Conflicts among Multinational Ethical and Scientific Standards for Clinical Trials of Therapeutic Interventions

National Health and Medical Research Council, Australian Research Council, and Australian Vice-Chancellors' Committee, National Statement on Ethical Conduct in Human Research, Australian Government, 2007: At 36.

National Health Service, Association of the British Pharmaceutical Industry, BioIndustry Association, “NHS-ABPI-BIA Clinical Trial Agreement 2006 version – Scotland (Clinical Trial Agreement for Pharmaceutical and Biopharmaceutical Industry Sponsored Research in Scottish Health Boards),” (a contractual agreement template): At 6, available at <http://www.cso.scot.nhs.uk/SuppScience/MCTA_NHS-ABPI-BIA_Scot.pdf> (last visited May 16, 2011).

World Medical Assocation, “Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects,” (last updated October 2008), available at <http://www.wma.net/en/30publications/10policies/b3/index.html> (last visited May 16, 2011).

See National Health Service, et. al., supra note 15, at 6.

International Conference on Harmonisation (ICH) Steering Committee, ICH Harmonised Tripartite Guideline: Guideline for Good Clinical Practice E6(R1) , Step 4 version (1996): At 17, available at <http://private.ich.org/LOB/media/MEDIA482.pdf> (last visited May 16, 2011); Statens Legemiddelverk (Norwegian Medicines Agency), “FOR 2003-09-24 nr 1202: Regulation relating to clinical trials on medicinal products for human use,” (Norwegian Government, 2003): At section 4–1, available at <http://www.legemiddelverket.no/upload/116328/FOR%202003-09-24%20nr%201202%20english.pdf> (last visited May 16, 2011); U.S. Food and Drug Administration, “A Guide to Informed Consent,” (FDA Information Sheets, 1998), available at <http://www.fda.gov/RegulatoryInformation/Guidances/ucm126431.htm> (last visited May 16, 2011); US Food and Drug Administration, “Sponsor – Investigator – IRB Interrelationship,” (FDA Information Sheets, 1998), available at <http://www.fda.gov/RegulatoryInformation/Guidances/ucm126425.htm> (last visited May 16, 2011); see Penslar , supra note 10, at chapter 3, section D; see 21 C.F.R. 50.25 (a) (5) (1996).

See Penslar , supra note 10, at chapter 3, section D and chapter 5, section B; see U.S. Food and Drug Administration, “A Guide to Informed Consent” and “Sponsor – Investigator – IRB Interrelationship,” supra note 18.

See Penslar , supra note 10, chapter 5, section B.

See U.S. Food and Drug Administration, “A Guide to Informed Consent,” supra note 18.

See Lakemedelsverket, supra note 2, at 13.

European Parliament and the Council of the European Union, Directive 2001/20/EC, preamble section 16 (Apr. 4 2001), available at <http://www.eortc.org/Services/Doc/clinical-EU-directive-04-April-01.pdf> (last visited December 19 2010).

See National Health Service, et. al., supra note 15, at 10.

Id.

National Patient Safety Agency (National Research Ethics Service, National Health Service of UK), Standard Operating Procedures for Research Ethics Committees, ver. 3.5 (May 2008), at 246, available at <http://www.nres.npsa.nhs.uk/EasySiteWeb/GatewayLink.aspx?alId=27101> (last visited May 16, 2011); Medicines and Healthcare Products Regulatory Agency (UK), “Medical devices research: Communications between MHRA and RECs,” (Apr. 2008): At para. 23, available at <www.nres.npsa.nhs.uk/EasySiteWeb/GatewayLink.aspx?alId=11474> (last visited May 16, 2011); European Commission, Detailed guidance on the application format and documentation to be submitted in an application for an Ethics Committee opinion on the clinical trial on medicinal products for human use , (EC, 2006): At 9, available at <http://ec.europa.eu/health/files/eudralex/vol-10/12_ec_guideline_20060216_en.pdf> (last visited May 16, 2011)

See European Commission, supra note 26, at 9.

21 C.F.R. 812.35 (1998).

American College of Surgeons Oncology Group, “Standard Operating Procedures: Institutional Review Board Approval,” (ACOSOG, 2003): At 4, available through <https://www.acosog.org>; REB Secretariat, Health Canada, Ethical Review of Research Involving Human Subjects: Administrative and Policy Procedure Manual for Health Canada Research Ethics Board (REB) , (Health Canada, 2006): At 34, available at <http://www.hc-sc.gc.ca/sr-sr/alt_formats/hpb-dgps/pdf/pubs/advice-avis/reb-cer-eng.pdf> (last visited May 16, 2011); Swissmedic (Swiss Agency for Therapeutic Products), “Clinical Trials of Medical Devices” (fact sheet; Swissmedic, 2008): At 3, available at <http://www.swissmedic.ch/leitfaden/00027/index.html?lang=en&download=NHzLpZeg7t,lnp6I0NTU042l2Z6ln1ad1IZn4Z2qZpnO2Yuq2Z6gpJCDdXt,gmym162epYbg2c_JjKbNoKSn6A> (last visited May 16, 2011).

21 C.F.R. 312.30(b)(2)(i)(b) (2009); see World Medical Association, supra note 16.

See International Conference on Harmonisation (E6), supra note 18, at 14.

Id.

See National Patient Safety Agency, supra note 26, at 17.

US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Center for Devices and Radiologic Health, Center for Food Safety and Nutrition, et al., Guidance for Industry: Computerized Systems Used In Clinical Trials, (US DHHS/FDA/CDER/CBER/CDRH/CFSAN/CVM/ORA, 1999), available at <http://www.fda.gov/RegulatoryInformation/Guidances/ucm126402.htm> (last visited May 16, 2011).

Id.

See Lakemedelsverket, supra note 2, at 16.

See International Conference on Harmonisation (E6), supra note 18, at 25.

American Academy of Orthopaedic Surgeons, Guide to Professionalism and Ethics in the Practice of Orthopaedic Surgery (AAOS, 2008): At 115, available at <http://www.aaos.org/about/papers/ethics/ethicalpractguide.pdf> (last visited May 16, 2011); see South African Orthopaedic Association, supra note 4.

European Parliament and the Council of the European Union, Directive 20015/28/EC (Apr. 8, 2005): Article 17, available at <http://ec.europa.eu/health/files/eudralex/vol-1/dir_2005_28/dir_2005_28_en.pdf> (last visited May 16, 2011).

See Committee for Ethics and Medico-Legal Affairs, supra note 13, at 14.

See National Health and Medical Research Council, supra note 14, at 36.

See International Conference on Harmonisation (E6), supra note 18, at 22.

Id, 18–19.

21 C.F.R. 312.62(c) (2002).

21 C.F.R. 812.140(d) (1998).

Id.

See International Conference on Harmonisation (E6), supra note 18, at 22.

21 C.F.R. 312.57(c) (2002).

U.S. Department of Health and Human Services, “Investigator Responsibilities, FAQs,” available at <http://answers.hhs.gov/ohrp/categories/1567> (last visited May 16, 2011).

See European Parliament (2005), supra note 39, article 17.

Id.

See Swissmedic, supra note 29, at 4.

Statni Ustav pro Kontrolu Leciv (State Institute for Drug Control, Czech Republic), ZP-21 Inspection of the Conduct of Clinical Evaluations on Medical Devices in the Premises of Healthcare Providers , (Czech Government, 2004): At 6 and 9, available at <http://www.sukl.cz/uploads/Pokyny_a_formulare_anglicky/ZP_21.pdf> (last visited May 16, 2011).

See Swissmedic, supra note 29, at 4.

See Statens Legemiddelverk, supra note 18, at section 5–3.

Id.; see Lakemedelsverket, supra note 2, at 24.

See Polish Government, supra note 3, article 47.

Department for Constitutional Affairs, Mental Capacity Act 2005 Code of Practice (United Kingdom Government, 2007): At 202, available at <http://webarchive.nationalarchives.gov.uk/+/http://www.dca.gov.uk/legal-policy/mental-capacity/mca-cp.pdf> (last visited May 16, 2011).

Id.

Royal College of Physicians, Guidelines on the Practice of Ethics Committees in Medical Research with Human Participants , 4th edition (London: RCP, 2007): At 40; see Lakemedelsverket Laakelaitos , supra note 2, at 8.

See American College of Surgeons Oncology Group, supra note 29, at 1; see REB Secretariat, Health Canada, supra note 29, at 26.

See Lakemedelsverket, supra note 2, at 12.

See Council for International Organizations of Medical Sciences, supra note 6.

Penslar R.L. , IRB Guidebook , (Office for Human Research Protections, United States Deptartment of Health and Human Services, 1993): At chapter 4, section E, available at <http://www.hhs.gov/ohrp/irb/irb_guidebook.htm> (last visited May 16, 2011).

See American Academy of Orthopaedic Surgeons, supra note 38, at 112; see South African Orthopaedic Association, supra note 4.

Council of Europe Bioethics Division, Additional Protocol to the Convention on Human Rights and Biomedicine, Concerning Biomedical Research, European Treaty Series 195, available at <http://conventions.coe.int/treaty/en/treaties/html/195.htm> (last visited Dec. 19 2010).

See Council for International Organizations of Medical Sciences, supra note 6.

See Royal College of Physicians, supra note 60, at 39.

Higgins J.P.T. Green S. , eds., Cochrane Handbook for Systematic Reviews of Interventions 4.2.6 [updated Sept. 2006], in The Cochrane Library , Issue 4 (Chichester, UK: John Wiley & Sons, Ltd., 2006): At section 6.3, available at <http://www.cochrane.org/sites/default/files/uploads/Handbook4.2.6Sep2006.pdf> (last visited May 16, 2011).

McConnell T. , “The Inalienable Right to Withdraw from Research,” Journal of Law, Medicine & Ethics 38 (2010): At 840–846.

The Nuremberg Code [from Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10. Nuremberg, October 1946-April 1949. Washington, D.C.: U.S. G.P.O., 1949–1953.], available at <http://ohsr.od.nih.gov/guidelines/nuremberg.html> (last visited May 16, 2011).

Jonas H. , “Philosophical Reflections on Experimenting with Human Subjects,” in Freund P. A. , ed., Experimentation with human subjects (New York: George Braziller Inc., 1969): 1–31; Murphy T. F. , “Self-Experimentation: The Peruvian Medical Student” and “Self-Experimentation: Cancerous Tissue,” in Case Studies in Biomedical Research Ethics (Cambridge: MIT Press, 2004): At 110–113.

Division of Biostatistics, Office of Surveillance and Biometrics, Center for Devices and Radiologic Health, U.S. Food and Drug Administration, “Chapter III – Design of a Clinical Trial, Section I – Trial Site and Investigator,” in Statistical Guidance for Clinical Trials of Non Diagnostic Medical Devices (FDA, 1996), available at <http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm106757.htm> (last visited May 16, 2011); see World Medical Association, supra note 16.

See Royal College of Physicians, supra note 60, at 38.

See Royal Australasian College of Physicians, supra note 11, at 44–45.

See American College of Surgeons Oncology Group, supra note 29, at 4.

See National Patient Safety Agency, supra note 26, at 176.

National Patient Safety Agency (National Research Ethics Service, National Health Service of UK), Approval for Medical Devices Research, ver. 2 (March 2008), at 25, available at <http://www.nres.npsa.nhs.uk/EasySiteWeb/GatewayLink.aspx?alId=11473> (last visited May 16, 2011).

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See Council for International Organizations of Medical Sciences, supra note 1.

See Council of Europe Bioethics Division, supra note 22, article 15(2.ii).

National Health and Medical Research Council et al., supra note 8, at 62.

See Statens Legemiddelverk, supra note 22, at section 4–2; see Department for Constitutional Affairs, supra note 16, at 210; European Parliament, supra note 14, article 4(i).

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See Penslar , supra note 12, at chapter 3, section A (emphasis added).

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See International Conference on Harmonisation (E6), supra note 19, at 23.

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45 C.F.R. 46.116 (2005).

45 C.F.R. 46.116(a)(6) (2005).

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See Penslar , supra note 12, at chapter 3, section B (emphasis added).

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See Royal College of Physicians, supra note 29, at 44.

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See International Conference on Harmonisation (E9), supra note 63, at 16.

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See Penslar , supra note 12, at chapter 4, section H.

See US Department of Health and Human Services et al., supra note 58, at 21.

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See Council for International Organizations of Medical Sciences, supra note 1.

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21 C.F.R. 312.60 (1996); see Department of Health (South Africa), supra note 9, at 49.

See Royal Australasian College of Physicians, supra note 73, at 36.

See National Health and Medical Research Council et al., supra note 8, at 63.

Kim S. Y. Schrock L. Wilson R. M. , “An Approach to Evaluating the Therapeutic Misconception,” IRB: Ethics and Human Research 31, no. 5 (September-October 2009): 7–14; see Sulmasy , supra note 46.

American Society of Hospital Pharmacists, “ASHP Statement on Pharmaceutical Research in Organized Health-Care Settings,” American Journal of Hospital Pharmacy 48 (1991): 1781.

Laakelaitos Lakemedelsverket (National Agency for Medicines, Finland), “Normative Guideline 1/2004, 12/30/2004 and 1/2007: Clinical Investigations on Medical Devices” Finnish Government, 2007, at sect. 2.3, available at <http://firstclinical.com/regdocs/doc/?showpage=7&db=INT_Finland_Clinical_Investigations_Devices> (last visited January 18, 2012); see Lakemedelsverket, supra note 20, at 9; see International Conference on Harmonisation (E6), supra note 19, at 13 (thanks to a reviewer for noting this overlooked standard).

Grant G. R. , “Surgical Innovation and Research,” in Emanuel , supra note 4, at 367–374.

Bethel M. Holman R. Haffner S. Califf R. Huntsman-Labed A. Hua T. McMurray J. , “Determining the Most Appropriate Components for a Composite Clinical Trial Outcome,” American Heart Journal 156, no. 4 (October 2008): 633–640.

Halpern S. D. , “Towards Evidence Based Bioethics,” BMJ 15, no. 331 (October 2005): 901–903; Schonfeld T. L. Brown J. S. Weniger M. Gordon B. , “Research Involving the Homeless: Arguments against Payment-in-Kind (PinK),” IRB: Ethics and Human Research 25, no. 5 (September-October 2003): 17–20.

Referring to Council of Europe Bioethics Division, supra note 22.

76 FR 44528.

See Penslar , supra note 12, main page.