When markets fail: Patents and infectious disease products

Food and Drug Law Journal

Volumn 73, Issue 3, 2018, Pages 361-382

  Darrow, Jonathan J ^a   Sinha, Michael S ^a   Kesselheim, Aaron S ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC AGENT;

ANTIBIOTIC RESISTANCE; ANTIMICROBIAL THERAPY; BASIC RESEARCH; DRUG COST; DRUG DEALING; DRUG LEGISLATION; DRUG MARKETING; FOOD AND DRUG ADMINISTRATION; GOVERNMENT; HUMAN; INFECTION; NON PROFIT ORGANIZATION; PATENT; REVIEW;

EID: 85055782204     PISSN: 1064590X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (128)

1. United States v. Univis Lens Co., 316 U.S. 241, 250 (1942)
2. A. Samuel Oddi, Un-Unified Economic Theories of Patents: The Not-Quite-Holy Grail, 71 NOTRE DAME L. REV. 267, 305 (1996)
3. Fritz Machlup, An Economic Review of the Patent System, Study No 15, Subcommittee on Patents, Trademarks, and Copyrights of the Senate Committee on the Judiciary, 85th Cong., 2d Sess., at 13 (1958).
4. Ellen 't Hoen, TRIPS, Pharmaceutical Patents, and Access to Essential Medicines: A Long Way from Seattle to Doha, 3 CHI. J. INT'L L. 27 (2002)
5. see also Jonathan J. Darrow, Essential Medicines: Why International Price Discrimination May Increasingly Be the Wrong Solution to a Global Drug Problem, 39 J. LAW MED. & ETHICS 291 (2011) (explaining why one proposed solution is problematic).
6. Michael D. Bednarek, Planning a Global Patent Strategy to Maximize Value: Where to Get the Most "Bang for Your Buck," 77 J. PAT. & TRADEMARK OFF. SOC'Y 381, 382 (1995) ("The value of the right to exclude⋯ largely depends on the importance of the market covered by the patent. Market size is, of course, the principal determinant of market importance.").
7. Jonathan J. Darrow & Aaron S. Kesselheim, Drug Development and FDA Approval, 1938-2013, 370(26) NEW ENG. J. MED. 2465 (2014), http://www.nejm.org/doi/full/10.1056/NEJMp1402114 [https://perma.cc/T9M6-T3XY]
8. see generally Jonathan J. Darrow & Aaron S. Kesselheim, Promoting Competition to Address Pharmaceutical Prices, HEALTH AFF., Mar. 15, 2018, https://www.healthaffairs.org/do/10.1377/hpb20180116.967310/full/ (examining market factors that can lead to increased drug prices).
9. 10×'20 Progress: Development of New Drugs Active Against Gram-Negative Bacilli: An Update from the Infectious Diseases Society of America, 56(12) CLIN. INFECTIOUS DISEASES 1685, 1687 (2013).
10. U.S. Federal Funding for HIV/AIDS: Trends Over Time, KAISER FAMILY FOUND., Nov. 9, 2017, https://www.kff.org/global-health-policy/fact-sheet/u-s-federal-funding-for-hivaids-trends-over-time/ [https://perma.cc/L49V-MZLS].
11. Targeted Drug Development: Why Are Many Diseases Lagging Behind?, FOOD & DRUG ADMIN., July 2015, at 11, https://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Reports/UCM454996.pdf
12. Erik De Clercq, The Design of Drugs for HIV and HCV, 6 NATURE REVS. DRUG DISCOVERY 1001, 1010 (2007).
13. Kevin Outterson & Anthony McDonnell, Funding Antibiotic Innovation with Vouchers: Recommendations on How to Strengthen a Flawed Incentive Policy, 35(5) HEALTH AFFAIRS 784, 784 (2016)
14. Adrian Towse & Priya Sharma, Incentives for R&D for New Antimicrobial Drugs, 18 INT'L J. ECON. BUS. 331, 336 (2011)
15. Aaron S. Kesselheim & Kevin Outterson, Fighting Antibiotic Resistance: Marrying New Financial Incentives to Meeting Public Health Goals, 29(9) HEALTH AFF. 1689, 1691 (2010).
16. Antibiotic Resistance Threats in the United States, CENTERS FOR DISEASE CONTROL & PREVENTION (2013), https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf [https://perma.cc/P3QA-HFC4].
17. See Thomas J. Hwang, Jonathan J. Darrow & Aaron S. Kesselheim, The FDA's Expedited Programs and Clinical Development Times for Novel Therapeutics, 2012-2016, 318(21) J. AM. MED. ASS'N 2137, 2138 (2017)
18. see also Jonathan J. Darrow, Jerry Avorn & Aaron S. Kesselheim, Speed, Safety, and Industry Funding: From PDUFA 1 to PDUFA 6, 377(23) NEW ENG. J. MED. 2278, 2280 fig.1 (2017) (illustrating that FDA review times alone can exceed 10 months).
19. Jonathan J. Darrow, Jerry Avorn & Aaron S. Kesselheim, New FDA Breakthrough-Drug Category: Implications for Patients, 370 NEW ENG. J. MED. 1252, 1253 (2014)
20. see also Jonathan J. Darrow, Jerry Avorn & Aaron S. Kesselheim, The FDA Breakthrough Drug Designation: Four Years of Experience, 378(15) NEW ENG. J. MED. 1444, 1451 (2018) (noting increasing use of the breakthrough pathway).
21. Final Trial Results Confirm Ebola Vaccine Provides High Protection Against Disease, WHO NEWS RELEASE, Dec. 23, 2016, http://www.who.int/mediacentre/news/releases/2016/ebola-vaccine-results/en/ [https://perma.cc/J2XD-62HE].
22. Stefano Merler et al., Containing Ebola at the Source with Ring Vaccination, 10 PLOS NEGLECTED TROP. DIS. e0005093, at 2 (2016).
23. Ebola Virus Disease Distribution Map: Cases of Ebola Virus Disease in Africa Since 1976, CENTERS FOR DISEASE CONTROL & PREVENTION, May 15, 2018, https://www.cdc.gov/vhf/ebola/history/distribution-map.html [https://perma.cc/AL89-VGZ3].
24. Associated Press, Obama Declares Swine Flu National Emergency, NBC NEWS, Oct. 25, 2009, http://www.nbcnews.com/id/33459423/ns/health-cold-and-flu/t/obama-declares-swine-flu-national-emergency/#.WfJRwI9Swuo [https://perma.cc/BQA2-ALTR].
25. Sabrina Tavernise & Donald G. McNeil, Zika Virus a Global Health Emergency, W.H.O. Says, N.Y. TIMES, Feb. 1, 2016, https://www.nytimes.com/2016/02/02/health/zika-virus-world-health-organization.html [https://perma.cc/67J9-TXWA].
26. Camila Domonoske, U.N. Admits Role in Haiti Cholera Outbreak that Has Killed Thousands, NAT'L PUB. RADIO, Aug. 18, 2016, http://www.npr.org/sections/thetwo-way/2016/08/18/490468640/u-n-admits-role-in-haiti-cholera-outbreak-that-has-killed-thousands [https://perma.cc/7NR8-7AG4].
27. JOHN M. BARRY, THE GREAT INFLUENZA: THE STORY OF THE DEADLIEST PLAGUE IN HISTORY (2004).
28. Jeffrey K. Taubenberger & David M. Morens, 1918 Influenza: The Mother of All Pandemics, 12 EMERGING INFECTIOUS DISEASES 15, 15 (2006).
29. Peter Loftus, Sanofi Stops Work on Two Zika Vaccines, WALL ST. J., Sept. 6, 2017, https://www.wsj.com/articles/sanofi-stops-work-on-two-zika-vaccines-1504734084 [https://perma.cc/2HHD-C389].
30. See generally Reed F. Beall, Jonathan J. Darrow & Aaron S. Kesselheim, A Method for Approximating Future Entry of Generic Drugs, VALUE IN HEALTH- (2018) (in press) (explaining that even the date on which exclusivity will end can only be estimated).
31. See Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States, 2017, CENTERS FOR DISEASE CONTROL & PREVENTION, at 2-3, https://www.cdc.gov/vaccines/schedules/downloads/adult/adult-combined-schedule.pdf [https://perma.cc/V8WJ-4Y6V].
32. MMR Vaccine: What You Need to Know, VACCINE INFORMATION STATEMENT, CENTERS FOR DISEASE CONTROL & PREVENTION, Apr. 20, 2012, at 1, https://www.cdc.gov/vaccines/hcp/vis/vis-statements/mmr.pdf [https://perma.cc/J3DE-H58M].
33. Paul Fine, Ken Eames & David L. Heymann, "Herd Immunity": A Rough Guide, 52 VACCINES 911, 914 (2011)
34. Jason B. Harris et al., Cholera, 379 LANCET 2466, 2472 (2012).
35. David Willman, Cost, Need Questioned in $433-Million Smallpox Drug Deal, L.A. TIMES, Nov. 13, 2011, http://articles.latimes.com/print/2011/nov/13/nation/la-na-smallpox-20111113 [https://perma.cc/68GR-UN3S]
36. Donald G. McNeil, Wary of Attack with Smallpox, U.S. Buys Up a Costly Drug, N.Y. TIMES, Mar. 12, 2013, http://www.nytimes.com/2013/03/13/health/us-stockpiles-smallpox-drug-in-case-of-bioterror-attack.html [https://perma.cc/74LD-GPEE].
37. See 2016 Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) Strategy and Implementation Plan, U.S. DEP'T OF HEALTH & HUMAN SERVS., at 20, https://www.medicalcountermeasures.gov/media/36937/2016-phemce-sip.pdf [https://perma.cc/UAD8-DKPV].
38. See Kevin Outterson et al., Repairing the Broken Market for Antibiotic Innovation, 34 HEALTH AFF. 277, 278 (2015).
39. See, e.g., Aaron S. Kesselheim & Kevin Outterson, Improving Antibiotic Markets for Long Term Sustainability, 11 YALE J. HEALTH L. POL'Y & ETHICS 101, 122 (2011).
40. Bo Wang, Jun Liu & Aaron S. Kesselheim, Variations in Time of Market Exclusivity Among Top-Selling Prescription Drugs in the United States, 175 J. AM. MED. ASS'N INTERNAL MED. 635, 636 (2015).
41. Neglected Tropical Diseases, WORLD HEALTH ORG., http://www.who.int/neglected-diseases/diseases/en/ [https://perma.cc/W2Z4-9HE3].
42. Celine Aerts et al., Are Public-Private Partnerships the Solution to Tackle Neglected Tropical Diseases? A Systematic Review of the Literature, 121 HEALTH POL'Y 745, 748 (2017)
43. Belen Pedrique et al., The Drug and Vaccine Landscape for Neglected Diseases (2000-11): A Systematic Assessment, 1 LANCET GLOBAL HEALTH 371, 371 (2013)
44. Joshua Cohen et al., Development of and Access to Products for Neglected Diseases, 5 PLOS ONE e10610, at 2 (2010).
45. Parasites-American Trypanosomiasis (also known as Chagas Disease): Epidemiology and Risk Factors, CENTERS FOR DISEASE CONTROL & PREVENTION, https://www.cdc.gov/parasites/chagas/epi.html.
46. Frank A. Sloan et al., Financing Vaccines in the 21st Century: Assuring Access and Availability, INST. OF MED., 1, 4, 138 (2003), https://www.nap.edu/catalog/10782/financing-vaccines-in-the-21st-century-assuring-access-and-availability [https://perma.cc/A86H-SXC6].
47. Vaccines for Children Program: CDC Vaccine Price List, CENTERS FOR DISEASE CONTROL & PREVENTION, July 3, 2017, https://www.cdc.gov/vaccines/programs/vfc/awardees/vaccine-management/price-list/ [https://perma.cc/BCS7-F97K].
48. Susan York Morris, Hepatitis C Treatment Costs: What You Should Know, HEALTHLINE.COM, Feb. 22, 2016, https://www.healthline.com/health/hepatitis-c-treatment-cost#1 [https://perma.cc/3JP9-2WCU].
49. See Patient Protection and Affordable Care Act, Pub. L. No. 111-148, Sec. 1001, § 2713, 124 Stat. 119, 131 (2010).
50. See Elisabeth Rosenthal, The Price of Prevention: Vaccine Costs Are Soaring, N.Y. TIMES, July 2, 2014, at A1.
51. Press Release, Clinton Foundation and UNITAID Announce Price Reductions on 16 AIDS Medicines for 66 Developing Countries, CLINTON FOUND., May 8, 2007, https://www.clintonfoundation.org/main/news-and-media/press-releases-and-statements/press-release-clinton-foundation-and-unitaid-announce-price-reductions-on-16-aid.html [https://perma.cc/GU6X-KYKV].
52. Kate Kelland, Africa to Get State-of-Art HIV Drugs for $75 a Year, REUTERS, Sept. 21, 2017, https://www.reuters.com/article/us-health-aids-medicines-exclusive/exclusive-africa-to-get-state-of-art-hiv-drugs-for-75-a-year-idUSKCN1BW169 [https://perma.cc/68YA-9PW9].
53. Reed Beall & Randall Kuhn, Trends in Compulsory Licensing of Pharmaceuticals Since the Doha Declaration: A Database Analysis, 9 PLOS MED. e1001154 (2012)
54. see also Kyung-Bok Son & Tae-Jin Lee, Compulsory Licensing of Pharmaceuticals Reconsidered: Current Situation and Implications for Access to Medicine, GLOBAL PUB. HEALTH 1, 4 (2017) (finding that approximately 73% of compulsory licensing attempts addressed infectious disease products).
55. Ulrich Worm, German Federal Patent Court Determines License Fee for a Compulsory License Under HIV Drug Patent, MAYER BROWN, Dec. 19, 2017, https://www.allaboutipblog.com/2017/12/german-federal-patent-court-determines-license-fee-for-a-compulsory-license-under-hiv-drug-patent/?utm-source=Mondaq&utm-medium=syndication&utm-campaign=View-Original [https://perma.cc/X3U3-PLA6].
56. Richard A. Spinello, Ethics, Pricing and the Pharmaceutical Industry, 11 J. BUS. ETHICS 617, 618 (1992).
57. Carolyn Y. Johnson & Brady Dennis, How an $84,000 Drug Got Its Price: 'Let's Hold Our Position⋯ Whatever the Headlines,' WASH. POST, Dec. 1, 2015
58. see generally Nathalie Vernaz et al., Drug Pricing Evolution in Hepatitis C, 11 PLOS ONE e0157098, at 2 (2016) (summarizing the evolution in cure rates, as well as prices, of Hepatitis C medicines).
59. Dare to Refuse the Exorbitant Price of Sovaldi!, 23 PRESCRIRE INT'L 278 (2014)
60. Robert Steinbrook & Rita F. Redberg, The High Price of the New Hepatitis C Virus Drugs, 174 JAMA INTERNAL MED. 1172, 1172 (2014)
61. Michael McCarthy, Hepatitis C Drug Maker Puts Profit Ahead of Patients, US Senate Report Charges, 351 BRITISH MED. J. h6573, at 1 (2015)
62. Margot Sanger-Katz, Why the Price of Sovaldi is a Shock to the System, N.Y. TIMES, Aug. 6, 2014, https://www.nytimes.com/2014/08/07/upshot/why-the-price-of-sovaldi-is-a-shock-to-the-system.html [https://perma.cc/Z6NA-EGGM]
63. Andrew Pollack, High Cost of Sovaldi Hepatitis C Drug Prompts a Call to Void Its Patents, N.Y. TIMES, May 19, 2015, https://www.nytimes.com/2015/05/20/business/high-cost-of-hepatitis-c-drug-prompts-a-call-to-void-its-patents.html [https://perma.cc/ZPM3-GXCG]
64. Olga Khazan, The True Cost of an Expensive Medication, ATLANTIC, Sept. 25, 2015, https://www.theatlantic.com/health/archive/2015/09/an-expensive-medications-human-cost/407299/[https://perma.cc/7UB2-HWNP].
65. Rebecca Robbins, Forced to Discount Pricey Hepatitis C Drugs, Gilead Misses Sales Target, STAT NEWS, Apr. 28, 2016, https://www.statnews.com/2016/04/28/gilead-hepatitis-c-revenue-down/ [https://perma.cc/FFG2-645A]
66. Ed Silverman, Ooh la la: France Negotiates a Steep Discount for Sovaldi from Gilead, WALL ST. J., Nov. 20, 2014, https://blogs.wsj.com/pharmalot/2014/11/20/ooh-la-la-france-negotiates-a-steep-discount-for-sovaldi/ [https://perma.cc/7TW5-QJNT].
67. Anne Steele, Gilead Revenue Falls as Hepatitis Drug Sales Drop, MARKETWATCH, Feb. 7, 2017, https://secure.marketwatch.com/story/gilead-revenue-falls-as-hepatitis-drug-sales-drop-2017-02-07?link=MW-home-latest-news[https://perma.cc/VD8U-2RVA]
68. Tess Stynes, Gilead Sales of Hepatitis C Drugs fall 19%; Harvoni Misses Expectations as Competition from Rival Drugs, Pricing Pressures Intensify, WALL ST. J., July 25, 2016
69. Arlene Weintraub, Merck Swallows $2.9B Write-Down of Experimental Hep C Drug as Market Plummets, FIERCE PHARMA, Feb. 24, 2017, https://www.fiercepharma.com/pharma/merck-swallows-1-9b-writedown-experimental-hep-c-drug-as-market-plummets [https://perma.cc/X5FW-LMF5].
70. Phaedra S. Corso et al., Assessing Preferences for Prevention Versus Treatment Using Willingness to Pay, 22 MED. DECISION MAKING S92, S97 (2002).
71. Simone Wright et al., Fear of Needles: Nature and Prevalence in General Practice, 38 AUSTRALIAN FAM. PHYSICIAN 172, 173 (2009)
72. Yael Nir et al., Fear of Injections in Young Adults: Prevalence and Associations, 68 AM. J. TROP. MED. & HYGIENE 341, 342 (2003).
73. Emuella M. Flood et al., A Survey of Children's Preferences for Influenza Vaccine Attributes, 29 VACCINE 4334, 4337 (2011)
74. Emuella M. Flood et al., Parent Preferences for Pediatric Influenza Vaccine Attributes, 50 CLINICAL PEDIATRICS 338, 343 (2011)
75. Anna Taddio et al., Reducing the Pain of Childhood Vaccination: An Evidence-Based Clinical Practice Guideline (Summary), 182 CANADIAN MED. J. 1989, 1999 (2010)
76. David Fassler, The Fear of Needles in Children, 55 AM. J. ORTHOPSYCHIATRY 371, 375 (1985).
77. Jonathan J. Darrow & Aaron S. Kesselheim, A New Wave of Vaccines for Non-Communicable Diseases: What Are the Regulatory Challenges?, 70 FOOD & DRUG L. J. 243, 246 (2015).
78. Martin Kaufman, The American Anti-Vaccinationists and their Arguments., 41 BULL. HIST. MED. 463, 464 (1967).
79. Neil D. Weinstein, Unrealistic Optimism About Future Life Events, 39 J. PERSONALITY & SOC. PSYCH. 806, 808 (1980)
80. Neil D. Weinstein, Unrealistic Optimism About Susceptibility to Health Problems, 5 J. BEHAV. MED. 441, 450 (1982).
81. Robert M. Wolfe & Lisa K. Sharp, Anti-Vaccinationists Past and Present, 325 BRIT. MED. J. 430, 431 (2002)
82. Emily Oster & Geoffrey Kocks, After a Debacle, How California Became a Role Model on Measles, N.Y. TIMES, Jan. 16, 2018, https://www.nytimes.com/2018/01/16/upshot/measles-vaccination-california-students.html [https://perma.cc/C3RK-62ZV] (noting that a 2014 measles outbreak in California that sickened at least 159 people was "the result of an inability to persuade a significant share of Californians that vaccines were important" but that "earlier generations knew [that] people die of measles, and of whooping cough, and of other diseases that vaccines can prevent").
83. PRESIDENT'S COUNCIL OF ADVISORS ON SCI. & TECH., REPORT TO THE PRESIDENT ON COMBATING ANTIBIOTIC RESISTANCE (2014), https://obamawhitehouse.archives.gov/sites/default/files/microsites/ostp/PCAST/pcast-carb-report-sept2014.pdf
84. Kevin Outterson et al., Will Longer Antimicrobial Patents Improve Global Public Health?, 7 LANCET 559, 562 (2007).
85. U.S. FOOD & DRUG ADMIN., GUIDANCE FOR INDUSTRY: TROPICAL DISEASE PRIORITY REVIEW VOUCHERS (2016) at 3.
86. Nina Jain et al., Association of the Priority Review Voucher with Neglected Tropical Disease Drug and Vaccine Development, 318 J. AM. MED. ASS'N 388, 389 (2017).
87. Aaron S. Kesselheim et al., Experience with the Priority Review Voucher Program for Drug Development, 314 J. AM. MED. ASS'N 1687, 1687 (2015)
88. Simone Garcia et al., Treatment with Benznidazole During the Chronic Phase of Experimental Chagas' Disease Decreases Cardiac Alterations, 49 ANTIMICROBIAL AGENTS & CHEMOTHERAPY 1521, 1522 (2005).
89. Jason B. Harris et al., Cholera, 379 LANCET 2466, 2472 (2012)
90. see also Cholera-Vibrio cholerae infection: Vaxchora® (lyophilized CVD 103-HgR), CENTERS FOR DISEASE CONTROL & PREVENTION, https://www.cdc.gov/cholera/vaccines.html (announcing the recent approval of Vaxchora, and the availability of three other cholera vaccines).
91. Jerry Avorn, Approval of a Tuberculosis Drug Based on a Paradoxical Surrogate Measure, 309 J. AM. MED. ASS'N 1349, 1349 (2013).
92. Kenneth I. Kaitin & Joseph A. DiMasi, Pharmaceutical Innovation in the 21st Century: New Drug Approvals in the First Decade, 2000-2009, 89 CLINICAL PHARMACOLOGY & THERAPEUTICS 183, 185 (2011)
93. Tim Anderson et al., Global Pharmaceuticals: R&D Productivity Finally Turning the Corner?! Important New Data Suggests It Is, BERNSTEIN, Sept. 22, 2015 (Exh. 7), https://kmrgroup.com/wp-content/uploads/2015/09/Bernstein-Global-Pharma-22Sept2015-RnD-Productivity-Trends.pdf.
94. Alexander Gaffney, Michael Mezher & Zachary Brennan, Regulatory Explainer: Everything You Need to Know About FDA's Priority Review Vouchers, REG. AFF. PROF. SOC'Y, Dec. 19, 2017, https://www.raps.org/regulatory-focus%E2%84%A2/news-articles/2017/12/regulatory-explainer-everything-you-need-to-know-about-fda%E2%80%99s-priority-review-vouchers.
95. See Aaron S. Kesselheim, Bo Wang, Jessica Franklin & Jonathan J. Darrow, Trends in Utilization of FDA Early-Access Drug Approval Programs, 351 BRITISH MED. J. h4633, at 6 figs. 2 & 3 (2015) (showing increasing utilization of expedited programs generally)
96. Jonathan J. Darrow, Pharmaceutical Efficacy: The Illusory Legal Standard, 70 WASH. & LEE L. REV. 2073, 2110 (2013).
97. Pub. L. No. 112-144, § 801, 126 Stat. 993, 1077 (2012) (codified at 21 U.S.C. § 355f).
98. 79 Fed. Reg. 32,464 at 32,465-32,466 (June 5, 2014) (establishing a list of qualifying pathogens under the Food and Drug Administration Safety and Innovation Act).
99. 21 U.S.C. § 355f(a) (2018) (The five year period is added to "the 4- and 5-year periods described in subsections (c)(3)(E)(ii) and (j)(5)(F)(ii) of section 355 of this title⋯."); see id. § 355(c)(3)(E)(ii) (measuring the 4- and 5-year periods from the date of approval of a new drug application).
100. Brad Spellberg et al., The Critical Impact of Time Discounting on Economic Incentives to Overcome the Antibiotic Market Failure, 11 NATURE REVS. DRUG DISCOVERY 168, 169 (2012).
101. See JAMES BOYLE, THE PUBLIC DOMAIN: ENCLOSING THE COMMONS OF THE MIND 23-34 (2008) (quoting McCauley for the proposition that distant payments are heavily discounted).
102. See Drugs for Neglected Diseases initiative, http://www.who.int/phi/documents/drugs-neglected-diseases-initiative.pdf (last visited Jan. 30, 2018).
103. Vision and Mission, DNDi, available at: https://www.dndi.org/about-dndi/vision-mission/ (last visited Jan. 30, 2018).
104. Mark T. Hoekenga, Treatment of Malaria with a Single Dose of Amodiaquine or Chloroquine, 149 J. AM. MED. ASS'N 1369, 1371 (1952)
105. Jing-Bo Jiang et al., Antimalarial Activity of Mefloquine and Qinghaosu, 320 LANCET 285, 287 (1982)
106. Sudaratana R. Krungkrai & Yongyuth Yuthavong, The Antimalarial Action on Plasmodium Falciparum of Qinghaosu and Artesunate in Combination with Agents which Modulate Oxidant Stress, 81 TRANS. R. SOC. TROP. MED. HYGIENE 710, 711 (1987).
107. The Use of Essential Drugs, World Health Org. Technical Report Series, Ninth Report of the WHO Expert Committee (including the revised Model List of Essential Drugs), 2000 at 26 (on file with author).
108. Barbara L. Herwaldt & Jonathan D. Berman, Recommendations for Treating Leishmaniasis with Sodium Stibogluconate (Pentostam) and Review of Pertinent Clinical Studies, 46 AM. J. TROP. MED. & HYGIENE 296, 297 (1992)
109. T.K. Jha et al., Miltefosine, an Oral Agent, for the Treatment of Indian Visceral Leishmaniasis, 341 NEW ENG. J. MED. 1795, 1799 (1999)
110. R.N. Davidson et al., Liposomal Amphotericin B in Drug-Resistant Visceral Leishmaniasis, 337 LANCET 1061, 1061 (1991).
111. Courtney Columbus, Drug for 'Neglected' Chagas Disease Gains FDA Approval Amid Price Worries, NAT'L PUB. RADIO, Sept. 10, 2017, http://www.npr.org/sections/health-shots/2017/09/10/547351794/drug-for-neglected-chagas-disease-gains-fda-approval-amid-price-worries.
112. Business Plan 2015-2023: A Dynamic Portfolio Approach to Address Neglected Patients' Needs, DNDi, https://www.dndi.org/wp-content/uploads/2009/03/DNDi-Business-Plan-2015-2023.pdf [hereinafter "DNDi Business Plan"].
113. New Hope for Novel Drugs for Leishmaniasis: Update of DNDi's Leishmaniasis Pipeline, DNDi (2017), https://www.dndi.org/wp-content/uploads/2017/05/DNDi-LeishmaniasisPipeline-2017.pdf.
114. Graeme Bilbe, Viewpoint, DNDi, Feb. 2017, https://www.dndi.org/2017/media-centre/news-views-stories/viewpoint/qna-results-of-rnd-affordable-available-to-patients/.
115. Joseph A. DiMasi et al., Innovation in the Pharmaceutical Industry: New Estimates of R&D Costs, 47 J. HEALTH ECON. 20, 28 (2016).
116. FY2018 Budget: National Institute of Allergy and Infectious Diseases, DEP'T OF HEALTH & HUMAN SERVS., NAT'L INST. OF HEALTH, https://www.niaid.nih.gov/sites/default/files/fy2018cj.pdf
117. FY2016 Budget; National Institute of Allergy and Infectious Diseases, DEP'T OF HEALTH & HUMAN SERVS., NAT'L INST. OF HEALTH, https://www.niaid.nih.gov/sites/default/files/fy2016cj.pdf
118. NIAID Role in Research: Improving the Health of Millions of People Around the World, NAT'L INST. OF ALLERGY & INFECTIOUS DISEASES, https://www.niaid.nih.gov/research/role.
119. Michael Sinha & Aaron S. Kesselheim, Regulatory Incentives for Antibiotic Drug Development: A Review of Recent Proposals, 24 BIOORGANIC & MEDICINAL CHEM. 6446, 6449 (2016).
120. The Race Against Superbugs, CARB-X ANNUAL REPORT 2016-2017, https://carb-x.org/wp-content/uploads/2018/01/2016-CARB-X-Annual-Report.pdf.
121. National Strategy for Combating Antibiotic-Resistant Bacteria, THE WHITE HOUSE, Sept. 2014, https://www.cdc.gov/drugresistance/pdf/carb-national-strategy.pdf
122. Owen Barder et al., Advance Market Commitments: A Policy to Stimulate Investment in Vaccines for Neglected Diseases, ECONOMISTS' VOICE, Feb. 2006, at 4.
123. The Advance Market Commitment for Pneumococcal Vaccine, UNICEF, (Apr. 2017), https://www.unicef.org/supply/index-60990.html [https://perma.cc/329Q-MF2Y]
124. Neisha Sundaram et al., Cost-Effectiveness of 13-Valent Pneumococcal Conjugate Vaccination in Mongolia, 35 VACCINE 1055, 1056 (2017).
125. See, e.g., Approval letter from Karen L. Goldenthal, FDA, to Jack D. Love, Lederle Labs. Div., Am. Cyanamid Co., Oct. 1, 2002 (Prevnar approval letter), https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm137200.htm.
126. Jens Plahte, Is the Pneumococcal Vaccine Advance Market Commitment Motivating Innovation and Increasing Manufacturing Capacity? Some Preliminary Answers, 30 VACCINE 2462, 2464 (2012).
127. Research and development to meet health needs in developing countries: strengthening global financing and coordination, Report of the Consultative Expert Working Group on Research and Development: Financing and Coordination, at 53, WORLD HEALTH ORGANIZATION [WHO], (Apr. 2012).
128. See Margaret K. Kyle et al., Strategic Interaction Among Governments in the Provision of a Global Public Good, 156 J. PUB. ECON. 185, 185 (2017).