by Sonia Shah
64. Ibid.
65. Francesca Lunzer Kritz, “Ask Your Doctor About . . . ,” Washington Post, June 6, 2000, Z09.
66. J. Van Steekelenburg et al., “Comparison of Five New Anti-histamines (H1-Receptor Antagonists) in Patients with Allergic Rhinitis Using Nasal Provocation Studies and Skin Tests,” Allergy 57 (2002): 346–50.
67. Schwartz, “FDA Relaxes Rules for On-Air Drug Ads.”
68. Freudenheim, “Influencing Doctor’s Orders.”
69. Gina Kolata, “U.S. Approves Sales of Impotence Pill; Huge Market Seen,” New York Times, March 28, 1998.
70. Henry A. Feldman et al., “Erectile Dysfunction and Coronary Risk Factors: Prospective Results from the Massachusetts Male Aging Study,” Preventive Medicine 30 (2000): 328–38.
71. Carol A. Derby et al., “Modifiable Risk Factors and Erectile Dysfunction: Can Lifestyle Changes Modify Risk?” Urology, August 2000, 302–6.
72. David Tuller, “Gentlemen, Start Your Engines?” New York Times, June 21, 2004, F1.
73. Peter Carlson, “Potent Medicine: A Year Ago, Viagra Hit the Shelves and the Earth Moved. Well, Sort Of,” Washington Post, March 26, 1999, C1.
74. Greider, The Big Fix, 118.
75. Tuller, “Gentlemen, Start Your Engines?”
76. Ibid.
77. “Viagra Swells Diagnosis Rates for Erectile Dysfunction,” BMJ, February 2003, 326.
78. Carlson, “Potent Medicine.”
79. Claude Lenfant, “Clinical Research to Clinical Practice—Lost in Translation?” New England Journal of Medicine, August 28, 2003, 868–74.
80. Carlson, “Potent Medicine.”
81. Judith Aldridge and Fiona Measham, “Sildenafil (Viagra) Is Used as a Recreational Drug in England,” BMJ, March 1999, 669.
82. Carlson, “Potent Medicine.”
83. Knight-Ridder, “Double Your Pleasure, Double Your Fun . . . ,” Toronto Star, June 14, 2003, C11.
84. Jay S. Cohen, Overdose: The Case Against the Drug Companies (New York: Jeremy P. Tarcher/Putnam, 2001), 51.
85. “The Lifestyle Drugs Outlook to 2005,” Executive Summary, Reuters Business Insight, February 1999, reprinted at www.inpharm.com/intelligence/rbi080299.html; “The Lifestyle Drugs Outlook to 2008: Unlocking New Value in Well-Being,” Summary, Reuters Business Insight, October 2003, at www.the-infoshop.com/study/rb16175_lifestyle_drugs.html.
86. Paul Abrahams, “Taking Health to Heart—How Much Cholesterol Is Too Much?” Financial Times, October 23, 1992, 18.
87. Marcia Angell, The Truth about the Drug Companies: How They Deceive Us and What to Do about It (New York: Random House, 2004), 54.
88. Hawthorne, The Merck Druggernaut, 69.
89. Jun Ma et al., “A Statistical Analysis of the Magnitude and Composition of Drug Promotion in the United States in 1998,” Clinical Therapeutics, May 2003, 1503–17.
90. Angell, The Truth about the Drug Companies, 133.
91. National Institute for Health Care Management Foundation, Prescription Drug Expenditures in 2001: Another Year of Escalating Costs, Washington, DC, May 6, 2002, 13; editorial, “The Statin Wars: Why AstraZeneca Must Retreat,” The Lancet, October 25, 2003.
92. Jeffrey J. Ellis et al., “Suboptimal Statin Adherence and Discontinuation in Primary and Secondary Prevention Populations,” Journal of General Internal Medicine, June 2004, 638.
93. Napoli, “Cholesterol Skeptics and the Bad News about Statin Drugs.”
94. Jonathan D. Quick et al., “Ensuring Ethical Drug Promotion—Whose Responsibility?” The Lancet, August 30, 2003.
95. Editorial, “The Statin Wars.”
96. Stephen S. Hall, “The Claritin Effect: Prescription for Profit,” New York Times Magazine, March 11, 2001, 40.
97. Cohen, Overdose, 92.
98. At least thirty-one cases of fatal rhabdomyolysis attributed to Baycol were reported to the FDA. According to the FDA, reports of adverse drug reactions constitute about 5 percent of the actual number of reactions. Ibid., 5.
99. Public Citizen press release, “Cases of Kidney Failure, Muscle Damage Should Prompt FDA to Ban Crestor,” Worst Pills, Best Pills, Washington, DC, March 4, 2004. The FDA rejected Public Citizen’s request that it ban the drug.
100. Cohen, Overdose, 148.
101. Craig G. Burkhart et al., “The Physicians’ Desk Reference Should Not Be Held as a Legal Standard of Medical Care,” Archives of Pediatric and Adolescent Medicine, June 1998, 609–10.
102. Cohen, Overdose, 149–50.
103. Joseph S. Ross et al., Medical Education Services Suppliers: A Threat to Physician Education, Public Citizen Health Research Group, Washington, DC, July 19, 2000.
104. “Myocardial Infarction: State-Required CME: No Effect on Heart Attack Care, Boosts Use of Branded Drugs,” Heart Disease Weekly, April 4, 2004, 89.
105. David A. Kessler et al., “Therapeutic-Class Wars—Drug Promotion in a Competitive Marketplace,” New England Journal of Medicine, November 17, 1994, 1350–53.
106. National Institute for Health Care Management Foundation, Prescription Drug Expenditures in 2001, 3.
107. NIH Director’s Panel on Clinical Research, Report to the Advisory Committee to the NIH Director, Executive Summary, December 1997, available at www.nih.gov/news/crp/97report/execsum.htm.
108. “Funding for Health Research and Development, According to Source of Funds: United States, Selected Fiscal Years 1970–99,” in Health, United States, 2001, 346.
109. Scott Hensley, “Remedial Lessons: When Doctors Go to Class, Industry Often Foots the Bill,” Wall Street Journal, December 4, 2002, A1.
110. Marcia Angell, “Is Academic Medicine for Sale?” New England Journal of Medicine, May 18, 2000, 1516–18.
111. Peter Jaret, “She Turns Her Pen on Drug Makers,” Los Angeles Times, August 9, 2004.
112. Jerry Avorn, Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugs (New York: Alfred A. Knopf, 2004), 53.
113. Plus, patient response to drugs can be colored by all sorts of underlying factors besides the drug’s pharmacologic mechanism, especially in short trials of poorly understood conditions. In one study of anxiety green pills worked better than pills of other colors, even though they had the same medicine in them; in a study of depression, yellow pills worked better than pills of other colors. Researchers can relieve pain in patients simply by telling them they are receiving an effective painkiller, even while giving them placebos instead. For some conditions no fewer than 30 percent of patients in clinical trials improve on placebos alone. Not only that: injected placebos work better than pills, and two placebos work better than one. In all of these studies placebos work only if the patients know they are getting some treatment; if the placebos are surreptitiously dropped into drinks or IV lines, they have no effect. In other words, “it is not the placebo itself . . . it is the knowledge of the placebo that does the trick.” Daniel Moerman, Meaning, Medicine, and the “Placebo Effect” (Cambridge: Cambridge University Press, 2002), 49, 105–6. See also Thomas Bodenheimer, “Uneasy Alliance—Clinical Investigators and the Pharmaceutical Industry,” New England Journal of Medicine, May 18, 2000, 1539–44.
114. Bodenheimer, “Uneasy Alliance.”
115. See depts.washington.edu/gim/faculty/psaty.htm
116. Gina Kolata, “Blood Pressure Drug Linked to Heart Risks,” Houston Chronicle, March 12, 1995, 4.
117. Warren King, “Risk Cited for Blood Pressure Drug—Chances Higher for Heart Attack,” Seattle Times, March 10, 1995.
118. “Controlling Your High Blood Pressure; Reports Cause Furor by Linking Some Drugs to Heart Attack Risk,” Washington Post, March 28, 1995, Z10.
119. Harry Schwartz, “The Great Calcium Channel Blocker Scare,” Pharmaceutical Executive, June 1994, 24.
120. R.A. Deyo et al., “The Messenger under Attack—Intimidation of Researchers by Special-Interest Groups,” New England Journal of Medicine, April 17, 1997, 1176–80.
121. National Institute
for Health Care Management Foundation, Prescription Drug Expenditures in 2001, 2; Greider, The Big Fix, 3.
122. Greider, The Big Fix.
123. Interview with Mark McClellan, October 9, 2003.
124. James S. Gordon, “The Risk of Taking the Right Drugs,” Washington Post, August 17, 2003, citing Archives of Internal Medicine studies.
125. Hilts, Protecting America’s Health, 307.
126. Cohen, Overdose, 4.
127. Greider, The Big Fix, 131.
128. National Institutes of Health, Guidelines for the Conduct of Research Involving Human Subjects at the National Institutes of Health, August 2004.
4: Uncaging the Guinea Pig
1. Roy Porter, The Greatest Benefit to Mankind: A Medical History of Humanity (New York: W.W. Norton, 1997), 38, 57–59, 138, 153.
2. Anita Guerrini, Experimenting with Humans and Animals: From Galen to Animal Rights (Baltimore: Johns Hopkins University Press, 2003); Porter, The Greatest Benefit to Mankind, 23, 67, 76, 132, 182.
3. Guerrini, Experimenting with Humans and Animals, 86.
4. Susan M. Reverby, ed., Tuskegee’s Truths: Rethinking the Tuskegee Syphilis Study (Chapel Hill: University of North Carolina Press, 2000), 19; Porter, The Greatest Benefit to Mankind, 166–67, 175, 190.
5. Reverby, ed., Tuskegee’s Truths, 67.
6. Laurie Garrett, Betrayal of Trust: The Collapse of Global Public Health (New York: Hyperion, 2000), 321; Reverby, ed., Tuskegee’s Truths, 367.
7. Margaret Humphreys, “Whose Body? Which Disease?” in Jordan Goodman, Anthony McElligot, and Lara Marks, eds., Useful Bodies: Humans in the Service of Medical Science in the Twentieth Century (Baltimore: Johns Hopkins University Press, 2003), 55, 64–69; Reverby, ed., Tuskegee’s Truths, 300.
8. Reverby, ed., Tuskegee’s Truths, 18, 80, 368.
9. Ibid., 269–72.
10. Ibid., 22–25.
11. Ibid., 28, 126.
12. Ibid., 15, 25; Guerrini, Experimenting with Humans and Animals, 109.
13. But penicillin, it seemed, was too good to pass up. Almost a third of the Tuskegee subjects managed, somehow, to get a few doses of the drug; around 7 percent received therapeutically adequate doses. The results from the trial were thus compromised. Reverby, ed., Tuskegee’s Truths, 26.
14. Jonathan D. Moreno, Undue Risk: Secret State Experiments on Humans (New York: W.H. Freeman, 2000), 29–31, 33–34, 66.
15. Ibid., 36–37.
16. Ibid., 215–18.
17. David S. Jones and Robert L. Martensen, “Human Radiation Experiments and the Formation of Medical Physics at the University of California, San Francisco and Berkeley, 1937–1962,” in Goodman, McElligot, and Marks, eds., Useful Bodies, 97.
18. Moreno, Undue Risk, 122–229.
19. Ibid., 50.
20. Daniel Callahan, What Price Better Health? Hazards of the Research Imperative (Los Angeles: University of California Press, 2003), 138.
21. Moreno, Undue Risk, 98.
22. Ibid., 72.
23. Ibid., 57.
24. Jones and Martensen, “Human Radiation Experiments,” 86.
25. Guerrini, Experimenting with Humans and Animals, 138.
26. Moreno, Undue Risk, 68.
27. Reverby, ed., Tuskegee’s Truths, 25.
28. Moreno, Undue Risk, 77.
29. Moreno, Undue Risk, 55; Porter, The Greatest Benefit to Mankind, 649.
30. Moreno, Undue Risk, 75.
31. Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law 2, no. 10 (1949): 181–82, available at ohsr.od.nih.gov/guidelines/nuremberg.html.
32. Moreno, Undue Risk, 80.
33. How much did good science depend upon good ethics, anyway? After the war U.S. officials actively recruited thousands of the best and brightest German scientists and engineers to work in American government agencies—including those who had been involved in Nazi medical experiments. Moreno, Undue Risk, 92–93, 101, 130; Advisory Committee on Human Radiation Experiments, “History of Prison Research Regulation,” Final Report, at tis.eh.doe.gov/ohre/roadmap/achre/chap9_4.html.
34. Guerrini, Experimenting with Humans and Animals, 123–28.
35. Moreno, Undue Risk, 132–33, 154.
36. Joel D. Howell and Rodney A. Hayward, “Writing Willow-brook, Reading Willowbrook,” in Goodman, McElligot, and Marks, eds., Useful Bodies, 193.
37. Reporter Geraldo Rivera exposed the appalling conditions at Willowbrook in a 1972 television program, ultimately leading to a class-action lawsuit. Shaila K. Dewan, “Recalling a Victory for the Disabled,” New York Times, May 3, 2000, 5; Margaret Engel, “Care for the Mentally Retarded: A Case History,” Washington Post, December 30, 1984.
38. Merck later capitalized on Krugman’s work by developing a hepatitis B vaccine, which they tested on their own executives. In a wry comment on Krugman’s trials a Merck scientist joked in 1975 that the company had “picked the most worthless people we could find in the world who would be the least likely to sue.” If Merck hadn’t, Krugman certainly had. Jon Cohen, Shots in the Dark: The Wayward Search for an AIDS Vaccine (New York: W.W. Norton, 2001), 79; David J. Rothman, Strangers at the Bedside: A History of How Law and Bioethics Transformed Medical Decision Making (New York: Basic Books, 1991), 77.
39. Guerrini, Experimenting with Humans and Animals, 139, citing Henry Beecher, “Ethics and Clinical Research,” New England Journal of Medicine 264 (1966): 1354–60; Howell and Hayward, “Writing Willowbrook, Reading Willowbrook,” 192.
40. Reverby, ed., Tuskegee’s Truths, 103.
41. Elizabeth W. Etheridge, “Historical Perspectives: History of CDC,” Morbidity and Mortality Weekly Report, June 28, 1996, 526–30, at www.cdc.gov/epo/mmwr/preview/mmwrhtml/00042732.htm.
42. Reverby, ed., Tuskegee’s Truths, 15, 26, 411.
43. Ibid., 152–54.
44. U.S. Bureau of Census, “National Health Expenditures—Summary, 1960 to 1999, and Projections, 2000 to 2010,” Statistical Abstract of the U.S.: 2001, Washington, DC, January 2002, 91.
45. Paul Starr, The Social Transformation of American Medicine: The Rise of a Sovereign Profession and the Making of a Vast Industry (New York: Basic Books, 1982), 381–82, 409, citing “It’s Time to Operate,” Fortune, January 1970, 79, and Ivan Illich, Medical Nemesis: The Expropriation of Health (New York: Pantheon, 1976).
46. Some sections of the medical community, however, were not nearly so provoked. An editorial in the October 1972 issue of the Southern Medical Journal condemned the “irresponsible press”: “In complete disregard of their abysmal ignorance, members of the fourth estate bang out anything on their typewriters which will make headlines,” the editorial fumed. “If the men having latent syphilis . . . had been forced to take adequate treatment (60 or more weekly doses of a metal [mercury]), cardiovascular syphilis might have been avoided in most. In our free society, antisyphilitic treatment has never been forced. Since these men did not elect to obtain treatment available to them, the development of aortic disease lay at the subject’s door and not in the Study’s protocol.” Reverby, ed., Tuskegee’s Truths, 2, 177, 199; Vernal G. Cave, “Proper Uses and Abuses of the Health Care Delivery System for Minorities, with Special Reference to the Tuskegee Syphilis Study,” Journal of the National Medical Association 67 (1975), reprinted in Reverby, ed., Tuskegee’s Truths, 399.
47. Reverby, ed., Tuskegee’s Truths, 229; Garrett, Betrayal of Trust, 322
48. Guerrini, Experimenting with Humans and Animals, 141–47.
49. World Medical Association, “Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects,” available at www.wma.net.
50. U.S. Food and Drug Administration, Guidance for Industry: Acceptance of Foreign Clinical Studies, March 2001; also Code of Federal Regulations Title 21, vol. 5, April 2005, 21CFR312.120; National Institutes of Health, Guidelines for the Conduct of Research Involving Human Subjects, August 2001.
5: HIV and the Second-r
ate Solution
1. World Medical Association, “Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects,” available at www.wma.net.
2. Laurie Garrett, The Coming Plague: Newly Emerging Diseases in a World Out of Balance (New York: Penguin Books, 1994), 302.
3. Philip J. Hilts, Protecting America’s Health: The FDA, Business, and One Hundred Years of Regulation (New York: Alfred A. Knopf, 2003), 242.
4. “As a profession, we doctors are not only determined, but also somewhat obsessed with primacy,” one commentator later noted, drily. “To the victors belongs more than mere mention in a medical textbook; discovering something first may be a medical investigator’s best shot at immortality.” Howard Markel, “‘Who’s on First?’—Medical Discoveries and Scientific Priority,” New England Journal of Medicine, December 30, 2004, 2792–93. See also Jon Cohen, Shots in the Dark: The Wayward Search for an AIDS Vaccine (New York: W.W. Norton, 2001), 18.
5. Cohen, Shots in the Dark, 41.
6. Mark Simpson, “Angry with a Capital A,” The Guardian, June 19, 1995, T42.
7. Barnaby J. Feder, “Drug Expected to Spur Growth and Profit of Its Maker,” Washington Post, September 6, 1988; editorial, “AZT’s Inhuman Cost,” New York Times, August 28, 1989, 16.
8. Interview with Jay Brooks Jackson, October 10, 2003.
9. Susan Okie, “Testing of New AIDS Drugs Beset by Conflicting Demands,” Washington Post, September 6, 1988.
10. Richard Lynn and G. Harold Mehlman, “Why ACT UP Did What It Did,” Washington Post, June 2, 1990, A17.
11. Okie, “Testing of New AIDS Drugs Beset by Conflicting Demands.”
12. Jay Brooks Jackson et al., “HIVNET 012: A Phase III Placebo-Controlled Trial to Determine the Efficacy of Oral AZT and the Efficacy of Oral Nevirapine for the Prevention of Vertical Transmission of HIV-1 Infection in Pregnant Ugandan Women and Their Neonates,” National Institute of Allergy and Infectious Disease IND#49,991 study protocol, June 5, 1997.
13. Peter Lurie and Sidney Wolfe, “Unethical Trials of Interventions to Reduce Perinatal Transmission of the Human Immunodeficiency Virus in Developing Countries,” New England Journal of Medicine, September 18, 1997.
