The death of jesse gelsinger: New evidence of the influence of money and prestige in human research

American Journal of Law and Medicine

Volumn 36, Issue 2-3, 2010, Pages 295-325

  Wilson, Robin Fretwell ^a  

^a WASHINGTON AND LEE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; CLINICAL TRIAL; CONFLICT OF INTEREST; ETHICS; FINANCIAL MANAGEMENT; GENE THERAPY; HUMAN; HUMAN EXPERIMENT; LEGAL ASPECT; MALE; RESEARCH SUBJECT; UNITED STATES;

CLINICAL TRIALS AS TOPIC; CONFLICT OF INTEREST; GENE THERAPY; HUMANS; MALE; RESEARCH SUBJECTS; RESEARCH SUPPORT AS TOPIC; THERAPEUTIC HUMAN EXPERIMENTATION; UNITED STATES;

EID: 77957276940     PISSN: 00988588     EISSN: None     Source Type: Journal    
DOI: 10.1177/009885881003600202     Document Type: Article

References (213)

1. See, e.g., Patricia C. Kuszler, Biotechnology Entrepreneurship and Ethics: Principles, Paradigms, and Products, 25 MED. & L. 491, 495 (2006) ("[L]apses in human subjects protection remains an ever-present hazard. This has been exemplified by a series of high profile research ethics scandals in the U.S.-the Jesse Gelsinger case in which a research subject in a gene-therapy experiment died and it was alleged that the researchers' financial interest in the vector influenced them to prematurely engage in the clinical trial that resulted in Mr. Gelsinger's death.");
2. Trudo Lemmens, Leopards in the Temple: Restoring Scientific Integrity to the Commercialized Research Scene, 32 J.L. MED. & ETHICS 641, 645 (2004) ("[Financial interests may negatively impact researchers' dealings with research subjects during a trial. When huge profits lure, and pressure mounts to bring novel drugs or therapies quickly to the market, potential risks may be perceived somewhat more lightly, and inclusion or exclusion criteria may become more flexible. This seems to have happened in the well-known case of Jesse Gelsinger.").
3. Scott Hensley, Targeted Genetics' Genovo Deal Leads to Windfall for Researcher, WALL ST. J., Aug. 10, 2000, at B12;
4. Telephone Interview with Michael Waitzkin, Attorney for James Wilson, Inst, for Human Gene Therapy, Univ. of Pa. Health Sys. (Mar. 31, 2008).
5. Memorandum from Kathleen A. Denis, Dir., Ctr. for Tech. Transfer, to Neil Nathanson, Chair, Conflict of Interest Standing Comm., at 1, 3 (Dec. 15, 1994) (quantifying shares to be held by Wilson and reporting the financial terms on which Genovo shares were purchased by a minority shareholder, Biogen) (on file with author).
6. E-mail from Paul Gelsinger to Robin Fretwell Wilson (Mar. 14, 2008) (on file with author).
7. See David B. Caruso, Feds Settle Suit Over Death in Penn Gene Therapy Study, AP ALERT - PA., Feb. 9, 2005.
8. See infra Part VI.
9. I received the documents presented here from Paul Gelsinger and the Gelsingers' attorney, Alan Milstein, who obtained them during the course of their litigation from a whistleblower inside Penn. While the amount of the Gelsingers' settlement was sealed at the time of settlement, the documents were not. The researchers declined requests to be interviewed by me, although Wilson provided information through his attorney.
10. See Hosp. of the U. of Pa. & The Children's Hosp. of Phila., Consent Agreement for Recombinant Adenovirus Gene Transfer in Adults with Partial Ornithine Transcarbarnylase Deficiency, at 11 (1999) (on file with author) [hereinafter Consent Form].
11. James M. Wilson, Lessons Learned from the Gene Therapy Trial for Orithine Transcarbarnylase Deficiency, 96 MOLECULAR GENETICS & METABOLISM 151, 155 (2009) [hereinafter Lessons Learned].
12. Rick Weiss, Boy's Cancer Prompts FDA to Halt Gene Therapy, WASH. POST, Mar. 4, 2005, at A02.
13. Consent Form, supra note 8, at 2.
14. Paul Gelsinger, Statement at the Forum on Research Ethics, University of South Carolina School of Law (Apr. 5, 2001) (transcript on file with author) [hereinafter Gelsinger Remarks'].
15. Id. at 4.
16. Id.
17. Letter from Mark L. Batshaw, Children's Nat'l Med. Ctr., Steven E. Raper, Assoc. Prof., Dep't of Surgery, Univ. of Pa. & James M. Wilson, Inst, for Human Gene Therapy, Univ. of Pa. Health Sys. (Sept. 23, 1999) (to be read at Jesse Gelsinger's funeral) (on file with author).
18. See, e.g., Alexis Gilbert, Penn Hit by Gene Therapy Lawsuit: Suit Calls Penn Negligent in Study that Led to Arizona Teen's Death Last Year, DAILY PENNSYLVANIAN, Sept. 19, 2000, at News Section, available at http://media.www.dailypennsylvanian.com/media/storage/paper882/news/2000/09/19/ News/Penn-Hit.By.Gene.Therapy.Lawsuit-2l61264.shtml (last visited Aug. 6, 2008).
19. Deborah Nelson & Rick Weiss, Hasty Decisions in the Race to a Cure?; Gene Therapy Study Proceeded Despite Safety, Ethics Concerns, WASH. POST, NOV. 21, 1999, at AOI. See also infra Part IV.
20. See generally The FDA's Drug Review Process: Ensuring Drugs Are Safe and Effective, http://www.fda.gov/drugs/resourcesforyou/consumers/ucml43534.htm (last visited Apr. 22, 2010).
21. Wilson, supra note 9, at 152.
22. Mark L. Batshaw et al., Recombinant Adenovirus Gene Transfer in Adults with Partial Ornithine Transcarbarnylase Deficiency (OTCD), 10 HUMAN GENE THERAPY 2419, 2429 (1999).
23. Wilson, supra note 9, at 152.
24. Consent Form, supra note 8, at 3.
25. Batshaw et al., supra note 20, at 2429.
26. UNIV. OF PENN. ALMANAC BETWEEN ISSUES, INST, FOR HUMAN GENE THERAPY RESPONDS TO FDA (Feb. 14, 2000), http://www.upenn.edu/almanac/between/ FDAresponse.html;
27. see also Wilson, supra note 9, at 152.
28. 26 Id.
29. Robin Fretwell Wilson, Estate of Gelsinger v. Trustees of University of Pennsylvania: Money, Prestige, and Conflicts of Interest in Human Subjects Research, in HEALTH LAW AND BIOETHICS: CASES IN CONTEXT 229, 236 (Sandra H. Johnson et al. eds., 2009).
30. See Lessons Learned, supra note 9, at 154.
31. 9Id. at 153.
32. Deborah Nelson & Rick Weiss, How We Uncovered The Hidden Fatality In A Clinical Trial, 49 SCIENCE WRITERS 1, 2 (2000). The Washington Post reporters who broke the story say Wilson was not forthcoming about the size of his financial stake. When first asked, "[i]n two separate conversations . . . [Wilson] told [Washington Post reporter Rick Weiss] that his company had no interest in the OTC experiment." Id. After more digging, the reporters found: SEC documents and online press releases showing the company had attracted tens of millions of dollars from companies interested in developing ways to deliver genes to the liver and lungs - and Wilson himself had said he considered OTC the perfect disease for testing a liver delivery system that could be used for an array of diseases. Rick called Wilson and had a heart-to-heart talk with him in which he candidly expressed his distress that Wilson had been less than forthcoming about the Genovo interests. It was a difficult conversation since Rick had covered Wilson's work over a number of years and both knew each other pretty well. Rick told Wilson he wasn't sure he'd be able to trust him any more. Wilson responded that he also felt bad but that he thought it must have been a miscommunication.
33. Id.
34. Jim Smith, Hospitals, Docs Settle with Feds in Gene-Therapy Death, PHILA. DAILY NEWS, Feb. 10, 2005, at 24.
35. See infra pg. 11 and footnote 10 (describing deaths in Paris genetherapy trials).
36. Michelle M. Mello et al., The Rise of Litigation in Human Subjects Research, 139 ANNALS INTERNAL MED. 40, 41 (2003).
37. See Arthur Allen, Bioethics Comes of Age, SALON, Sept. 28, 2000, http://www.salon.com/health/feature/2000/09/28/caplan/index.html (last visited Aug. 6, 2008). Caplan's advice represented the traditional wisdom at the time.
38. See Wilson, supra note 27, at 235. Ethicists now question whether healthy subjects should ever be subjected to more than minimal risks.
39. See, e.g., Nancy M.P. King & Odile Cohen-Haguenauer, En Route to Ethical Recommendations for Gene Transfer Clinical Trials, 16 MOLECULAR THERAPY 432, 436 (2008).
40. See Wilson, supra note 26, at 248;
41. Allen, supra note 33.
42. See Press Release, U.S. Attorney's Office, Eastern District, Pennsylvania, U.S. Settles Case of Gene Therapy Study That Ended with Teen's Death (Feb. 9, 2005) (on file with author).
43. Id.
44. Lessons Learned, supra note 9.
45. See Caruso, supra note 5.
46. Rick Weiss & Deborah Nelson, Penn Settles Gene Therapy Suit; University Pays Undisclosed Sum to Family of Teen Who Died, WASH. POST, Nov. 4, 2000, at A04.
47. At least one other death has resulted in a gene-therapy trial. In 1998, researchers in Paris began gene-therapy trials on 11 children suffering from X-linked Severe Combined Immunodeficiency (X-SCID) or the 'bubble boy" disease, a rare immune system disorder caused by a single gene defect. Four of the 11 children developed T-cell leukemia, one of whom died in October 2004. Weiss, supra note 10. "There is no doubt, in the Paris cases," the BBC reported, "that the leukemia was caused by the gene therapy, where the introduced gene was implanted next to, and switched on, an oncogene (a cancer causing gene).
48. " Q&A: Gene Therapy Cancer Case, BBC NEWS, Dec. 18, 2007, available at http://news.bbc.co.uk/2/hi/health/7149460.stm.
49. Consent Form, supra note 8, at 3.
50. Gelsinger Remarks, supra note 12.
51. Nonetheless, sprinkled throughout the Consent Form are references to evidence that "gene therapy for [OTCD] may be helpful." Consent Form, supra note 8, at 3.
52. The mixed messages about the therapeutic value of participating are problematic because they could mislead participants. See Nancy King, Defining and Describing Benefit Appropriately in Clinical Trials, 28 J. L., MED. & ETHICS 332 (2000).
53. Consent Form, supra note 8, at 7.
54. Sheryl Gay Stolberg, The Biotech Death of Jesse Gelsinger, N.Y. TIMES MAG., Nov. 28, 1999, at 137 (quoting Steven E. Raper).
55. Paul Smaglik, After Gene Therapy Death: Investigators Ponder What Went Wrong, 13 THE SCIENTIST 1, 1 (1999).
56. Consent Form, supra note 8, at 7.
57. 7 Id. at 8.
58. PAUL GELSINGER, JESSE'S INTENT 5 (2001), available at http://www.circare.org/submit/jintent.pdf (last visited April 26, 2010).
59. Nelson & Weiss, supra note 17;
60. Nelson & Weiss, supra note 30, at 2 ("The original consent form reviewed by the RAC disclosed that monkeys died after receiving a high dose of a similar genetically-altered virus carrying the OTC gene. Yet the monkey deaths had disappeared from the consent form that Jesse received, which we got from Penn after obtaining Jesse's father's permission.").
61. Consent Form, supra note 8, at 3, 7.
62. Memorandum from Ruth Clark, Assoc. Dir. of Reg. Affairs, Committee on Studies Involving Human Beings, Office of Research Admin, to Mark L. Batshaw, Children's Nat'l Med. Ctr. (Oct. 6,1995) (IRB approval letter) (on file with author).
63. On November 21, 1995, the researchers responded to comments by members of the Recombinant DNA Advisory Committee ("RAC"), which together with the FDA exercised oversight authority at the federal level. Memorandum from Mark Batshaw, Steven Raper, & James Wilson, Univ. of Pennsylvania Health Sys., to Nelson Wivel (Nov. 21, 1995) (on file with author). In one part of that correspondence, the researchers suggest new text for the Consent Form in response to the RAC comments.
64. Id.
65. Crucially, the disclosure of monkey and mice deaths is identical to the disclosure on the 10/02/95 form. Consent Agreement for Recombinant Adenovirus Gene Transfer in Adults with Partial Ornithine Transcarbarnyalase Deficiency at 7 (1995) (on file with author) [hereinafter "1995 Consent Form"].
66. 1995 Consent Form, supra note 52, at 4.
67. Consent Form, supra note 8, at 3. The IRB that exercised regulatory oversight for Jesse's trial seems to have done everything right-they policed the disclosure, they told the researchers not to change it without permission-but then the IRB trusted that the researchers would respect the rules. The mandatory post-approval monitoring suggested in Part VI presumably would have uncovered this important change in the approved disclosure to participants.
68. See id. at 4-6.
69. 6 Id. at 7.
70. Id.
71. Gelsinger Remarks, supra note 12.
72. Consent Form, supra note 8, at 10-11.
73. 60 Id. at 11.
74. See Press Release, supra note 35;
75. Letter from Steven A. Masiello, Dir., Office of Compliance & Biologies Quality, FDA. Ctr. for Biologics Evaluation & Research to Mark L. Batshaw, Children's Nat'l Med. Ctr. 7 (Nov. 30, 2000), available at http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2000/ucm159922.htm (warning letter);
76. see also Letter from Dennis E. Baker, Assoc. Comm'r for Regulatory Affairs, FDA. Ctr. for Biologics Evaluation & Research to James M. Wilson, Inst. for Human Gene Therapy, Univ. of Pa. Health Sys. (Feb. 8, 2002), available at http://www.fda.gov/RegulatoryInformation/FOI/ElectronicReadingRoom/ ucm144564.htm (notice of opportunity for hearing).
77. Interview with David Hoffman, Former Assistant U.S. Attorney, in Phila., Pa. (June 6, 2008).
78. See Letter from Steven A. Masiello, Dir., FDA Office of Compliance & Biologics Quality, Ctr. for Biologics Evaluation & Research to James M. Wilson, Inst, for Human Gene Therapy, Univ. of Pa. Health Sys. 3 (Nov. 30, 2000), available at www.fda.gov/foi/nidpoe/n121.pdf (follow Wilson, James M., M.D., Ph.D. (PDF-1.37 MB) hyperlink) (notice of initial disqualification proceeding and opportunity to explain). The Washington Post first reported these adverse events after multiple interviews with Wilson and others. In their final fact-checking, which included reading Wilson's previous statements back to him before the story was published, the reporters reveal that,
79. ]hen [Deborah Nelson] reached a section that parroted his earlier representation to us that none of the volunteers preceding Jesse had suffered any serious side effects, he nervously cleared his throat. Maybe, he said, you'd better say there were no life-threatening adverse events. Nelson & Weiss, supra note 30, at 3.
80. Lessons Learned, supra note 9, at 152.
81. Letter from Masiello to Wilson (Nov. 30, 2000), supra note 63, at 5;
82. Lessons Learned, supra note 9, at 154.
83. Lessons Learned, supra note 9, at 154.
84. 68Zd.
85. Federal regulations define a "Significant Financial Interest" as "anything of monetary value, including but not limited to, salary or other payments for services (e.g., consulting fees or honoraria); equity interests (e.g., stocks, stock options or other ownership interests); and intellectual property rights (e.g., patents, copyrights and royalties from such rights)." 42 C.F.R. § 50.603 (2008). The definition excludes: An equity interest that when aggregated for the Investigator and the Investigator's spouse and dependent children, meets both of the following tests: Does not exceed $10,000 in value as determined through reference to public prices or other reasonable measures of fair market value, and does not represent more than a five percent ownership interest in any single entity;
86. Salary, royalties or other payments that when aggregated for the Investigator and the Investigator's spouse and dependent children over the next twelve months, are not expected to exceed $10,000.
87. Id.
88. Wilson, supra note 27, at 244 (adapted with permission from Aspen Publishers).
89. See Memorandum from Denis, supra note 3.
90. See Conflict of Interest Standing Committee Report on Genovo Case, Final Draft, from Neal Nathanson, Chair, CISC, to Barry Cooperman, Vice Provost for Research (Apr. 5, 1995) (on file with author) ("This SRA will be used only to fund work in Dr. Wilson's laboratory and not in the laboratories of other members of his department (Department of Molecular and Cellular Engineering) or the laboratories of members of the Institute for Human Gene Therapy.");
91. Memorandum from Denis, supra note 3.
92. Nelson & Weiss, supra note 17.
93. See Letter from Barry S. Cooperman, Vice Provost, Research, to James Wilson (June 29, 1995) (on file with author).
94. See Hensley, supra note 2.
95. 77 Id.
96. Id.
97. See Memorandum from Denis, supra note 3.
98. See University of Pennsylvania, CISC Procedures (April, 1995), attached to Memorandum from Neal Nathanson to CISC Members (May 7, 1995) (describing the functions of the CISC) (on file with author).
99. Memorandum from Dale M. Lombardi, Sec'y, CISC, to Members of CISC (Mar. 28, 1995) (on file with author). After Jesse's death, an external review panel established to examine Jesse's death, the Danforth Commission, would hone in on the relationship between Wilson and Caplan as a structure that does not permit the ethicist to give independent advice.
100. William H. Danforth et al., Report of the Independent Panel Reviewing the University of Pennsylvania's Institute for Human Gene Therapy, 46 U. PA. ALMANAC, at 4, 4-7 (May 30, 2000), available at http://www.upenn.edu/almanac/ v46/n34/IHGT-review.html (last visited Aug. 7, 2008).
101. Memorandum from Dale Lombardi, Sec'y, CISC, to CISCI Members (Mar. 28, 1995) (on file with author) (draft minutes of Mar. 13, 1995 meeting).
102. See Memorandum from Denis, supra note 3.
103. Memorandum from Dale Lombardi, Sec'y, CISC, to CISC Members (Mar. 3, 1995) (on file with author) (draft minutes of Feb. 6, 1995 meeting).
104. Memorandum from Dale Lombardi, Sec'y, CISC, to CISC Members (Mar. 20, 1995) (on file with author) (final minutes of Feb. 6, 1995 meeting).
105. Memorandum from Lombardi to CISC Members, supra note 82.
106. Id.
107. Memorandum from Seth Kreimer, Prof. of Law, Univ. of Pa., to Dale Lombardi, Sec'y, CISC (May 18, 1995) (on file with author).
108. 90 Id.
109. Id.
110. Fax from Carol Grande, Dir., Ctr. for Venture & Indus. Relationships, to Dale Lombardi, Sec'y, CISC (June 8, 1995) (attached to the Kreimer Memo, supra note 88) (on file with author).
111. Fax from Louis Girifalco to Dr. Barry Cooperman, Vice Provost, Research (July 12, 1995) (on file with author).
112. Id.
113. Id.
114. Id.
115. Fax from Louis Girifalco to Dr. Barry Cooperman, Vice Provost, Research (July 18, 1995) (on file with author).
116. Id.
117. Id.
118. Comments on draft CISC recommendations from Robert Terrell, Assoc. Gen. Counsel, Univ. of Pa., to Barry Cooperman, Vice Provost for Research (Apr. 5, 1995) (on file with author).
119. Id. at 2-3.
120. Fax from Paul Soven, Member, CISC, to Dale Lombardi, Sec'y, CISC (May 31, 1995) (on file with author).
121. Id.
122. Fax from Neal Nathanson, Chair, CISC to Barry S. Cooperman, Vice Provost for Research, CISC (June 20, 1995) (on file with author).
123. Id.
124. Letter from Cooperman to Wilson, supra note 74.
125. Id.
126. Id.
127. Two provisions reiterated existing Penn policies: that human research be approved by Penn's IRB and that animal research be approved by the relevant oversight body.
128. Id.
129. Two other provisions required Wilson to forego the "inventor's share of equity" and "inventor's share of royalties" that Wilson would otherwise have received.
130. Id.
131. Id.
132. Wilson, supra note 9, at 155.
133. Id.
134. (noting that "in this kind of situation, perception can quickly become reality").
135. Id.
136. JERRY MENIKOFF & EDWARD P. RICHARDS, WHAT THE DOCTOR DIDN'T SAY: THE HIDDEN TRUTH ABOUT MEDICAL RESEARCH 226-27 (2006).
137. Nelson & Weiss, supra note 17.
138. Wilson, supra note 9, at 154.
139. Id.
140. Id.
141. Id.
142. Nelson & Weiss, supra note 30, at 1, 2 ("The original consent form reviewed by the RAC disclosed that monkeys died after receiving a high dose of a similar genetically-altered virus carrying the OTC gene. Yet the monkey deaths had disappeared from the consent form that Jesse received, which we got from Penn after obtaining Jesse's father's permission.").
143. See Nelson & Weiss, supra note 17.
144. See supra footnote 52 and accompanying text.
145. Lessons Learned, supra note 9, at 155.
146. Id.
147. Nelson & Weiss, supra note 17.
148. Just as the fact of a conflict does not prove an impact on judgment, neither does the fact of participation by Wilson tell us whether better or different rules would have made a difference in Jesse's trial. This kind of proof will likely never be present when a trial ends badly, unless the conflicted researcher issues a mea culpa. Institutional conflicts of interest have also come under fire. Universities as a group are the single largest patent holder in the world, and make money as a result of translating research of individual faculty into the marketplace. Presumably, if the adenovirus developed by Wilson performed well, Penn would have gained directly, either by licensing the virus or as a result of its equity interest in the licensing body, here Genovo. Thus, while the institutional conflict of interest would likely have been present in any arrangement that Penn authorized, the individual conflict of interest would not have been nearly as pronounced if Penn had required Wilson to divest his shares in Genovo. Cf. supra Part IV (discussing financial conflicts of interest).
149. Concerns for patient trust comprise a third narrative. See, e.g., Kevin P. Weinfurt et al., Effects of Disclosing Financial Interests on Attitudes Toward Clinical Research, 23 J. GEN. INTERNAL MED. 862, 864 (2008) (finding in a survey of adults suffering from diabetes or asthma that disclosures of financial conflicts "were associated with some respondents trusting the researchers less, although trust among some respondents increased," and observing that the "findings regarding trust area important given how central trust can be to participation in research and to public acceptance of research findings, and considering the need to ensure that the clinical research enterprise merits the trust that participants confer on it.").
150. AMERICAN COUNCIL ON SCIENCE AND HEALTH, COLLABORATION BETWEEN SCIENCE AND INDUSTRY: PRO'S AND CON'S OF THE CONFLICTS-OF-INTEREST MOVEMENT 4 (2008). 129
151. Id.
152. Id. at 9.
153. Id.
154. Id. at 10.
155. Id. at 11. The report also criticizes the "conflicts-of-interest movement" for focusing solely on "financial conflicts of interest." Id. It recognizes the complexity of human motivation, discussing factors as varied as political views, age, and sexual orientation, and concludes that "money is not the only basis for a conflict of interest."
156. Id.
157. Id.
158. Steven E. Raper et al., Fatal Systemic Inflammatory Response Syndrome in a Orithine Transcarbamylase Deficient Patient Following Adenoviral Gene Transfer, 80 MOLECULAR GENETICS & METABOLISM 148,157 (2003);
159. see also Steven R. Raper et al., A Pilot Study of In Vivo Liver-Directed Gene Transfer with an Adenoviral Vector in Partial Ornithine Transcarbamylase Deficiency, 13 HUM. GENE THERAPY 163, 174 (2002).
160. Consent Form, supra note 9, at 11.
161. Weinfurt et al., supra note 127, at 861.
162. See Memorandum from Denis, supra note 3.
163. When asked, potential research subjects view equity ownership as much more problematic than receiving per capita payments or other financial conflicts. Weinfurt et al., supra note 127, at 863;
164. Lindsay A. Hampson et al, Patients' Views on Financial Conflicts of Interest in Cancer Research Trials, 355 NEW ENG. J. MED. 2330, 2336 (2006).
165. Letter from Cooperman to Wilson, supra note 74.
166. Lessons Learned, supra note 9, at 154.
167. Id.
168. See supra Part V (discussing comments by the Associate General Counsel Robert Terrell and the Conflict of Interest Standing Committee chair Neal Nathanson, among others).
169. Id.
170. INST. OF MED., CONFLICT OF INTEREST IN MEDICAL RESEARCH, EDUCATION, AND PRACTICE 117-18 (Bernard M. Lo & Marilyn J. Field eds., 2009) ("This recommendation covers principal investigators and others who share substantial responsibility for the design, conduct, or reporting of the findings of clinical studies.").
171. Id. at 117.
172. Jesse A. Goldner, Childress Lecture: Regulating Conflicts of Interest in Research: The Paper Tiger Needs Real Teeth, 53 ST. LOUIS U. L.J. 1211, 1223 (2009)
173. (citing Christine Grady et al., The Limits of Disclosure: What Research Subjects Want to Know About Investigator Financial Interests, 34 J.L. MED. & ETHICS 592, 595 (2006)).
174. INST. OF MED., supra note 145, at 118.
175. Id. at 118-19- Like the IOM, the Association of American Medical Colleges and the Association of American University in a joint report in 2008 recommended that institutions carefully define "compelling circumstances" under which conflicted investigators may participate in research.
176. AAMC-AAU ADVISORY COMM. ON FIN. CONFLICTS OF INTEREST IN HUMAN SUBJECTS RESEARCH, PROTECTING PATIENTS, PRESERVING INTEGRITY, ADVANCING HEALTH: ACCELERATING THE IMPLEMENTATION OF COI POLICIES IN HUMAN SUBJECTS RESEARCH 6-7 (2008). As the joint report explains, "[w]hether the circumstances are deemed compelling will depend in each case upon the nature of the science, the nature of the interest, how closely the interest is related to the research, and the degree to which the interest may be affected by the research."
177. Id. at 6.
178. Kathleen M. Boozang et al., THE CTR. FOR HEALTH & PHARM. LAW & POLICY, SETON HALL LAW SCH., CONFLICTS OF INTEREST IN CLINICAL TRIAL RECRUITMENT AND ENROLLMENT: A CALL FOR INCREASED OVERSIGHT 1 (2009) [hereinafter "WHITE PAPER"].
179. Id.
180. Id. at 28.
181. Id.
182. Id. at 29. This is consistent with the approach taken by most research universities, 81% of which allow researchers with "significant financial interests" to participate in human research in compelling circumstances.
183. See SUSAN EHRINGHAUS & DAVID KORN, U.S. MEDICAL SCHOOL POLICIES ON INDIVIDUAL FINANCIAL CONFLICTS OF INTEREST: RESULTS OF AN AAMC SURVEY, ASS'N OF AM. MED. C. 4 (Sept. 2004), available at http://www.aamc.org/research/coi/ coiresults2003.pdf.
184. WHITE PAPER, supra note 150, at 29.
185. Letter from Cooperman to Wilson, supra note 74.
186. Lessons Learned, supra note 9, at 156.
187. Institutions with post-approval monitoring programs include the University of Virginia, http://www.virginia.edu/vpr/pam/index.html;
188. University of Cincinnati, http://researchcompliance.uc.edu/PAM/Default. html;
189. University of California-Davis, http://safetyservices.ucdavis.edu/iacuc/ policies/post-approval-monitoring-program;
190. Georgia State University, http://www.gsu.edu/research/22242.html;
191. East Tennessee State University, http://www.etsu.edu/ucac/monitoring. aspx;
192. and University of Mississippi, https://secure4.olemiss.edu/umpolicyopen ((follow "Table of Contents" hyperlink;
193. then follow "RSP Research and Sponsored Programs" hyperlink; then follow "RI Research Integrity" hyperlink; then follow "301 Institutional Review Board" hyperlink; then follow "RSP.RI.301.020 IRB Post Approval Monitoring Program hyperlink) (all last visited April 26, 2010).
194. Post Approval Monitoring, University of Virginia, available at http://www.virginia.edu/vpr/pam/index.html (last visited April 26, 2010).
195. Professor Jesse Goldner has also urged institutional reforms to conflict of interest committees, such as regulating membership criteria and mandating inclusion of committee members with no institutional connections. Goldner, supra note 147, at 1247. Additionally, "all financial conflicts of interest of any amount" would be disclosed to the conflict of interest committee as well as on a NIH-sponsored website and in the trial's consent form.
196. Id. at 1248. Conflict of interest committees should describe conflicts of interest in the same section of the informed consent document as the "description of any reasonably foreseeable risks or discomforts to the subject."
197. Id. at 1249-50 (quoting 45 C.F.R. § 46.116(a)(2)).
198. For an example, see The Human Subjects Research Post Approval Monitoring Program, University of Cincinnati, available at http://researchcompliance.uc. edu/PAM/Default.html (last visited April 26, 2010).
199. For an example, see Post Approval Monitoring FAQ, University of Virginia, available at http://www.virginia.edu/vpr/pam/faq.html (last visited April 26, 2010).
200. Of course, had Wilson been required to divest his shares in Genovo, or if Penn had chosen to run the SRA between Biogen and Penn, decisions in Jesse's trial may have nonetheless unfolded precisely as they did. Obviously in the absence of a conflict, the reform urged here would not have flagged Jesse's trial for special vigilance. Institutions nonetheless could choose to police the possibility of errors in non-conflicted trials through random postapproval monitoring or other mechanisms used by the institution to ensure regulatory compliance.
201. See supra notes 24-25, 43-47 (discussion between Paul and Jesse about the risk of death).
202. Weinfurt et al., supra note 127, at 862, 864 (reporting that many subjects would enroll notwithstanding certain financial ties). In a study of cancer patients receiving experimental treatment, 80% expressed no concern "that the doctor running their study might have 'financial ties with the company that makes the drug used in the study.
203. '" Hampson et al., supra note 139, at 2332. "Less than 15% of patients reported that knowledge of a financial tie would have kept them from participating in the cancer trial."
204. Id. Contrasting that statistic with the 13 to 34% of patients who felt that financial ties should be barred led the authors to suspect "that for seriously ill patients, disclosure [of financial ties] is unlikely to provide protection against the potential harm of financial interests."
205. Id. at 2336. Obviously, the risk-benefit calculation of patients in need of experimental therapy for an underlying disease may not predict the assessments that would be made by relatively healthy, functioning participants like Jesse.
206. Nelson & Weiss, supra note 30, at 2 (showing that four successive volunteers suffered side effects so serious that Penn should have halted the study and notified the FDA immediately in every case - but didn't do so for the third or fourth participants).
207. It may be difficult to predict what a market value might be but a probable range could be provided.
208. Nelson & Weiss, supra note 17.
209. Lessons Learned, supra note 9, at 154.
210. Jeffrey J. Rachlinski, A Positive Psychological Theory of Judging in Hindsight, 65 U. CHI. L. REV. 571, 576 (1998).
211. Id. at 579-80.
212. Lessons Learned, supra note 9, at 155.
213. Nelson & Weiss, supra note 30, at 3.