Burden of Paediatric Rotavirus Gastroenteritis & Potential Impact of Rotavirus Vaccination

Carlo GIAQUINTO Pediatrics Department University of Padova, Italy Burden of Paediatric Rotavirus Gastroenteritis & Potential Impact of Rotavirus Vaccination Preliminary results 7th International Rotavirus Symposium Lisbon, June 2006

REVEAL Study Design Rotavirus gastroenteritis Epidemiology and Viral types in Europe Accounting for Losses in Public Health & Society Prospective multicentre observational study 7 European regions from Oct 1, 2004 Sept 30, 2005 Study population: - Children <5 years of age with AGE - living in the defined study area Sweden 3 Settings - all Hospitals in study area (n total =12) - all Emergency Dept. in study area (n total =16) - GPs and/or Peadiatricians (n total =139) U.K. Belgium Germany France Selected Study objectives: -Annual rate of consultation due to AGE at hospitals, emergency rooms, GP, FP or Paediatricians -Costs of RV disease Spain Italy 2

Objectives To assess the burden of RVGE* and the impact of Rotavirus vaccination from 2 perspectives: the health care payer (direct costs) the society (direct + indirect costs). Means:By amodel comparing 2 cohorts up to age 5. No rotavirus vaccination Universal rotavirus vaccination program in infants Outcomes Costs of RVGE* Outcomes Residual costs of RVGE* * RVGE = Rotavirus gastroenteritis 3

Overview of the Model : Decision Tree Subtree No rotavirus or no symptomatic RVGE Hospital acquired RVGE (No Payoff) Birth cohort No RV Vaccination programme Community-acquired RVGE RVGE seeking care No medical attendance for RVGE GP pattern pgp Emergency pattern per Hospitalisation pattern phosp Phone call No phone call (No Payoff (No Payoff (No Payoff (No Payoff (No Payoff RV vaccination programme Vaccinated No vaccinated [+] [+] Subtree Subtree Model: Performed on Excel software. Adapted from the US model of Tucker et al. (JAMA 1998). Takes into account rotavirus nosocomial infections and «phone consultations». 4

Which Data Do We Use in the Model? REVEAL Epidemiological and Cost Study Incidence of FP visits for RVGE Incidence of emergency visits for RVGE Incidence of hospitalisations for RVGE Health care resource utilisation (number of consultations, medicines ) Unit Cost data National Official sources Literature / Expert assumptions % of rotavirus not seeking care Distribution of serotypes Incidence of nosocomial infections REST (Rotavirus Efficacy and Safety Trial) with pentavalent Rotavirus vaccine Reduction in hospitalisations, emergency visits, physician visits 5

Model Inputs Pentavalent Rotavirus Vaccine Efficacy / Effectiveness Efficacy data based on REST clinical study publication (Vesikari et al. NEJM 2006) and experts assumptions. 3 scenarios for efficacy: Base Minimum Highest Focus on the base- case scenario of efficacy GP cases Emergency cases Hospitalisations Nosocomial infections Deaths Cases not seeking care Efficacy for children receiving at least 1 dose Waning rate Coverage rate Effectiveness to reduce 86.00 % * [95%CI: 73.9% - 92.5%] ** 93.70 % * [95%CI: 88.8% - 96.5%] ** 95.80 % * [95%CI: 90.5% - 98.2%] ** 95.80 % * [95%CI: 90.5% - 98.2%] ** 95.80 % * [95%CI: 90.5% - 98.2%] ** 86.00 % * [95%CI: 73.9% - 92.5%] ** 60 % * 10 % after 2 years * 90 % * [70 % - 80 %] ** * Base-case efficacy ** [Minimum efficacy, Highest efficacy] 6

Incidence rate of AGE and RVGE per 1000 children per year in each area stratified by setting Incidence rate dependent on country Health System 70 60 50 40 # children Emergency room AGE RVGE # children 180 160 140 120 100 80 60 40 20 0 GP/FP AGE RVGE country Belgium France Germany Italy Spain Sweden UK 30 20 10 0 25 20 15 Belgium France Germany Italy Spain Sweden country UK # children Hospital AGE RVGE 10 5 REVEAL study 0 country Belgium France Germany Italy Spain Sweden UK

Main Epidemiological Inputs based on REVEAL Study - Italy RVGE Incidences Value Incidence of hospitalised cases* 5.3/1000 Incidence of emergency cases* 18.9/1000 Incidence of cases seen by physicians* 22.7/1000 * In children < 5 years 8

Main Epidemiological Inputs - Italy Value Source / Justification Birth cohort 531,000 UNICEF statistics (year 2003) Incidence of nosocomial infections* 1.6/1000 Assumption based on Gleizes et al. PIDJ (2006): For 1 community-acquired RV, 0.6 Rotavirus nosocomial infection % of cases not seeking medical attention 42.3 % Itzler et al. PAS Annual Meeting (2005) Number of deaths / year* 10 Soriano-Gabarro et al. PIDJ (2006) * In children < 5 years 9

Main Economic Inputs based on Reveal Cost study - Italy REVEAL Cost Study Cost of RVGE cases used in the model Items FP* office visit Unit costs 18.5 Perspective Payer Society Nurse home visit Emergency room visit 14.5 20.7 FP case 23 292 Assessment Ward 267.0 Hospitalisation stay Stool test (viral) 1262.2 6.3 Emergency case 202 600 Work day lost 148.0 Baby-sitter 8.5 /h Hospitalised case 1 255 1 901 Healthcare resources utilised during REVEAL multiplied by Italian unit costs enable an estimation of a mean cost per RVGE case. 10 * Family Paediatrician

Main Economic Inputs - Italy Payer Society Nosocomial infections* 154 359 Cases treated at home** 0 39 * Gianino et al. JHI (2002), Soriano et al. PIDJ (2006) ** OECD Indicators, Eurostat (2002) 11

Need to target a high coverage rate to ensure optimal reduction of RVGE burden 0% 90 % Coverage rate 80 % Coverage rate 70 % Coverage rate -20% Reduction in RVGE Burden -40% -60% -80% -80% -75% -70% -71% -67% -59% -62% -59% -52% -100% Highest case efficacy Base-case efficacy Minimum case efficacy 12

Impact of the Pentavalent Rotavirus Vaccine on the RVGE Burden in Italy 10 Deaths Without vaccination 4 248 Nosocomial Infections 14 061 Hospitalisations 50 180 Emergency Visits 60 269 Physician Visits 91 285 Not seeking care - 75% With rotavirus vaccination Base-case efficacy 531 000 children Coverage rate = 90% 2 Deaths 2 014 Nosocomial 2 775 Hospitalisations 9 950 Emergency 15 759 Physician 23 869 Not seek 13

Impact of the Pentavalent Rotavirus Vaccine to Reduce Cost of Gastroenteritis in Italy (coverage rate 90%) Payer Perspective Societal Perspective Direct Costs Direct + Indirect Costs 80 80 70 70 60 60 Millions 50 40 30-79% Millions 50 40 30 75-78% 20 10 0 28 No Rotavirus Vaccination 6 Rotavirus Vaccination 20 10 0 No Rotavirus Vaccination 16 Rotavirus Vaccination Cost of RVGE disease Base-case scenario 531 000 children Coverage rate = 90% 14

Need to target a high coverage rate to ensure optimal reduction of RVGE burden 0% 90 % Coverage rate 80 % Coverage rate 70 % Coverage rate -20% Reduction in RVGE Burden -40% -60% -80% -80% -75% -70% -71% -67% -59% -62% -59% -52% -100% Highest case efficacy Base-case efficacy Minimum case efficacy 15

Impact of the Vaccine on the RVGE Burden in Italy - 59% Without program With program between the 2 Policies Deaths 10 4-6 Hospitalisations 14 061 5 283-8 778 Nosocomial infections 4 248 2 511-1 737 Emergency visits 50 180 9 950-40 229 Physician visits 60 269 25 650-34 619 Cases treated at home 91 285 38 850-52 435 Base-case scenario Birth cohort : 531 000 children Coverage rate = 70% 16

Main Limitations of the Model A few assumptions required experts opinions Impact on families not included No assessment of Quality of Life The price of the vaccine may differ in European countries, according also to the vaccination policy adopted. A model considering different scenarios including different prices, coverage etc is being developed. 17

Conclusions High Burden of RVGE in Italy: More than 220 000 cases Total cost = 75 Millions Positive Impact of Pentavalent Rotavirus Vaccine: With a 70-90% coverage rate vaccination would reduce the burden of RVGE by 59-75 %: - 8 800-11 300 hospitalisations - 32 000-40 200 emergency visits - 35 000-44 300 physician visits, - considerable work days lost. 18

Acknowledgements All PIs: C. Giaquinto J. Paricio L. Gothefors P. Todd F. Huet M. Tomàs C. Hülße P. Van Damme All FPs Cenbiotech & Sanofi-Pasteur MSD Teams And all the children and families 19

BACK-UP SLIDES 20

Model Inputs Pentavalent Rotavirus Vaccine Efficacy / Effectiveness GP cases Emergency cases Hospitalisations Nosocomial infections Deaths Cases not seeking care Efficacy for children receiving at least 1 dose Waning rate Coverage rate * Base-case efficacy ** [Minimum efficacy, Highest efficacy] Efficacy 86.00 % * [95%CI: 73.9 % - 92.5 %] ** 93.70 % * [95%CI: 88.8 % - 96.5 %] ** 95.80 % * [95%CI: 90.5 % - 98.2 %] ** 95.80 % * [95%CI: 90.5 % - 98.2 %] ** 95.80 % * [95%CI: 90.5 % - 98.2 %] ** 86.00 % * [95%CI: 73.9 % - 92.5 %] ** 60 % * 10 % after 2 years * 90 % * [70 % - 80 %] ** Source / Justification Vesikari et al. New Engl J Med (2006) Assumption: same as hospitalised cases Assumption: same as hospitalised cases Assumption: same as GP cases Vesikari et al. New Engl J Med (2006) Assumption: based on REST data Estimations of coverage rates for infants 21

Main Economic Inputs - Italy Payer Society Source / Justification Nosocomial infections 154 359 Extra length of stay: 1.7 day Gianino et al. JHI (2002) Soriano et al. PIJD (2006) Cases treated at home 0 39 0.5 work day lost for working mothers (55%) (OECD indicators), Eurostat (2002) 22

Huge Impact of the Vaccine on the RVGE Burden in Italy - 75% Without program With program between the 2 Policies Deaths 10 2-8 Hospitalisations 14 061 2 775-11 286 Nosocomial infections 4 248 2 014-2 234 Emergency visits 50 180 9 950-40 229 Physician visits 60 269 15 759-44 510 Cases treated at home 91 285 23 869-67 417 Base-case scenario Birth cohort : 531 000 children Coverage rate = 90% 23

Huge Impact of the Vaccine on the RVGE Burden in Italy - 67% Without program With program between the 2 Policies Deaths 10 3-7 Hospitalisations 14 061 4 029-10 032 Nosocomial infections 4 248 2 262-1 986 Emergency visits 50 180 14 420-35 759 Physician visits 60 269 20 704-39 564 Cases treated at home 91 285 31 359-59 926 Base-case scenario Birth cohort : 531 000 children Coverage rate = 80% 24