Scientific secrecy and "spin": The sad, sleazy saga of the trials of remune

Law and Contemporary Problems

Volumn 69, Issue 3, 2006, Pages 47-68

  Haack, Susan ^a,b  

^a University of Miami   (United States)

^b UNIVERSITY OF MIAMI   (United States)

Author keywords

[No Author keywords available]

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EID: 33750142954     PISSN: 00239186     EISSN: 00239186     Source Type: Journal    
DOI: None     Document Type: Article

References (156)

1. Charles Sanders Peirce, Pearson's Grammar of Science, Annotations on the First Three Chapters (1901), in 8 Collected Papers 1143 (Charles Hartshorne, Paul Weiss, and Arthur Burks, eds. 1931-1958).
2. Barbara J. Culliton, The Academic-Industrial Complex, 216 Science 960, 960 (1982).
3. Arnold Relman, Dealing With Conflicts of Interest, 310 New Eng. J. Med. 1182, 1182 (1984).
4. Dorothy Nelkin, The Performance of Science, 352 Lancet 893, 893 (1998).
5. Editorial, 355 Lancet 857, 857 (2000).
6. John Ziman, Real Science 79 (2000).
7. Zilch for Maker in AIDS Drug Suit, S.F. Chron., Sept. 11, 2001, at A10.
8. See In re Immune Response Sees. Litig., 375 F. Supp. 2d 983, 994 (S.D. Cal. 2005).
9. The case originated in ten separate class action suits, id. at 994 n.1; the lead plaintiff, Florence Hirschfeld, filed her case on July 10, 2001.
10. Hirschfeld v. Immune Response Corp., No. 01-CV-1237 (S.D. Cal. 2001).
11. Press Release, Immune Response Corporation, The Immune Response Corporation Announces That REMUNE Has Been Selected For A New HIV Clinical Trial Sponsored by The U.S. National Institutes of Health (March 29, 2005), available at http://www.imnr.com/news/2005/ 2005Mar29.htm.
12. This section presents briefly some ideas worked out more thoroughly in Susan Haack, Defending Science - Within Reason: Between Scientism and Cynicism (2003) [hereinafter Haack, Defending Science], especially chapters 1, 3, 4, and 11.
13. I first introduced this analogy in Susan Haack, Rebuilding the Ship While Sailing on the Water, in Perspective On Quine 111, 116 (Robert Barrett & Roger Gibson eds., 1990);
14. developed it further in Susan Haack, Evidence and Inquiry: Towards Reconstruction in Epistemology 81-89 (1993);
15. and, in Haack, Defending Science, supra note 10, at 57-121, applied it specificaily to scientific evidence and method.
16. For amplification, see Susan Haack, The Ideal of Intellectual Integrity, in Life and Literature, 36 New Literary Hist. 359 (2005).
17. This honorific usage seems also to have left its mark on Justice Blackmun's opinion in Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579 (1993).
18. See Haack, Defending Science, supra note 10, at 251-52;
19. Susan Haack, Trial and Erron The Supreme Court's Philosophy of Science, 95 Am. J. Pub. Health S66 (2005).
20. "Helps" is Francis Bacon's word: "Effects are produced by the means of instruments and helps, which the understanding requires no less than the hand...."Francis Bacon, Novum Organum (1620), Book 1, aphorism 2, reprinted in Advacement of Learning and Novum Organum 309, 315 (Colonial Press 1900).
21. Albert Einstein, Physics and Reality, in Ideas and Opinions 290, 290 (Carl Seelig ed. Sonja Bargmann trans., 1954).
22. Gustav Bergmann, Philosophy of Science 20 (1957).
23. See Bettyann Holtzmann Kesvles, Naked to the Bone: Medical Imaging in the Twentieth Century (1997).
24. William James, The Will to Believe (1896), in The Will to Beleive and Other Essays in Popular Philosophy 1, 17 (1897; repr. 1956).
25. Pierce, Lectures on Pragmatism, Lecture VI: Three Types of Reasoning, in 5 Collected Papers, supra note 1, 1172.
26. Problems about multiple authorship are a major theme of the short pieces in the 1998 colloquium Publication and Promotion, 352 Lancet 891.
27. See, e.g., Nelkin, supra note 4.
28. Conference Announcement, Sequestered Science: the Consequences of Undisclosed Knowledge, October 14-15, 2004, (on file with Law & Contemporary Problems).
29. On Nazi science, see Alan D. Beyerchen, Scientists Under Hitler: Politics and the Physics Community in the Third Reich (1977),
30. and Alan D. Beyerchen, What We Now Know About Nazism and Science, 59 Soc. Res. 615 (1992).
31. On Soviet biology, see Valery N. Soyfer, Lysenko and the Tragedy of Soviet Science (Leo Gruliow & Rebecca Gruliow trans., 1994).
32. See generally Morton Hunt, The New Know-Nothings: The Political Foes of the Scientific Study of Human Nature (1999) (arguing that the social sciences are presently stultified by pressure to be "politically correct").
33. Joshua A. Newberg & Richard L. Dunn, Keeping Secrets in the Campus Lab: Law, Values and Rules of Engagement for Industry-University R&D Partnerships, 39 Am. Bus. L.J. 187, 193 (2002).
34. See also Sheldon Krimsky, Science in the Private Interest: Has the Lure of Profits Corrupted Biomedical Research? 27-32 (2003) (providing similar statistics).
35. Paul Smaglik, Reservoirs Dog AIDS Therapy, 405 Nature 270, 272 (2000).
36. The Immune Response Corporation, Corporate Snapshot, http://wwww.imnr.com/corp/corporate.htm.
37. See, e.g., Smaglik, supra note 25, at 272.
38. Thomas H. Maugh II, Firm Disputes Handling of Drug Study, L.A.Times, Nov. 1, 2000, at A3.
39. In re Immune Response Secs. Litig., 375 F. Supp. 2d 983, 997-98 (S.D. Cal. 2005).
40. Amended Complaint at 8, Hirschfeld v. Immune Response Corp., No. 01-CV-1237 (S.D. Cal. Jul. 10, 2001) [hereinafter Hirschfeld Complaint].
41. 405 Nature 270, 272 (2000).
42. Hirschfeld Complaint at 7-8.
43. Stock Comment-New York, Market Letter, Feb. 26, 1996.
44. 6/IL CD4 Cell Counts: A Randomized Controlled Trial, 284 J. Am. Med. Ass'n 2193, 2193 (2000).
45. Id. at 2193-94.
46. Id. at 2194.
47. Maugh, supra note 28;
48. Kahn et al., supra note 33, at 2195.
49. Maugh, supra note 28.
50. Id.
51. John S. James, Bitter Publication Dispute on Remune Study: More Than Meets the Eye?, AIDS Treatment News, Nov. 3, 2000, at 4.
52. Maugh, supra note 28.
53. Id.;
54. Hirschfeld Complaint, supra note 30, at 7.
55. Maugh, supra note 28. 43.
56. Id.
57. Id.
58. Derhsing Lai & Taff Jones, Remune Immune Response, 3 Current Opinion in Investigation Drugs 391, 391 (2002). The Kahn-Lagakos study was also a Phase III trial. According to an FDA program director: Phase I studies are early clinical trials in which the principal objective is an assessment of safety. This usually involves minimal numbers of patients, usually does not include a control group and may include very limited dosage assessments. In Phase II the study is typically larger, includes dose ranging studies, and may in addition to safety endpoints, have assessments of drug activity or efficacy as well as include a control group. By Phase III it is expected that the safety profile of the product is better understood and that a potentially effective dose has been identified. These studies are predominantly aimed at efficacy evaluations, although safety is critically evaluated as well and some continued dose ranging may be done. Such studies are often the basis of product license applications if they show a favorable risk/benefit profile. E-mail from Amy Rosenberg, Program Director, Food and Drug Administration, to Susan Haack (Nov. 3, 2005) (on file with Law and Contemporary Problems).
59. Penni Crabtree, Scientists Say Firm Tried to Gag Them; Tell of Releasing AIDS Vaccine Data, San Doedgo Union-Tribune, Nov. 7, 2000, at B1.
60. Scientists Say Firm Tried to Gag Them; Tell of Releasing AIDS Vaccine Data
61. Scientists Say Firm Tried to Gag Them; Tell of Releasing AIDS Vaccine Data
62. Thomas M. Burton, Unfavorable Drug Study Sparks Battle Over Publication of Results, Wall St. J., Nov. 1, 2000, at B1.
63. Id.
64. Id.
65. Crabtree, supra note 46.
66. Katherine S. Mangan, Company Seeks $10 Million from Scientist and University, Chron. Higher Ed. Nov. 17, 2000, at A48, A50.
67. Kahn et al., supra note 33.
68. Id. at 2199.
69. Id. at 2200.
70. Maugh, supra note 28.
71. See also Kahn et al., supra note 33, at 2202;
72. James O. Kahn & Stephen Lagakos, In Reply, 285 J. Am. Med. Ass'n 2193, 2194 (2001).
73. Maugh, supra note 28.
74. Sabin Russell, Firm That Paid for UCSF Study Seeks Damages, S.F. Chron., Nov. 1, 2000, at A3 (quoting John Turner).
75. Catherine D. DeAngelis, Conflict of Interest and the Public Trust, 284 J. Am. Med. Ass'n 2237, 2238 (2000).
76. Scott Gottlieb, Firm Tried to Block Report on Failure of AIDS Vaccine, 321 Brit. Med. J. 1173, 1173 (2000).
77. Nguyen V. Dat, Letter to the Editor, Outcomes of a Trial of HIV-1 Immunogen in Patients with HIV Infection, 285 J. AM. Med. Ass'n 2191, 2191 (2001).
78. Id.
79. Frances M. Gotch & Nesrina Imami, Letter to the Editor, Outcomes of a Trial of HIV-1 Immunogen in Patients with HIV Infection, 285 J. Am. Med. Ass'n 2191, 2191-92 (2001).
80. Billi Goldberg & Raphael B. Stricker, Letter to the Editor, Outcomes of a Trial of HIV-1 Immunogen in Patients with HIV Infection, 285 J. Am. Med. Ass'n 2192 (2001).
81. Peter Lurie & Sidney M. Wolfe, Letter to the Editor, Outcomes of a Trial of HIV-1 Immunogen in Patients with HIV Infection, 285 J. Am. Med. Ass'n 2193 (2001).
82. Donald M. Poretz, Letter to the Editor, Outcomes of a Trial of HIV-1 Immunogen in Patients with HIV Infection, 285 J. Am. Med. Ass'n 2192, 2192-93 (2001).
83. Penni Crabtree, Analysts Try to Sort Out Flap Over Remune, San Diego Union-Trib., Nov. 1, 2000, at C1.
84. Cheryl Clark & Penni Crabtree, Carlsbad Firm Under Fire on Vaccine Study, San Diego Union-Trib., Nov. 1, 2000, at A1.
85. Crabtree, supra note 68.
86. Clark & Crabtree, supra note 69.
87. Id.
88. Gottlieb, supra note 61.
89. Russell, supra note 59.
90. Carol Cruzan Morton, Company, Researchers Battle Over Data Access, 290 Science 1063 (2000).
91. Id.
92. Russell, supra note 59.
93. Cheryl Clark, A Medical and Ethical Quandary; Fallout Over Vaccine, San Diego Union-Trib., Nov. 4,2000, at A1.
94. Id.
95. Crabtree, supra note 68.
96. Eric Niiler, Company, Academics Argue over Data, 18 Nature Biotechnology 1235, 1235 (2000).
97. Id.
98. The Immune Response Corporation & The Regents of the University of California, Research Agreement (executed Sept. 25, 1995) [hereinafter Research Agreement] (on file with Law and Contemporary Problems).
99. Clark & Crabtree, supra note 69.
100. The American Arbitration Association (AAA) is a nonprofit group offering binding settlements of disputes in many professional areas without the cost, but also without some of the safeguards, of a court case. Proceedings are private, conducted without a jury, and cannot be appealed. Mangan, supra note 53, at A50.
101. Clark & Crabtree, supra note 69.
102. Rhonda L. Rundle, Immune Response Shares Soar 43% as Thai Doctors Back AIDS Drug, Wall St. J., Mar. 24, 2000, at B6.
103. Hirschfeld Complaint, supra note 30, at 7.
104. J. L. Turner et al., The Effects of an HIV-1 Immunogen (Remune) on Viral Load, CD4 Cell Counts and HIV-Specific Immunity in a Double-Blind, Randomized, Adjuvant-Controlled Subset Study in HIV Infected Subjects Regardless of Concomitant Antiviral Drugs, 2 HIV MED. 68 (2001).
105. Id. at 68.
106. Penni Crabtree, Analysis Boosts Carlsbad Biotech; Immune Response Stock Surges with AIDS Drug Results, San Diego Union-Trib., Apr. 24,2001, at C1.
107. Hirschfeld Complaint, supra note 30, at 14.
108. Id at 15.
109. Id. at 2.
110. Immune Response Stock Falls After Pfizer Ends Deal, N.Y. Times, July 7,2001, at C3.
111. Zilch for Maker in AIDS Drug Suit, S.F. Chron., Sept. 11, 2001, at A10.
112. Immune Response Corp.: Company Lays Off Workers, Shuffles Senior Management, Wall St. J., Sept. 10, 2002.
113. Morning Edition: Company Founded by the Late Dr. Jonas Salk Close to Going out of Business (NPR radio broadcast Nov. 22, 2002) (transcript on file with Law and Contemporary Problems).
114. Press Release, Immune Response Corporation, The Immune Response Corporation Signs a $15 Million Financing Agreement (July 18, 2005), available at http://www.imnr.com/news/2005/2005Jul18.htm.
115. Press Release, Immune Response Corporation, The Immune Response Corporation Presents REMUNE Data at The International AIDS Society Meeting in Rio (July 27, 2005), available at http://www.imnr.com/news/ 2005/2005Jul27.htm.
116. Press Release, Immune Response Corporation, supra note 9.
117. Id.
118. As of August 1, 2006, IRC was still a going concern; the stock price was two cents a share. The same day, IRC announced that it had received approval for expansion of a phase II trial of IR103, described as "a more potent formulation" based on Remune. http://www.marketwatch.com (last visited Aug. 1, 2006)
119. and http://www.imnr.com/news/2006/2006AUG01.htm (last visited Aug. 1, 2006) [And as of that date, the securities case was still pending, and Remune still not approved by FDA.]
120. Telephone Interview with James O. Kahn, Professor of Clinical Medicine, UCSF, in San Francisco, Cal. (Dec. 18, 2004).
121. Id.
122. Mangan, supra note 84, at A50 (quoting Marcia Angell, Editor-in-Chief of the New England Journal of Medicine).
123. Shannon Brownlee, Bitter Medicine, Mother Jones, Sept.-Oct. 2004, at 83, 83 (reviewing Marcia Angell, The Truth About Drug Companies: How They Decieve Us and What To Do About It (2004) and Jerome Kassirer, On The Take: How Big Business Is Corrupting American Medicine (2004)).
124. See also Anna Wilde Mathews, House Panel Grills FDA, Drug Firms, Wall St. J., Sept. 10, 2004, at B5 (describing House panel questioning of FDA and drug companies about disclosure of negative research findings).
125. Brownlee, supra note 105.
126. Id.
127. Well before the present brouhaha, I had noted manufacturers' efforts to play down possible risks of Vioxx and Celebrex. See Haack, Defending Science supra note 10, at 320
128. (citing Thomas M. Burton and Gardiner Harris, Note of Caution: Study Raises Specter of Cardiovascular Risk for Hot Arthritis Pills, Wall St. J., Aug. 22, 2001, at A1).
129. As of August 17, 2006, there are around 14,200 Vioxx lawsuits pending against Merck; of the nine tried so far, Merck has won three, with a split verdict in a fourth. See John Carreyrou & Greg Edwards, Merck's Net Soars on Strong Sales, WALL ST. J., July 25, 2006, at A2;
130. Merck Wins Vioxx Case in New Jersey, N.Y. Times, July 14, 2006, at C4;
131. Andrew Simons & Heather Won Tesoriero, Merck Wins California Vioxx Case, Widening Edge on Trial Score Card, WALL ST. J., Aug. 3, 2006, at A8;
132. Heather Won Tesoriero, Merck Suffers Vioxx-Case Setback, WALL ST. J., Aug. 18, 2006, at A2.
133. For example, and quite to the present purpose, testing an unproven AIDS vaccine on healthy patients who are then deliberately exposed to AIDS.
134. F. H. Bradley, Ethical Studies 226 (2d ed. 1927).
135. DeAngelis, supra note 60, at 2237.
136. Mangan, supra note 84, at A50.
137. Editorial, Collaborative Conflicts, 1 Nature Immunology 449 (2000).
138. Editorial, Knee-Jerk Response, 18 Nature Biotechnology 1223 (2000).
139. DeAngelis, supra note 60, at 2237.
140. Yale University, Yale University Faculty Handbook 112 (2002), available at http://www.yale.edu/provost/handbook/faculty_handbook.pdf.
141. Krimsky, supra note 24, at 130.
142. Id. at 48.
143. Mildred K. Cho, Ryo Shohara, Anna Schissel & Drummond Rennie, Policies on Faculty Conflicts of Interest at U.S. Universities, 284 J. Am. Med. Ass'n 2203, 2203 (2000).
144. David Wickert, UW Seldom Cuts Researcher, Corporate Ties, News Trib. (Tacoma, Wash). Oct. 14, 2002, at A10.
145. Kevin A. Schulman et al., A National Survey of Provisions in Clinical-Trial Agreements Between Medical Schools and Industry Sponsors, 374 New Eng. J. of Med. 1335, 1339 (2002).
146. See Research Agreement, supra note 83, at 3-6.
147. At Kahns suggestion, see supra note, 102, I requested from UCSF copies of the contract with IRC and of the template contract in effect at that time. Eventually I obtained, from the Office of the Chancellor, copies of UCSF's template agreement; the preliminary Research Agreement between UCSF and IRC, "effective 1/1/95," executed September 25, 1995; the "Investigational Site Agreement," effective May 24, 1996, superseding the earlier agreement; and a document entitled "Clinical Endpoint Study, Protocol Number 806" (apparently I first asked for these documents in January 2005; receiving no response; in February I asked again, this time referring to my rights "pursuant to the California Public Records Act, Government Code sections 6254 et seq., and the California Constitution, as amended by passage of Prop. 59 on November 3, 2004." After several more (increasingly urgent and strongly-worded) requests, I finally received the documents in late August 2005. My colleague William Widen helped me sort through the material and tentatively identify, from internal clues, the relation between the preliminary and the revised (and superseding) agreement, et cetera. incorporated into the Investigational Site Agreement as "Exhibit A").
148. Clinical Endpoint Study, Protocol Number 806: A Multicenter, Double-Blind, Phase III, Adjuvant-Controlled Study of the Effect of 10 Units of HIV-1 Immunogen Compared to IFA Alone Every 12 Weeks on Aids-Free Survival in Subjects with HIV Infection and CD4 T Lymphocytes Between 300 and 549 Cells/uL Regardless of Concomitant HIV Therapies 55 (signed Feb. 15, 1996) (on file with Law & Contemporary Problems) [hereinafter Protocol 806].
149. Id.
150. Elizabeth A. Boyd & Lisa A. Bero, Assessing Faculty Financial Relationships With Industry: A Case Study, 284 J. Am. MED. Ass'n 2209, 2213-14 (2000).
151. This is not intended to suggest that only private funding poses such problems; that, unfortunately, would be over-optimistic to say the least. See, e.g., Bernard Wysocki, Jr., Cash Injection: As Universities Get Billions in Grants, Some See Abuses: Cornell Director Blows Whistle Over Use of Federal Funds, Alleging Phantom Studies; Defending a Star Professor, Wall St. J., Aug. 16, 2005, at A1 (reporting numerous instances of alleged misuse of federal grant money).
152. Current UCSF guidelines aver that "[i]n pursuing relationships with industry, the University must keep the public trust and maintain institutional independence and integrity to permit faculty and students to pursue learning and research freely," and preclude "assigning to extramural sources the right to keep or make final decisions about what may be published," or allowing a sponsor to "exercise any editorial control." Memo Operating Guidance, University of California, Guidelines on University-Industry Relations (June 6, 1989) [hereinafter Guidelines], available at http://www.ucop.edu/raohome/cgmemos/89-20.html;
153. University of California, San Francisco, Frequently Asked Questions, http://www.research.ucsf.edu/icd/icdFAQ.asp (on file with Law and Contemporary Problems). The Guidelines also describe the university as "exploring innovative ... approaches to assure support of worthy research... that provide[s] significant contributions to ... scholarship ... [and ] that [is] responsive to industry interests." Guidelines, supra (emphasis added).
154. Krimsky, supra note 24, at 47.
155. Thorstein Veblen, The Higher Learning in America 224 (1919).
156. Id at 190.