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
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 & Women’s 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
World Health Day
7 April 2011
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
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.
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
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
Systemic Antibacterial NMEs
Approved by the FDA (1980-2009)
NMEs
Approved
Marketed
Priority Review
Marketed = Products still in the market in August 1, 2010.
Discontinued NMEs and BLAs.
Approved by the FDA (1980-1999)
% NMEs & BLAs
Discontinued
from Market
Systemic Antibacterials Approved by
the FDA (1980-2009).
Marketed Drugs, Linear Trend
5
CUSFTA
CAFC
Bayh-Dole Act
TRIPS
Bioshield
ODA
Ped Excl.
OB
TRIPS
India +
AUSFTA
4
3 3
3
2
2
1
0
2
1
1 1
0
1 1
1
0
1
2
2
1
0
1 1
0
1
0
1
0
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
0
3
2
1
0
3
Sec.505
Marketed NMEs and BLAs Approved by the FDA
by Selected Therapeutic Classes
as a % Total Approvals (1980-2009)
1980s
1990s
2000s
% Total NMEs & BLAs
Cardiovascular System Drugs Approved by
the FDA (1980-2009). Marketed Drugs, Linear
Trend & 5 Year Moving Average
10
9
8
8
7
7
6
5
5
4 4
4
4
3
3
3
2
2
4
2
4
3
3
2 2
2
3
2
1 1 1 1
0
980
981
982
983
984
985
986
987
988
989
990
991
992
993
994
995
996
997
998
999
000
001
002
003
004
005
006
007
008
009
0
3
2
1 1
1
0
3
Antineoplastic & Immunomodulating Agents
Approved by the FDA (1980-2009). Marketed Drugs,
Linear Trend & 5 Year Moving Average
10
9
9
8
8
8
7
7
7
6
5
5
5
4
4
3 3
3
2
2
2
1 1
1
0
1
3
4
3
2
5 5 5
4
3
2
1 1
0
980
981
982
983
984
985
986
987
988
989
990
991
992
993
994
995
996
997
998
999
000
001
002
003
004
005
006
007
008
009
0
5
Contingent
Proposal 1P4P
• 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
• 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
Social Value of the ABX gap
DALY Value
US & CAN
HI 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)
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)
Strategic
ABX
Reserve
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
Further Issues
• Funding
• Access/price to patients
• Industry capture/targets
• Informational problems with
value & efficacy)
• IP coordination
Invitation
• Harvard Center for
Communicable Disease
Dynamics Conference, Boston
• Oct. 3-4, 2011
• 2.5 hour program on abx
incentives on Oct. 4
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