1. ECONOMIC ASPECTS OF COMBINED VACCINES Malta, 22-23 October 2001 Philippe Beutels Centre for the Evaluation of Vaccination WHO collaborating centre for the prevention and control of viral hepatitis Epidemiology and Community Medicine University of Antwerp Belgium

2. Pin cushion syndrome l USA & W-Europe: »1989: ca. 8 injections < 16 y »2000: USA: 16 injections < 16 y, (EUR: ca. 8-16) l Pipeline / Future: »pneumococcal conjugate, meningococcal C, varicella, hepatitis A, rotavirus Demand for combined vaccines from parents, health care providers and decision makers

3. Supply of combined vaccines l Complex R&D and clinical trials l Major competitive advantage / improved product -Clear incentives for some manufacturers to supply such vaccines -Increases barriers of entrance onto the vaccine market -Increased monopolistic behaviour (consequences in supply, choice and price?)

4. Complete economic evaluation  Comparing different alternatives:  E.g., “combined vaccine” versus “same separate vaccines” versus “same separate vaccines minus one or more”  Analysing both economic costs and medical effects:  If not: cost analysis or effectiveness analysis

5. Effectiveness l Free rider effect »for important vaccines with an image problem (HBV) »for not so important vaccines (HAV, VZV, mumps) l Danger: new vaccine scare stories: important vaccines could be dragged down by less important vaccines (e.g., measles) greater coverage and improved compliance against more agents

6. Change in coverage of at least one antigen l Affects both costs and effects l Above the herd immunity threshold: »nonlinear influence on effects l Below herd immunity threshold: »linear influence on effects

7. Unit vaccination costs = Administration + Adverse events + Price

8. Administration Costs l Fewer injections & fewer visits »Lower administration costs –time vaccinators –storage, transportation, material and equipment (?) »Reduced time, money and pain losses of children and parents (direct personal and indirect costs) »Fewer side effects and related treatment »Safety improves

9. Safety of injection, developing countries l In some countries, up to 80% of disposable needles are re- used l Safety of injection is more related to adapting the needle (auto-disable syringes in immunisation programmes) than to providing combined vaccines The role of combined vaccination in reducing unsafe injection is limited

10. Administration costs, developing countries l EPI with HBV versus EPI without HBV: »Addis Ababa, 1996: (Edmunds et al, 2000) –Increase in programme costs by 43% –79% for buying vaccines (28% in current EPI) »The Gambia, 1989: (Hall et al, 1993) –Increase in programme costs by 63% –82% for buying vaccines (16% in current EPI) Administration costs are an important, not THE most important marginal cost factor

11. Multiple injections & visits and Willingness To Pay –$25 for reduction from 3 to 2 injections Study in N-California, parents of 1-8 m infants (Lieu et al, Vaccine 2000): l median WTP: –$25 for reduction from 4 to 3 injections l greater value of avoiding adverse events ($50) than of avoiding third or fourth injection –$50 for reduction from 2 to 1 injections

12. Unit vaccination costs = Administration + Adverse events + Price =  +  + ? Trade off: value of fewer injections and side effects versus price How much higher can the price of the combination be before it is less interesting than the combination of prices?

13. Vaccination costs Addis Ababa, 1996 (Edmunds et al, 2000) DTP-HB preferable if price <$0.77/dose (+54%)

14. Economic evaluation of combined vaccines l Most EE: incremental analysis of one component (eg, MMRV versus MMR; DTPa versus DTPw; HB-Hib versus Hib) l Some EE: summation of two programmes (eg, HA & HB) versus doing nothing l Few/missing EE: Complete joint analysis of a combined vaccine versus the same components, separately

15. Cost-effectiveness of combined vaccines versus same components, separately l Very likely: Effectiveness Cost-effectiveness l Very likely: Costs upfront l Very likely: Downstream costs l Condition: no bad publicity or excess price Examples: combinations of DTP-IPV-Hib-HBV

16. Incremental cost-effectiveness of a new addition to an existing (combined) vaccine l Very likely: Effectiveness Cost-effectiveness l Very likely: Costs upfront l Very likely: Downstream costs ? Examples: MMRV, HB-Hib, HA-HB

17. CONCLUSION l Very likely that combined vaccines versus separate components is cost-saving, conditional on »price setting »avoiding bad publicity l Cost-effectiveness of new additions to an existing vaccine depends l Not generalisable, dependent on vaccine and starter situation l Till now rarely investigated