More regulation of industry-supported biomedical research: Are we asking the right questions?

Journal of Law, Medicine and Ethics

Volumn 37, Issue 3, 2009, Pages 420-430

  Fry Revere, Sigrid ^a   Malmstrom, David Bjorn ^b  

^a Center for Ethical Solutions   (United States)

^b GEORGE MASON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CONFERENCE PAPER; CONFLICT OF INTEREST; DRUG APPROVAL; DRUG INDUSTRY; ETHICS; FINANCIAL MANAGEMENT; HUMAN; LEGAL ASPECT; MANAGEMENT; MEDICAL RESEARCH; UNITED STATES;

BIOMEDICAL RESEARCH; CONFLICT OF INTEREST; DRUG APPROVAL; DRUG INDUSTRY; HUMANS; POLICY MAKING; RESEARCH SUPPORT AS TOPIC; UNITED STATES;

EID: 69649083475     PISSN: 10731105     EISSN: 1748720X     Source Type: Journal    
DOI: 10.1111/j.1748-720X.2009.00403.x     Document Type: Conference Paper

References (70)

1. If the reader believes that certain conflicts are unavoidable, it is worth noting that some authors have argued that conflicts of interests or researcher biases are unavoidable, and because of this, it is only proper to consider the conflicts in a graded fashion. Thus, there should be no per se prohibition against these conflicts depending where they fall on the continuum from minor to serious. See generally J. I. Gallin and F. P. Ognibene, eds., Principles and Practice of Clinical Research (Burlington, MA : Academic Press, 2007 at 248.
2. See, e.g., T. P. Stossel Regulating Academic-Industrial Research Relationships - Solving Problems or Stifling Progress New England Journal of Medicine 353, no. 10 (2005 1060 1065, at 1061 ("The death rate in industry-sponsored phase 1 oncology trials has not changed during the past 10 years, despite growing collaboration between academe and industry. To conclude that the hope of financial gain contributed at all to any errors leading to Gelsinger's death, in the absence of a confession or other evidence, is purely speculative.").
3. M. Andersen, J. Kragstrup, and J. Sondergaard How Conducting a Clinical Trial Affects Physicians' Guideline Adherence and Drug Preferences JAMA 295, no. 23 (2006 2759 2764
4. T. A. Brennan et al., "Health Industry Practices That Create Conflicts of Interest: A Policy Proposal for Academic Medical Centers," JAMA 295, no. 4 (2006): 429-433.
5. See Andersen, supra note 3, at 2764.
6. J. E. Bekelman, Y. Li, and C. P. Gross Scope and Impact of Financial Conflicts of Interest in Biomedical Research: A Systematic Review JAMA 289, no. 4 (2003 454 465, at 463 ("Despite the prevalence of these relationships and the broad concerns they have generated, a relative paucity of data has been published describing the impact of financial ties on biomedical research.") available at http://www.medscape.com/viewarticle/468818
7. L. S. Friedman and E. D. Richter, "Relationship Between Conflicts of Interest and Research Results," Journal of General Internal Medicine 19 (2004): 51-56, available at http://www.medscape.com/viewarticle/468818 last visited May 27, 2009) ("Because of the limitations of our data, we are unable to determine the reasons for the observed association between [conflicts of interest] and reported findings.").
8. See, e.g., E. G. Campbell et al. Financial Relationships between Institutional Review Board Members and Industry New England Journal of Medicine 355, no. 22 (2006 2321 2329
9. see Brennan et al., supra note 3
10. see Brennan et al., supra note 3; V. Colliver, UCSF Study Questions Drug Trial Results, San Francisco Chronicle, June 5, 2007, at B-1
11. D. Korn Conflict of Interest in Biomedical Research available at http://www.hhs.gov/ohrp/coi/korn.htm last visited May 27, 2009). (However, "the existence of conflicts of interest cannot be eradicated; their existence must be accepted and not equated with professional misconduct.").
12. See Campbell, supra note 6, at 2323 (emphasis mine). The authors conclude that one potential limitation with their study is that the conflicts of interests identified were de minimis because they treated rather insignificant financial interests the same as significant financial interests. This is part of the ongoing problem of defining "conflict of interest" that is slowly developing into a catchall that tells us little; a binary treatment of this issue does not get us away from simple correlations to actual causation.
13. Id.
14. T. Bodenheimer Uneasy Alliance - Clinical Investigators and the Pharmaceutical Industry New England Journal of Medicine 342, no. 20 (2000 1539 1544, at 1543 (quoting Lee Goldman, chairman of the Department of Medicine, University of California at San Francisco, "... companies translate biological advances into useable products for patients. They do it for a profit motive, but they do it, and it needs to be done.") Another example is the hepatitis B vaccine that resulted from the biotechnology industry that formed after a joint venture of academic researchers and venture capitalist. (Pubitemid 30318291)
15. See Stossel, supra note 2, at 1060
16. C. D. DeAngelis, Editorial, "The Influence of Money on Medical Science," JAMA 296, no. 8 (2006): 996-998, at 996 ("The discovery of new medications, devices, and techniques is funded primarily by for-profit companies; testing new modalities of treatment is funded primarily by for-profit companies; and the manufacture and profitable marketing aspects of these modalities appropriately falls in the purview of this industry.").
17. See generally Bodenheimer, supra note 8, at 1539 (The infusion of industry dollars into an industry-investigator partnership has clearly improved clinical practice.)
18. See, e.g., R. Porter and T. Malone, Biomedical Research: Collaboration and Conflict of Interest (Maryland : The Johns Hopkins University Press, 1992 at 128 ("... the role of a talented consultant -who may also have equity in the company - in bringing a product to the marketplace may be invaluable; such a person may play a very positive, constructive role.").
19. Industry professionals are no less ethical than their contemporaries are, and it is in the best interest of industry to seek the truth. Quoting Bloch, a company's fundamental approach to science is "antithetical to biased reporting or interpretation of research results." This is so because, eventually, the "truth will out" any failures or misbehavior when the product is being used by patients. Thus, it is in the best interest to avoid any biases because it will harm both the patients whom they serve, and the companies themselves. See Porter, supra note 12, at 132.
20. P. Taylor End of the Line Looms for Able Laboratories Pharama Technologist, available at http://www.in-pharmatechnologist.com/news/ng.asp?id= 61928-able-laboratories-quality-control-liquidation last visited May 27, 2009) (After the incident Able entered into negotiations with the FDA for a 'rescue' package that was later denied and has since sold off all the assets of the business).
21. R. J. Porter, Conflicts of Interest in Research: The Fundamentals in Biomedical Research: Collaboration and Conflict of Interest, R. J. Porter and T. E. Malone, eds. (Baltimore and London : The Johns Hopkins University Press, 1992 at 122-123.
22. S. Chopra Industry Funding of Clinical Trials: Benefit or Bias JAMA 290, no. 1 (2003 113 114.
23. See Bekelman, supra note 5, at 464
24. It is worth noting that government sponsored clinical trials are not immune to conflicts of interests. See L. Barclay BMJ: Pharmaceutical Industry-Physician 'Entanglement' Affects Research, Care Medscape Medical News, June 3, 2003, available at http://www.medscape.com/viewarticle/456554 last visited May 28, 2009). (Quoting Joel Lexchin, M.D., associate professor of health policy and management at York University in Toronto, Ontario, Canada "Government-funded studies may have biases too; for example, their bias might be to show that the least expensive drug for a given indication is as good as the most expensive...").
25. The study recognizes the limitations of interviewing patients with serious life-threatening illnesses; more research on the patients' perspective on financial conflicts of interest is welcome. L. Hampson et al. Patients' Views on Financial Conflicts of Interest in Cancer Research Trials New England Journal of Medicine 355, no. 22 (2006 2330 2337, at 2330.
26. E. G. Nabel, Editorial, "Conflict of Interest - or Conflict of Priorities New England Journal of Medicine 355, no. 22 (2006 2365 2367, at 2633.
27. Despite the rarity of deceit in clinical trials, there is circumstantial evidence that trials conducted with blinding result in even less incorrect results due to bias than trials without blinding. See Gallin, supra note 1, at 246.
28. This method is used by the federal government in their prohibition against employees participating in an official capacity in matters affecting their own financial interests. See generally Gallin, supra note 1, at 115.
29. For a discussion of the potential problems with requiring disclosure, see P. N. Ossorio Pills, Bills and Shills: Physician-Researcher's Conflicts of Interest Widener Law Symposium 8, no. 1 (2001 75 103, at 100-102.
30. Alliance for Human Research Protection, Seattle Times Series on Fred Hutchinson Cancer Center, available at http://www.ahrp.org/ethical/ SeattleTimesHutchinson.php last visited May 28, 2009).
31. P. Shanks, Human Genetic Engineering: A Guide for Activists, Skeptics, and the Very Perplexed (New York : Nation Books, 2005 at 137-140.
32. Drug Trial Victim's 'Hell' Month BBC News, available at http://news.bbc.co.Uk/2/hi/health/5121824.stm last visited May 28, 2009).
33. See generally Campbell et al. supra note 6
34. "There are even disagreements about the definition of a conflict of interest. Many attach qualifiers, such as 'potential' or 'apparent,' in an attempt, it often seems, to be delicate or nonjudgmental." J. P. Kassirer and M. Angell, Editorial Financial Conflicts of Interest in Biomedical Research New England Journal of Medicine 329 no. 8 (1993 570 571
35. The one noteworthy exception is Ossorio, supra note 21.
36. (quoting J. Palca NIH Grapples with Conflict of Interest Ethics in Science 245, no. 4913 1989 at 23
37. See Porter, supra note 12, at 125
38. Conflict of interest Merriam-Webster Online Dictionary, 2007, available at http://www.merriam-webster.com last visited May 28, 2009).
39. B. A. Garner, ed., Black's Law Dictionary, 8th ed. (St. Paul : West Group, 2004).
40. We use the words "official" and "professional," "personal" and "private," and "responsibilities" and "duties" interchangeably. We realize that they do not mean exactly the same thing, but for the purposes of this discussion, the distinctions are negligible.
41. Nor does the American Bar Association or the American Medical Association provide a definition of "appearance of impropriety." Both organizations provide multiple examples of which might cause an appearance of impropriety but do not specifically give a definition.
42. Thessalonians 5:22.
43. Complaints (Appearance of Impropriety), Navy Inspector General, available at http://www.ig.navy.mil/Complaints/ Complaints%20%20(Appearance%20of%20Impropriety).htm last visited May 28, 2009).
44. See R. Rotunda Judicial Ethics, the Appearance of Impropriety, and the Proposed New ABA Judicial Code Hofstra Law Review 34, no. 4 (2006 1337 1377, at 1337 (2006). (The ABA has not defined the "appearance of impropriety" with any precision and specifically avoided including a restriction on appearances of impropriety for lawyers, Professor Rotunda strongly urges that the same rule be removed from the ABA Judicial Codes for the same reasons
45. R. M. Levin, Fighting the Appearance of Corruption, available at >http://www.wulaw.wustl.edu/journal/6/p171-Levin.pdf< (last visited May 28, 2009)
46. This distinction has been made concerning presidential campaigns, but we believe the point lends itself well to medical ethics. See generally R. M. Levin Fighting the Appearance of Corruption available at http://www.wulaw.wustl.edu/ journal/6/p171-Levin.pdf last visited May 28, 2009).
47. For a similar distinction and suggestion see Porter, supra note 12, at 128.
48. Interest," Merriam-Webster Online Dictionary, 2007, available at http://www.merriam-webster.com last visited May 28, 2009).
49. Obligation," Merriam-Webster Online Dictionary, 2007, available at http://www.merriam-webster.com last visited May 28, 2009).
50. J. Salmond, Jurisprudence, or, the Theory of Law (London : Stevens and Haynes, 1907 at 427.
51. This fundamental confusion between research subjects and patients is affecting the media and others alike. It is important for all to remember that experiments are experiments, thus the ex ante justification (if rightful and noble) for engaging in an experiment ought to be paramount to any ex post criticism absent any willful and negligent disregard for the participant's life and well-being.
52. Informed Consent: Chapter 8: Finding Clinical Trials Thomson Center Watch, available at http://www.centerwatch.com/patient/ifcn-08.html#Section1 last visited May 28, 2009).
53. P. C. Gotzsche, Research Letter to Editor, "Constraints on Publication Rights in Industry-Initiated Clinical Trials JAMA 295, no. 14 (2006 1645 1646, at 1645.
54. See Andersen, supra note 3, at 2759
55. See Campbell, supra note 6.
56. Pilar Ossorio makes this point. It is "merely good business" to direct money towards promising drugs. Thus, arguments that articles sponsored by a single pharmaceutical company are more likely to support outcomes favoring that company's drug are not necessarily spawned by financial conflicts. "Pharmaceutical manufacturers presumably support researchers whose preliminary data suggest a favorable outcome for the manufacturer's drug." See Ossorio, supra note 21, at 92.
57. T. J. Moore et al. Serious Adverse Drug Events Reported to the Food and Drug Administration, 1998-2005 Archives of Internal Medicine 167, no. 16 (2007 1752 1759, at 1752.
58. The authors themselves dismiss this possibility as unlikely but go on to state that there is insufficient data to accurately decide one way or another. Thus, as unlikely as Thomas Moore and his colleagues would like this possibility to be, they admit the rate of increase in adverse events could be possible due to an increase in reporting. They try to argue against this possibility by pointing out that the reporting for some drugs has not gone up, but has actually gone down, and that this is proof that there has not been a general trend towards more reporting. But, they defeat their own argument when they admit that the rate of adverse events vary from one drug to another and for the same drug over time. They also argue that if the increase in adverse events reported were due to an increase in reporting, then the rate of reporting by physicians should increase at the same rate as the rate of reporting by manufacturers. This is a simple non sequitur. All that can be deduced from this observation is that whatever has motivated an increase in reporting by manufacturers has not motivated the same rate of reporting by health professionals or consumers, neither of which is proof that the actual rate of adverse events has gone up.
59. Id., at 1754.
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64. See Ossorio, supra note 21, at 98.
65. R. M. Wolfe Expenditures for U.S. Industrial R&D Continue to Increase in 2005; R&D Performance Geographically Concentrated National Science Foundation Info Brief: Science Source Statistics, NSF 07-335 (2007 available at http://www.nsf.gov/statistics/infbrief/nsf07335/nsf07335.pdf last visited June 2, 2009).
66. S. S. Buchkowsky and P. J. Jewesson Industry Sponsorship and Authorship of Clinical Trials Over 20 Years Annals Pharmacotherapy 38, no. 4 (2004) 579 585.
67. Id.
68. J. J. Cohen and E. K. Siegel Academic Medical Centers and Medical Research: The Challenges Ahead JAMA 294, no. 11 (2005 1367 1372.
69. H. Brody, Hooked: Ethics, The Medical Profession, and the Pharmaceutical Industry (New York : Rowman & Littlefield Publishers, Inc., 2007).
70. For an additional "solution," see P. Tereskerz, Riding the Green Wave: Financial Conflicts of Interest in Industry-Sponsored Clinical Research (Hagerstown, Maryland: University Publishing Group, 2007): at 159, 164 (Tereskerz, argues for the establishment of "a U.S. government research brokerage firm or clearing house" which would "rank all the proposals [for new drugs] it receives, based on scientific merit" and then decide which of competing investigators would be granted the privilege of doing the necessary clinical trials at the companies expense, including funding the government clearing house through a "required indirect cost rate added to all study budgets.").