1. © 2007 Kimberly M. Thompson Workshop A4: Global Poliomyelitis Eradication: Challenges & Benefits National Immunization Conference Kansas City, Missouri March 5-8, 2007

2. © 2007 Kimberly M. Thompson Workshop Objectives To describe the public health & economic benefits that have resulted from poliomyelitis elimination in the U.S. To discuss the achievements and remaining challenges for the global Polio Eradication Initiative

3. © 2007 Kimberly M. Thompson Epidemiology of Polio – U.S.A. (I) Routine childhood immunization program –IPV (1950s) & OPV (1960s) –Elimination of indigenous wild polio (1979) & controlled imported wild polio (1993) Adverse effects of oral polio vaccine –VAPP: average 9 cases / year –Accepted as necessary consequence of OPV use, to reduce risk of imported wild polio

4. © 2007 Kimberly M. Thompson Epidemiology of Polio – U.S.A. (II) Cessation of OPV in U.S. –Global polio eradication progress in 1990s: Lower risk of imported wild poliovirus in USA Changing benefit / risk ratio for OPV VAPP = unacceptable risk –Transition to IPV: Sequential IPV-OPV schedule (1997) All IPV schedule (2000) –Last VAPP cases occurred in 1999

5. © 2007 Kimberly M. Thompson Paralytic Polio Cases and OPV Doses Distributed United States, 1990-2003 Year VAPP cases OPV doses in millions IPV-OPV All-IPV

6. © 2007 Kimberly M. Thompson Epidemiology of Polio – U.S.A. (Conclusion) The U.S. has reached an important milestone – elimination of VAPP – through OPV cessation & transition to IPV. A low risk of polio cases or outbreaks in the U.S. remains until the world is polio-free. The risk of paralytic poliomyelitis includes vaccine- derived as well as wild polioviruses.

7. © 2007 Kimberly M. Thompson Polio Vaccine Use Worldwide, 2004 IPV only IPV/OPV OPV only The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.  WHO 2005. All rights reserved

8. © 2007 Kimberly M. Thompson Kimberly M. Thompson, Sc.D. Harvard Kids Risk Project and MIT Sloan School Health and Economic Benefits

9. © 2007 Kimberly M. Thompson Collaborators Radboud J. Duintjer Tebbens, Ph.D. CDC Jim Alexander, Lorraine Alexander, Brenton Burkholder, Victor Cáceres, Steve Cochi, Howard Gary, John Glasser, Steve Hadler, Karen Hennessey, Hamid Jafari, Denise Johnson, Bob Keegan, Olen Kew, Nino Khetsuriani, Naile Malakmadze, Steve McLaughlin, Mark Pallansch, Becky Prevots, Hardeep Sandhu, Nalinee Sangrujee, Jean Smith, Peter Strebel, Linda Venczel, Margie Watkins WHO Bruce Aylward, Fred Caillette, Claire Chauvin, Esther deGourville, Hans Everts, Ulla Griffiths, David Heymann, Scott Lambert, Asta Lim, Jennifer Linkins, Patrick Lydon, Chris Maher, Roland Sutter, Chris Wolff, David Wood Others Harrie van der Avoort, Francois Bompart, Laurent Coudeville, Walt Dowdle, Paul Fine, Shanelle Hall, Tracy Lieu, Marc Lipsitch, Anton van Loon, Van Hung Nguyen, Christina Pedreira, Robert Weibel Funding - CDC Grant Number U50/CCU300860

10. © 2007 Kimberly M. Thompson Topics Context Why study the past? What about the future? Discussion © 2003 Brad Veley. All rights reserved.

11. © 2007 Kimberly M. Thompson Kids Risk Project Develop the field of pediatric risk analysis to help inform decisions related to managing child health risks and put risks in context for all stakeholders Look for mismatches between perception and reality in children’s risks and explanations for these, including depiction of risks in the media

12. © 2007 Kimberly M. Thompson Review of pediatric literature (Thompson and Elkin, in progress) Review of existing published peer-reviewed pediatric CEAs and CBAs (1998) – Insights: –Vaccines main contributor to the database –Economic analyses are great tools, but… –Ignore uncertainty, variability, preferences and other attributes, troubles with zeros, criteria for “acceptability” –Difficulties in using QALYs, in part due to dramatic changes that occur throughout childhood –Very little validation (3 studies – neonatal herpes, pertussis, and Hib) –No consideration of changes over time

13. © 2007 Kimberly M. Thompson Time matters! Optimal strategies change with time Dynamics may be very important to model (e.g., to characterize the benefits of herd immunity) Times of major shifts (e.g., perceptions of risk and benefits change going from wild type cases to vaccine-associated cases with eradication) When we assess the CE ratio may matter in terms of the estimates and policy

14. © 2007 Kimberly M. Thompson Polio www.ks.uiuc.edu/Research/ vmd/images/polio.gif

15. © 2007 Kimberly M. Thompson 50 Years – April 12, 1955 Francis T, Jr., Korns RF, Voight RB, et al. “An evaluation of the 1954 poliomyelitis vaccine trials. Summary report.” American Journal of Public Health. May 1955; 45(suppl):1-50. News media that day: “The vaccine works.” “It is safe, effective and potent.”

16. © 2007 Kimberly M. Thompson Progress made History of polio in the United States since 1921

17. © 2007 Kimberly M. Thompson Dynamic outbreak sub-model Differential equation-based infection transmission model Assume homogeneous mixing in every (sub)population Distinguish several immunity groups with different durations of infectiousness and probabilities of infection given exposure –Fully susceptibles –Recent live virus infection (i.e., with OPV, VDPV or WPV) –Historic live virus infection –Only IPV-vaccinated –Infected by outbreak virus (“removeds,” fully immune against reinfection in the same outbreak) 25 age groups with different initial immunity profiles Secondary OPV spread and seasonality factored in

18. © 2007 Kimberly M. Thompson Retrospective modeling shows dynamics matter a lot! Thompson KM, Duinter Tebbens RJ. Retrospective cost-effectiveness analyses for polio vaccination in the United States. Risk Analysis 2006; 26(6). Estimated net benefits $180 billion US (1955 NPV)

19. © 2007 Kimberly M. Thompson What about the future? Approaching global eradication –Complicated choices –Variability - BIG –Uncertainty - BIG –Multiple stakeholders & decision makers –Competing priorities for scarce health care resources Use a model to help understand the risks, costs, and benefits of options –Collaboration with CDC/WHO –On-going project

20. © 2007 Kimberly M. Thompson So far… Sangrujee et al. “Policy Decision Options During the first Five Years Following Certification of Polio Eradication.” Medscape General Medicine 2003(December 19);5(4). Duintjer Tebbens et al. “A dynamic model of poliomyelitis outbreaks: Learning from the past to help inform the future.” American Journal of Epidemiology 2005 (August); 162(4):358-72 Risk Analysis Special Issue on Post-eradication Polio Risk Management (2006, Vol. 26, No. 6) Thompson and Duintjer Tebbens: “Retrospective Cost-Effectiveness Analyses for Polio Vaccination in the United States” Aylward et al: “Risk Management in a Polio-Free World” Duintjer Tebbens et al.: “Risks of Paralytic Disease Due to Wild or Vaccine-Derived Poliovirus After Eradication” Duintjer Tebbens et al.: “The Costs of Future Polio Risk Management Policies” Thompson et al.: “Evaluation of Response Scenarios to Potential Polio Outbreaks Using Mathematical Models” de Gourville et al.: “Global Surveillance and the Value of Information: The Case of the Global Polio Laboratory Network” Thompson et al.: “Development and Consideration of Global Policies for Managing the Future Risks of Poliovirus Outbreaks: Insights and Lessons Learned Through Modeling”

21. © 2007 Kimberly M. Thompson Outbreak & Response Dealing with a contagious disease in a changing world… Duintjer Tebbens RJ, Pallansch MA, Kew OM, Cáceres VM, and Thompson KM. “A dynamic model of poliomyelitis outbreaks: Learning from the past to help inform the future.” American Journal of Epidemiology 2005 (August); 162(4):358-72 Thompson KM, Duintjer Tebbens RJ. Evaluation of response scenarios to potential polio outbreaks using mathematical models. Risk Analysis 2006;26(6). Decision options Risks & Conditions Paralytic cases Outbreak & Response Financial costs Health costs

22. © 2007 Kimberly M. Thompson Response trade-offs Use outbreak model to analyze attributes of outbreak response: –Delay from outbreak detection to mass immunization –Coverage –Vaccine –Number of rounds –Target age groups Insights –Important to respond FAST –Benefit of mOPV over tOPV –Target groups in context of routine IPV may need to include older children/adults Outbreak size as a function of response delay and coverage Low-income country with 10 million people, IPV routine immunization (68% coverage) for 5 years after OPV cessation, AFP surveillance, and low-medium R 0. Response targets children < 5 yrr. with mOPV at 30-day intervals with the 2 nd and 3 rd rounds achieving 90% coverage.

23. © 2007 Kimberly M. Thompson Link options to impacts

24. © 2007 Kimberly M. Thompson "It is technically feasible to interrupt polio transmission worldwide." "Here is the key question: are we now in a position to overcome the operational and financial obstacles?"

25. © 2007 Kimberly M. Thompson What about the high costs? Compare intense vaccination contingent on perceived cost per case being below a “tolerable” level vs. intense vaccination until eradication Focus on perceived high cost per case yields: Lower costs in short-run, but never achieve eradication Cumulate many more cases AND much higher costs in the long-run Wavering commitment not optimal

26. © 2007 Kimberly M. Thompson WHO Urgent Stakeholder Consultation

27. © 2007 Kimberly M. Thompson Thank you