Manufacturing uncertainty: Adverse effects of drug development for women

International Journal of Law and Psychiatry

Volumn 26, Issue 5, 2003, Pages 515-532

  Peppin, Patricia ^a  

^a QUEEN S UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

FENFLURAMINE; NEUROLEPTIC AGENT; PHENTERMINE;

BREAST ENDOPROSTHESIS; CANADA; CLINICAL TRIAL; DECISION MAKING; DRUG MANUFACTURE; DRUG MARKETING; FOOD AND DRUG ADMINISTRATION; GOVERNMENT; HEALTH CARE POLICY; HUMAN; HUMAN RIGHTS; INFORMATION PROCESSING; LAW; LEGAL ASPECT; PHASE 2 CLINICAL TRIAL; PHASE 3 CLINICAL TRIAL; POSTMARKETING SURVEILLANCE; REPRODUCTIVE HEALTH; REVIEW; SIDE EFFECT; UNITED STATES; VALVULAR HEART DISEASE;

EID: 0242384035     PISSN: 01602527     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0160-2527(03)00084-0     Document Type: Article

References (79)

1. United States, FDA, Michelle Meadows, "Why Drugs Get Pulled Off the Market" FDA Consumer Magazine, Jan.-Feb. 2002, p. 2 online - http://www.fda.gov/fdac/features/2002/102_drug.html (accessed Jan. 2, 2002); FDA, "Safety-Based Drug Withdrawals (1997-2001)" FDA Consumer Magazine, Jan.-Feb. 2002, online - http://www.fda.gov/fdac/features/2002/ chrtWithdrawals.html (accessed Jan. 1, 2003).
2. United States, FDA, Michelle Meadows, "Why Drugs Get Pulled Off the Market" FDA Consumer Magazine, Jan.-Feb. 2002, p. 2 online - http://www.fda.gov/fdac/features/2002/102_drug.html (accessed Jan. 2, 2002); FDA, "Safety-Based Drug Withdrawals (1997-2001)" FDA Consumer Magazine, Jan.-Feb. 2002, online - http://www.fda.gov/fdac/features/2002/ chrtWithdrawals.html (accessed Jan. 1, 2003).
3. Institute of Medicine, "Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Trials." vol. 1 (1994).
4. Whynne Caves, Women and Heart Disease: Same Disease, Different Trials (1998) 9(2) Canadian Journal of Cardiovascular Nursing 29.
5. United States, General Accounting Office, "Women's Health: Women Sufficiently Represented in New Drug Testing, but FDA Oversight Needs Improvement" GAO-01-754 (July 2001), p. 6; Canada, Therapeutic Products Directorate Drugs. http://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/index_drugs_e.htm.
6. The Pharmaceutical Advertising Advisory Board (PAAB): www.paab.ca/index_en.html. See Patricia Peppin and Elaine Carty, "Semiotics, Stereotypes, and Women's Health: Signifying Inequality in Drug Advertising" (2001) 13 Canadian Journal of Women and the Law 326-360 at 331.
7. Ann Silversides, "Direct-to-consumer prescription drug ads getting bolder" Canadian Medical Association Journal 165(4). Aug. 21, 2001, 462.
8. Angela Campbell and Kathleen Cranley Glass, "The Legal Status of Clinical and Ethics Policies, Codes, and Guidelines in Medical Practice and Research" (2001) 46 McGill Law Journal 473.
9. The WHI Steering Committee and Writing Group, "Risks of Postmenopausal Hormone Replacement" (letter). Journal of the American Medical Association 288(22); 2823-2824 (Dec. 11, 2002).
10. Vanessa Merton, "The Exclusion of Pregnant, Pregnable, and Once-Pregnable People (a.k.a. Women) from Biomedical Research" (1993) 19 American Journal of Law and Medicine 369.
11. Institute of Medicine, supra.
12. Theresa M. Wizemann and Mary-Lou Pardue (eds.), Committee on Understanding the Biology of Sex and Gender Differences, Board on Health Sciences Policy, Institute of Medicine, Exploring the Biological Contributions to Human Health: Does Sex Matter? National Academy Press: 2001.
13. United States, General Accounting Office, "Women's Health: Women Sufficiently Represented in New Drug Testing, but FDA Oversight Needs Improvement: GAO-01-754 (July, 2001).
14. These changes are analyzed in more detail in Patricia Peppin and Elaine Carty, "Innovation, Myths and Equality: Constructing Drug Knowledge in Research and Advertising" (2001) 23 Sydney Law Review 543-576.
15. United States, General Accounting Office, "National Institutes of Health: Problems in Implementing Policy on Women in Study Populations" GAO/T-HRD-90-38 (18 June 1990).
16. United States, Food and Drug Administration, Final Rule on Investigational New Drug Applications and New Drug Applications, Federal Register, Feb. 11, 1998; effective August 10, 1998.
17. United States, General Accounting Office, "Women's Health: NIH has Increased its Efforts to Include Women in Research" GAO/HEHS-00-96 (2 May 2000).
18. United States, National Institutes of Health, "Monitoring Adherence to the NIH Policy on the Inclusion of Women and Minorities as Subjects in Clinical Research: Comprehensive Report (1 September 2000).
19. GAO 2001, "Women's Health", pp. 2-3. See also the resources cited in the Center for Drug Evaluation and Research (CDER) Women's Health site at http://www.fda.gov/cder/audiences/women/default.htm (accessed Jan. 2, 2003).
20. Ibid. GAO 2001.
21. Ibid., p. 19.
22. Ibid., p. 22.
23. United States, FDA, "FDA Issues Guidance for Collection of Race and Ethnicity Data in Clinical Trials for FDA Regulated Products" T03-07 (January 23, 2003) http://www.fda.gov/cder/guidance/5054dft.doc.
24. Ruth Merkatz, "Inclusion of Women in Clinical Trials: An Historical Overview of Scientific, Ethical, and Legal Issues" (1998) 27(1) Journal of Obstetric, Gynecologic, and Neonatal Nursing 78-84.
25. United States, FDA, "Guidance for Industry: Establishing Pregnancy Exposure Registries" (August 2002) http://www.fda.gov/cder/guidance/index. htm (accessed Jan. 2, 2003), p. 2.
26. Health Canada, Therapeutic Products Directorate Guidelines, "Inclusion of Women in Clinical Trials" (April 17, 1997).
27. Ibid., see also FDA, Office of Women's Health, "Establishing Pregnancy Registries" (Sept. 20, 2002).
28. Lawrence O. Gostin, Public Health Law: Power, Duty, Restraint. Berkeley: University of California Press, 2000, pp. 113-142.
29. Vivian Pinn, NIH Associate Director for Research on Women's Health, Interview, "Women's Health at NIH: Catalyst for Change" (Fall 1997) (http://www.nih.gov/news/nf/womenshealth/1.html).
30. Pharmaceutical Research and Manufacturers of America, 2001 Survey, New Medicines in Development for Women "Women's Health Revolution Continues with 358 Medicines in the Pipeline for Diseases that Primarily Affect Women" http://www.phrma.org/newmedicines/resources/2002-06-01.90.pdf (accessed Jan. 1, 2003).
31. United States, FDA, MedWatch, The FDA Safety Information and Adverse Event Reporting Program" online - http://www.fda.gov/medwatch/how.htm (accessed Jan. 1, 2003); John Henkel, "MedWatch: FDA's 'Heads Up' on Medical Product Safety" FDA Consumer Magazine (Nov.-Dec. 1998); online - http:// www.fda.gov/fdac/features/1998/698_med.html (accessed Jan. 1, 2003).
32. United States, FDA, MedWatch, The FDA Safety Information and Adverse Event Reporting Program" online - http://www.fda.gov/medwatch/how.htm (accessed Jan. 1, 2003); John Henkel, "MedWatch: FDA's 'Heads Up' on Medical Product Safety" FDA Consumer Magazine (Nov.-Dec. 1998); online - http:// www.fda.gov/fdac/features/1998/698_med.html (accessed Jan. 1, 2003).
33. United States, GAO (2002) "Prescription Drugs: FDA Oversight of Direct-to-Consumer Advertising has Limitations" GAO-03-177 (October 2002), p. 10.
34. D.A. Kessler, "Introducing MedWatch" Journal of the American Medical Association 269 (1993): 2765-68.
35. Jasón Lazarou et al., "Incidence of Adverse Drug Reactions in Hospitalized Patients" (1998) JAMA 279(15) (April 15, 1998) 1200-1205.
36. Peter Montague, "Prescription Drugs that Kill: Another Kind of Drug Problem" Rachel's Environment and Health Weekly #632 (January 7, 1999), http://consumerlawpage.com/article/drugs_that_kill.shtml (accessed Jan. 2, 2003).
37. United States General Accounting Office, "Adverse Drug Events: The Magnitude of Health Risk is Uncertain Because of Limited Incidence Data" GAO/HEHS-00-21 (January 2000).
38. Ibid., p. 9.
39. Ibid., at 11.
40. GAO, "Adverse Events: Surveillance Systems for Adverse Events and Medical Errors" (Feb. 9, 2000) T-HEHS-00-61; GAO, "Adverse Drug Events: Substantial Problem but Magnitude Uncertain" (Feb. 1, 2000) HEHS-00-53.
41. GAO, "Adverse Events: Surveillance Systems for Adverse Events and Medical Errors" (Feb. 9, 2000) T-HEHS-00-61; GAO, "Adverse Drug Events: Substantial Problem but Magnitude Uncertain" (Feb. 1, 2000) HEHS-00-53.
42. Cost restraints and staffing issues have imposed pressures on this capacity. HDP Group, "Functional Review of Post-Approval Drug Assessment Operational Activities for Therapeutic Products Programme Bureau of Drug Surveillance"(1999) concluded that the unit was "significantly under-resourced to meet its current mandated post-approval assessment responsibilities." A year ago in a "Health Canada Progress Update," Dr. Robert Peterson, Director-General of the Therapeutic Products Programme, noted the new budgetary allocation and new staffing for postapproval surveillance, and stated that in the future a new directorate was planned, along with increasing international links and a new database for ADRs (p. 10) (accessed Jan. 2, 2003). Creation of a successful database has been a significant continuing problem (see HDP Group, above).
43. DES Action Canada, in collaboration with the Working Group on Women and Health Protection, Barbara Mintzes and Rosanna Baraldi, "How Safe Are Our Medicines? Monitoring the Risks of Drugs After They are Approved for Marketing" (DES Action Canada, 2000).
44. I b i d.
45. Thomas J. Moore et al., "Time to Act on Drug Safety" Journal of the American Medical Association 279(19) (May 20, 1998) 1571-1573.
46. Lucinda Finley, "Female Trouble: The Implications of Tort Reform for Women" (1997) 64 Tennessee Law Review 847 at 869. United States, General Accounting Office, "FDA Drug Review: Postapproval Risks 1976-1985" (1990) GAO PEMD-90-15. In his analysis of Prozac and other SSRIs, Glenmullen described what he saw as a 10-20-30 year pattern of adverse effects. At 10 years, problems emerge, but since we lack reporting mechanisms, it is 20 years before enough data are available for the problem to be undeniable and for enough doctors to sound the alarm, and 30 years before professional organizations and regulators take action. Dr. Glenmullen gave the example of thorazine, one of the major antipsychotic drugs, which had been prescribed to 50 million U.S. patients by the 10-year mark and grew to 250 million worldwide. Extensive litigation followed and, at the 30-year mark in 1985, the FDA added warnings. Joseph Glenmullen, Prozac Backlash New York: Simon and Schuster, 2000 (p. 52).
47. Lucinda Finley, "Female Trouble: The Implications of Tort Reform for Women" (1997) 64 Tennessee Law Review 847 at 869. United States, General Accounting Office, "FDA Drug Review: Postapproval Risks 1976-1985" (1990) GAO PEMD-90-15. In his analysis of Prozac and other SSRIs, Glenmullen described what he saw as a 10-20-30 year pattern of adverse effects. At 10 years, problems emerge, but since we lack reporting mechanisms, it is 20 years before enough data are available for the problem to be undeniable and for enough doctors to sound the alarm, and 30 years before professional organizations and regulators take action. Dr. Glenmullen gave the example of thorazine, one of the major antipsychotic drugs, which had been prescribed to 50 million U.S. patients by the 10-year mark and grew to 250 million worldwide. Extensive litigation followed and, at the 30-year mark in 1985, the FDA added warnings. Joseph Glenmullen, Prozac Backlash New York: Simon and Schuster, 2000 (p. 52).
48. Lucinda Finley, "Female Trouble: The Implications of Tort Reform for Women" (1997) 64 Tennessee Law Review 847 at 869. United States, General Accounting Office, "FDA Drug Review: Postapproval Risks 1976-1985" (1990) GAO PEMD-90-15. In his analysis of Prozac and other SSRIs, Glenmullen described what he saw as a 10-20-30 year pattern of adverse effects. At 10 years, problems emerge, but since we lack reporting mechanisms, it is 20 years before enough data are available for the problem to be undeniable and for enough doctors to sound the alarm, and 30 years before professional organizations and regulators take action. Dr. Glenmullen gave the example of thorazine, one of the major antipsychotic drugs, which had been prescribed to 50 million U.S. patients by the 10-year mark and grew to 250 million worldwide. Extensive litigation followed and, at the 30-year mark in 1985, the FDA added warnings. Joseph Glenmullen, Prozac Backlash New York: Simon and Schuster, 2000 (p. 52).
49. United States, General Accounting Office, "Drug Safety? Most Drugs Withdrawn in Recent Years had Greater Health Risks for Women" (January 19, 2001) GAO-01-286R. A Pulitzer Prize winning series by the Los Angeles Times indicated how the political demands for speeded-up approval processes ultimately led to the withdrawal of seven drugs after reports of serious adverse effects, including 1002 reports of deaths possibly linked to the drugs. David Willman, "How A New Policy Led to Seven Deadly Drugs" Los Angeles Times, December 20, 2000.
50. United States, General Accounting Office, "Drug Safety? Most Drugs Withdrawn in Recent Years had Greater Health Risks for Women" (January 19, 2001) GAO-01-286R. A Pulitzer Prize winning series by the Los Angeles Times indicated how the political demands for speeded-up approval processes ultimately led to the withdrawal of seven drugs after reports of serious adverse effects, including 1002 reports of deaths possibly linked to the drugs. David Willman, "How A New Policy Led to Seven Deadly Drugs" Los Angeles Times, December 20, 2000.
51. The class action litigators website: www.burke-eisner.com/fen/medwatchqa. htm.
52. United States, General Accounting Office, "Drug Safety" supra, at p. 5.
53. Food and Drug Regulations, C.R.C., C. 870, as amended, s. C.01.044.
54. Erin N. Marcus, "When TV Commercials Play the Doctor" New York Times (Jan. 3, 2003).
55. Robert Goldman, Reading Ads Socially London: Routledge,1992.
56. Melody Petersen, "Heartfelt Advice, Hefty Fees" New York Times (August 11, 2002); Melody Petersen, "CNN to Reveal When Guests Promote Drugs for Companies" New York Times (August 23, 2002).
57. Melody Petersen, "Heartfelt Advice, Hefty Fees" New York Times (August 11, 2002); Melody Petersen, "CNN to Reveal When Guests Promote Drugs for Companies" New York Times (August 23, 2002).
58. Peppin and Carty, "Semiotics" supra.
59. Gerry V. Stimson, "The Message of Psychotropic Drug Ads" (1975) 25 Journal of Communication 153.
60. Kate A. Stewart and J. Newmann, "FDA Actions against Misleading or Unsubstantiated Economic and Quality-of-Life Promotional Claims: An Analysis of Warning Letters and Notices of Violation" (2002) Value in Health 5(5): 389-396.
61. See, for example, United States, GAO, "Prescription Drugs: FDA Oversight of Direct-to-Consumer Advertising Has Limitations" GAO-03-177 (October 28, 2002); Robert Pear, "Investigators Find Repeated Deception in Ads for Drugs" New York Times, Dec. 3, 2002.
62. See, for example, United States, GAO, "Prescription Drugs: FDA Oversight of Direct-to-Consumer Advertising Has Limitations" GAO-03-177 (October 28, 2002); Robert Pear, "Investigators Find Repeated Deception in Ads for Drugs" New York Times, Dec. 3, 2002.
63. Hollis v. Dow Corning Corp., [1995] 4 S.C.R. 634; Buchan v. Ortho Pharmaceutical (Canada) Ltd., (1986), 54 O.R. (2d) 92 (C.A.).
64. Institute of Medicine, Safety of Silicone Breast Implants. Washington, D.C.: National Academy Press, 2000, p. 2.
65. The companies making and promoting this product had more information than they made available to physicians and through them to women making this decision. And the amount of information made available was considerably less than necessary to make an informed decision.
66. Hollis, supra.
67. When the FDA General and Plastic Surgery Devices Panel reviewed the data, it concluded that insufficient data were available about the risks and benefits of the product and recommended removal from the market, with limited access and more gathering of data. "However, much of the information was not available. This did not necessarily mean that the implants were unsafe, but it did mean that FDA could not - as the law requires - vouch for their safety. With insufficient data on safety and effectiveness, FDA determined that breast implants could not be approved, and therefore gel-filled implants were removed from the market. . ."U.S. FDA, "Breast Implant An Information Update (March 1996), at p. 1.
68. Bendall v. McGhan Medical (1993), 14 O.R. 3d 734 (Gen. Div.) at 735.
69. As a result, the million American women and 150,000 Canadian women who had the implants by 1992 were left to worry and wonder about the long-term effects of "their" decision to have the implants.
70. Advisory Panel to the FDA (1992).
71. Michael Hugo, "Vaccine Manufacturers and Breast Implant Manufacturers: Same Game, Same Strategies, A Mere Coincidence?" (1996), American Trial Lawyers Syllabus, reprinted at http://www.consumerlawpage.com/ article/vaccine.shtml (accessed Jan. 1, 2003).
72. A jury found in favour of Maria Stern, who claimed that her autoimmune disease was caused by Dow Corning implants, and awarded US$211,000 in compensatory damages and US$1.5 million in punitive damages. (Frontline/WGBH Educational Foundation Breast Implant Chronology). The evidence was sealed by court order after the jury verdict - evidence that the manufacturers should have reported to the regulator (Congressional hearing chaired by the late Ted Weiss).
73. See David B. Sarwer, Jodi E. Nordmann, and James D. Herbert, "Cosmetic Breast Augmentation Surgery: A Critical Overview" (2000) 9(8) J. Women's Health and Gender-Based Medicine 843-856.
74. Michael Hugo, supra.
75. Marcia Angell, Science on Trial: The Clash of Medical Evidence and the Law in the Breast Implant Case London: W.W. Norton, 1997, at 60.
76. Sidney M. Wolfe, "Statement to Institute of Medicine Committee on the Safety of Silicone Breast Implants", HRG Publications #1448, July 24, 1998. http://www.citizen.org/publications/.
77. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators, D. George Wyse et al., "A Comparison of Rate Control and Rhythm Control in Patients with Atrial Fibrillation" 347(23) New England Journal of Medicine, December 5, 2002, pp. 1825-1833. See also the study of early antiarrhythmia drugs by Thomas J. Moore, Deadly Medicine. New York: Simon and Schuster, 1995.
78. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators, D. George Wyse et al., "A Comparison of Rate Control and Rhythm Control in Patients with Atrial Fibrillation" 347(23) New England Journal of Medicine, December 5, 2002, pp. 1825-1833. See also the study of early antiarrhythmia drugs by Thomas J. Moore, Deadly Medicine. New York: Simon and Schuster, 1995.
79. Isabelle C. Van Gelder et al., "A Comparison of Rate Control and Rhythm Control in Patients with Recurrent Persistent Atrial Fibrillation" 347(23) New England Journal of Medicine, December 5, 2002, pp. 1834-1840.