1. Rotavirus Vaccine & Health Care Utilization for Diarrhea in U.S Children N Engl J Med 2011;365:1108-17 Vanessa Craven Clinical Research Fellow

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3. The Global Picture D&V in < 5yrs 111 million stay at home 25 million clinic visits 2 million hospitalisations 611 000 deaths Joint Committee on Vaccination & Immunisation statement on rotavirus vaccine; 2008

4. And at Home…. 130 000 episodes 12 700 hospitalised 3-4 deaths Joint Committee on Vaccination & Immunisation statement on rotavirus vaccine 2008

5. The Vaccines RotarixRotaTeq

6. The Vaccines Rotarix Live attenuated Oral 2 doses £35 per dose 6/52  6/12 No GI symptoms RotaTeq Live attenuated Oral 3 doses £25 per dose 6/52  6/12 ? Mild gut irritation Protection from 5 serotypes (88%) Intussusception & Kawasaki’s disease

7. The UK Stance NOT COST EFFECTIVE

8. What they did… < 5 yrs in U.S Comparison of: –Pre vaccine (01-06) vs Post vaccine (07-09) RV5 = RotaTeq Diarrhoea & specifically rotavirus Heath care use Costs

9. Highest age risk population Vaccine vs no vaccine Outcomes: Health care use (not just hospitals), direct & indirect effects & economics Not vaccine risk or full uptake Large number studied Data available Unvalidated economic tool What data was unavailable or incomplete?

10. Large numbers studied MarketScan database Studied those >6 months (not immunised) but analysed in age groups Medicaid NOT included 1/3 vaccine = immunised Vaccine rates not measured in universal programmes (13 states)

11. Accurate database? Partially vaccinated included Unvalidated vaccine coverage data & economic model RV1 excluded Non blinded Inpatient, ED, outpatient Excluded transition year Included indirect benefits Outcomes: Diarrhoea (all causes) & rotavirus Is rotavirus always tested for, especially if vaccine status is known

12. Only 2 years studied post vaccine Yearly fluctuations Unknown how many children had partial data

14. 32% vaccinated (73% <1yr) by end of 2008 Hospitalisation RV ↓75% - all ages (07-08) ; ↓60% - proportional to coverage E.g↓26% in 2-4yrs (08-09) Largest effect in <1yr (↓76%) Diarrhoea↓33% (07-08) & ↓25% (08-09) Greatest ↓ during RV season & indirect ED visits ↓9% (07-08) & similar (08-09) except the West OP visits ↓3% (07-08) & similar (08-09) except the West But ED & OP ↑ in 08-09 in 2-4yrs, Vaccinated vs Unvaccinated 89% ↓RV hospitalisation (small numbers in some regions) 44%/58% ↓Diarrhoea hospitalisation 37%/48% ↓ED 9%/12% ↓OP Similar indirect effect Geographical variation 08-09: $278 million saved

15. Complete dataset? Need more follow up Effect of partial immunisation Economic data Yes! Big effects Incomplete data Important adverse effects data excluded

16. Pre licensure study: ↓59% diarrhoea hospitalisation vaccinated vs unvaccinated Developed country Different vaccination system & healthcare system/approach Low socioeconomic group not included

17. Summary & Conclusions Obvious positive effects –Direct & indirect Adverse effects fully appreciated? Morbidity enough to justify investment?