The ethical analysis of risk

Journal of Law, Medicine and Ethics

Volumn 28, Issue 4, 2000, Pages 344-361

  Weijer, Charles ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

CLINICAL TRIAL; HUMAN; HUMAN EXPERIMENT; MEDICAL ETHICS; PROFESSIONAL STANDARD; REVIEW; RISK ASSESSMENT; STANDARD; UNITED STATES;

CLINICAL TRIALS; ETHICS, MEDICAL; HUMAN EXPERIMENTATION; HUMANS; PROFESSIONAL STAFF COMMITTEES; RISK ASSESSMENT; UNITED STATES;

EID: 0034574910     PISSN: 10731105     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1748-720X.2000.tb00686.x     Document Type: Article

References (107)

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4. 45 C.F.R. § 46.111(a).
5. National Commission, supra note 3.
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9. C. Weijer, "Placebo-Controlled Trials in Schizophrenia: Are They Ethical? Are They Necessary?" Schizophrenia Research, 35 (1999): 211-18.
10. P. Zimbardo, "Inducing Hearing Deficit Generates Experimental Paranoia," Science, 212 (1981): 1529-31.
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12. S. Phillips, "Asking the Sensitive Question: The Ethics of Survey Research and Teen Sex," IRB, 16, no. 6 (1994): 1-7.
13. Id.
14. J.P. Struewing et al., "The Risk of Cancer Associated with Specific Mutations of BRCA1 and BRCA2 Among Ashkenazi Jews," N. Engl. J. Med., 336 (1997): 1401-08.
15. K.C. Glass et al., "Structuring the Review of Human Genetics Protocols Part II: Diagnostic and Screening Studies," IRB, 19, no. 3-4 (1997): 1-11, 13.
16. Levine, supra note 7, at 42-57.
17. Levine, "The Role of Assessment of Risk Benefit Criteria in the Determination of the Appropriateness of Research Involving Human Subjects," supra note 6, at 2.5-2.44.
18. B. Gray, "Bioethics Commissions: What Can We Learn from Past Successes and Failures?" in R. Bulger, E. Bobby, and H. Fineberg, eds., Society's Choices: Social and Ethical Decision Making in Biomedicine (Washington, D. C.: National Academy Press, 1995): 261-306.
19. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research on the Fetus: Report and Recommendations, DHEW Pub. No. (OS) 76-127 (Washington, D.C: U.S. Gov't Printing Office, 1975); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Prisoners: Report and Recommendations, DHEW Pub. No. (OS) 76-131 (Washington, D.C.: U.S. Gov't Printing Office, 1976); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Children: Report and Recommendations, DHEW Pub. No. (OS) 77-0004 (Washington, D.C.: U.S. Gov't Printing Office, 1977); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Those Institutionalized as Mentally Infirm: Report and Recommendations, DHEW Pub. No. (OS) 78-0006 (Washington, D.C.: U.S. Gov't Printing Office, 1978); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Institutional Review Boards: Report and Recommendations, DHEW Pub. No. (OS) 78-0008 (Washington, D.C.: U.S. Gov't Printing Office, 1978); National Commission, The Belmont Report, supra note 3.
20. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research on the Fetus: Report and Recommendations, DHEW Pub. No. (OS) 76-127 (Washington, D.C: U.S. Gov't Printing Office, 1975); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Prisoners: Report and Recommendations, DHEW Pub. No. (OS) 76-131 (Washington, D.C.: U.S. Gov't Printing Office, 1976); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Children: Report and Recommendations, DHEW Pub. No. (OS) 77-0004 (Washington, D.C.: U.S. Gov't Printing Office, 1977); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Those Institutionalized as Mentally Infirm: Report and Recommendations, DHEW Pub. No. (OS) 78-0006 (Washington, D.C.: U.S. Gov't Printing Office, 1978); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Institutional Review Boards: Report and Recommendations, DHEW Pub. No. (OS) 78-0008 (Washington, D.C.: U.S. Gov't Printing Office, 1978); National Commission, The Belmont Report, supra note 3.
21. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research on the Fetus: Report and Recommendations, DHEW Pub. No. (OS) 76-127 (Washington, D.C: U.S. Gov't Printing Office, 1975); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Prisoners: Report and Recommendations, DHEW Pub. No. (OS) 76-131 (Washington, D.C.: U.S. Gov't Printing Office, 1976); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Children: Report and Recommendations, DHEW Pub. No. (OS) 77-0004 (Washington, D.C.: U.S. Gov't Printing Office, 1977); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Those Institutionalized as Mentally Infirm: Report and Recommendations, DHEW Pub. No. (OS) 78-0006 (Washington, D.C.: U.S. Gov't Printing Office, 1978); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Institutional Review Boards: Report and Recommendations, DHEW Pub. No. (OS) 78-0008 (Washington, D.C.: U.S. Gov't Printing Office, 1978); National Commission, The Belmont Report, supra note 3.
22. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research on the Fetus: Report and Recommendations, DHEW Pub. No. (OS) 76-127 (Washington, D.C: U.S. Gov't Printing Office, 1975); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Prisoners: Report and Recommendations, DHEW Pub. No. (OS) 76-131 (Washington, D.C.: U.S. Gov't Printing Office, 1976); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Children: Report and Recommendations, DHEW Pub. No. (OS) 77-0004 (Washington, D.C.: U.S. Gov't Printing Office, 1977); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Those Institutionalized as Mentally Infirm: Report and Recommendations, DHEW Pub. No. (OS) 78-0006 (Washington, D.C.: U.S. Gov't Printing Office, 1978); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Institutional Review Boards: Report and Recommendations, DHEW Pub. No. (OS) 78-0008 (Washington, D.C.: U.S. Gov't Printing Office, 1978); National Commission, The Belmont Report, supra note 3.
23. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research on the Fetus: Report and Recommendations, DHEW Pub. No. (OS) 76-127 (Washington, D.C: U.S. Gov't Printing Office, 1975); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Prisoners: Report and Recommendations, DHEW Pub. No. (OS) 76-131 (Washington, D.C.: U.S. Gov't Printing Office, 1976); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Children: Report and Recommendations, DHEW Pub. No. (OS) 77-0004 (Washington, D.C.: U.S. Gov't Printing Office, 1977); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Those Institutionalized as Mentally Infirm: Report and Recommendations, DHEW Pub. No. (OS) 78-0006 (Washington, D.C.: U.S. Gov't Printing Office, 1978); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Institutional Review Boards: Report and Recommendations, DHEW Pub. No. (OS) 78-0008 (Washington, D.C.: U.S. Gov't Printing Office, 1978); National Commission, The Belmont Report, supra note 3.
24. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research on the Fetus: Report and Recommendations, DHEW Pub. No. (OS) 76-127 (Washington, D.C: U.S. Gov't Printing Office, 1975); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Prisoners: Report and Recommendations, DHEW Pub. No. (OS) 76-131 (Washington, D.C.: U.S. Gov't Printing Office, 1976); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Children: Report and Recommendations, DHEW Pub. No. (OS) 77-0004 (Washington, D.C.: U.S. Gov't Printing Office, 1977); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Those Institutionalized as Mentally Infirm: Report and Recommendations, DHEW Pub. No. (OS) 78-0006 (Washington, D.C.: U.S. Gov't Printing Office, 1978); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Institutional Review Boards: Report and Recommendations, DHEW Pub. No. (OS) 78-0008 (Washington, D.C.: U.S. Gov't Printing Office, 1978); National Commission, The Belmont Report, supra note 3.
25. Levine, supra note 7, at 297-98.
26. National Commission, Research on the Fetus, supra note 19, at 6.
27. Id.
28. Id.
29. Id. at 73.
30. Id. at 74.
31. Levine, supra note 7, at 298.
32. 45 C.F.R. § 208(a).
33. National Commission, Research Involving Prisoners, supra note 19, at x.
34. Id. at xi.
35. Id.
36. Id. at 20.
37. Id. at 15.
38. National Commission, Research Involving Prisoners, supra note 19, at 20.
39. 45 C.F.R. § 46.306(a)(2)(A); 45 C.F.R. § 46.303(d).
40. National Commission, Research Involving Children, supra note 19.
41. Levine, supra note 7, at 239.
42. National Commission, Research Involving Children, supra note 19, at xx.
43. 45 C.F.R. § 46.120(i).
44. National Commission, Research Involving Children, supra note 19, at 20.
45. Id. at 2.
46. Id. at 5.
47. Id. at 5-6.
48. Id. at 7.
49. National Commission, Research Involving Children, supra note 19, at 7-8.
50. Id. at 139.
51. Id. at 148.
52. See discussion in the text under the subheading "Ethical Analysis of Entire Protocols" supra.
53. Id. at 7.
54. 45 C.F.R. § 46.102(i).
55. National Commission, Research Involving Children, supra note 19, at 2.
56. National Commission, Research Involving Those Institutionalized as Mentally Infirm, supra note 19.
57. Id. at 8.
58. National Commission, Institutional Review Boards, supra note 19, at xx.
59. Id. at 23.
60. Id. at 19-20.
61. National Commission, The Belmont Report, supra note 3.
62. Id.
63. Levine, "The Boundaries Between Biomedical or Behavioral Research and the Accepted and Routine Practice of Medicine," supra note 6, at 1.9-1.10.
64. Levine, supra note 7, at 250-51.
65. 45 C.F.R § 46.111(a).
66. Id.
67. 45 C.F.R § 46.208(a).
68. 45 C.F.R. § 46.404-07.
69. 45 C.F.R. § 46.111(a)(1)-(2).
70. B. Freedman, A. Fuks, and C. Weijer, "Demarcating Research and Treatment: A Systematic Approach for the Analysis of the Ethics of Clinical Research," Clinical Research, 40 (1992): 653-60; Weijer, supra note 1.
71. B. Freedman, "Equipoise and the Ethics of Clinical Research," N. Engl. J. Med. 317 (1987): 141-45.
72. R. Peto et al., "Design and Analysis of Randomized Clinical Trials Requiring Prolonged Observation of Each Patient: I. Introduction and Design," British Journal of Cancer, 34 (1976): 585-612; R. Peto and C. Baigent, "Trials: The Next 50 Years," British Medical Journal, 317 (1998): 1170-71; C. Weijer, K.C. Glass, and S. Shapiro, "Why Clinical Equipoise, and not the Uncertainty Principle, is the Moral Underpinning of the RCT," British Medical Journal, 321 (2000): 756-57.
73. R. Peto et al., "Design and Analysis of Randomized Clinical Trials Requiring Prolonged Observation of Each Patient: I. Introduction and Design," British Journal of Cancer, 34 (1976): 585-612; R. Peto and C. Baigent, "Trials: The Next 50 Years," British Medical Journal, 317 (1998): 1170-71; C. Weijer, K.C. Glass, and S. Shapiro, "Why Clinical Equipoise, and not the Uncertainty Principle, is the Moral Underpinning of the RCT," British Medical Journal, 321 (2000): 756-57.
74. R. Peto et al., "Design and Analysis of Randomized Clinical Trials Requiring Prolonged Observation of Each Patient: I. Introduction and Design," British Journal of Cancer, 34 (1976): 585-612; R. Peto and C. Baigent, "Trials: The Next 50 Years," British Medical Journal, 317 (1998): 1170-71; C. Weijer, K.C. Glass, and S. Shapiro, "Why Clinical Equipoise, and not the Uncertainty Principle, is the Moral Underpinning of the RCT," British Medical Journal, 321 (2000): 756-57.
75. Freedman, supra note 66.
76. K.M. Taylor, R. Margolese, and C.L. Soskolne, "Physicians' Reasons for Not Entering Eligible Patients in a Randomized Clinical Trial of Surgery for Breast Cancer," N. Eng. J. Med., 310 (1984): 1363-67.
77. Freedman, supra note 66.
78. B. Freedman, "Placebo-Controlled Trials and the Logic of Clinical Purpose," IRB, 12, no. 6 (1990): 1-6.
79. World Medical Association Declaration of Helsinki, "Ethical Principles for Medical Research Involving Human Subjects" (October 2000) (visited Dec. 11, 2000) 〈www.wma.net/e/ policy/17-c_e.html〉.
80. J. Kane, "Schizophrenia," N. Engl. J. Med., 334 (1996): 34-41.
81. B. Freedman, K.C. Glass, and C. Weijer, "Placebo Orthodoxy in Clinical Research. I: Empirical and Methodological Myths," Journal of Law, Medicine & Ethics, 24 (1996): 243-51; B. Freedman, K.C. Glass, and C. Weijer, "Placebo Orthodoxy in Clinical Research. II: Ethical, Legal, and Regulatory Myths," Journal of Law, Medicine & Ethics, 24 (1996): 252-59; Weijer, supra note 9.
82. B. Freedman, K.C. Glass, and C. Weijer, "Placebo Orthodoxy in Clinical Research. I: Empirical and Methodological Myths," Journal of Law, Medicine & Ethics, 24 (1996): 243-51; B. Freedman, K.C. Glass, and C. Weijer, "Placebo Orthodoxy in Clinical Research. II: Ethical, Legal, and Regulatory Myths," Journal of Law, Medicine & Ethics, 24 (1996): 252-59; Weijer, supra note 9.
83. 45 C.F.R. § 46.102(d).
84. 45 C.F.R. § 46.111(a)(1).
85. 45 C.F.R. § 46.111(a)(2).
86. B. Freedman, "Scientific Value and Validity as Ethical Requirements for Research: A Proposed Explication," IRB, 9, no. 6 (1987): 7-10.
87. C. Weijer, "Protecting Communities in Research: Philosophical and Pragmatic Challenges," Cambridge Quarterly of Healthcare Ethics, 8 (1999): 501-13.
88. C. Weijer, G. Goldsand, and E.J. Emanuel, "Protecting Communities in Research: Current Guidelines and Limits of Extrapolation," Nature Genetics, 23 (1999): 275-80.
89. C. Weijer and E.J. Emanuel, "Protecting Communities in Biomedical Research," Science, 289 (2000): 1142-44.
90. Australia National Health and Medical Research Council (NHMRC), National Statement on Ethical Conduct in Research Involving Humans (Canberra: NHMRC, 1999); Medical Research Council of Canada, Natural Sciences and Engineering Research Council of Canada, Social Sciences and Humanities Research Council of Canada, Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (Ottawa: Public Works and Government Services Canada, 1998); Council for International Organizations of Medical Sciences (CIOMS), International Ethical Guidelines for Biomedical Research Involving Human Subjects (Geneva: CIOMS, 1993); Council of Europe, Convention for the Protection of Human Rights and Dignity of the Human Being with Regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (Oviedo: European Treaty Series, 1997); Royal College of Physicians of London, Guidelines on the Practice of Ethics Committees in Medical Research Involving Human Subjects (London: Royal College of Physicians of London, 1996); 45 C.F.R. § 46.
91. Australia National Health and Medical Research Council (NHMRC), National Statement on Ethical Conduct in Research Involving Humans (Canberra: NHMRC, 1999); Medical Research Council of Canada, Natural Sciences and Engineering Research Council of Canada, Social Sciences and Humanities Research Council of Canada, Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (Ottawa: Public Works and Government Services Canada, 1998); Council for International Organizations of Medical Sciences (CIOMS), International Ethical Guidelines for Biomedical Research Involving Human Subjects (Geneva: CIOMS, 1993); Council of Europe, Convention for the Protection of Human Rights and Dignity of the Human Being with Regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (Oviedo: European Treaty Series, 1997); Royal College of Physicians of London, Guidelines on the Practice of Ethics Committees in Medical Research Involving Human Subjects (London: Royal College of Physicians of London, 1996); 45 C.F.R. § 46.
92. Australia National Health and Medical Research Council (NHMRC), National Statement on Ethical Conduct in Research Involving Humans (Canberra: NHMRC, 1999); Medical Research Council of Canada, Natural Sciences and Engineering Research Council of Canada, Social Sciences and Humanities Research Council of Canada, Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (Ottawa: Public Works and Government Services Canada, 1998); Council for International Organizations of Medical Sciences (CIOMS), International Ethical Guidelines for Biomedical Research Involving Human Subjects (Geneva: CIOMS, 1993); Council of Europe, Convention for the Protection of Human Rights and Dignity of the Human Being with Regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (Oviedo: European Treaty Series, 1997); Royal College of Physicians of London, Guidelines on the Practice of Ethics Committees in Medical Research Involving Human Subjects (London: Royal College of Physicians of London, 1996); 45 C.F.R. § 46.
93. Australia National Health and Medical Research Council (NHMRC), National Statement on Ethical Conduct in Research Involving Humans (Canberra: NHMRC, 1999); Medical Research Council of Canada, Natural Sciences and Engineering Research Council of Canada, Social Sciences and Humanities Research Council of Canada, Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (Ottawa: Public Works and Government Services Canada, 1998); Council for International Organizations of Medical Sciences (CIOMS), International Ethical Guidelines for Biomedical Research Involving Human Subjects (Geneva: CIOMS, 1993); Council of Europe, Convention for the Protection of Human Rights and Dignity of the Human Being with Regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (Oviedo: European Treaty Series, 1997); Royal College of Physicians of London, Guidelines on the Practice of Ethics Committees in Medical Research Involving Human Subjects (London: Royal College of Physicians of London, 1996); 45 C.F.R. § 46.
94. Australia National Health and Medical Research Council (NHMRC), National Statement on Ethical Conduct in Research Involving Humans (Canberra: NHMRC, 1999); Medical Research Council of Canada, Natural Sciences and Engineering Research Council of Canada, Social Sciences and Humanities Research Council of Canada, Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (Ottawa: Public Works and Government Services Canada, 1998); Council for International Organizations of Medical Sciences (CIOMS), International Ethical Guidelines for Biomedical Research Involving Human Subjects (Geneva: CIOMS, 1993); Council of Europe, Convention for the Protection of Human Rights and Dignity of the Human Being with Regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (Oviedo: European Treaty Series, 1997); Royal College of Physicians of London, Guidelines on the Practice of Ethics Committees in Medical Research Involving Human Subjects (London: Royal College of Physicians of London, 1996); 45 C.F.R. § 46.
95. 45 C.F.R. § 46.102(i).
96. B. Freedman, A. Fuks, and C. Weijer, "In Loco Parentis. Minimal Risk as an Ethical Threshold for Research upon Children," Hastings Center Report, 23, no. 2 (1993): 13-19.
97. 45 C.F.R. § 46.102(i).
98. Id.
99. L. Kopelman, "Estimating Risk in Human Research," Clinical Research, 29, (1981): 1-8.
100. Freedman, Fuks, and Weijer, supra note 84, at 16.
101. Id.
102. 45 C.F.R. § 46.110(b).
103. 45 C.F.R. § 46.102(i).
104. Freedman, supra note 78, at 9.
105. 45 C.F.R. § 46.111(b).
106. C. Weijer, "Research Involving the Vulnerable Sick," Accountability in Research, 7 (1999): 21-36.
107. National Bioethics Advisory Commission, Research Involving Persons with Mental Disorders that May Affect Decisionmaking Capacity (Rockville: National Bioethics Advisory Commission, 1998).