1. Antibiotic Incentives For Global Health WHO CEWG 2011 Kevin Outterson Boston University Schools of Law & Public Health Harvard Center for Communicable Disease Dynamics Papers at www.ssrn.com

2. Public Health Implications of Antimicrobial Drug Regulation Kevin Outterson, JD, LLM (Project Co-Director) Boston University School of Law Rosa Rodriguez-Monguio, PhD (Project Co-Director) University of Massachusetts, School of Public Health Enrique Seoane-Vazquez, PhD Massachusetts College of Pharmacy Aaron S. Kesselheim, MD, JD, MPH, Brigham & Womens Hospital, Harvard Medical School Marc Lipsitch, PhD Harvard School of Public Health John H. Powers, MD George Washington University School of Medicine Funded by the Boston University School of Law & the Robert Wood Johnson Foundation

3. World Health Day 7 April 2011

4. Coordination Abx = common pool resource No real global coordination on new production or use (withdrawals) Hospitals, physicians, patients, payors, drug companies & drug sellers all lack financial incentives to conserve See R. Laxminarayan; K. Outterson; E. Kades; A.S. Kesselheim; A. Malani; R. Saver; S. Mechoulan; Sage & Hyman

5. Patent Holder Waste Sub-therapeutic animal uses Label extensions to CAP/cSSSI/AOM Narrow v. broad spectrum Dx Resistance within & across classes Outterson K, et al., LID 2007; 7:559-566; Outterson K, Cardozo L Rev 2010; Kesselheim AS, Outterson K, Health Affairs 2010; 29(9):1689-96.

6. Conservation Commercial incentives undermine conservation Poor incentives at patient, provider & industry levels Complex delivery, cultural & infrastructure issues, esp. globally Kesselheim AS, Outterson K, 11 YJHPLE 2011

7. Production New molecules are needed, else class and sector exhaustion Stewardship and infection control diminish market incentives Declining returns to R&D observed Kesselheim AS, Outterson K, 11 YJHPLE 2011

8. Systemic Antibacterial NMEs Approved by the FDA (1980-2009) Marketed Priority Review Approved NMEs Marketed = Products still in the market in August 1, 2010.

9. Discontinued NMEs and BLAs. Approved by the FDA (1980-1999) % NMEs & BLAs Discontinued from Market

10. Systemic Antibacterials Approved by the FDA (1980-2009). Marketed Drugs, Linear Trend Bayh-Dole Act CAFC ODA CUSFTATRIPS OB Ped Excl. Bioshield TRIPS India + AUSFTA Sec.505

11. Marketed NMEs and BLAs Approved by the FDA by Selected Therapeutic Classes as a % Total Approvals (1980-2009) % Total NMEs & BLAs 1980s 1990s 2000s

12. Cardiovascular System Drugs Approved by the FDA (1980-2009). Marketed Drugs, Linear Trend & 5 Year Moving Average

13. Antineoplastic & Immunomodulating Agents Approved by the FDA (1980-2009). Marketed Drugs, Linear Trend & 5 Year Moving Average

14. Proposal 1 Value-based rbx for social value of abx Financing mechanism is OECD health system rbx Contingent on meeting global conservation & health targets Scalable globally Kesselheim AS & Outterson K, Improving Antibiotic Markets, 11 YJHPLE (2011); Kesselheim AS & Outterson K, Health Affairs Sept. 8, 2010. Contingent P4P

15. Current metric: Ability to pay With de-linkage: –Cost of resistant infections? –Cost of current ID burden? –Cost of avoided infections? Room for adjustment if SV>PV by an order of magnitude Contingent P4P

16. Social Value of the ABX gap DALY ValueUS & CANHI Europe $50k$73.3$66.3 $75k$110.0$99.5 $100k$146.7$132.6 $125k$183.3$165.8 In billions of US Dollars at various DALY value levels. Underlying data on burden of disease from WHO 2008. Estimates by Outterson (2009)

17. Further Issues OECD willingness to rbx Setting & measuring realistic global conservation targets –Industry capture –Top down bias Voluntary contracts with companies (no change to IP rules)

18. Proposal 2 $$ for conservation, not use Voluntary, science-driven Significant $$ demonstration Complete de-linkage for 1-2 especially valuable molecules Kesselheim AS & Outterson K, Improving Antibiotic Markets,11 YJHPLE (2011); Kesselheim AS, Outterson K, Health Affairs 2010; 29(9):1689-96; Love J, Prizes, not patents, to stimulate antibiotic R&D, SciDev.Net (26 March 2008); So AS, et al. Drug Resistance Updates 2011 Strategic ABX Reserve

19. Further Issues Funding Access/price to patients Industry capture/targets Informational problems with value & efficacy) IP coordination

20. Invitation Harvard Center for Communicable Disease Dynamics Conference, Boston Oct. 3-4, 2011 2.5 hour program on abx incentives on Oct. 4

21. Antibiotic Incentives For Global Health WHO CEWG 2011 Kevin Outterson Boston University Schools of Law & Public Health Harvard Center for Communicable Disease Dynamics Papers at www.ssrn.com