The Body Hunters (35 page)

23
. Chandra Gulhati, “Illegal, Unethical Promotion Hits New Highs,”
Monthly Index of Medical Specialties India
, posted to e-drug list, April 1, 2004.

24
. S.M. Moazzem Hossain, “Community Development and Its Impact on Health: South Asian Experience,”
BMJ
, April 3, 2004, 830–31.

25
. Anita K.M. Zaidi et al., “Burden of Infectious Diseases in South Asia,”
BMJ
, April 3, 2004, 811.

26
. Ganapati Mudur, “Hospitals in India Woo Foreign Patients,”
BMJ
, June 5, 2004, 1338.

27
. FDA News, “New Indian Patent Law Heralds Multinationals' Return,”
Daily International Pharma Alert
, January 31, 2005.

28
. FDA News, “Drug Majors Anticipate Final Approval for India's Patent Reform,”
Daily International Pharma Alert
, January 25, 2005.

29
. James Love, “Options to Traditional Patents,”
Financial Express
, April 6, 2005.

30
. Narayan Kulkarni, “The Trials Leader,”
Biospectrum
, June 10, 2003.

31
. Interview with Ken Getz, October 2003.

32
. “Lifting India's Barriers to Clinical Trials,”
CenterWatch
, August 2003, 1.

33
. D'Silva and Doctor, “Clinical Trials in Dock.”

34
. Sandhya Srinivasan, “Discussion on Biomedical Research on Humans in India: A Short Review,” Achutha Menon Centre for Health Science Studies and Sree Chitra Tirunal Institute for Medical Sciences and Technology, October 2000, 14.

35
. D'Silva and Doctor, “Clinical Trials in Dock.”

36
. “Lifting India's Barriers to Clinical Trials,”
CenterWatch
, 6.

37
. Atul Gawande, “Dispatch from India,”
New England Journal of Medicine
, December 18, 2003, 2383–86.

38
. Interview with Nadeem Rais, November 25, 2003.

39
. Reshma Patil and Toufiq Rashid, “Strong Medicine,”
Sunday Express
, December 28, 2003, 11.

40
. Gawande, “Dispatch from India.”

41
. Jayaprakash Narayan, “Healthcare Is Sick,”
Humanscape
, September 2003, 17.

42
. Interview with Yash Lokhandwala, November 28, 2003.

43
. Madhumita Bose, “Doctor, Heal Thyself,”
Business India
, June 24–July 7, 2002, 107.

44
. Soma Wadha, “Hypocratic Practice,”
Outlook
, February 3, 2003, 51.

45
. Geoff Dyer, “Sepsis Treatment Makes Slow Start at Eli Lilly,”
Financial Times
, March 5, 2002, 20.

46
. Eli Lilly press release, “Lilly Launches World's Largest Severe Sepsis Clinical Trial: 11,000 Patients to Be Enrolled in Study of Xigris Use in Patients with Low Risk of Death,” September 17, 2002.

47
. “Eli Lilly Launches Xigris to Combat ‘Blood Poisoning,'”
Business Line
, October 19, 2002.

48
. Thomas M. Burton, “Left on the Shelf: Why Cheap Drugs That Appear to Halt Fatal Sepsis Go Unused—Steroids Need Big Human Trial, but Pharmaceutical Makers Lack Incentive to Fund One—Dr. Meduri's 15-Year-Quest,”
Wall Street Journal
, May 17, 2002, A1.

49
. Society of Critical Care Medicine, “ICU Issues and Answers: Sepsis: What You Should Know,” available at
www.sccm.org/patient_family_resources/support_brochure
.

50
. When the reaction causes blood pressure to drop, depriving organs of oxygen, it's called “septic shock.” When the infection is in the bloodstream itself, it's called “septicemia.” Eli Lilly
press release, “Lilly Launches World's Largest Severe Sepsis Clinical Trial”; Society of Critical Care Medicine, “ICU Issues and Answers.”

51
. Jane E. Brody, “New Hope for Taming Deadly Septic Shock,”
New York Times
, March 5, 2002, F1.

52
. Gina Kolata, “Halted at the Market's Door: How a $1 Billion Drug Failed,”
New York Times
, February 12, 1993, A1; Sandra Sugawara, “FDA Test Concerns Send Centocor's Stock Plunging,”
Washington Post
, April 16, 1992, B11.

53
. E.J. Ziegler et al., “Treatment of Gram-Negative Bacteremia and Septic Shock with HA-1A Human Monoclonal Antibody Against Endotoxin. A Randomized, Double-Blind, Placebo-Controlled Trial,”
New England Journal of Medicine
, February 14, 1991, 429–36.

54
. Tim Friend, “Drug's Value ‘Like Penicillin,'”
USA Today
, February 14, 1991, 1A.

55
. Sandra Sugawara, “FDA Test Concerns Send Centocor's Stock Plunging,”
Washington Post
, April 16, 1992, B11.

56
. As Martin Tobin later pointed out, “If mortality is significantly decreased in one subgroup but overall mortality is not changed, logic dictates that some patients must have had an increased mortality.” Martin J. Tobin, “The Role of a Journal in a Scientific Controversy,”
American Journal of Respiratory and Critical Care Medicine
168 (2003): 512.

57
. Sally Squires, “Sepsis,”
Washington Post
, October 1, 1991, Z11.

58
. “Mortality rates in the patients without gram-negative bacteremia were as follows: placebo, 37% (292 of 793) and HA-1A, 41% (318 of 785).” If those on the drug had survived at the same rate as those on placebo, only 290 would have died rather than 318 (37 percent of 785). Richard V. McCloskey et al., “Treatment of Septic Shock with Human Monoclonal Antibody HA-1A,”
Annals of Internal Medicine
, July 1, 1994, 1–5.

59
. “Murphy to Up Stake,”
New Orleans Times-Picayune
, January 19, 1993, C1.

60
. “Drugmaker Takes a Nosedive,”
Cleveland Plain Dealer
, January 19, 1993, 1F.

61
. Kolata, “Halted at the Market's Door.”

62
. FDA Center for Drug Evaluation and Research, Anti-infective Drugs Advisory Committee, transcript, October 16, 2001, 12.

63
. See
www.vericc.org/01_new/media_pbn_030908.htm
.

64
. Burton, “Left on the Shelf.”

65
. Ibid.

66
. Gordon R. Bernard et al., “Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis,”
New England Journal of Medicine
, March 8, 2001, 699–709.

67
. Not to mention the fact that the steroid researchers had refused to let their placebo patients suffer for very long. After ten days, if patients hadn't responded, they were switched to the treated group. The move, while compassionate, could have muddied the results. Burton, “Left on the Shelf.”

68
. Bernard et al., “Efficacy and Safety of Recombinant Human Activated Protein C.”

69
. Ibid.

70
. See
content.nejm.org/early_release/
.

71
. “‘Sepsis: The Peril of Infection' a ‘Cutting Edge Medical Report' iTV Special Premieres on the Health Network March 10,”
PR Newswire
, March 8, 2001.

72
. “Bayer to Form International Sepsis Forum,”
Pharmaceutical Business News
, March 26, 1997.

73
. According to the FDA analysis, there was but a one in twelve chance that this trend toward diminishing effectiveness and even harm had occurred simply by random chance. Bolstering the worrying trend was the fact that in unrelated studies sepsis researchers had similarly linked the severity of the disease with patients' responses to treatment, i.e. P=.08. FDA Center for Drug Evaluation and Research, Anti-infective drugs advisory committee, transcript, October 16, 2001.

74
. FDA Center for Drug Evaluation and Research, Anti-infective Drugs Advisory Committee, 247; H. Shaw Warren et al., “Risks and Benefits of Activated Protein C Treatment for Severe Sepsis,”
New England Journal of Medicine
, September 26, 2002, 1027–30.

75
. Ibid.

76
. Since the probability of the disturbing data on Xigris occurring by chance was higher than one out of twenty, neither the agency nor scientific convention required Lilly to mention it. The only hint emanating from the FDA was its statement that
“not everyone will benefit” from Xigris. FDA Center for Drug Evaluation and Research, Anti-infective Drugs Advisory Committee, 323; U.S. Food and Drug Administration press release, “FDA Approves First Biologic Treatment for Sepsis,” November 21, 2001.

77
. Jane E. Brody, “New Hope for Taming Deadly Septic Shock,”
New York Times
, March 5, 2002, F7.

78
. Burton, “Left on the Shelf.”

79
. Eli Lilly press release, “Lilly Launches World's Largest Severe Sepsis Clinical Trial.”

80
. Warren et al., “Risks and Benefits of Activated Protein C Treatment.”

81
. FDA Center for Drug Evaluation and Research, Anti-infective Drugs Advisory Committee, 263.

82
. “Eli Lilly to Make India Sourcing Hub,”
India Business World
, October 2002.

83
. Eli Lilly press release, “Lilly Launches World's Largest Severe Sepsis Clinical Trial.”

84
. Interview with Farhad Kapadia, November 25, 2003.

85
. Feroze Ahmed, “Parents Have the Heart to Let Them Die,”
Hindu Online
, August 18, 2003.

86
. Eli Lilly clinical trials Web site, at
www.lillytrials.com
.

87
. John Wurzelmann, “Presentation on Eastern Europe,” in Globalization of Clinical Trials panel, Maximizing Clinical Efficiency Phases conference (Washington, DC, October 9, 2003).

88
. Edward Abraham, “Exploration of Drotrecogin Alfa (Activated) in Adult Patients with Severe Sepsis at Lower Risk of Death,” presentation, American College of Chest Physicians annual meeting (Seattle, WA, October 2004).

89
. Dante Landucci, “The Surviving Sepsis Guidelines: ‘Lost in Translation,'”
Critical Care Medicine
31, no. 7 (2004): 1598–99.

90
. See
www.esicm.org/PAGE_sursepsis/?1hmi
.

91
. Correspondence with D. Annane, February 2005.

92
. P.C. Minneci et al., “Meta-Analysis: The Effect of Steroids on Survival and Shock During Sepsis Depends on the Dose,”
Annals of Internal Medicine
, July 2004, 47–56.

93
. “Eli Lilly Slashes Therapy Cost for Sepsis by 40 Pc,” Global News Wire, July 31, 2004.

94
. Greg S. Martin, “Ask the Experts about General Critical Care: Drotrecogin Alfa and Sepsis,” Medscape from WebMD, posted September 1, 2004, on
www.medscape.com/viewarticle/487221
.

95
. Andrew Pollack, “Viagra Shows Promise as Lung Therapy,”
New York Times
, October 28, 2004, C8.

96
. Abraham, “Exploration of Drotrecogin Alfa.”

97
. FDA Web site,
Medwatch
, February 11, 2005. Also, Xigris, “Postmarking Study Commitments,” on
www.accessdata.fda.gov
.

98
. See
www.xigris.com
.

99
. Edward Abraham et al., “Drotrecogin Alfa (Activated) for Adults with Severe Sepsis and a Low Risk of Death,”
New England Journal of Medicine
, September 29, 2005.

100
. Alex Berenson, “Blockbuster Drugs Are So Last Century,”
New York Times
, July 3, 2005.

101
. “I don't have the actual details of the trial,” he said. From correspondence with Dr. Farhad Kapadia, February 16, 2005.

 

1
. Interview with Ruth Faden, 2001.

2
. David J. Rothman, “The Shame of Medical Research,”
New York Review of Books
, November 30, 2000; Public Citizen, “Letter to the World Medical Association Expressing Alarm at the Current Draft Revised Version of the Declaration of Helsinki,” HRG Publication #477, March 29, 1999.

3
. Susan Okie, “Health Officials Debate Ethics of Placebo Use: Medical Researchers Say Guidelines Would Impair Some Studies,”
Washington Post
, November 24, 2000, A3.

4
. David Brown, “Medical Research Group Revises Guidelines on Placebos,”
Washington Post
, October 8, 2000.

5
. World Medical Association, “WMA History: Declaration of Helsinki,” available at
www.wma.net/e/history/helsinki.htm
; World Medical Association, “Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects,” available at
www.wma.net
; U.S. Food and Drug Administration,
Guidance for Industry: Acceptance of Foreign Clinical Studies
, March 2001, available at/
www.fda.gov/cder/guidance/fstud.htm
.