A critical literature review of health economic evaluations of rotavirus vaccination

Figures & data

Table 1. Overview of included studies

Continent	^Ref	Type	Author	Title	Country	Source	Vaccine evaluated	Sponsor	Type of analysis
Europe	^13	Poster	Fruytier 2006	Vaccination with RIX4414 is cost-effective in a belgian setting	Belgium	ISPOR 2006	Rotarix	GSK	BIA + CEA (CUA)
	^14	Article	Dhont 2008	Burden of rotavirus gastroenteritis and potential benefits of a pentavalent rotavirus vaccination in Belgium	Belgium	Journal of Medical Economics	RotaTeq	SPMSD	BIA
	^15	Article	Bilcke 2008	Cost-effectiveness of rotavirus vaccination: exploring caregiver(s) and “no medical care” disease impact in Belgium	Belgium	Medical Decision Making	Rotarix and RotaTeq	Independent	BIA + CEA (CUA) + threshold analysis
	^16	Article	Nohynek 2009	Finland introduces rotavirus vaccine into the national vaccination program in September 2009	Finland	Eurosurveillance	Rotarix and RotaTeq	Independent	CEA (CUA)
	^17	Poster	Trichard 2007	Budget impact of a universal rotavirus vaccination program with RotaTeq® in France	France	ISPOR 2007	RotaTeq	SPMSD	BIA
	^18	Article	Huet 2007	Burden of pediatric rotavirus gastroenteritis and potential bene□ts of a universal rotavirus vaccination program with RotaTeq in France	France	Vaccine	RotaTeq	SPMSD	BIA
	^19	Article	Melliez 2007	Cost and cost-effectiveness of childhood vaccination against rotavirus in France	France	Vaccine	Rotarix and RotaTeq	Independent	BIA + CEA (CUA)
	^20	Article	Standaert 2008	Cost-effectiveness analysis of vaccination against rotavirus with RIX4414 in France	France	Applied Health Economics and Health Policy	Rotarix	GSK	CEA (CUA)
	^21	Poster	Bénard 2009	Economic evaluation of a pentavalent universal rotavirus vaccination program in France	France	ESPID 2009	RotaTeq	SPMSD	BIA
	^22	Poster	Hammerschmidt 2007	Epidemiologic and economic impact of routine vaccination of infants against rotavirus gastroenteritis in Germany: a preliminary analysis	Germany	ISPOR 2007	Rotarix	GSK	CEA (CUA)
	^23	Article	Buesch 2007	Burden of pediatric rotavirus gastroenteritis and potential benefits of a universal vaccination program in Germany	Germany	ISPOR 2007	RotaTeq	SPMSD	BIA + CEA
	^24	Poster abstract	Greiner 2008	Potential health and economic outcomes of implementing universal rotavirus vaccination program with RotaTeq® in Europe - the example of Germany	Germany	ESPID 2008	RotaTeq	Independent	BIA
	^25	Poster	Brüggenjürgen 2009	Economic evaluation of universal pentavalent rotavirus vaccination program in Germany	Germany	ESPR 2009	RotaTeq	SPMSD	BIA + CEA
	^26	Article	Syriopoulou 2011	Evaluation of potential medical and economic benefits of universal rotavirus vaccination in Greece	Greece	Acta Paediatrica	RotaTeq	SPMSD	BIA
	^27	Poster	Redmon 2009	Cost effectiveness of universal rotavirus vaccination in Ireland: a preliminary analysis	Ireland	ISPOR 2009	Rotarix	GSK	BIA + CEA (CUA)
	^28	Article	Tilson 2011	Cost-effectiveness of universal rotavirus vaccination in reducing rotavirus gastroenteritis in Ireland	Ireland	Vaccine	Rotarix and RotaTeq	Independent	BIA + CEA (CUA)
	^29	Article	Panatto 2009	Burden of rotavirus disease and cost-effectiveness of universal vaccination in the Province of Genoa (Northern Italy)	Italy	Vaccine	Rotarix	GSK	BIA + CEA (CUA)
	^30	Article	Giammanco 2009	An economic analysis of rotavirus vaccination in Italy	Italy	Vaccine	Rotarix or RotaTeq	Independent	BIA + CEA + threshold analysis
	^31	Poster	Welte 2001	Economic evaluation of rotavirus vaccination for the Netherlands	Netherlands	ISPOR 2001	RotaTeq (assumed)	Independent	Threshold analysis
	^32	Article	Goossens 2008	The cost-utility of rotavirus vaccination with Rotarix (RIX4414) in the Netherlands	Netherlands	Vaccine	Rotarix	GSK	BIA + CEA (CUA)
	^33	Article	Zomer 2008	Assessing the introduction of universal rotavirus vaccination in the Netherlands	Netherlands	Vaccine	Rotarix or RotaTeq	Independent	BIA + CEA + threshold analysis
	^34	Article	Mangen 2010	Is it cost-effective to introduce rotavirus vaccination in the Dutch national immunization program	Netherlands	Vaccine	Rotarix and RotaTeq	Independent	BIA + CEA
	^35	Article	Rozenbaum 2011	Cost-effectiveness of rotavirus vaccination in the Netherlands; the ] results of a consensus model	Netherlands	BioMed Central	RotaTeq (not explicit)	SPMSD	BIA + CEA (CUA) + threshold analysis
	^36	Poster	André 2008	Cost-effectiveness of vaccination with rotarix in Portugal	Portugal	Europediatrics 2008	Rotarix	GSK	BIA + CEA (CUA)
	^37	Poster	Rubio-Terres 2008	Cost impact of pediatric rotavirus gastroenteritis (RVGE) and potential benefits of a universal vaccination program in Spain	Spain	ESPID 2008	Rotarix	GSK	BIA
	^38	Article	Rubio-Perez 2011	Socio-economic modeling of rotavirus vaccination in Castilla y León, Spain	Spain (Castilla y León)	Le Infezioni in Medicina	Rotarix	Independent	BIA + CEA (CUA)
	^39	Poster	Largeron 2006	Cost-effectiveness analysis of rotavirus vaccination program in the UK	UK	ISPOR 2006	RotaTeq	SPMSD	BIA + CEA
	^40	Article	Jit 2007	Evaluating rotavirus vaccination in England and Wales Part II The potential cost-effectiveness of vaccination	UK	Vaccine	Rotarix and RotaTeq	Independent	BIA + CEA (CUA)
	^41	Article	Lorgelly 2008	Exploring the cost effectiveness of an immunization program for rotavirus gastroenteritis in the United Kingdom	UK	Epidemiology and Infection	Rotarix or RotaTeq	Independent	BIA + CEA + threshold analysis
	^42	Article	Martin 2009	Cost-effectiveness of infant vaccination with RIX4414 (Rotarix) in the UK	UK	Vaccine	Rotarix	GSK	BIA + CEA (CUA)
	^43	Article	Jit 2009	The cost-effectiveness of rotavirus vaccination: Comparative analyses for five European countries and transferability in Europe	Belgium	Vaccine	Rotarix and RotaTeq	Independent	CEA (CUA) + threshold analysis
					England and Wales
					Finland
					France
					Netherlands
	^44	Article	Jit 2010	The cost-effectiveness of rotavirus vaccination: Comparative analyses for five European countries and transferability in Europe	Belgium	Vaccine	Rotarix and RotaTeq	Independent	CEA (CUA) + threshold analysis
					England and Wales
					Finland
					France
					Netherlands
Latin American studies	^45	Article	Soárez 2008	Cost-effectiveness analysis of routine rotavirus vaccination in Brazil	Brazil	Panam Salud Publica	Rotarix	Independent	BIA + CEA + threshold analysis
	^46	Article	Constenla 2008	Economic impact of a rotavirus vaccine in Brazil	Brazil	Journal of Health Population and Nutrition	Rotarix	Independent	BIA + CEA
	^47	Poster	Valentim 2009	Cost estimates in the economic evaluations of vaccination programmes: the cases of rotavirus and varicella in Brazil	Brazil	ISPOR 2009	Rotarix	Independent	CEA
	^48	Article	Constenla 2006	Potential cost effectiveness of a rotavirus vaccine in Chile	Chile	Revista Medica de Chile	Rotarix	GSK	BIA + CEA
	^49	Article	De la Hoz 2010	Potential epidemiological and economical impact of two rotavirus vaccines in Colombia	Colombia	Vaccine	Rotarix and RotaTeq	GSK	BIA + CEA
	^50	Article	Valencia-Mendoza 2008	Cost-effectiveness of introducing a rotavirus vaccine in developing countries: the case of Mexico	Mexico	Biomed Central	RotaTeq	Merck	BIA + CEA
	^51	Article	Constenla 2009	Economic impact of a rotavirus vaccination program in Mexico	Mexico	Panam Salud Publica	Rotarix	GSK	BIA + CEA + threshold analysis
	^52	Article	Constenla 2008	Economic impact of rotavirus vaccination in Panama	Panama	Annals of Pediatric	Rotarix	GSK	BIA + CEA
	^53	Article	Clark 2009	Cost-effectiveness of rotavirus vaccination in Peru	Peru	The Journal of Infectious Diseases	Rotarix	GSK	BIA + CEA
	^54	Article	Constenla 2006	Assessment of the economic impact of the antiretroviral vaccine in Venezuela	Venezuela	Panam Salud Publica	Rotarix	GSK	BIA + CEA
	^55	Article	Rheingans 2007	Potential cost-effectiveness of vaccination for rotavirus gastroenteritis in eight Latin American and Caribbean countries	Argentina	Panam Salud Publica	Rotarix	GSK	BIA + CEA
					t
					Chile
					Dominican Republic
					Honduras
					Mexico
					Panama
					Venezuela
Asia / Pacific studies	^56	Article	Newall 2007	The cost-effectiveness of rotavirus vaccination in Australia	Australia	Vaccine	Rotarix and RotaTeq	Independent	BIA + CEA (CUA)
	^57	Article	Wang 2009	Potential cost-effectiveness of a rotavirus immunization program in rural China	China	Clinical Infectious Diseases	not vaccine specific	Independent	BIA + CEA
	^58	Article	Ho 2008	Rotavirus vaccination for Hong Kong children: an economic evaluation from the Hong Kong Government perspective	Hong Kong	Archives of Disease in Childhood	RotaTeq	Independent	CEA + threshold analysis
	^59	Article	Rose 2009	Public health impact and cost effectiveness of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in India: model based analysis	India	British Medical Journal	Rotarix	Independent	BIA + CEA
	^60	Article	Esposito 2010	Projected Impact and Cost-Effectiveness of a Rotavirus Vaccination Programm in India, 2008	India	Clinical Infectious Diseases	Rotarix	Independent	BIA + CEA + threshold analysis
	^61	Article	Chodick 2009	Potential impact and cost-effectiveness analysis of rotavirus vaccination of children in Israel	Israel	European Journal of Public Health	Rotarix and RotaTeq	Independent	BIA + CEA (CUA) + threshold analysis
	^62	Poster	Igarashi 2009	Cost-utility analysis of rotavirus vaccine (Rotarix®) in Japan	Japan	ISPOR 2009	Rotarix	Independent	BIA + CEA (CUA)
	^63	Poster	Kang 2010	Public Health and Economic Impact of Rotavirus Vaccination in Korea	Korea	ISPOR 2010	RotaTeq	Merck	BIA
	^64	Article	Flem 2009	Costs of diarrheal disease and the cost-effectiveness of a rotavirus vaccination program in Kyrgyzstan	Kyrgyzstan	The Journal of Infectious Diseases	Rotarix	Independent	BIA + CEA + threshold analysis
	^65	Article	Milne 2009	Budget impact and cost-effectiveness of including a pentavalent rotavirus vaccine in the New Zealand childhood immunization schedule	New-Zealand	Value in Health	RotaTeq	Merck (partial)	BIA + CEA (CUA) + threshold analysis
	^66	Article	Wu 2009	Cost-effectiveness analysis of rotavirus vaccination program in Taiwan	Taiwan	Vaccine	Rotarix and RotaTeq	Independent	BIA + CEA + threshold analysis
	^67	Article	Chotivitayatarakorn 2010	Cost-effectiveness of Rotavirus vaccination as part of the national immunization program for Thai children	Thailand	Southeast Asian Journal of Tropical Medicine Public Health	Rotarix	Independent	BIA + CEA + threshold analysis
	^68	Article	Isakbaeva 2006	Rotavirus disease in Uzbekistan: cost-effectiveness of a new vaccine	Uzbekistan	Vaccine	Rotarix (assumed)	Independent	BIA + CEA
	^69	Article	Fischer 2005	Health care costs of diarrheal disease and estimates of the cost-effectiveness of rotavirus vaccination in Vietnam	Vietnam	The Journal of Infectious Diseases	Rotarix	Independent	CEA + threshold analysis
	^70	Article	Kim 2009	Cost-effectiveness of Rotavirus vaccination in Vietnam	Vietnam	Biomed Central	Rotarix	Independent	BIA + CEA + threshold analysis
	^71	Article	Podewils 2005	Projected cost-effectiveness of rotavirus vaccination for children in Asia	Asia	The Journal of Infectious Diseases	Rotarix	Independent	BIA + CEA + threshold analysis
USA studies	^72	Article	Widdowson 2007	Cost-effectiveness and potential impact of rotavirus vaccination in the United States	USA	Pediatrics	RotaTeq	Independent	BIA + CEA + threshold analysis
	^73	Article	Shim 2009	Impact of transmission dynamics on the cost-effectiveness of rotavirus vaccination	USA	Vaccine	Rotarix and RotaTeq	Independent	BIA + CEA (CUA) + threshold analysis
	^74	Article	Weycker 2009	Cost of routine immunization of young children against rotavirus infection with Rotarix vs. RotaTeq	USA	Vaccine	Rotarix vs RotaTeq	GSK	BIA
African studies	^75	Article	Ortega 2009	Cost-Benefit analysis of a Rotavirus Immunization program in the arab republic of Egypt	Egypt	The Journal of Infectious Diseases	Rotarix	Independent	CEA (although presented as CBA)
	^76	Article	Tate 2009	Rotavirus disease burden and impact and cost-effectiveness of a rotavirus vaccination program in Kenya	Kenya	The Journal of Infectious Diseases	Rotarix	Independent	BIA + CEA + threshold analysis
	^77	Article	Berry 2010	The Cost-Effectiveness of Rotavirus Vaccination in Malawi	Malawi	The Journal of Infectious Diseases	Rotarix	Independent	BIA + CEA
	^78	Article	Tate 2011	Projected health benefits and costs of pneumococcal and rotavirus vaccination in Uganda	Uganda	Vaccine	Rotarix	Independent	BIA + CEA
All countries	^79	Article	Rheingans 2009	Economic costs of rotavirus gastroenteritis and cost-effectiveness of vaccination in developing countries	Africa	The Journal of Infectious Diseases	Rotarix	GSK	CEA
					America
					Eastern Mediterranean
					Europe
					Southeast Asia
					Western Pacific
	^80	Article	Atherly 2009	Rotavirus Vaccination: Cost-Effectiveness and Impact on Child Mortality in Developing Countries	Region of the Americas	The Journal of Infectious Diseases	Rotarix	Independent	BIA + CEA
					European Region
					African region
					Eastern Mediterranean region
					Southeast Asian region
					Western Pacific region
					All GAVI Alliance regions

BIA = Budget Impact Analysis; CEA = Cost-Effectiveness Analysis, CUA = Cost-Utility Analysis; ISPOR = International Society for Pharmacoeconomics and Outcomes Research

Table 2. Summary of what is done, critical evaluation and recommendations for future studies

Aspect	Summary of what is done in studies	Critical evaluation	Recommendations for future studies
Model structure	Most models are static Markov models, using a 5- year timeframe.	Herd protection generally ignored.	We recommend developing dynamic models to account for herd protection effects of vaccination. A 5-y timeframe is appropriate for static models, but a longer timeframe is recommended for dynamic models.
Vaccine-specific data	Most evaluations used efficacy data from clinical trials, sometimes considering waning of vaccine protection.	Effect of the vaccine in real life could be different from the effect measured in clinical trials, especially for developing countries.	We recommend using effectiveness data considering waning of vaccine protection, with adjustment on serotype if possible. Efficacy between doses and efficacy of partial vaccination should be differentiated.
		The effect of Rotarix in preventing outpatient visits was not measured in clinical trials.
		The efficacy in preventing deaths was assumed equal to efficacy against hospitalizations.
Epidemiology	Main sources used included surveillance systems, large health system databases, and the prospective observational study REVEAL.	There is an under-reporting issue in administrative databases.	We recommend using recent national real-life data whenever possible. Ideally the incidence rates of clinical events should be derived from prospective observational studies conducted over several seasons. Adjustments for under-reporting should be considered when using administrative databases.
		REVEAL study was performed during season with high incidence.
		There are little data in developing countries, and the population accessing to vaccination programs may not be the children at highest risk of complications.
Costs	Included costs, in addition to vaccination, were generally physician visits and hospitalizations, and sometimes ED visits, as well as lost productivity.	Sensitivity analyses around vaccine price often not reported, although the price was not known.	We recommend conducting sensitivity analysis on vaccine costs. Data should be collected on workdays lost as lost productivity account for a large proportion of costs from societal perspective.
	Vaccine costs were often assumed by authors.	Lack of data about the probability of taking time off work and duration of absence for parents.
Health-state utilities	Sources for children were based on utility instruments.	Utility instruments are not validated for children under 5.	Further research on the utility associated with RVGE in young children should be conducted, using choice-based technique. The disutility associated with mild cases in particular should be assessed.
		There was only one source for caregivers’ utility, or for mild RVGVE.
		No utility data for non-consulting cases.

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