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Economic Incentives for Antibacterial Drug Development: Alternative Market Structures to Promote Innovation

  • Marina L. Kozak
  • Joseph C. Larsen
Chapter
Part of the Emerging Infectious Diseases of the 21st Century book series (EIDC)

Abstract

The current economic model for antibacterial drug development and commercialization does not provide sufficient financial returns that reflect the societal value that new antibacterial agents provide. As such, the pharmaceutical industry has largely focused their development efforts on therapeutic areas where greater profit potential exists resulting in a substantial innovation gap in antibacterial drug development. The number of new antibiotics in development is likely too small to withstand technical attrition and increasing rates of bacterial resistance. New market models are needed that reward innovation in antibacterial drug development and provide a stronger return on investment for companies still operating in this space. While rewarding innovation, these models should also promote stewardship of new antibacterial drugs and ensure access to all patients that need them. This chapter explores various proposals for alternative market models and their associated policy considerations.

Abbreviations

ADAPT

Antibiotic Development to Advance Patient Treatment

AMR

Antimicrobial resistance

BARDA

Biomedical Advanced Research and Development Authority

CDC

US Centers for Disease Control and Prevention

CMS

US Centers for Medicare & Medicaid Services

DISARM

Developing an Innovative Strategy for Antimicrobial Resistant Microorganisms Act

DNDi

Drugs for Neglected Diseases Initiative

DRG

Diagnosis-Related Group

DRIVE-AB

Driving Re-investment in R&D and Responsible Antibiotic Use

ENPV

Expected Net Present Value

FDA

US Food and Drug Administration

GAIN

Generating Antibiotic Incentives Now

GARD

Global Antibiotic Research and Development Partnership

GUARD

Global Union for Antibiotics Research and Development

HHS

Health and Human Services

IDSA

Infectious Diseases Society of America

IMI

Innovative Medicines Initiative

IP

Intellectual Property

JPIAMR

Joint Programming Initiative on Antimicrobial Resistance

MER

Market Entry Reward

ND4BB

New Drugs for Bad Bugs

NIAID

National Institute for Allergy and Infectious Diseases

NIH

US National Institutes of Health

NPV

Net Present Value

NTAP

New Technology Add-on Payment

OTA

Other Transactional Authority

PACCARB

President Advisory Committee on Combating Antibiotic-Resistant Bacteria

PCAST

President’s Council of Advisors for Science and Technology

PRV

Priority Review Voucher

QIDP

FDA qualified infectious disease products

R&D

Research and Development

READI

Reinvigorating Antibiotic and Diagnostic Innovation Act

ROI

Return on Investment

TATFAR

TransAtlantic Task Force on Antimicrobial Resistance

TIPR

Transferable Intellectual Property Rights

WHO

World Health Organization

References

  1. 1.
    B20 Health Initiative. Stepping Up Global Health Towards Resilient, Responsible and Responsive Health Systems. 2017. Available: https://www.b20germany.org/fileadmin/user_upload/B20_Germany_Policy_Paper_Health_Initiative.pdf. Accessed May 2017.
  2. 2.
    Baker J. Medicare payment system for hospital inpatients: diagnosis-related groups. J Health Care Finance. 2002:28.Google Scholar
  3. 3.
    Berry SM, Broglio KR, Groshen S, Berry DA. Bayesian hierarchical modeling of patient subpopulations: efficient designs of phase II oncology clinical trials. Clin Trials. 2013;10CrossRefGoogle Scholar
  4. 4.
    Boston Consulting Group, Öpp Deutschland AG & Technische Universität Berlin. Breaking through the Wall Enhancing Research and Development of Antibiotics in Science and Industry. Global Union for Antibiotics Research and Development (GUARD) Initiative. 2017. Available: https://www.bundesgesundheitsministerium.de/fileadmin/Dateien/5_Publikationen/Gesundheit/Berichte/GUARD_Follow_Up_Report_Full_Report_final.pdf. Accessed May 24 2017.
  5. 5.
    Boucher HW, Ambrose PG, Chambers HF, Ebright RH, Jezek A, Murray BE, Newland JG, Ostrowsky B, Rex JH & INFECTIOUS DISEASES SOCIETY OF AMERICA 2017. White paper: developing antimicrobial drugs for resistant pathogens, narrow-spectrum indications, and unmet needs. J Infect Dis.Google Scholar
  6. 6.
    Brogan D, Mossialos E. Systems, not pills: the options market for antibiotics seeks to rejuvenate the antibiotic pipeline. Soc Sci Med. 2016;151:167–72.CrossRefGoogle Scholar
  7. 7.
    Butler MS, Blaskovich MA, Ma C. Antibiotics in the clinical pipeline in 2013. J Antibiot. 2013:66.Google Scholar
  8. 8.
    Centers for Disease Control. Antibiotic resistance threats in the United States. 2013. Available: https://www.cdc.gov/drugresistance/threat-report-2013/index.html. Accessed May 2017.
  9. 9.
    Chatham House Working Group. Towards a New Global Business Model for Antibiotics: Delinking Revenues from Sales. 2015. Available: https://www.chathamhouse.org/publication/towards-new-global-business-model-antibiotics-delinking-revenues-sales. Accessed May 2017.
  10. 10.
    Davos Declaration. Declaration by the Pharmaceutical, Biotechnology and Diagnostics Industries on Combating Antimicrobial Resistance. 2016. Available: https://www.ifpma.org/partners-2/declaration-by-the-pharmaceutical-biotechnology-and-diagnostics-industries-on-combating-antimicrobial-resistance-amr/. Accessed May 2017.
  11. 11.
    Deak D, Outterson K, Powers J, Kesselheim A. Progress in the fight against multidrug-resistant Bacteria? A review of U.S. Food and Drug Administration-approved antibiotics, 2010-2015. Ann Intern Med. 2016;165:363–72.CrossRefGoogle Scholar
  12. 12.
    Duke-Margolis Center for Health Policy. Antimicrobial Payment Reform Project. 2016. Available: https://healthpolicy.duke.edu/antimicrobial-payment-reform-project. Accessed May 2017.
  13. 13.
    Fagnan de GA, Stein RM, Fernandez JM, Lo AW. Financing drug discovery for orphan diseases. Drug Discov Today. 2014;19:533–8.CrossRefGoogle Scholar
  14. 14.
    Fernandez J, Stein R, Lo A. Commercializing biomedical research through securitization techniques. Nat Biotechnol. 2012;30:964–75.CrossRefGoogle Scholar
  15. 15.
    Ferraro J, Towse A, Mestreferrandiz A. Incentives for New Drugs to Tackle Anti-Microbial Resistance. 2017. Available: https://www.ohe.org/publications/incentives-new-drugs-tackle-anti-microbial-resistance. Accessed May 2017.
  16. 16.
    Food and Drug Administration. The Orphan Drug Act. 1983. Available: https://www.gpo.gov/fdsys/pkg/STATUTE-96/pdf/STATUTE-96-Pg2049.pdf. Accessed May 2017.
  17. 17.
    Garde D. Merck dumps 120 Cubist researchers after its $9.5B merger. 2015. Available: http://www.fiercebiotech.com/r-d/merck-dumps-120-cubist-researchers-after-its-9-5b-merger. Accessed May 2017.
  18. 18.
    Global Antibiotic Research and Development Partnership. Developing new antibiotic treatments, promoting responsible use, and ensuring access for all. 2015. Available: http://www.dndi.org/GARD. Accessed May 2017.
  19. 19.
    Grabowski H, Ridley D, Moe J. Encouraging innovative treatment of neglected diseases through priority review vouchers. In:Prescribing cultures and pharmaceutical policy in the Asia-Pacific; 2009.Google Scholar
  20. 20.
    Harbarth S, Theuretzbacher U, Hackett J, Drive-AB Consortium. Antibiotic research and development: business as usual? J Antimicrob Chemother. 2015:70.Google Scholar
  21. 21.
    Innovative Medicines Initiative. ENABLE project. 2014. Available: http://nd4bb-enable.eu/. Accessed June 2017.
  22. 22.
    Innovative Medicines Initiative. Incentives to stimulate antibiotic innovation: The preliminary findings of DRIVE-AB. 2016. Available: http://drive-ab.eu/events/drive-ab-project-events/drive-ab-conference-2016/. Accessed June 2017.
  23. 23.
    Joint Programming On Antimicrobial Resistance. Strategic Research Agenda. 2014. Available: http://www.jpiamr.eu/document-library/workshop-reports/. Accessed June 2017.
  24. 24.
    Mcdonnell A, Rex J, Goossens H, Bonten M, Fowler V, Dane A. Efficient delivery of investigational antibacterial agents via sustainable clinical trial networks. Clin Infect Dis. 2016;63(Suppl 2):S57–9.CrossRefGoogle Scholar
  25. 25.
    Montazerhodjat V, Frishkopf J, Lo A. Financing drug discovery via dynamic leverage. Drug Discov Today. 2016;21:410–4.CrossRefGoogle Scholar
  26. 26.
    National Institutes of Health. Antimicrobial Resistance Rapid, Point-of-Need Diagnostic Test’ Challenge. 2017. Available: http://www.cccinnovationcenter.com/challenges/antimicrobial-resistance-diagnostic-challenge/. Accessed May 2017.
  27. 27.
    O'neill J. Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations. 2014. Available: https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf. Accessed May 2017.
  28. 28.
    O'neill J. Securing new drugs for future generations. The pipeline of antibiotics. 2015. Available: https://amr-review.org/sites/default/files/SECURING%20NEW%20DRUGS%20FOR%20FUTURE%20GENERATIONS%20FINAL%20WEB_0.pdf. Accessed May 2017.
  29. 29.
    Outterson K, Mcdonnell A. Funding antibiotic innovation with vouchers: recommendations on how to strengthen a flawed incentive policy. Health Aff (Millwood). 2016;35:784–90.CrossRefGoogle Scholar
  30. 30.
    Outterson K, Rex J, Jinks T, Jackson P, Hallinan J, Karp S, Hung D, Franceschi F, Merkeley T, Houchens C, Dixon D, Kurilla M, Aurigemma R, Larsen J. Accelerating global innovation to address antibacterial resistance: introducing CARB-X. Nat Rev Drug Discov. 2016;15:589.CrossRefGoogle Scholar
  31. 31.
    Pew Charitable Trusts. Antibiotics Currently in Clinical Development. 2016a. Available: http://www.pewtrusts.org/~/media/assets/2016/12/antibiotics_datatable_201612.pdf?la=en. Accessed May 2017.
  32. 32.
    Pew Charitable Trusts. A Scientific Roadmap for Antibiotic Discovery. 2016b. Available: http://www.pewtrusts.org/en/research-and-analysis/reports/2016/05/a-scientific-roadmap-for-antibiotic-discovery. Accessed May 2017.
  33. 33.
    Pharmaceutical Research and Manufacturers of America. Medicines in Development for Cancer. 2015. Available: http://www.phrma.org/report/medicines-in-development-for-cancer-2015-report. Accessed April 2017.
  34. 34.
    PRNewswire. CMS Grants New Technology Add-on Payment to DIFICID® for Treatment of Clostridium difficile-associated Diarrhea. 2012. Available: http://www.prnewswire.com/news-releases/cms-grants-new-technology-add-on-payment-to-dificid-for-treatment-of-clostridium-difficile-associated-diarrhea-164717586.html. Accessed May 2017.
  35. 35.
    Renwick M, Brogan D, Mossialos E. A systematic review and critical assessment of incentive strategies for discovery and development of novel antibiotics. J Antibiot (Tokyo). 2016;69:73–88.CrossRefGoogle Scholar
  36. 36.
    Renwick Mj BD, Mossialos E. A systematic review and critical assessment of incentive strategies for discovery and development of novel antibiotics. J Antibiot. 2016;69.CrossRefGoogle Scholar
  37. 37.
    Rex J, Outterson K. Antibiotic reimbursement in a model delinked from sales: a benchmark-based worldwide approach. Lancet Infect Dis. 2016;16:500–5.CrossRefGoogle Scholar
  38. 38.
    Ridley D, Régnier S. The commercial market for priority review vouchers. Health Aff (Millwood). 2016;35:776–83.CrossRefGoogle Scholar
  39. 39.
    Sciarretta, K., Røttingen, J., Opalska, A., Van Hengel, A. & Larsen, J. 2017. Pull incentives for antibacterial drug development: an analysis by the trans-Atlantic task force on antimicrobial resistance. Clin Infect Dis 63.Google Scholar
  40. 40.
    Seabury S & Sood N. Toward A New Model For Promoting The Development Of Antimicrobial Drugs. 2017. Available: http://healthaffairs.org/blog/2017/05/18/toward-a-new-model-for-promoting-the-development-of-antimicrobial-drugs/. Accessed June 2017.
  41. 41.
    Sertkaya A, Eyraud J, Birkenbach A, Franz C, Ackerley N, Overton V, Outterson K. Analytical Framework For Examining The Value Of Antibacterial Products. 2014. Available: https://aspe.hhs.gov/report/analytical-framework-examining-value-antibacterial-products. Accessed June 2017.
  42. 42.
    Sharma P, Towse A. New Drugs to Tackle Antimicrobial Resistance: Analysis of EU Policy Options. 2011. Available: https://www.ohe.org/publications/new-drugs-tackle-antimicrobial-resistance-analysis-eu-policy-options. Accessed June 2017.
  43. 43.
    Spellberg B, Miller L, Kuo M, Bradley J, Scheld W, Edwards JJ. Societal costs versus savings from wild-card patent extension legislation to spur critically needed antibiotic development. Infection. 2007;35:167–74.CrossRefGoogle Scholar
  44. 44.
    The White House. National Strategy For Combating Antibiotic Resistant Bacteria. 2014. Available: https://obamawhitehouse.archives.gov/sites/default/files/docs/carb_national_strategy.pdf. Accessed June 2017.
  45. 45.
    The White House. National Action Plan For Combating Antibiotic-Resistant Bacteria. 2015. Available: https://obamawhitehouse.archives.gov/the-press-office/2015/03/27/fact-sheet-obama-administration-releases-national-action-plan-combat-ant. Accessed June 2017.
  46. 46.
    US Congress. S.15 - Project BioShield Act of 2004. 2004. Available: https://www.congress.gov/bill/108th-congress/senate-bill/15. Accessed June 2017.
  47. 47.
    US Congress. H.R.2182 - To provide incentives for the development of qualified infectious disease products. 2012. Available: https://www.congress.gov/bill/112th-congress/house-bill/2182. Accessed June 2017.
  48. 48.
    US Congress. H.R.4187 - DISARM Act of 2014. 2014. Available: https://www.congress.gov/bill/113th-congress/house-bill/4187. Accessed June 2017.
  49. 49.
    US Congress. H.R.2629 - Antibiotic Development to Advance Patient Treatment Act. 2015a. Available: https://www.congress.gov/bill/114th-congress/house-bill/2629. Accessed June 2017.
  50. 50.
    US Congress. H.R.3539 - Reinvigorating Antibiotic and Diagnostic Innovation Act of 2015. 2015b. Available: https://www.congress.gov/bill/114th-congress/house-bill/3539. Accessed June 2017.
  51. 51.
    US Congress. H.R.6 - To accelerate the discovery, development, and delivery of 21st century cures, and for other purposes. 2016. Available: https://www.congress.gov/bill/114th-congress/house-bill/6. Accessed June 2017.
  52. 52.
    US Congress. H.R.1776 - Improving Access To Affordable Prescription Drugs Act. 2017. Available: https://www.govtrack.us/congress/bills/115/hr1776/text. Accessed June 2017.
  53. 53.
    World Health Organization. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. 2017. Available: http://www.who.int/medicines/publications/global-priority-list-antibiotic-resistant-bacteria/en/. Accessed May 2017.

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Health Scientist, Division of CBRN Medical CountermeasuresBiomedical Advanced Research and Development AuthorityWashington, DCUSA
  2. 2.Division of CBRN Medical CountermeasuresBiomedical Advanced Research and Development AuthorityWashington, DCUSA

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