Published online by Cambridge University Press: 01 February 2021
Access to medicine remains a core challenge of global health, despite progress in bringing affordable HIV/AIDS drugs to developing countries. Yet, the debate seems to have shifted. For a long time it focused on two specific issues: (1) whether and to what extent international trade agreements that strengthen patent protection hindered states and NGOs in their efforts to promote access to life-saving medicines at reasonable costs; and (2) whether access to life-saving therapies could be seen as a component of the right to health. The challenge for access to medicines appears at this point, however, to be more political than legal. Indeed, from a legal perspective, it seems fairly settled that international trade agreements permit, under certain conditions, the production and sale or export of generic versions of pharmaceutical products that address an important public health threat in developing countries. The concept of the right to health has often been invoked in this international context. An increasing number of domestic court decisions also explicitly acknowledge that access to life-saving therapies can be seen as a component of the right to health.
1 See Paige E. Goodwin, Right Idea, Wrong Result – Canada's Access to Medicines Regime, 34 AM. J.L. & MED. 567, 583 (2008) (citing Stephen Lewis, U.N. Secretary General's Special Envoy for HIV/AIDS (Sept. 25, 2003)) (“I want to emphasize that there is absolutely nothing standing in the way of such an initiative except a paralysis of political will and the influence of the big pharmaceutical companies.”).
2 See Abbott M. Frederick, The Doha Declaration on the TRIPS Agreement and Public Health: Lighting a Dark Corner at the WTO, 5 J. INT’L ECON. L. 469, 495 (2002); see also CARLOS M. CORREA, INTELLECTUAL PROPERTY RIGHTS, THE WTO AND DEVELOPING COUNTRIES: THE TRIPS AGREEMENT AND POLICY OPTIONS 88 (2000).
3 For example, in the context of HIV/AIDS medicines, see The Minister of Health v. Treatment Action Campaign (TAC) 2002 (5) SA 721 (CC) (S. Afr.), Glenda Lopez v. Instituto Venezolano de Seguras Sociales 487-060401 (Venezuela), Cruz del Valle Bermudez y otros v. MSAS, and Asociacion Benhalensis y otros v. Ministerio de Salud y Accion Social, 323 Fallos 1339 (2000). See also Soobramoney v. Minister of Health (Kwazulu-Natal) 2002 (1) (SA) (CC) 32/97 (S. Afr.). The Canadian Supreme Court has found, in an otherwise controversial decision, that access to therapies in the context of wait times is a component of the right to life. Chaoulli v. Quebec (Attorney General), [2005] 1 S.C.R. 791 (Can.).
4 See Judit Rius Sanjuan, James Love & Robert Weissman, Protection of Pharmaceutical Test Data: A Policy Proposal, CONSUMER PROJECT ON TECH. (2006), available at http://www.cptech.org/ip/health/data/CPTech-Test-Data.pdf; see also Judit Rius Sanjuan et al., A Cost Sharing Model to Protect Investments in Pharmaceutical Test Data, CONSUMER PROJECT ON TECH. (2006), available at http://www.cptech.org/publications/policybrief-no1-cost-sharing.pdf.
5 Agreement on Trade-Related Aspects of Intellectual Property Rights, Apr. 15, 1994, Marrakesh Agreement Establishing the World Trade Organization, Annex 1C, in THE LEGAL TEXTS: THE RESULTS OF THE URUGUAY ROUND OF MULTILATERAL TRADE NEGOTIATIONS 320 (1999), 1869 U.N.T.S. 299, 33 I.L.M. 1197 (1994) [hereinafter TRIPS Agreement]. For a list of relevant bilateral trade agreements, see A Survey of Data Exclusivity Legislations, EXPRESS PHARMA PULSE, http://www.expresspharmaonline.com/20021121/oped.shtml (last visited Jan. 29, 2012).
6 For a solid recent discussion of this issue, see Joanna Erdman, Access to Information on Safe Abortion: A Harm Reduction and Human Rights Approach, 34 HARV. J.L. & GENDER 413 (2011).
7 For a similar claim, see a short paper by Rodrigo Salinas, Open Access to Research Protocols and Results: Intellectual Property and the Right to Health, in 4 GLOBAL FORUM UPDATE ON RESEARCH FOR HEALTH: EQUITABLE ACCESS: RESEARCH CHALLENGES FOR HEALTH IN DEVELOPING COUNTRIES 47-48 (2007).
8 See, e.g., Tracy R. Lewis, Jerome H. Reichman & Anthony D. So, The Case for Public Funding and Oversight of Clinical Trials, ECONOMISTS’ VOICE (2007), available at http://www.bepress.com/ev/vol4/iss1/art3/; see also Jerome H. Reichman, Rethinking the Role of Clinical Trial Data in International Intellectual Property Law: The Case for a Public Goods Approach, 13 MARQ. INTELL. PROP. L. REV. 1 (2009). The “public good” approach also seems to be embraced by reports of the Knowledge Ecology International. See, in particular, Sanjuan, Love & Weissman, supra note 4, and Sanjuan et al., supra note 4. See discussion infra; see also Alex J. London, Jonathan Kimmelman & Marina E. Emborg, Beyond Access vs. Protection in Trials of Innovative Therapies, 328 SCI. 829 (2010) (suggesting that preclinical research can be considered a social good).
9 See, e.g., SHELDON KRIMSKY, SCIENCE IN THE PRIVATE INTEREST: HAS THE LURE OF PROFIT CORRUPTED BIOMEDICAL RESEARCH? 229 (2003); Wayne A. Ray & C. Michael Stein, Reform of Drug Regulation − Beyond an Independent Drug-Safety Board, 354 NEW ENG. J. MED. 194 (2006); MARCIA ANGELL, THE TRUTH ABOUT THE DRUG COMPANIES: HOW THEY DECEIVE US AND WHAT TO DO ABOUT IT (2004). In an earlier publication, one of us supported these recommendations, without using the “public good” language. See Trudo Lemmens, Leopards in the Temple: Restoring Scientific Integrity to the Commercialized Research Scene, 32 J.L. MED. & ETHICS 641, 652-653 (2004).
10 See discussion infra Part II and references therein.
11 For an overview and discussion of trial registration and results reporting initiatives, particularly focusing on the Americas, see Karmela Krleža-Jerić et al., Prospective Registration and Results Disclosure of Clinical Trials in the Americas: A Roadmap Towards Transparency, 30 PANAM. J. PUB. HEALTH 87 (2011) [hereinafter Krleža-Jerić et al., Prospective Registration].
12 See infra Part II.D.
13 See Kay Dickersin & Drummond Rennie, Registering Clinical Trials, 290 JAMA 516 (2003) (detailing the history of trial registration).
14 Id. at 516.
15 See Iain Chalmers et al., The Oxford Database of Perinatal Trials: Developing a Register of Published Reports of Controlled Trials, 7 CONTROLLED CLINICAL TRIALS 306 (1986); Kay Dickersin, Report from the Panel on the Case for Registers of Clinical Trials at the Eighth Annual Meeting of the Society for Clinical Trials, 9 CONTROLLED CLINICAL TRIALS 76 (1988); Curtis L. Meinert, Toward Prospective Registration of Clinical Trials, 9 CONTROLLED CLINICAL TRIALS 1 (1988).
16 See R. J. Simes, Publication Bias: The Case for an International Registry of Clinical Trials, 4 J. CLINICAL ONCOLOGY 1529 (1986).
17 Dickersin, supra note 15, at 77.
18 Simes gives the example of meta-analysis of survival benefits associated with combination therapy of ovarian cancer. Simes, supra note 16. The published literature suggested a survival benefit, whereas a meta-analysis of all the trials registered with the International Cancer Research Data Bank led to the opposite conclusion. Dickersin also invokes this example, referring to Simes. See Dickersin, supra note 15, at 77.
19 This original purpose of providing information to stimulate trial participation (rather than focusing on providing information about trials and their results) may help to explain why several of the most recent clinical trials registration initiatives focus primarily on the creation of a registry that contains a core set of minimal data. It also explains why there is still debate around whether trial registration requires overall transparency (for example, including the research protocol and all results). See infra Part V.A.2.
20 See, e.g., FOOD & DRUG ADMIN., U.S. DEP't OF HEALTH & HUMAN SERVS., Guidance for Industry: Information Program on Clinical Trials for Serious or Life-Threatening Diseases 2-3 (2002), available at http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm126838.pdf.
21 Health Omnibus Programs Extension of 1988, 42 U.S.C. § 201 (1988).
22 Food and Drug Administration Modernization Act of 1997, 21 U.S.C. § 301 (2006).
23 Drummond Rennie suggests this case in particular made trial registration an “irresistible” idea. Drummond Rennie, Trial Registration. A Great Idea Switches from Ignored to Irresistible, 292 JAMA 1359, 1359 (2004). For a detailed discussion of one of the controversial studies involved and the selective publication practices, see Jon N. Jureidini, Leemon B. McHenry & Peter R. Mansfield, Clinical Trials and Drug Promotion: Selective Reporting of Study 329, 20 INT’L J. RISK & SAFETY MED. 73 (2008).
24 The case was settled out of court through a consent order, according to which GSK agreed, among other things: (1) to pay two and a half million dollars to the State of New York; (2) to set up an online and publicly available clinical trials register with summaries of all sponsored clinical study reports since December 27, 2000; and (3) to ensure accuracy of information provided to doctors related to off-label prescription of its products. See New York v. GlaxoSmithKline, No. 04-CV-5304 MGC, 2004 WL 1932763 (S.D.N.Y. Aug. 26, 2004).
25 Richard Horton, Vioxx, the Implosion of Merck and Aftershocks at the FDA, 364 THE LANCET 1595 (2004); Eric J. Topol, Failing the Public Health – Rofecoxib, Merck, and the FDA, 351 NEW ENG. J. MED. 1707 (2004).
26 See Joseph S. Ross et al., Guest Authorship and Ghostwriting in Publications Related to Rofecoxib: A Case Study of Industry Documents From Rofecoxib Litigation, 299 JAMA 1800, 1800 (2008); Bruce M. Psaty & Richard A. Kronmal, Reporting Mortality Findings in Trials of Rofecoxib for Alzheimer Disease or Cognitive Impairment: A Case Study Based on Documents From Rofecoxib Litigation, 299 JAMA 1813, 1813 (2008).
27 See GlaxoSmithKline, 2004 WL 1932763, at *2.
28 Rennie, supra note 23, at 1360.
29 See Davina Ghersi & Tikki Pang, From Mexico to Mali: Four Years in the History of Clinical Trial Registration, 2 J. EVIDENCE-BASED MED. 1 (2009). An important early initiative was the development of the Current Controlled Trials web site, which includes a meta-register of clinical trials registered on four different continents and the International Standard Randomized Controlled Trial Number system. See Frequently Asked Questions, CURRENT CONTROLLED TRIALS (June 2009), http://www.controlled-trials.com/information/faqs.asp.
30 The Ministerial Summit on Health Research, Mexico City, Mex., Nov. 16-20, 2004, The Mexico Statement on Health Research, Knowledge for Better Health: Strengthening Health Systems 3 (Nov. 16-20, 2004), available at http://www.who.int/rpc/summit/agenda/en/mexico_statement_on_health_research.pdf; see also WORLD HEALTH ASSEMBLY, WHA58.34: Ministerial Summit on Health Research, WORLD HEALTH ORG., available at http://apps.who.int/gb/ebwha/pdf_files/WHA58/WHA58_34-en.pdf.
31 The items include: the primary registry and the trial identifier number; date of registration; sources of financial or material support; the primary and secondary sponsor; contact information for public and scientific queries; the public and scientific titles; the countries of recruitment; the health conditions or problems studies; the intervention; the key inclusion and exclusion criteria; the study type; the date of first enrolment; the target sample size; the recruitment status; and the primary and secondary outcomes. See About Registries, WORLD HEALTH ORG., http://www.who.int/ictrp/network/trds/en/index.html (last visited Dec. 24, 2011).
32 See, e.g., Karmela Krleža-Jerić, Clinical Trial Registration: The Differing Views of Industry, the WHO, and the Ottawa Group, 2 PLOS MED. e378 1093, 1095 (2005) [hereinafter Krleža-Jerić, Clinical Trial Registration]; Karmela Krleža-Jerić, Draft – The Ottawa Statement, Part Two: Principles of Operationalisation for International Trial Registration, OTTAWA GROUP (Jan. 6, 2006), available at http://ottawagroup.ohri.ca/docs/draft_Ottawa_Statement_Part2.pdf [hereinafter Krleža- Jerić, Draft—The Ottawa Statement]. For the first most influential consensus statement on trial registration and results reporting of the Ottawa Group, see Karmela Krleža-Jerić et al., Principles for International Registration of Protocol Information and Results from Human Trials of Health Related Interventions: Ottawa Statement (part 1) 330 BRIT. MED. J. 956 (2005) [hereinafter Krleža-Jerić et al., Principles for International Registration]. For a list of the signatories, see Ottawa Hospital Research Institute, Group Signatories, OTTAWA STATEMENT ON TRIAL REGISTRATION, http://ottawagroup.ohri.ca/signatories.html (last visited Jan. 29, 2012).
33 Krleža-Jerić, Draft – The Ottawa Statement, supra note 32.
34 Pan American Health Organization [PAHO], 49th Directing Council, 61st Session of the Regional Committee of WHO for the Americas, Policy on Research for Health, at 10, PAHO Doc. CD49/10 (July 10, 2009), available at http://new.paho.org/hq/dmdocuments/2009/CD49-10-e.pdf.
35 Primary registries are those key registries that collaborate directly with the WHO Registry Network. According to the WHO web site, “Primary Registries in the WHO Registry Network meet specific criteria for content, quality and validity, accessibility, unique identification, technical capacity and administration. Primary Registries meet the requirements of the [International Conference of Medical Journal Editors].” See About Registries: Primary Registries in the WHO Registry Network, WORLD HEALTH ORG., http://www.who.int/ictrp/network/primary/en/index.html (last visited Dec. 25, 2011). For information on the International Conference of Medical Journal Organization, see INT’L CONFERENCE OF MED. JOURNAL ORG., http://www.icmje.org (last visited Dec. 25, 2011).
36 See Krleža-Jeric et al., Prospective Registration, supra note 11, at 91-94.
37 Id. at 91.
38 Id. at 90.
39 World Medical Association General Assembly, WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects, WORLD MED. ASS’N, http://www.wma.net/en/30publications/10policies/b3/ (last visited Dec. 25, 2011).
40 Id.
41 See Food and Drug Administration Amendments Act of 2007, Pub. L. No. 110-85, § 801, 121 Stat. 823, 904-22 (2007).
42 Eur. Comm’n, Communication from the Commission Regarding the Guideline on the Data Fields Contained in the Clinical Trials Database Provided for in Article 11 of Directive 2001/20/EC to be Included in the Database on Medicinal Products Provided for in Article 57 of Regulation (EC) No 726/2004, 2008 OFFICIAL J. EUR. UNION C 168/3, C 168/3 (2008), available at http://ec.europa.eu/health/files/eudralex/vol-10/2008_07/c_16820080703en00030004_en.pdf.
43 Eur. Comm’n, Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 Laying Down Community Procedures for the Authorisation and Supervision of Medicinal Products for Human and Veterinary Use and Establishing a European Medicines Agency, 2004 OFFICIAL J. EUR. UNION L 136/1, L 136/22-23 (2004), available at http://ec.europa.eu/health/files/eudralex/vol-1/reg_2004_726_cons/reg_2004_726_cons_en.pdf.
44 Ministerio de Salud, Resolucion 102/2009, Créase el Registro de Ensayos Clínicos en Seres Humanos, LEGISALUD ARGENTINA, http://test.e-legis-ar.msal.gov.ar/leisref/public/showAct.php?id=12916.
45 F.No. 12-01/09-DC-(Pt-32) Directorate General of Health Services, Office of Drugs Controller General (India) (New Drug Division), available at http://cdsco.nic.in/CTRegistration.doc.
46 See Roderick F. Viergever & Davina Ghersi, The Quality of Registration of Clinical Trials, 6 PLOS ONE at 1, 7 (2011) (citing Japanese Ministry of Health, Labour and Welfare, Statement on Japan Primary Registries Network, MINISTRY OF HEALTH, LABOUR & WELFARE (2008), available at http://www.mhlw.go.jp/topics/2008/10/tp1017-1.html).
47 The following statement can be found on the web site of the South African Department of Health: “Section 11(r) of the National Health Act of 2004 focuses specifically on research. Regulations in general and clinical trials registration in particular are being drafted. They will require: (a) all research and clinical trials to receive ethics clearance from an accredited ethics committee and (b) all health research will be required to be registered and receive a research register number prior to commencement of the trial.” Registration and Regulation, S. AFR. NAT’L CLINICAL TRIAL REG., http://www.sanctr.gov.za/Registrationandregulation/tabid/194/Default.aspx (last visited Dec. 26, 2011).
48 See, e.g., CANADIAN INST. OF HEALTH RESEARCH, NATURAL SCI. & ENGINEERING COUNCIL OF CANADA, SOC. SCI. & HUMANITIES RESEARCH COUNCIL OF CAN., Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, PANEL ON RESEARCH ETHICS, 1, 156, 164 (2010).
49 Seth W. Glickman et al., Ethical and Scientific Implications of the Globalization of Clinical Research, 360 NEW ENG. J. MED. 816, 816 (2009).
50 Global Clinical Trial Business Report & Analysis 2008-2018, VISIONGAIN (Oct. 7, 2008), http://www.visiongain.com/Report/315/Global-Clinical-Trial-Business-Report-Analysis-2008-2018.
51 See, e.g., Ghersi & Pang, supra note 29; Krleža-Jeric et al., Prospective Registration, supra note 11.
52 There are currently at least twelve WHO primary registries that meet the criteria of the ICTRP. One registry, the U.S. registry ClinicalTrials.gov, also meets the criteria, but has maintained its independence because of its perceived need to remain legally independent.
53 World Health Organization [WHO], WHO's Role and Responsibilities in Health Research: Bamako Global Ministerial Forum on Research for Health, at 4, WHO Doc. EB124/12 Add.2 (Jan. 6, 2009), available at http://new.paho.org/hq/dmdocuments/2009/Bamako-Annex.pdf.
54 See Krleža-Jerić et al., Prospective Registration, supra note 11, at 91.
55 For a discussion of how the lack of strict regulatory requirements of trial registration or results reporting may make companies reluctant to share data out of concern for loss of data protection, see infra Part IV.
56 See, for example, the implementation of the ICH GCP in the Canadian regulatory structure. It is considered a “guidance document,” with no clear sanctions attached to non-compliance. Health Canada, the regulatory agency, can monitor compliance and issue a notice of non-compliance, but monitoring remains limited, and remedies will usually be negotiated.
57 Deborah A. Zarin et al., Trial Registration at ClinicalTrials.gov Between May and October 2005, 353 NEW ENG. J. MED. 2779, 2780 (2005).
58 The FDA status update concluded: “While progress has been made, participation by the pharmaceutical industry is less than expected despite a federal law, a final guidance document, a targeted education program, and an easy-to-use web-based data entry tool. Some pharmaceutical companies do not provide required clinical trials, some provide only limited information, while others voluntarily list trials that go beyond the criteria specified in the guidance.” FDA OFFICE OF SPECIAL HEALTH ISSUES, DEP't OF HEALTH AND HUMAN SERVS., FDAMA SECTION 113: STATUS REPORT ON IMPLEMENTATION (2005), available at http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ParticipatinginClinicalTrials/ucm143810.htm.
59 Zarin et al., supra note 57, at 2784-86.
60 Peter Gotzsche & Anders W. Jorgensen, Opening Up Data at the European Drug Medicines Agency, 342 BRIT. MED. J. 1184 (2011). One of the drugs has since been taken off the European market. See Tracy Hampton, European Drug Agency Under Fire, 306 JAMA 593, 593 (2011).
61 Gotzsche & Jorgensen, supra note 60, at 1185. The EMA has also been criticized for the poor and inconsistent documentation it provides on Phase III trials in its drug assessment reports. See Hampton, supra note 60, at 594.
62 Rennie, supra note 23, at 1361.
63 Federal Food, Drug, and Cosmetic Act of 2007, § 303(f), 21 U.S.C. § 333 (3)(A)(B) (2011). For an overview of the requirements and penalties, see Registration at ClinicalTrials.gov: As Required by Public Law 110-85, Title VIII, CLINICALTRIALS.GOV (Oct. 27, 2009), http://prsinfo.clinicaltrials.gov/s801-fact-sheet.pdf.
64 See CLINICALTRIALS.GOV, supra note 63.
65 See Eur. Comm., Enter. and Indus. Dir. Gen., List of Fields Contained in the ‘Eudract’ Clinical Trials Database to be Made Public, in Accordance with Article 57(2) of Regulation (EC) No 726/2004 and its Implementing Guideline 2008/C168/02, EU Doc. ENTR/F/2/SF D (2009) 3687 (Feb. 4, 2009), available at http://ec.europa.eu/health/files/eudralex/vol-10/2009_02_04_guideline_en.pdf [hereinafter List of Fields]
66 See Pharmaceuticals: Today, the EU Register of Clinical Trials is Launched, EUROPA (Mar. 22, 2011), http://europa.eu/rapid/pressReleasesAction.do?reference=IP/11/339&format=HTML&aged=0&language=EN. For details about what is included in the database, see Eur. Comm’n, supra note 42. The Commission cites the “legitimate interests of the sponsors” as the overall reason for restrictions on disclosure. See List of Fields, supra note 65.
67 See Krleža-Jerić, Clinical Trial Registration, supra note 32; see also Charlotte Haug, Peter C. Gotzsche & Torben V. Schoeder, Registries and Registration of Clinical Trials, 353 NEW ENG. J. MED. 2811, 2812 (2005).
68 One of us, Lemmens, has participated in one of the meetings organized by the ICTRP during the development of the ICTRP and the minimal data set, and has been involved in initiatives to implement trial registration in the PAHO region. These comments are based on interpretations of various conversations with those involved in the trial registration initiatives.
69 Davina Ghersi et al., Reporting the Findings of Clinical Trials: A Discussion Paper, 86 BULL. WHO 492, 492 (2008).
70 Sally Hopwell et al., CONSORT for Report Randomized Controlled Trials in Journal and Conference Abstracts: Explanation and Elaboration, 5 PLOS MED. 0001, 0006-07 (2008).
71 See About the ICTRP, WORLD HEALTH ORG., http://www.who.int/ictrp/about/details/en/index1.html
72 For an official statement, see EU Clinical Trials Register Recognized as “Primary Registry” of WHO's International Clinical Trials Registry Platform (European Meds. Agency, London, U.K.), Sept. 14, 2011. The team also reiterated, in a personal communication, the WHO senior management's continued commitment towards results reporting and indicated that it is actively seeking funding to strengthen the ICTRP. Personal communications by e-mail with Karam Gassam, WHO IT officer, and Charlotte Bouesseau, February 9, 2012.
73 REPORT OF THE AUDITOR GENERAL OF CANADA TO THE HOUSE OF COMMONS, CHAPTER 4: REGULATING PHARMACEUTICAL DRUGS—HEALTH CANADA, at 12 (2011), available at http://www.oag-bvg.gc.ca/internet/docs/parl_oag_201111_04_e.pdf.
74 Id.
75 See infra note 147; Matthew Herder, Unlocking Health Canada's Cache of Trade Secrets: Mandatory Disclosure of Clinical Trials Results, CAN. MED. ASS’N J. (Aug. 29, 2011), available at http://ecmaj.ca/content/early/2011/08/29/cmaj.110721.full.pdf+html.
76 HEALTH CAN., HEALTH PRODUCTS & FOOD BRANCH, Blueprint for Renewal II (2007), available at http://www.hc-sc.gc.ca/ahc-asc/alt_formats/hpfb-dgpsa/pdf/hpfb-dgpsa/blueprint-plan_lleng.pdf.
77 HEALTH CAN., Notice: Registration and Disclosure of Clinical Trial Information (Nov. 2007), available at http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/prodpharma/notice_ctreg_avis_ecenr-eng.pdf.
78 See Ann Silversides, Withdrawal of Clinical Trials Policy by Canadian Research Institute Is a “Lost Opportunity for Increased Transparency”, 342 BRIT. MED. J. 1 (2011), available at http://www.bmj.com/content/342/bmj.d2570.full.pdf; Tom Blackwell, Reversal of Drug Trial Disclosure Policy Draws Fire, NAT’L POST (May 29, 2011), http://news.nationalpost.com/2011/05/29/reversal-on-drug-trial-disclosure-policy-draws-fire/.
79 See supra note 48. The overlap between these policies, CIHR officials suggested, would create “confusion and inconsistent application of the requirements.” Blackwell, supra note 78.
80 Alain Beaudet, Message from the President—Policy on ethical conduct for research involving humans, CANADIAN INSTS. OF HEALTH RESEARCH (June 15, 2011), http://www.cihrirsc.gc.ca/e/43756.html.
81 Personal communication between Trudo Lemmens and Karmela Krleža-Jerić (Nov. 21, 2011).
82 See Rennie, supra note 23, at 1360, for a discussion of the various responses by individual companies and pharmaceutical industry groups. See also Lisa Grimes, Clearer Road Ahead: An Industry Standard for Publicizing Clinical-Trial Results is a Ways Off, But Pharma's Openness to More Transparent Procedures is Moving Things in the Right Direction, 25 PHARMACEUTICAL EXECUTIVE 104 (2005); Ronald L. Krall, Trial Registration: Putting Principles into Practice, 330 BRIT. MED. J. 956 (2005).
83 Grimes, supra note 82, at 104.
84 Id. at 104-05 (“Registries also offer implied benefits, such as a potential reduction in the negative news coverage that currently undermines consumers’ faith in the clinical-trial process.”).
85 Eur. Comm’n, supra note 42, at C 168/3 (referring to “legitimate interests of sponsors”).
86 The fifth issue is connected to competitive advantage. Because of its unique link to international trade regulations, we discuss it in Part V.
87 Grimes, supra note 82, at 112.
88 Dickersin & Rennie, supra note 13, at 520 (citing written communication from I. Chalmers (May 27, 2002)).
89 Dickersin & Rennie, supra note 13, at 520.
90 Grimes, supra note 82, at 111.
91 Sheila Jasanoff, Transparency in Public Science: Purposes, Reasons, Limits, 69 LAW & CONTEMP. PROBS. 21, 34 (2006). Jasanoff suggests that some limits on transparency in public science are appropriate. One can distill from her discussion of the Paxil and Vioxx controversies, however, that the industry practice of hiding drug safety and effectiveness data clearly does not fit her “legitimate concealment” category. Id.
92 The European Commission emphasizes, for example, also that information made publicly available has to be “meaningful for the public,” but it suggests that this is in part done by “following agreed standards at international level.” See Eur. Comm’n, supra note 42, at C 168/3.
93 Gary Humphreys, Clinical Trials Initiative: Patients or Patents?, 84 BULL. WORLD HEALTH ORG. 509, 513 (2006).
94 Id. at 514.
95 Id.
96 See, for example, Grimes, supra note 82, which also fails to mention patents as a concern.
97 WORLD HEALTH ORG., DEP't OF RESEARCH POL’Y & COOPERATION, Summary: International Clinical Trials Registry Platform: Formal Consultation on Disclosure Timing (Apr. 26, 2006), available at http://www.who.int/ictrp/WHO_Formal_Consultation_Disclosure_Timing.pdf (personal notes of the meeting by Trudo Lemmens).
98 Trudo Lemmens & Ron A. Bouchard, Comments on the Legal, Regulatory and Ethical Aspects of the WHO Clinical Trial Registry Platform, WORLD HEALTH ORG. (Apr. 2006), available at http://www.who.int/ictrp/011_Lemmens_Bouchard_5April06.pdf (submitted to the World Health Organization as part of its Formal Consultation on Disclosure Timing Policy, Geneva, Apr. 2006).
99 See WORLD HEALTH ORG., DEP't OF RESEARCH POL’Y & COOPERATION, supra note 97. Davina Ghersi, who led the ICTRP secretariat until the reorganization of 2011, is also of the opinion that there are no convincing examples of how patents will be affected by registration. See Humphreys, supra note 93, at 514.
100 See, e.g., Letter from Alan Goldhammer, Associate Vice President, U.S. Regulatory Affairs, to ICTRP, RE: PhRMA's Second Round Comments on International Clinical Trials Registry Platform (ICTRP): Disclosure Timing, WORLD HEALTH ORG. (2006), available at http://www.who.int/ictrp/002-PhRMA_29March06.pdf; Grimes, supra note 82, at 4-5.
101 Draft Issue Identification Paper: Registration and Disclosure of Clinical Trial Information, HEALTH CAN., at 16 (2005), http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfbdgpsa/pdf/prodpharma/draftiipctrd_june_ddeebaucheedec_juin_2005-eng.pdf.
102 See, e.g., Letter from Alan Goldhammer, supra note 100.
103 Ida Sim, Trial Registration for Public Trust: Making the Case for Medical Devices, 23 J. GEN. INTERNAL MED. 64, 67 (Supp. 2007).
104 See THE EUR. FED’N OF PHARM. INDUS. & ASS’NS., THE INT’L FED’N OF PHARM. MFRS. & ASS’NS., THE JAPANESE PHARM. MFRS. ASS’N, AND THE PHARM. RESEARCH & MFRS. OF AM., Joint Position on the Disclosure of Clinical Trial Information via Clinical Trial Registries (2005), available at http://www.roche.com/joint_position_clinicaltrials.pdf.
105 See COMM. ON CLINICAL TRIAL REGISTRIES, DEVELOPING A NATIONAL REGISTRY OF PHARMACOLOGIC AND BIOLOGIC CLINICAL TRIALS: WORKSHOP REPORT 30-32 (2006); see also Karmela Krleža-Jerić, Clinical Trial Registration, supra note 32.
106 See Trudo Lemmens & Ron Bouchard, Mandatory Clinical Trial Registration: Rebuilding Trust in Medical Research, in 4 GLOBAL FORUM UPDATE ON RESEARCH FOR HEALTH, supra note 7, at 40.
107 Id. at 41-42.
108 Id. at 42.
109 See, e.g., HEALTH CAN., supra note 101, at 16; Salinas, supra note 7, at 47-48.
110 With the latter, we refer to the bilateral trade agreements which offer more protection for brand-name companies than TRIPS itself. See A Survey of Data Exclusivity Legislations, supra note 5.
111 TRIPS Agreement, supra note 5, at art. 39.
112 Id.
113 See CARLOS MARIA CORREA, PROTECTION OF DATA SUBMITTED FOR THE REGISTRATION OF PHARMACEUTICALS: IMPLEMENTING THE STANDARDS OF THE TRIPS AGREEMENT 14 (2002) [hereinafter CORREA, PROTECTION OF DATA].
114 Id.
115 TRIPS Agreement, supra note 5, at art. 39.
116 Id.
117 See DANIEL GERVAIS, THE TRIPS AGREEMENT: DRAFTING HISTORY AND ANALYSIS 185 (3d ed. 1998).
118 TRIPS Agreement, supra note 5, at art. 39
119 We are grateful to Kevin Outterson for this point.
120 TRIPS Agreement, supra note 5, at art. 39.3 (“Members, when requiring, as a condition of approving the marketing of pharmaceutical or of agricultural chemical products which utilize new chemical entities, the submission of undisclosed test or other data, the origination of which involves a considerable effort, shall protect such data against unfair commercial use. In addition, Members shall protect such data against disclosure, except where necessary to protect the public, or unless steps are taken to ensure that the data are protected against unfair commercial use.”).
121 GERVAIS, supra note 117, at 424.
122 Id.
123 Id.
124 Id.
125 See id.
126 See CORREA, PROTECTION OF DATA, supra note 113, at 8-9; Carlos M. Correa, Unfair Competition Under the TRIPS Agreement: Protection of Data Submitted for the Registration of Pharmaceuticals, 3 CHI. J. INT’L L. 69, 70-71 (2002) [hereinafter Correa, Unfair Competition]; Reichman, supra note 8, at 30; Sanjuan, Love & Weissman, supra note 4.
127 See CORREA, PROTECTION OF DATA, supra note 113, at 25-46; Correa, Unfair Competition, supra note 126, at 69.
128 The terms “data exclusivity” and “market exclusivity” are often confused. Data exclusivity strictly means that generic companies cannot rely on the data produced and paid for by the innovator to obtain regulatory approval of a generic version, even when the patent expired. Because of the costs involved in clinical trials, data exclusivity often results in de facto market exclusivity. A strict market exclusivity rule prohibits companies from selling a generic version for the period of market exclusivity. Market exclusivity can also focus on a disease and specify that a particular drug product will be the sole product allowed on the market for the treatment of this condition. This is used, for example, to stimulate the development of orphan drugs. For an overview of exclusivity provisions under FDA statutes and regulations, see Small Business Assistance: Frequently Asked Questions for New Drug Product Exclusivity, U.S. FOOD & DRUG ADMIN. (July 1, 2010), http://www.fda.gov/ Drugs/DevelopmentApprovalProcess/SmallBusinessAssistance/ucm069962.htm. Note that the FDA does not use the terms “data exclusivity” and “market exclusivity.” For a good discussion of the terms and the confusion surrounding them in the context of recent controversy surrounding recent biosimilar legislation in the United States, see Market Exclusivity, Data Exclusivity and S. 3921, HOLMAN's BIOTECH IP BLOG (Feb. 16, 2011, 10:03 AM), http://holmansbiotechipblog.blogspot.com/2011/02/market-exclusivity-data-exclusivity-and.html.
129 Drug Price Competition and Patent Term Restoration (Hatch-Waxman) Act of 1984, Pub. L. No. 98-417, 98 Stat. 1585 (1984). For a discussion of the exclusivity provisions, see Kevin Outterson, Pharmaceutical Arbitrage: Balancing Access and Innovation in International Prescription Drug Markets, 5 YALE J. HEALTH POL’Y L. & ETHICS 193, 215-16 (2005).
130 Outterson, supra note 129, at 216. For an in depth discussion of the data protection provisions in one of these bilateral trade agreements, see Saad Abughanm, THE PROTECTION OF PHARMACEUTICAL PATENTS AND DATA UNDER TRIPS AND US-JORDAN FTA: EXPLORING THE LIMITS OF OBLIGATIONS AND FLEXIBILITIES: A STUDY OF THE IMPACTS ON THE PHARMACEUTICAL SECTOR IN JORDAN, at 255-344 (2012) (unpublished S.J.D. dissertation, University of Toronto) (on file with author).
131 See COMM’N ON INTELLECTUAL PROP. RIGHTS, INNOVATION & PUB. HEALTH, WORLD HEALTH ORG., PUBLIC HEALTH, INNOVATION AND INTELLECTUAL PROPERTY RIGHTS 124 (2006), available at http://www.who.int/entity/intellectualproperty/documents/thereport/ENPublicHealthReport.pdf. The United Nations Conference on Trade and Development (UNCTAD) also suggested that article 39.3 does not prevent “authorities … from using knowledge of such data, for instance, to assess subsequent applications by third parties for the registration of similar products.” UNCTAD Secretariat, The TRIPS Agreement and Developing Countries, U.N. Doc. UNCTAD/ITE/1, at 48 (1996).
132 CORREA, PROTECTION OF DATA, supra note 113, at 41-46; GERVAIS, supra note 117, at 429.
133 CORREA, PROTECTION OF DATA, supra note 113, at 41 (giving, as examples, “competitor's misrepresentation, fraud threats, defamation, disparagement, enticement of employees, betrayal of confidential information commercial bribery, among others”).
134 Id.
135 An agreement on the use of data is often agreed upon in the context of patent settlement agreements. In the United States, such agreements are common in the context of procedures under paragraph IV of the Hatch-Waxman Act. Outterson, supra note 129, at 215-16. Through such settlements, generics and brand-name companies agree how generics will be allowed to use the data and at what cost in exchange for the halting of the legal proceedings. Settlements often also involve a pledge by originators to delay the launch of an “authorized generic,” i.e., a generic version of a brand drug marketed by the originator or by a third person. We are grateful to Saad Abughanm for this point. See FED. TRADE COMM’N, AUTHORIZED GENERIC DRUGS: SHORT-TERM EFFECTS AND LONG-TERM IMPACT 139-53 (2001), available at http://www.ftc.gov/os/2011/08/2011genericdrugreport.pdf; see also FED. TRADE COMM’N, PAY-FOR-DELAY: HOW DRUG COMPANY PAY-OFFS COST CONSUMERS BILLIONS 5 (2010), http://www.ftc.gov/os/2010/01/100112payfordelayrpt.pdf.
136 Animal welfare concerns are mentioned by CORREA, PROTECTION OF DATA, supra note 113, at 44.
137 We are grateful to Saad Abughanm for valuable discussions on these issues.
138 We are grateful to Kevin Outterson for alerting us to this issue.
139 Federal Insecticide, Fungicide, and Rodenticide Act, 7 U.S.C. § 136 (2006).
140 See CORREA, PROTECTION OF DATA, supra note 113, at 8-9; Correa, Unfair Competition, supra note 126, at 70-71; Reichman, supra note 8, at 30; Sanjuan, Love & Weissman, supra note 4.
141 This argument was provided to us by Saad Abughanm.
142 See Joseph A. DiMasi, Ronald W. Hansen & Henry G. Grabowski, The Price of Innovation: New Estimates of Drug Development Costs, 22 J. HEALTH ECON. 151 (2003); see also Z. John Lu & William S. Comanor, Strategic Pricing of New Pharmaceuticals, 80 REV. ECON. & STAT. 108, 108 (1998), both providing higher cost estimates, which are invoked by industry. Contra Donald W. Light & Joel Lexchin, Foreign Free Riders and the High Price of US Medicines, 331 BRIT. MED. J. 958 (2005), available at http://www.bmj.com/content/331/7522/958.full; Donald W. Light, Will Lower Drug Prices Jeopardize Drug Research? A Policy Fact Sheet, 4 AM. J. BIOETHICS W1, W3 (2005).
143 See Bayer Inc. v. Canada (Attorney General), [1999] 1 F.C. 553 (Can.), where the appellate court ruled that indirect reference to the data filed by an originator's New Drug Submission in an Abbreviated New Drug Submission (ANDS) by a generic company for the purpose of the establishment of pharmaceutical and biological equivalency implies neither an “evaluation” of nor a “reliance” on the originator's data. The court thus held that the ANDS procedure as it was conceived at that time was not in violation with the minimum data exclusivity period provided for in the North American Free Trade Agreement. See also the discussion in CORREA, PROTECTION OF DATA, supra note 113, at 36-37.
144 Id. at 22; see also SUSAN K. SELL, PRIVATE POWER, PUBLIC LAW: THE GLOBALIZATION OF INTELLECTUAL PROPERTY RIGHTS 139 (2003). Also see Sell's interesting overview of the global campaign to “correct” this neglect of the public health impact of TRIPS’ patent provisions. SELL, supra, 145-59.
145 Note, Secretariat of the World Trade Org., “Necessity Tests” in the WTO, S/WPDR/W/27 (Dec. 2, 2003), available at http://ictsd.org/downloads/2008/04/nectest.pdf.
146 Correa, Unfair Competition, supra note 126, at 76 (citing MICHAEL J. TREBILCOCK & ROBERT HOWSE, THE REGULATION OF INTERNATIONAL TRADE 140 (2d ed. 1999)).
147 Access to Information Act, R.S.C. 1985, c. A-1 (Can.). This also seems to be the approach taken by the European Medicines Agency in the controversy discussed infra.
148 Access to Information Act, supra note 147, at c. A-1.
149 See Trudo Lemmens & Ron A. Bouchard, Regulation of Pharmaceuticals in Canada, in CANADIAN HEALTH LAW AND POLICY 318, 340 (Jocelyn Downie, Timothy Caulfield & Colleen Flood eds., 3d ed. 2007).
150 JOEL LEXCHIN, TRANSPARENCY IN DRUG REGULATION: MIRAGE OR OASIS 7 (2004), available at http://www.policyalternatives.ca/sites/default/files/uploads/publications/National_Office_Pubs/transparency.pdf.
151 See the discussion in GERVAIS, supra note 117, at 336-53, and, in particular, decisions cited id. at 346-50.
152 Id.
153 Christopher Doyle, Gimme Shelter: The “Necessary” Element of GATT Article XX in the Context of the China-Audiovisual Products Case, 29 B.U. INT’L L.J. 143, 163 (2011).
154 TRIPS Agreement, supra note 5.
155 We are grateful to Saad Abughanm for reminding us of the relevance of these provisions in this context.
156 As Rebecca S. Eisenberg points out, “[t]he loss from secrecy is likely to be compounded as progress in information technology opens up greater possibilities for data mining across numerous studies.” Rebecca S. Eisenberg, The Role of the FDA in Innovation Policy, 13 MICH. TELECOMM. & TECH. L. REV. 345, 383 (2007).
157 Lewis, Reichman & So, supra note 8; see also Reichman, supra note 8. Kevin Outterson also defends the value of publicly funded clinical trials, albeit in the context of development of “lost drugs,” i.e., valuable drug candidates that would otherwise not be developed due to a lack of patentability. See Kevin Outterson, Death from the Public Domain?, 87 TEX. L. REV. 45, 53-54 (2009).
158 For a detailed discussion see Reichman, supra note 8. The argument of benefit to drug companies is particularly interesting, as it runs counter to the common claim that drug regulation and governmental control associated with it hamper innovation. More direct governmental control over the generation of reliable data could in fact save costs to the industry by reducing the waste associated with duplication of trials, costs associated with highly competitive research recruitment strategies, and so on. The argument that governmental control over drug development can be of financial benefit to drug manufacturers has also been made by Ariel Katz. In his 2007 paper, he reacts against the traditional argument that innovation is hampered by costs and delays associated with drug approval. Ariel Katz, Pharmaceutical Lemons: Innovation and Regulation in the Drug Industry, 14 MICH. TELECOMM. & TECH. L. REV. 1 (2007). He suggests that drug regulation performs a valuable quality assurance function, which helps avoid the entry into the market of pharmaceutical “lemons,” and which may thereby stimulate useful innovation. In our view, current drug regulatory requirements that largely rely on self-reporting by industry may contribute currently to a proliferation of concealed lemons. That is, the regulatory seal of approval may help industry sell off lemons as oranges. Governmentally controlled clinical trials, however, would help avoid this problem and contribute to a more reliable quality assurance program.
159 Reichman, supra note 8, at 60.
160 See generally PHILIP J. HILTS, PROTECTING AMERICA's HEALTH: THE FDA, BUSINESS, AND ONE HUNDRED YEARS OF REGULATION (2003) (discussing FDA history). See also ANGELL, supra note 9. For a recent discussion of problems at the regulatory level in Europe, see the concerns expressed by the European Parliament about conflicts of interests and failures in appropriate action by the COMM. ON BUDGETARY CONTROL, EUR. PARLIAMENT, Report on Discharge in Respect of the Implementation of the Budget of the European Medicines Agency for the Financial Year 2009 (2011), available at http://www.europarl.europa.eu/sides/getDoc.do?pubRef=-//EP//NONSGML+REPORT+A7-2011-0153+0+DOC+PDF+V0//EN. See also Inspection General Des Affaires Sociales, Enquête sur le Mediator® (RM2011-001P) Rapport definitive, DECISIONS SANTE (2011), http://www.decisionsante.com/fileadmin/uploads/MEDIATOR.pdf (describing the controversy in France surrounding Mediator).
161 Rebecca S. Eisenberg discusses how the drug regulator plays an increasingly important role in the promotion of innovation. See, e.g., Eisenberg, supra note 156; Rebecca S. Eisenberg, Patents, Product Exclusivity, and Information Dissemination: How Law Directs Biopharmaceutical Research and Development, 72 FORDHAM L. REV. 477 (2003). While she seems to embrace this dual role of drug regulators (protecting consumers and promoting innovation), one of us has argued elsewhere that this leads to regulatory confusion. In the current economic and regulatory system surrounding pharmaceutical product development it creates significant tensions and undermines the public health role of government drug regulators. See Lemmens, supra note 9.
162 Health Omnibus Programs Extension of 1988, 42 U.S.C. § 201 (2006); Food and Drug Administration Modernization Act of 1997, 21 U.S.C. § 301 (2006).
163 Public statement at ICTRP Formal Consultation on Disclosure Timing Policy, Geneva, April 2006 (notes of Trudo Lemmens).
164 Id.
165 To get a sense of what regulatory and ethical issues this may raise, see the controversy surrounding VanTx, which was the subject of a report by the regulatory authorities of the Canton Basel and resulted in reorganization of the research ethics structure in the Canton Basel. See Marie Hirtle, Trudo Lemmens & Dominique Sprumont, A Comparative Analysis of Research Ethics Review Mechanisms and the ICH Good Clinical Practice Guideline, 7 EUR. J. HEALTH L. 265 (2000).
166 See Grimes, supra note 82.
167 See id.
168 See Justin E. Bekelman, Yan Li & Cary P. Gross, Scope and Impact of Financial Conflicts of Interest in Biomedical Research, 289 JAMA 454 (2003); Joel Lexchin et al., Pharmaceutical Industry Sponsorship and Research Outcome and Quality: Systematic Review, 326 BRIT. MED. J. 1167 (2003).
169 For an overview of recent legal action and the unprecedented level of penalties imposed, see David Evans, Big Pharma's Crime Spree, BLOOMBERG MKTS. (Dec. 2009), http://www.bloomberg.com/apps/news?pid=nw&pname=mm_1209_story2.html.
170 See, e.g., Adriane J. Fugh-Berman, The Haunting of Medical Journals: How Ghostwriting Sold ‘HRT’, 7 PLOS MED. 1, 1 (2010) (promoting HRT); David Healy & Dinah Cattell, Interface between Authorship, Industry and Science in the Domain of Therapeutics, 183 BRIT. J. PSYCHIATRY 22 (2003) (promoting Zoloft); Jureidini, McHenry & Mansfield, supra note 23 (promoting Paxil); Psaty & Kronmal, supra note 26 (promoting Vioxx); Ross et al., supra note 26; Michael A. Steinman et al., Narrative Review: The Promotion of Gabapentin: An Analysis of Internal Company Documents, 145 ANNALS OF INTERNAL MED. 284 (2006); S. Swaroop Vedula et al., Outcome Reporting in Industry-Sponsored Trials of Gabapentin for Off-label Use, 361 NEW ENG. J. MED. 1963 (2009) (promoting Neurontin).
171 See Fugh-Berman, supra note 170, at 2.
172 See HOUSE OF COMMONS HEALTH COMM., THE INFLUENCE OF THE PHARMACEUTICAL INDUSTRY, FOURTH REPORT, 2004-5, H.C. 42-I (U.K.), available at http://www.parliament.thestationery-office.co.uk/pa/cm200405/cmselect/cmhealth/cmhealth.htm; Enquête sur le Mediator®, supra note 160, § 731 (regarding the recent report by the French General Inspectorate of Social Affairs on regulatory failure and manipulation of data surrounding the obesity drug Mediator by the company. The report indicates that the company concealed evidence of lack of effectiveness and serious safety concerns related to its product, which according to preliminary estimates may have caused between 500 and 1000 deaths.).
173 In a recent article published in PLoS Medicine, Simon Stern and one of the authors argue that academic guest authors of ghostwritten publications should be held liable for fraud. See Simon Stern & Trudo Lemmens, Legal Remedies for Medical Ghostwriting: Imposing Fraud Liability on Guest Authors of Ghostwritten Articles, 8 PLOS MED. 1 (2011).
174 Erick H. Turner et al., Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy, 358 NEW ENG. J. MED. 252 (2008).
175 See id. at 256, 258.
176 See id. at 256.
177 See id.
178 See, e.g., id. The Turner study suggests that bias of industry-organized publications cannot be explained solely by the reluctance of journals to publish negative studies, and indicates that there is more going on.
179 See, e.g., Dean Fergusson et al., Association between Suicide Attempts and Selective Serotonin Reuptake Inhibitors: Systematic Review of Randomised Controlled Trials, 330 BRIT. MED. J. 396 (2005) (describing the lack of appropriate disclosure of adverse events in antidepressant trials).
180 See, e.g., Joel Lexchin, Those Who Have the Gold Make the Evidence: How the Pharmaceutical Industry Biases the Outcomes of Clinical Trials of Medications, SCI. & ENGINEERING ETHICS (2011).
181 Emma C. Davies et al., Adverse Drug Reactions in Hospital In-Patients: A Prospective Analysis of 3695 Patient-Episodes, 4 PLOS ONE 1 (2009), available at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0004439; Jason Lazarou, Bruce H. Pomeranz & Paul N. Corey, Incidence of Adverse Drug Reactions in Hospitalized Patients: A Meta-Analysis of Prospective Studies, 279 JAMA 1200 (1998).
182 Daniel S. Budnitz et al., National Surveillance of Emergency Department Visits for Outpatient Adverse Drug Events, 296 JAMA 1858, 1860 (2006); see also Karin Wester et al., Incidence of Fatal Adverse Drug Reactions: A Population Based Study, 65 BRIT. J. CLINICAL PHARMACOLOGY 573, 574 (2008) (noting that prior studies found the prevalence of hospital admissions from adverse effects of medication to range from 2.4% to 12.0%).
183 Budnitz et al., supra note 182, at 1863.
184 Lisa Girion, Scott Glover & Doug Smith, Drug Deaths Now Outnumber Traffic Fatalities in U.S., Data Show, L.A. TIMES, Sept. 17, 2011, http://articles.latimes.com/2011/sep/17/local/la-medrugs-epidemic-20110918.
185 See id.
186 Topol, supra note 25, at 1708. Topol estimates myocardial infarction or stroke in 160,000 of every ten million people taking the drug. Graham keeps it at between 88,000 to 144,000 excess cases of coronary heart problems between 2001 and 2004, of which up to forty-four percent may have been fatal. See David J. Graham et al., Risk of Acute Myocardial Infarction and Sudden Cardiac Death in Patients Treated with Cyclo-Oxygenase 2 Selective and Non-Selective Non-Steroidal Anti- Inflammatory Drugs: Nested Case-Control Study, 365 LANCET 475, 480 (2005).
187 See Klim McPherson & Elina Hemminki, Synthesising Licensing Data to Assess Drug Safety, 328 BRIT. MED. J. 518, 518-19 (2004).
188 Id. at 518.
189 It is estimated, for example, that in 1999, in the U.S. alone, 15 million people were taking HRT. See Adam L. Hersh, Marcia L. Stefanick & Randall S. Stafford, National Use of Postmenopausal Hormone Therapy: Annual Trends and Response to Recent Evidence, 291 JAMA 47 (2004).
190 See, e.g., Prithwish De et al., Breast Cancer Incidence and Hormone Replacement Therapy in Canada, 102 J. NAT’L CANCER INST. 1489, 1493 (2010); Peter M. Ravdin et al., The Decrease in Breast-Cancer Incidence in 2003 in the United States, 356 NEW ENG. J. MED. 1670 (2007). The reported statistics also reveal how publication of data can impact prescription rates. The U.S. study reports, for example, that prescription of the two most commonly prescribed HRT drugs declined in the United States from sixty-one million in 2001 to twenty-seven million in 2003, likely as a result of the publication of the Women's Health Initiative study results. De et al., supra. Although this does not prove a causal relation, the results are remarkable. A common representation of the increased risk is that out of every 10,000 women treated with HRT, eight more women are likely to have developed breast cancer than in a population of untreated women. Id. Combining the number of prescriptions with this estimate gives an idea of the scale of the impact: thousands of women are likely to have been affected.
191 See, e.g., Turner et al., supra note 174. It should be noted that action has been taken in some of the most troubling cases, when publication of data could be associated, for example, with the illegal promotion of off-label prescription. The FDA and state prosecutors have intervened in several cases, resulting in very significant penalties. See, e.g., Civil Settlement Agreement, United States v. Purdue Frederick Co., Inc., 495 F. Supp. 2d 569 (W.D. Va. 2007), available at http://www.vawd.uscourts.gov/PurdueFrederickCo/Exhibit-D.pdf. The civil settlement agreement, agreed statement of facts, non-prosecution agreement, plea bargains of several company officials, and other documents reveal disturbing promotional practices, including the use of misrepresented data of a highly addictive pain medication.
192 For a discussion of some of the key regulatory challenges, see Curt D. Furberg et al., The FDA and Drug Safety: A Proposal for Sweeping Changes, 166 ARCHIVES INTERNAL MED. 1938 (2006); Wayne A. Ray & C. Michael Stein, Reform of Drug Regulation—Beyond an Independent Drug-Safety Board, 354 NEW ENG. J. MED. 194 (2006); Lemmens, supra note 9. Recent publications also heavily criticize the weakness of the regulatory review for medical devices. See, e.g., Sanket S. Dhruva, Lisa A. Bero & Rita F. Redberg, Strength of Study Evidence Examined by the FDA in Premarket Approval of Cardiovascular Devices, 302 JAMA 2679 (2009); Jonas Z. Hines et al., Left to Their Own Devices: Breakdowns in United States Medical Device Premarket Reviews, 7 PLOS MED. 1 (2010); Diana M. Zukerman, Paul Brown & Steven E. Nissen, Medical Device Recalls and the FDA Approval Process, 171 ARCHIVES INTERNAL MED. 1006 (2011).
193 See Turner et al., supra note 174, at 256.
194 See McPherson & Hemminki, supra note 187, at 519.
195 See, e.g., ANGELL, supra note 9; JEROME P. KASSIRER, ON THE TAKE: HOW MEDICINE's COMPLICITY WITH BIG BUSINESS CAN ENDANGER YOUR HEALTH (2004); Ray & Stein, supra note 192.
196 See Lemmens, supra note 9, at 652-54.
197 Description of The Cochrane Collaboration, THE COCHRANE COLLABORATION, http://www.cochrane.org/policy-manual/11-description-cochrane-collaboration (last visited Jan. 29, 2012).
198 Krall, supra note 82, at 957.
199 See Krleža-Jerić, Draft – The Ottawa Statement, supra note 32. Early recommendations for trial registration also suggested the need for more details on the clinical trials. See Meinert, supra note 15, at 2-3.
200 S. Swaroop Vedula and colleagues recently analyzed internal company documents that were made available in the context of class action litigation and compared these with the outcome reporting in industry-sponsored trials of gabapentin (Neurontin). They documented substantial differences between the definitions of the primary outcomes in the clinical trial protocols and those in the published results. Primary outcomes were sometimes not reported, or were altered, or turned into secondary outcomes, or inadequately distinguished in the published study from secondary outcomes. In some cases, new primary outcomes were added. This was done without explicit acknowledgment of the practice in the final publication. “[A]ll the changes that took place between what was specified in the protocol, what was known before publication … and what was reported to the public,” Swaroop Vedula and colleagues write, “led to a more favorable presentation in the medical literature of gabapentin's efficacy for unapproved indications.” Vedula et al., supra note 170, at 1969. They conclude that “existing trial registration systems need to go further … and should include registration of the full protocol and amendments.” Id. at 1970; see also Rennie, supra note 23, at 1361; Steven Piantadosi & David P. Byar, Letter to the Editor: A Proposal for Registering Clinical Trials, 9 CONTROLLED CLINICAL TRIALS 82 (1988) (recommending the registration of full protocols).
201 See McPherson & Hemminki, supra note 187, at 518, 519 and accompanying text.
202 Dickersin & Rennie, supra note 13, at 517.
203 Id.
204 Id.
205 Rennie, supra note 23, at 1361; see also McPherson & Hemminki, supra note 187, at 519.
206 Salinas has made the claim that the right to health requires access to information. Salinas, supra note 7, at 47-48. There is an interesting connection to arguments about the human right to enjoy the benefits of scientific progress. See Audrey R. Chapman, The Human Rights Implications of Intellectual Property Protection, 5 J. INT’L ECON. L. 861, 867, 872 (2002).
207 The Cochrane Collaboration is an independent international network of more than 28,000 researchers and academics with the goal of helping healthcare providers, governments, patients, and others in making well-informed healthcare decisions based on the best-available medical evidence. With its international network of researchers, the Cochrane Collaboration has the capacity and the credibility to scrutinize the available medical evidence and to provide a critical independent and public voice in the context of drug safety and effectiveness through the highly credible Cochrane Reviews. See About Us, THE COCHRANE COLLABORATION, http://www.cochrane.org/about-us (last visited Dec. 26, 2011)
208 The Constitution of South Africa explicitly recognizes the right to health. See Soobramoney v. Minister of Health (Kwazulu-Natal), supra note 3; Minister of Health, supra note 3. In India, the constitutionally protected right to life has been interpreted as including a right to health. See Paschim Banga Khet Mazdoor Samity & Ors v. State of West Bengal and Anor, A.I.R. 1996 S.C. 2426, (1996) 4 S.C.C. 37 (India).
209 International Covenant on Economic, Social and Cultural Rights, G.A. Res. 2200A (XXI), U.N. GAOR, 21st Sess., Supp. No. 16, U.N. Doc. A/6316, at 49 (Dec. 16, 1966).
210 Special Rapporteur on the Right to Health, Addendum to the Report of the Special Rapporteur, U.N. Comm’n on Human Rights, Mission to the World Trade Organization, ¶ 15, U.N. Doc. E/CN.4/2004/49/Add.1 (Mar. 1, 2004) [hereinafter Report of the Special Rapporteur].
211 Constitution of the World Health Organization, preamble, available at http://apps.who.int/gb/bd/PDF/bd47/EN/constitution-en.pdf.
212 G.A. Res. 2002/31, U.N. GAOR, 58th Sess., U.N. Doc. E/CN.4/RES/2002/31 (Apr. 24, 2002). The Special Rapporteur's mandate was extended in 2007 by the newly formed Human Rights Council. U.N. Human Rights Council, Res. 6/29, 33rd Mtg., U.N. Doc. A/HRC/RES/6/29 (Dec. 14, 2007).
213 Paul Hunt, former U.N. Special Rapporteur on the Right to Health, commented in 2003 that discussions between the World Trade Organization and NGOs on the right to health were “[w]ithout exception … constructive,” even if “it is not well understood that the right to health is supported by an extensive and nuanced body of law.” Paul Hunt, Towards Development: Human Rights and the WTO Agenda, Panel Presentation at World Trade Organization Ministerial Conference, Cancun, Mex. (Sept. 12, 2003), available at http://www.3dthree.org/pdf_3D/Righttohealthandeconomicpolicy-English09-03.pdf.
214 Report of the Special Rapporteur, supra note 210, ¶¶ 18-20.
215 Id. ¶¶ 33-38. We note that accurate information is specifically identified as a key dimension of accessibility.
216 WORLD HEALTH ORG., ENGAGING FOR HEALTH: ELEVENTH GENERAL PROGRAMME OF WORK 2006-2015, at 2 (2006), available at http://whqlibdoc.who.int/publications/2006/GPW_eng.pdf.
217 The characterization of access to information as a “determinant” is borrowed from Paul Hunt, former U.N. Special Rapporteur on the Right to Health, who broadly defines the scope of the right to health to include both freedom from discrimination in the delivery of healthcare as well as access to the underlying determinants of health, such as potable water, sanitation, access to essential medicines, and we would argue, information about those medicines. Report of the Special Rapporteur, supra note 210, ¶¶ 18-19.
218 SANDRA COLIVER, THE RIGHT TO KNOW: HUMAN RIGHTS AND ACCESS TO REPRODUCTIVE HEALTH INFORMATION 45 (1995).
219 International Covenant on Civil and Political Rights, G.A. Res. 2200A (XXI), U.N. GAOR, 21st Sess., Supp. No. 16, 999, U.N. Doc. A/6316, at 52 (Dec. 16, 1966) [hereinafter ICCPR]. Freedom of expression and the right to information are also expressly recognized in essentially the same terms in the Universal Declaration of Human Rights (article 19), the U.N. Convention on the Rights of the Child (article 13), the American Convention (article 13), the European Convention for the Protection of Human Rights and Fundamental Freedoms (article 10), and the African (Banjul) Charter on Human and Peoples’ Rights (article 9). The United Nations referred to freedom of information as a freestanding right, though not formally through inclusion in one of the covenants: “Freedom of information is a fundamental human right and is the touchstone of all of the freedoms to which the United Nations is consecrated.” Calling of an International Conference on Freedom of Information, G.A. Res. 59(I), U.N. GAOR, 1st Sess., U.N. Doc. A/RES/59(I) (Dec. 14, 1946), available at http://daccess-dds-ny.un.org/doc/RESOLUTION/GEN/NR0/033/10/IMG/NR003310.pdf?OpenElemen t; see also COLIVER, supra note 218, at 46.
220 Calling of an International Conference on Freedom of Information, G.A. Res. 59(I), supra note 219, at 46.
221 Council of Eur., European Convention for the Protection of Human Rights and Fundamental Freedoms, E.T.S. 5 (Nov. 4, 1950), available at http://www.unhcr.org/refworld/docid/3ae6b3b04.html.
222 Id. at 9.
223 Open Door and Dublin Well Women v. Ireland, No. 14234/88, Eur. Ct. H.R. 68 (1992). The determination was made in the context of a proportionality analysis; the court found that the absolute prohibition on information about an activity that was not in fact illegal (i.e. it was not illegal to travel abroad for an abortion) was overly broad and disproportionate. See id. ¶¶ 67-77.
224 Id. ¶ 68.
225 COLIVER, supra note 218, at 46-47. See Gaskin v. United Kingdom, 160 Eur. Ct. H.R. (ser. A), at 36 (stating that there might “be positive obligations inherent in an effective respect; for family life”); Informationsverein Lentia et al. v. Austria (1993), 276 Eur. Ct. H.R. (ser. A), at 93 (stating that the government is the “ultimate guarantor” of media pluralism, implying that it has a corresponding duty to promote media freedom); see also Rebecca J. Cook & Mahmoud F. Fathalla, Duties to Implement Reproductive Rights, 67 NORDIC J. INT’L L. 1 (1998).
226 The Sunday Times v. The United Kingdom, 30 Eur. Ct. H.R. (ser. A), at 245 (1979).
227 See HILTS, supra note 160, at 144-65.
228 Id.
229 The Sunday Times, 30 Eur. Ct. H.R. (ser. A), ¶ 66.
230 Ontario (Public Safety and Security) v. Criminal Lawyers’ Association, [2010] 1 S.C.R. 815 9 (Can.).
231 Ontario (Attorney General) v. Fraser, [2011] 2 S.C.R. 3 20 (Can.).
232 U.N. Educational, Scientific, and Cultural Organization, General Comment 14: The Right to the Highest Attainable Standard of Health, U.N. CESCR, 22nd Sess., Apr. 25 – May 12, 2000, U.N. Doc. E/C.12/2000/4 (Aug. 11, 2000) [hereinafter CESCR, GC 14]. While not binding instruments, general comments are generally viewed as having “considerable legal weight.” MATTHEW C. R. CRAVEN, THE INTERNATIONAL COVENANT ON ECONOMIC, SOCIAL, AND CULTURAL RIGHTS: A PERSPECTIVE ON ITS DEVELOPMENT 91 (1995).
233 CESCR, GC 14, supra note 232, ¶ 11.
234 Id. ¶ 12(b).
235 RAJAT KHOSLA & PAUL HUNT, HUMAN RIGHTS GUIDELINES FOR PHARMACEUTICAL COMPANIES IN RELATION TO ACCESS TO MEDICINES: THE SEXUAL AND REPRODUCTIVE HEALTH CONTEXT 8 (2009), available at http://www2.essex.ac.uk/human_rights_centre/rth/docs/Final%20pharma%20for%20website.pdf. The necessity of information to informed decision-making is echoed in Committee on the Elimination of Discrimination against Women, General Recommendation 24: Women and Health, U.N. CEDAW, 20th Sess., U.N. Doc. A/54/38, ¶ 20 (1999).
236 CESCR, GC 14, supra note 232.
237 Id. ¶ 4.
238 Id. ¶ 8.
239 Id. ¶ 11.
240 The Secretary-General, The Right of Everyone to the Enjoyment of the Highest Attainable Standard of Physical and Mental Health, U.N. GAOR, 61st Sess., U.N. Doc. A/61/338, ¶ 61 (Sept. 13, 2006).
241 Id. ¶ 49.
242 Id. ¶ 71; see also Report of the Special Rapporteur, supra note 210, ¶ 38.
243 For a good discussion, see Katz, supra note 158, at 12-18.
244 It should be noted here that direct-to-consumer advertising (DTCA) occurs even in countries with a more prohibitory approach. For a discussion of DTCA in the Canadian context, see BARBARA MINTZES, DIRECT-TO-CONSUMER ADVERTISING OF PRESCRIPTION DRUGS IN CANADA: WHAT ARE THE PUBLIC HEALTH IMPLICATIONS? (Health Council of Can. ed., 2006), and Colleen M. Flood, The Evidentiary Burden for Overturning Government's Choice of Regulatory Instrument: The Case of Direct-to-Consumer Advertising of Prescription Drugs, 60 U. TORONTO L.J. 397 (2010).
245 See Lemmens, supra note 9.
246 See Tarsasag a Szabadsagjogokert v. Hungary, No 37374.05, Eur. Ct. H.R. 618 (2009).
247 Id. ¶ 36.
248 See 3D -> TRADE - HUMAN RIGHTS - EQUITABLE ECONOMY, TOWARDS HUMAN RIGHTSCONSISTENT TRADE POLICIES: SAMPLES AND SUGGESTIONS FOR ENGAGING WITH HUMAN RIGHTS TREATY BODIES 2 (2008), available at http://www.3dthree.org/pdf_3D/HR&tradepolicies.pdf [hereinafter 3D].
249 Committee on Economic, Social, and Cultural Rights: Rep. on the 25th, 26th & 27th Sessions, Apr. 23-May 11, 2001, Aug. 13-31, 2001, Nov. 12-30, 2001, Human Rights and Intellectual Property, ¶ 4-5, U.N. ESCOR, 27th Sess., Annex XIII UN Doc. E/C.12/2001/15 (2001) [hereinafter CESCR, Human Rights and Intellectual Property]. The Committee on Economic, Social, and Cultural Rights goes on to differentiate between human rights, which are “fundamental, inalienable and universal,” and intellectual property rights as instrumental, temporary, and “increasingly focused on protecting business and corporate interests and investments.” Id. ¶ 6.
250 See Chapman, supra note 206; Laurence R. Helfer, Human Rights and Intellectual Property: Conflict or Coexistence, 5 MINN. INTELL. PROP. REV. 47, 48 n.3 (2003) (citing Robert Howse & Makau Mutua, Protecting Human Rights in a Global Economy: Challenges for the World Trade Organization (Int’l Ctr. for Human Rights & Democratic Dev., Policy Paper, 2000), available at http://www.ichrdd.ca/english/commdoc/publications/globalization/wtoRightsGlob.html)); see also Lisa Forman, An Elementary Consideration of Humanity? Linking Trade-Related Intellectual Property Rights to the Human Right to Health in International Law, 14 J. WORLD INTELL. PROP. 155 (2011.
251 For example, the Committee on the Rights of the Child asserts that states parties to the Convention on the Rights of the Child “should conduct an assessment of the impact of international intellectual property rights agreements on the accessibility of affordable generic medicines, with a view to ensuring children's enjoyment of the highest attainable standard of health.” Committee on the Rights of the Child, Consideration of Reports Submitted by States Parties Under Article 44 of the Convention: Concluding Observations – El Salvador, ¶ 48, U.N. Doc. CRC/C/15/Add.232, 36th Sess., (June 30, 2004); see also 3D, supra note 248, at 6-7.
252 Clinical drug trials invoke ethical obligations to both those participating in the trials and the public at large. For discussions of the ethical implications see Catherine D. De Angelis et al., Is This Clinical Trial Fully Registered? A Statement From the International Committee of Medical Journal Editors, 293 JAMA 2927, 2927 (2005); Dickersin & Rennie, supra note 13, at 517-18; Ghersi et al., supra note 69, at 492; Krleža-Jerić et al., Principles for International Registration, supra note 32 at 957; Krleža-Jerić, Clinical Trial Registration, supra note 32, at 1093, 1095; Lemmens & Bouchard, supra note 106, at 40-41.
253 Trips Agreement, supra note 5, at art. 39.3.
254 World Trade Organization, Ministerial Declaration of 14 November 2001, Declaration on the TRIPS Agreement and Public Health, WT/MIN(10)/DEC/2, 41 I.L.M. 755 (2002). See, in particular, paragraphs 4 and 5.
255 Id. ¶ 4.
256 See Christopher Butler, Human Rights and the World Trade Organization: The Right to Essential Medicines and the TRIPS Agreement, 45 J. INT’L L. & POL’Y 5:1, 5:20-:26 (2007).
257 COLIVER, supra note 218, at 46.
258 Erdman, supra note 6, at 423. Erdman's paper focuses on two human rights paradigms— human rights as a tool to advocate for government action, as described above, and human rights as a tool for assessing government objectives and interventions—and notably draws on the work of Sophia Gruskin. See id. at 423 nn.52-53.
259 Organization of American States, American Convention on Human Rights, art. 26, Nov. 22, 1969, O.A.S.T.S. No. 36, 1144 U.N.T.S. 123 [hereinafter American Convention]. Article 26 of the American Convention, the “progressive realization” provision, in fact refers to realization of the rights implicit in the standards set forth in the Charter of the Organization of American States, Apr. 30, 1948, 119 U.N.T.S. 3, as amended by the Protocol of Buenos Aires, Feb. 27, 1967, O.A.S.T.S. No. 1- A, 721 U.N.T.S. 324. The standards set out in the Charter include “equality of opportunity, the elimination of extreme poverty, equitable distribution of wealth and income and the full participation of [States parties’] peoples in decisions relating to their own development,” as well as “[p]rotection of man's potential through the extension and application of modern medical science.” Charter of the Organization of American States, supra, at art. 34.
260 Additional Protocol to the American Convention on Human Rights in the Area of Economic, Social and Cultural Rights, Nov. 17, 1988, O.A.S.T.S. No. 69, available at http://www.cidh.org/Basicos/English/basic5.Prot.Sn%20Salv.htm [hereinafter San Salvador Protocol].
261 Id. at art. 10.
262 TARA MELISH, PROTECTING ECONOMIC, SOCIAL AND CULTURAL RIGHTS IN THE INTERAMERICAN HUMAN RIGHTS SYSTEM: A MANUAL ON PRESENTING CLAIMS 46 (2002).
263 Jorge Odir Miranda Cortez et al. v. El Salvador, Case 12.249, Inter-Am. Comm’n. H.R. Report No. 29/01, OEA/Ser.L/V/II. 111, doc. 20 rev. ¶ 1 (2000).
264 Id. ¶ 47.
265 Id. ¶ 5 n.2.
266 See, e.g., U.N. Office of the High Comm’r for Human Rights, Fact Sheet No. 16 (Rev. 1), The Committee on Economic, Social and Cultural Rights, July 1991, http://www.ohchr.org/Documents/Publications/FactSheet16rev.1en.pdf [hereinafter OHCHR, Fact Sheet No. 16]; Inter-Am. Comm’n H.R., Annual Report of the Inter-American Commission on Human Rights, 1983-1984, § V(II)(2), OEA/Ser.L/V/II.63 doc. 10 (Sept. 24, 1984); see also MELISH, supra note 262, at 54.
267 This has been cited as a particular problem in the context of equality and discrimination. The WHO has pointed out that health-related human rights are often enforced or not enforced in a discriminatory manner, i.e., with regard to women, indigenous peoples, minorities, persons with disabilities, etc., because of major gaps in health-related policy-making. See WORLD HEALTH ORG., supra note 216, at 8.
268 Any person, group of persons, or nongovernmental entity legally recognized in one or more members of the Organization of American States may bring an individual petition before the Inter- American Commission on Human Rights alleging violations on the part of states. American Convention, supra note 259, at art. 44. But see San Salvador Protocol, supra note 260, at art. 19.6.
269 Comm. on Econ., Soc. and Cultural Rights: Report on the 5th Session, Nov. 26-Dec. 14, 1990, General Comment 3: The Nature of States Parties Obligations, ¶ 9, U.N. Doc. E/1991/23; ESCOR, 5th Sess., Annex III (1990) [hereinafter CESCR, GC 3].
270 Under the American Convention, temporary derogations from the obligations set out in that instrument, including the obligation of progressive realization under article 26, are permissible only in times of “war, public danger, or other emergency,” American Convention, supra note 259, at art. 27(1), while general limitations are acceptable only for the “security of all” and the “just demands of the general welfare, in a democratic society,” id. at art. 32.
271 CESCR, GC 3, supra note 269, ¶ 9; OHCHR, Fact Sheet No. 16, supra note 266.
272 CESCR, Human Rights and Intellectual Property, supra note 249, ¶ 12.
273 CESCR, GC 3, supra note 269, ¶ 10.
