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Journal of Clinical Oncology, Vol 25, No 24 (August 20), 2007: pp. 3567-3569 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.11.9800
The Sound and the Fury: Financial Conflicts of Interest in OncologyH. Lee Moffitt Cancer Center & Research Institute and the Department of Interdisciplinary Oncology, University of South Florida, Tampa, FL
Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
Division of Hematology/Oncology, Department of Medicine, Northwestern University University Feinberg School of Medicine; Robert H. Lurie Comprehensive Cancer Center; Jesse Brown Veterans Affairs Medical Center; and the Veterans Affairs Center for Management of Complex Chronic Care, Chicago, IL In 1957, two game theorists wrote, "In all of man's written record there has been a preoccupation with conflict of interest; possibly only the topics of God, love, and inner struggle have received comparable attention."1 However, conflicts of interest—the problem of how to align competing interests—was not considered from the policy perspective until the 1960s. In this issue of the Journal of Clinical Oncology, Parascandola2 shares a fascinating historical case study of the first conflicts of interest policy at National Academy of Sciences. A fundamental debate in this case was whether one can simply declare a financial interest or whether one must admit that this financial interest is a potential source of bias. Real or perceived threats to research integrity depend, to some extent, on funding sources. In the early 20th century, research was supported by private resources. By 1960, the government supported more than 60% of scientific research.2 Since then, collaboration between industry and academia has increased dramatically. In 1980, the Bayh-Dole Act passed, resulting in the watershed moment that stimulated private-public partnership. This act allowed private entities to patent products of government-sponsored research.3 Today, the leading funder of medical research and education is the pharmaceutical industry.4,5 Public concern about conflicts of interest has paralleled this changing funding dynamic. Early conflicts of interest policies were focused on federally funded university research. Society was increasingly concerned about potential for government and special interests to shape unfairly the research agenda and compromise researchers' objectivity and credibility. In the 1970s, public attention shifted to environmental researchers' ties to the radiation, tobacco, chemical pesticides, and food additives industries.2 As biomedical research has increased during the last 10 to 15 years, public attention has moved to potential conflicts of interest in pharmaceutical industry–sponsored clinical research. What is at stake? The only way to conquer cancer is to develop effective preventive and treatment strategies that the public trusts. However, financial incentives often spur drug development.6,7 As a result, new discoveries are made with the financial and intellectual help of commercial entities.5,7 Many researchers have gained their expertise, in part, through participation in privately financed research. But, here lies the crux of the problem: the goals of pharmaceutical companies, the National Cancer Institute, policy makers, cancer researchers, and society may differ. To develop better cancer treatment strategies, individual researchers and clinicians enter what some would perceive as a Faustian relationship, resulting in perceived or real damage to research integrity. Commercial interests, perhaps unintentionally, may prevail over unbiased assessments of efficacy, safety, and cost effectiveness. Industry involvement also influences conflicts of interest in politics, especially in light of recent reports disclosing that at least 15 former legislators, federal government officials, and congressional staffers who worked to pass medical bills such as Medicare Part D, now work for large pharmaceutical companies and lobbies.8 To date, ethical principles have in large part guided the analysis of the benefits and risks of the relationship between industry and physicians on research, education, and dissemination of research findings.9-11 Detailed empirical evaluation of the impact of conflicts of interest on cancer care is largely lacking. In this issue of the Journal of Clinical Oncology, Hampson et al12 provide needed empirical data on the frequency, type, and monetary value of financial conflicts of interest in cancer clinical research. Hampson et al12 defined personal financial interests as self-reported stock ownership, consulting, honoraria, expert testimony, and other financial interests. Research funding and employment or leadership positions were not counted. Using data from the 2004 and 2005 Annual Meetings of the American Society of Clinical Oncology (ASCO), they estimate that 6% of authors (presenting 23% of abstracts) had personal financial interests.12 Unfortunately, the authors did not break down the dollar amount according to the type of research (eg, randomized controlled trials, cost-effectiveness analyses, and so on), and did not assess methodologic details to deduce potential bias. Between 45% and 60% of authors of presentations with the greatest impact on patient care (plenary and educational sessions) disclosed personal financial interests in the pharmaceutical industry.12 This finding may indicate that drug companies impose undue influence on the scientific process. However, the most prestigious sessions at medical conferences may be more likely to be led by researchers with personal financial interests for a different reason: the expense of discovering important therapeutic advances frequently requires the financial backing of large companies. As Hampson et al12 note, the absolute amount of monetary involvement should be compared with overall income or wealth. Psychology research shows that a $100,000 reward to a millionaire may have less utilitarian value than $100 to a person with no income.13,14 This concept should inform public policy on conflicts of interest, such as the recent US Food and Drug Administration (FDA) proposal to prevent those with more than $50,000 in annual pharmaceutical income from serving on FDA advisory panels.15 In fact, the accepted thresholds for financial interests are based on ethical judgments, resulting in disparity among acceptable financial interests. For example, the de minimus level of personal conflicts of interest according to the Public Health Service and some universities is $10,000, whereas the American Medical Association and the Pharmaceutical Research and Manufacturers of America suggest a limit of $100.16-18 In contrast, the conflicts of interest policy from ASCO states that "disclosure of the conflicting or potentially conflicting interest will itself suffice to protect the integrity of the subject activity."19 According to the ASCO policy, potential conflicts may be resolved through full disclosure and, in effect, are not related to the financial value of the potential conflict. The policy does not have empirical backing at this time. It represents a balancing act between ethical concerns and pragmatic approach to medical research and education. However, guidelines for disclosure are not always followed. Amid growing public pressure, the US Department of Health and Human Services recently indicated that it will revisit 103 cases of conflicts of interest involving investigators at the National Institutes of Health.20 Currently, five states and the District of Columbia have laws mandating state disclosure of payments made to physicians by pharmaceutical companies.21 As noted by Ross et al,16 these laws do not provide ready access to payment information for the public. In a recent editorial, Brennan and Mello22 point out that the major harm of financial conflicts may in fact be to the pharmaceutical industry itself. Attempts to evade regulation and industry-set ethical standards will likely only catalyze the escalating public mistrust of the industry, resulting in more stringent regulation. The crucial question is when do financial conflicts of interest ultimately cloud judgments of scientists, educators, and clinicians? The current study by Hampson et al12 is seemingly reassuring: most authors' personal financial interests were valued at less than $10,000. Personal financial interests of larger amounts were usually associated with employment.12 However, it should be noted that these data are based on self-reporting, and therefore may represent an underestimate. Furthermore, research funding and leadership positions were not included in the measure of financial conflicts of interest by Hampson et al, even though ASCO requires disclosure of these relationships as well. The existing (albeit limited) empirical data on this topic are mixed. Commercial research can adversely affect research agenda, choice of control interventions, publication, and dissemination of results.4,23-26 Additionally, industry support has been correlated with pro-industry conclusions as well as restrictions on data sharing and publication.4,25,27 However, methodologic quality of industry-sponsored studies may often be better.4,28 In addition to commercial interests, many nonfinancial competing interests also affect judgment. Even when physicians attempt to make objective decisions, research shows they are often unintentionally and unconsciously biased toward making the most self-serving decisions.29 Thus, we should not automatically assume that studies by authors with personal financial conflicts of interests are biased, whereas studies by authors without financial conflicts of interest are trustworthy. Much as open debate was necessary to form the National Academy of Science policy described by Parascandola,2 the cancer community, policy makers, and patients need to have an open debate about the totality of financial and other conflicts of interest. Currently, the onus to deduce the trustworthiness of clinical research claims rests with the reader. Although transparency, explicitness, and disclosure can help in facilitating these judgments, the reader is asked to make complex judgments about the values of research findings based on source of funding and financial conflicts of interest. Parascondola2 warns that dealing with conflicts of interest by placing burden with the reader relies on the false premise that the reader is capable of making these complex judgements. As he has pointed out, "it is not the neutrality of individual investigators that keeps us honest, but the diversity of opinions and critical outlook of the scientific community as a whole."30 In other words, the problem of conflicts of interest cannot be handled by shifting the burden to the end-user through disclosure policies—policies that fail to highlight true conflicts. The solution to the problem of conflicts of interest will be found through more empirical research on the effects of personal financial interests on research results and the difficult process of consensus-building at the level of the scientific community. Conflict of interest has been linked with avoidable deaths related to tobacco, pesticide, radiation, and toxic food additives.2 However, there is a lack of solid empirical data to determine if, on balance, relationships between physicians and industry ultimately harm or benefit society. Parascandola2 and Hampson et al12 provide us with guidelines for the way forward. Their approach should be refined and applied more broadly to examine financial conflicts of interest among journal publications, editorial boards, and FDA advisory committee members. Ultimately, we would hope that additional empirical research and ethical analyses should be able to give us an answer to the crucial question: when, if ever, is conflicts of interest acceptable? AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: None Consultant or Advisory Role: Charles L. Bennett, Amgen (C) Stock Ownership: None Honoraria: Charles L. Bennett, Amgen Research Funding: Charles L. Bennett, Amgen Expert Testimony: None Other Remuneration: None AUTHOR CONTRIBUTIONS Conception and design: Benjamin Djulbegovic, Cara Angelotta, Kjersti E. Knox, Charles L. Bennett Financial support: Charles L. Bennett Administrative support: Charles L. Bennett Data analysis and interpretation: Benjamin Djulbegovic, Cara Angelotta, Kjersti E. Knox, Charles L. Bennett Manuscript writing: Benjamin Djulbegovic, Cara Angelotta, Kjersti E. Knox, Charles L. Bennett Final approval of manuscript: Benjamin Djulbegovic, Cara Angelotta, Kjersti E. Knox, Charles L. Bennett REFERENCES 1. Luce RD, Raiffa H: Games and Decisions. New York, NY, Dover Publications, 1957 2. Parascandola M: A turning point for conflicts of interest: The controversy over the National Academy of Sciences' first conflict of interest disclosure policy. J Clin Oncol 25:3609-3614, 2007 3. Bayh-Dole Act, 35 USC 4. Lexchin J, Bero LA, Djulbegovic B, et al: Pharmaceutical industry sponsorship and research outcome and quality: Systematic review. BMJ 326:1167-1170, 2003 5. Moses H III, Dorsey ER, Matheson DH, et al: Financial anatomy of biomedical research. JAMA 294:1333-1342, 2005 6. Barton JH, Emanuel EJ: The patents-based pharmaceutical development process: Rationale, problems, and potential reforms. JAMA 294:2075-2082, 2005 7. Stossel TP: Regulating academic-industrial research relationships: Solving problems or stifling progress? N Engl J Med 353:1060-1065, 2005 8. CBS News: Under the influence. http://www.cbsnews.com/stories/2007/03/29/60minutes/printable2625305.shtml 9. Angell M: The Truth About Drug Companies. New York, NY, Random House, 2004 10. Kassirer JP: On the Take: How Medicine's Complicity With Big Business Can Endanger Your Health. New York, NY, Oxford University Press, 2004 11. Kassirer J: On the take. New York, NY, Oxford University Press, 2005 12. Hampson LA, Joffe S, Fowler R: The frequency, type, and monetary value of financial conflicts of interest in cancer clinical research. J Clin Oncol 25:10.1200/JCO.2006.09.3633 13. Tversky A, Kahneman D: The framing of decisions and the psychology of choice. Science 211:453-458, 1981 14. Tversky A, Kahneman D: Prospect theory: An analysis of decisions under risk. Econometrica 47:263-291, 1979[CrossRef] 15. Harris, Gardiner: FDA limits role of adviser tied to industry. New York Times, March 22, 2007, p A1 16. Ross JS, Lackner JE, Lurie P, et al: Pharmaceutical company payments to physicians: Early experiences with disclosure laws in Vermont and Minnesota. JAMA 297:1216-1223, 2007 17. Pharmaceutical Research and Manufacturers of America: Code on interactions with healthcare professionals. http://www.phrma.org/code_on_interactions_with_healthcare_professionals/ 18. American Medical Association: Gifts to physicians from industry. http://www.ama-assn.org/ama/pub/category/8484.html 19. American Society of Clinical Oncology: Revised conflict of interest policy. J Clin Oncol 24:519-521, 2006 20. Tanne JH: Investigators will review conflicts of interest at NIH. BMJ 334:767a, 2007 21. National Conference of State Legislatures: Pharmaceuticals: Overview and NCSL Resources Marketing and direct-to-consumer advertising of pharmaceuticals. http://www.ncsl.org/programs/health/pharm.htm 22. Brennan TA, Mello MM: Sunshine laws and the pharmaceutical industry. JAMA 297:1255-1257, 2007 23. Djulbegovic B, Cantor A, Clarke M: The importance of preservation of the ethical principle of equipoise in the design of clinical trials: Relative impact of the methodological quality domains on the treatment effect in randomized controlled trials. Account Res 10:301-315, 2003[Medline] 24. Djulbegovic B, Lacevic M, Cantor A, et al: The uncertainty principle and industry-sponsored research. Lancet 356:635-638, 2000[CrossRef][Medline] 25. Bekelman JE, Li Y, Gross CP: Scope and impact of financial conflicts of interest in biomedical research: A systematic review. JAMA 289:454-465, 2003 26. Djulbegovic B, Adams JR, Lyman GH, et al: Evaluation and appraisal of randomized controlled trials in myeloma. Ann Oncol 12:1611-1617, 2001 27. Friedberg M, Saffran B, Stinson TJ, et al: Evaluation of conflict of interest in economic analyses of new drugs used in oncology. JAMA 282:1453-1457, 1999 28. Knox KS, Adams JR, Djulbegovic B: Reporting and dissemination of industry versus non-profit sponsored economic analyses of six novel drugs used in oncology. Ann Oncol 11:1591-1595, 2000 29. Dana J, Loewenstein G: A social science perspective on gifts to physicians from industry. JAMA 290:252-255, 2003 30. Parascandola M: Objectivity and the neutral expert. J Epidemiol Community Health 57:3-4, 2003 Related Articles
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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200-212, 1980
