.; Mangen, M.-J. J.

doi:10.1186/s12916-018-1134-3

Table 1 Parameters for model input

From: Updated cost-effectiveness and risk-benefit analysis of two infant rotavirus vaccination strategies in a high-income, low-endemic setting

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	Statistics Netherlands [46, 47]	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	Community-based cohort study [12]; virological rotavirus surveillance data [5]	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 years^a	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	RoHo study [14]; indirect estimated annual hospitalizations [2]; RIVAR AGE surveillance [18]	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	See Additional file 1: Table S2 in Bruijning et al. [11]				RoHo study [14];	Same as [11]
Intussusception (IS) incidence
Vaccine-induced IS risk	1/50,000 vaccinated children			Fixed	[32,33,34,35]
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]	50% of estimate for moderate, similar to [11, 17, 31, 49]
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	Statistics Netherlands [46]; Expert panel [11]	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) Additional GP consultations for hospitalized cases same as in [11], based on [50]
GP home visit (€/unit)	€50				Dutch reference prices [22]
GP telephone consultation (€/unit)	€17				Based on cohort studies [12, 13, 51]
Drug costs incl. Prescription fee (€/unit)	€43				Based on cohort studies [12, 13, 51]
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)	Pert	RoHo study [11]
Uncomplicated IS (€/hospitalization)	€1423			Fixed	Hospital administrative data (see Additional file 1); Valk et al. [53]	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 AGE^b
Without medical care	Additional diapers			Uniform	Assumption	For details see [11, 17]
Requiring GP visit	Additional diapers and travel costs			Pert	Assumptions and guidelines for health economic evaluation [22]
Hospitalization	Travel costs			Pert
Nosocomial rotavirus	Not applicable
Productivity losses caregiver
Cost per hour paid work loss	€32				Statistics Netherlands [54] and guidelines for health economic evaluation [22]
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	Estimated based on LMR data (see Additional file 1) and Statistics Netherlands [54]	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	Table 2 in Bruijning et al. [11]			Pert	Vaccine trials [55,56,57]
Herd protection	See Table 2	Not applicable		Fixed	Published estimates, see Table 2	Only for universal vaccination scenarios
Vaccination costs
Vaccine costs/infants^c	€75	€135.32		Fixed	Free market price for targeted vaccination [29]; for universal vaccination based on assumption as in [11, 31]
Application and administration costs	€12.36	€12.36		Fixed	[30]
Start-up cost first year	€233,760			Fixed	[17]

LOS length of hospital stay, LE life expectancy, RIVAR Risk-Group Infant Vaccination Against Rotavirus, LMR Netherlands National Medical Registry
^aOf which 80% is aged 5–9 years and 20% is aged 10–14 years
^bNote, we did not consider any patient and family costs for IS cases
^cReported vaccine costs exclude costs for spillage; 2% spillage costs was added in the model
^dBased on population statistics for the year 2014 [54], the most recent year available, we calculated similarly as in Mangen et al. [38] the average working hours/week for a primary caregiver. For this we assumed that, except for single-father households, the female is the primary caregiver taking care of a sick child. In 2014 73.4% of primary caregivers had paid employment, for an average of 22.3 h/week. For an average primary caregiver in the Netherlands this corresponds to 16.4 h/week

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