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“Investigators are required to disclose to an official(s) designated by the institution a listing of Significant Financial Interests (and those of his/her.
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Interest An interest may be defined as a commitment, goal, or value held by an individual or an institution.
Examples include a research project to be completed, gaining status through promotion or recognition, and protecting the environment. Interests are pursued in the setting of social interactions.
Conflict of Interest (COI) A conflict of interest exists when two or more contradictory interests relate to an activity by an individual or an institution. The conflict lies in the situation, not in any behavior or lack of behavior of the individual. That means that a conflict of interest is not intrinsically a bad thing.
Examples include a conflict between financial gain and meticulous completion and reporting of a research study or between responsibilities as an investigator and as a treating physician for the same trial participant.
Institutional examples include the unbalancing of the institutional mission by acceding to the space requests of a large donor for an idiosyncratic program.
Other definitions include:
Conflicts of interest are “situations in which financial or other personal considerations may compromise, or have the appearance of compromising, an investigator’s judgement in conducting or reporting research.” AAMC, 1990
“A conflict of interest in research exists when the individual has interests in the outcome of the research that may lead to a personal advantage and that might therefore, in actuality or appearance compromise the integrity of the research.” NAS, Integrity in Scientific Research
When an individual COI exists, then independent of the behavior of the investigator, those knowledgeable about the study must take the COI into account when judging the validity of the study.
Beyond that, in clinical research, the well being of the subjects may also be compromised by a COI and this has become an overarching factor in the
regulation of financial COIs in clinical research. As noted above, the well being of the participants is paramount and trumps the completion of the research.
The Bayh-Dole act of 1980 made it possible for institutions and individuals to recover substantial financial rewards for their intellectual property as royalties and as equity. Furthermore, the reliance of research sponsors on the expertise of faculty to support a trial agent encouraged substantial payments to accrue to faculty as consultants, often on a continuing basis. Optimizing these financial interests produces a COI situation in relation both to the conduct of the research and to the welfare of trial subjects. Responding to these realities, the NIH, FDA and individual institutions developed rules for investigators to limit the impact of investigator COIs under Federal rules. A reminder follows http://grants2.nih.gov/grants/guide/notice-files/NOT-OD-05-013.html
The actual rules can be found at this URL http://grants.nih.gov/grants/guide/notice-files/not95-179.html
The key provisions are, redacted:
“Investigators are required to disclose to an official(s) designated by the institution a listing of Significant Financial Interests (and those of his/her spouse and dependent children) that would reasonably appear to be affected by the research proposed for funding by the PHS. The institutional official(s) will review those disclosures and determine whether any of the reported financial interests could directly and significantly affect the design, conduct, or reporting of the research and, if so, the institution must, prior to any expenditure of awarded funds, report the existence of such conflicting interests to the PHS Awarding Component and act to protect PHS-funded research from bias due to the conflict of interest.
The definition of "Significant Financial Interest" in 50.603 has been changed in several respects. The exception for financial interests in business enterprises includes salary, royalties or other payments not reasonably expected to exceed $10,000 per annum. Alternative measures of $10,000 in value include stock or no more than five percent ownership interest.”
In my view, $10,000 or an ownership position even if it has no cash value constitutes a significant COI and should be at least disclosed. Disclosure requirements are very poor in that the statute limits them to the institutional administrators and the COI committee. They should be required to disclose every time they present or publish research.
The people who need to know about the COI are those who learn about the results of a study and have to interpret it.
The decision about disclosure of a COI should never be left to the possessors of the COI because they are susceptible to self-deception or worse about the influence of the COI on their research behavior.
Thus, NIH and other funding agencies, Professional Societies sponsoring research meetings, and the leading journals now require disclosure of COIs as a precondition for reviewing, editing, presenting and publishing research and research proposals but there is no means of enforcing the requirement. Voluntary revelation of a COI precludes the reviewing, of a grant or paper. A COI must be disclosed in presenting science.
The Appearance of a COI must be avoided or disclosed. Consider the NY Times test. “Would you want the relationship published in the NY Times?” The presence of Conflicts of Interest tends to diminish the credibility of a study.
The most common conflicts of interest in research are between financial or career rewards and the integrity of a research study, report, presentation, or review. It’s necessary to manage outside income, for consultations for lectures, for courses, for research when conducting a clinical trial.
Full disclosure of conflicts of interest should be required in consent forms, papers, lectures and presentations. COIs may result in:
A new kind of COI has just come to light as the practice has become much more widespread through investigative reporting of the Seattle Times. Many investigators are recruited to consult for financial entities including venture capital firms, hedge funds and investment houses to inform them of the latest developments in their field. The pay is good and the investigators feel quite
flattered. Sometimes, the investigators have provided privileged information about an ongoing clinical trial about which both they and their institutions signed confidentiality statements. In all instances, the goal of the consulting groups is to learn information of investment value before the competition. After the initial concern, apparently this area of concern has lost immediacy.
Dr. Zhivago, in NIH supported research, made remarkable progress in memory studies by identifying a new receptor “C” responsible for instilling and preserving memories. In mice and rats substantial improvements in memory were produced in a short time as demonstrated by performance studies. Activating C in monkeys permitted substantial acceleration in achieving cognitive skills and great enhancement in cognitive capability. Zhivago approached her institution’s Office of Technology to arrange for patent and licensing.
The University had just established a research incubator to carry its inventions to a more advanced stage so that it would be able to retain a greater portion of the financial benefits to come from the products of discovery.
The Office of Technology suggested that Zhivago establish a company with the university to exploit her discovery and develop small molecule receptor agonists for use in treating certain forms of mental retardation as well as Alzheimer’s and other disorders. Neither Zhivago, nor the university officials were unaware of the fact that once approved, the agonists would most likely be taken by normal persons to augment their intellectual capabilities. Zhivago was told that the university would advance up to 1 million dollars of its endowment on this company and that as funding requirements grew, depending on the situation, either more new funds would be allocated or venture capitalists would be invited to invest. Zhivago, figuring that if she reduced her clinical burden and got out of teaching, which were easily arranged, she could spare 30% of time for this project and suggested to her senior technician Anna Karenina that she take a job at the new company, LEARN, with a significant salary increase, and manage the practical details of creating C-receptor agonists under Zhivago’s direction. When the time came, Zhivago would test her drug first in mentally retarded children, her specialty.
Dr. Zhivago delayed publication of her discovery for four months in order to accomplish the patent and license work.
Upon learning of the discovery, a couple of very large drug companies with an interest in mental health volunteered financial support for priority in the bidding for the new agent when it was developed.
You are a member of your institution’s conflict of interest committee charged with the responsibility of determining the significance of Eric Jensen’s conflicts of interest (COI) and to manage it. You are the primary reviewer for Jensen’s proposal. He has invented an electrical device that markedly accelerates the fracture-healing rate. This was brought to the intellectual property office where a patent was requested. Jensen also formed a company to exploit the patent with the University. They induced a large medical apparatus company to manufacture and market the device. The university and Jensen’ company would receive equity and royalties.
Jensen receives a prototype of the commercial version of the device and decides to conduct a clinical trial on healing rates comparing the device with conventional treatment. He will carry out a blinded study using the device appropriately or in an inactive mode.
Going through your E-mails you find the following:
Hansen and Question, a commercial analysis company, is conducting in depth 30 minute interviews with thought leaders in your field about dilational cardiomyopathy for which a new molecular mechanism was just uncovered.
The E-mail indicates that they have been commissioned by a pharmaceutical company to get a further understanding of approaches to the management of this condition. They are willing to pay you $500 for a 30 minute, one on one interview. The E-mail indicates that all your opinions will be reported anonymously in the final report.
As an expert on cardiomyopathy with definite views, you feel that might have a lot to offer the company; after all, you are the PI on a sophisticated study of cardiomyopathy at this very moment.
Cohen, J. J. (2001). "Trust Us to Make a Difference: Ensuring Public Confidence in the Integrity of Clinical Research." Acad Med 76(2): 209-214. Investigators’ and institutions’ financial conflicts of interest in clinical research raise serious questions about the objectivity of such research, the safety of human subjects, and the threat to public trust in the integrity of clinical research. Yet the author makes clear that a conflict of interest is a state of affairs, not a behavior, and therefore not automatically a manifestation of improper actions. But it is clear that both non-financial conflicts of interest and financial ones are double-edged: they can motivate individuals to do their best work but also can compromise judgment and undermine objectivity. The author offers eight suggestions for what academic medicine's leaders might do in this regard (comply with existing full- disclosure requirements; establish principles governing institutional conflicts of interest; etc.). He closes by reiterating that the pursuit of clinical research depends entirely on the ability and willingness of the research community to merit public trust.
(2003). "Protecting Subjects, Preserving Trust, Promoting Progress I: Policy and Guidelines for the Oversight of Individual Financial Interests in Human Subjects Research." Acad Med 78(2): 225-236. (From the Executive Summary) In December 2001, the AAMC Task Force on Financial Conflicts of Interest in Clinical Research released this report, the first of two (both published in this issue of Academic Medicine). This report focuses on gaps in existing federal financial disclosure regulations of individual conflicts of interests, finding that additional scrutiny is recommended in two areas: human subjects research and privately sponsored research. The task force suggests that when potential conflicts exist, a conflicts of interest committee should apply a rebuttable presumption against engaging in human subjects research. The task force recommends that the circumstances giving rise to the presumption against the proposed activity be balanced against compelling circumstances in favor of the conduct of the research. The AAMC task force delineates core principles to guide institutional policy development. First, an institution should regard all significant financial interests in human subjects research as requiring close scrutiny. Second, in the event of compelling circumstances, an individual holding a significant financial interest may be permitted to conduct the research. Whether 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. Four other core principles for development of institutional policies are identified in the report, pertaining to reporting, monitoring, management of conflicts, and accountability.
(2003). "Protecting Subjects, Preserving Trust, Promoting Progress II: Principles and Recommendations for Oversight of an Institution's Financial Interests in Human Subjects Research." Acad Med 78(2): 237-245. (From the Executive Summary) The AAMC Task Force on Financial Conflicts of Interest in Clinical Research issued this report, the second of two, in October 2002. (The first report is also published in this issue of Academic Medicine.) This report offers a unique perspective on the new phenomenon of "institutional" conflicts of interest. The task force acknowledges the diverse obligations of academic institutions that conduct research and also invest in--and accept the philanthropy of--commercial research sponsors. The task force emphasizes the importance of disclosing institutional financial interests as an integral part of the research process, critical to allaying public concerns, and to strengthening the trust relationship between research subjects, the public and the scientific community. The task force found that the safety and welfare of research subjects and the objectivity of the research could be--or could appear to be--compromised whenever an institution holds a significant financial interest that may be affected by the outcome of the research. Thus, the task force recommends separating the functional and administrative responsibilities related to human subjects research from those related to investment managing and
Blumenthal, D., N. Causino, et al. (1996). "Relationships between Academic Institutions and Industry in the Life Sciences -- An Industry Survey." N Engl J Med 334(6): 368-374. Despite growing acceptance of relationships between academia and industry in the life sciences, systematic, up-to-date information about their extent and the consequences for the parties involved remains scarce. They surveyed a representative sample of life-science companies in the United States to determine their relationships with academic institutions by telephone from senior executives of 210 life-science companies (69%). Ninety percent of the companies had relationships with an academic institution in 1994. Fifty-nine percent supported research, providing approximately 11.7 percent of their research-and- development funding. Over 60 percent of those companies had received patents, products, and sales as a result. The companies also reported that they often had agreements to keep the results of research secret beyond the time needed to file a patent. These relationships need greater scrutiny.
Bodenheimer, T. (2000). "Uneasy Alliance -- Clinical Investigators and the Pharmaceutical Industry." N Engl J Med 342(20): 1539-1544. The author details the uncomfortable relationship between clinical investigators who carry out research on new drugs and industry that has a powerful vested interest in the success of their products. Conflicts of interest are widespread with adverse consequences for the science.
Boyd, E. A. and L. A. Bero (2000). "Assessing Faculty Financial Relationships With Industry: A Case Study." JAMA 284(17): 2209-2214. The authors reviewed disclosure forms at UCSF to determine more about clinical and basic science faculty relationships with industry. By 1999, almost 7.6% of faculty investigators reported personal financial ties with sponsors of their research, including paid speaking engagements 34%. 33% had consulting agreements, and 32% involved the investigator holding a position on a scientific advisory board or board of directors. 14% involved equity ownership, and 12% involved multiple relationships. The advisory panel recommended managing perceived conflicts of interest in 26% of the cases. They considered this to be a growing problem that required management.
Boyd, E. A., M. K. Cho, et al. (2003). "Financial Conflict-of-Interest Policies in Clinical Research: Issues for Clinical Investigators." Acad Med 78(8): 769-774. They questioned faculty at UCSF and Stanford who conducted clinical research about their knowledge of and attitudes towards conflict of interest policies. The campus COI policies were a mystery to more than half of those interviewed. Many investigators felt that, rather than the university, monitoring COIs was the job of professional societies, (who have no clout) the public (that understands nothing about this) and, individual investigators (who routinely engage in self-deception) should monitor conflicts of interest. Administrators and policymakers is have to find a way to convince investigators, both clinical and nonclinical, of the serious problems of bias and co-option associated with financial relationships with industry.
Brainard, J. (2001). Federal Rules on Conflicts of Interest in Biomedical Research Are Inadequate, GAO Finds. The Chronicle of Higher Education. Washington. The GAO pointed out what everyone knew and was glad of, namely that COI regulations were weak and unenforceable.
Bramstedt, K. (2003). "Research subject advocates: to whom are they loyal?" Clin Invest Med 26(2): 64-9. The author deals with the issue of conflicts of interest in the activities of Research Subject Advocates. This is based largely on who is paying them. Of course, the main issue is what are they paying them for. GCRC RSAs, for example are paid to support the subjects and they should normally operate in that manner. She deals with the Abiomed artificial heart case in which the subject advocate was sued as wrongly representing the institution. How hard is it for subjects to get the kind of support they need in difficult studies with considerable risk?
Brownlee, S. (2004). Doctors Without Borders: Why you can't trust medical journals anymore. Washington Monthly. This reporter discusses the Nemaroff case in which a physician wrote a review article for Nature Neuroscience in which he failed to reveal his many and profitable conflicts of interest in recommending
drug treatments for psychiatric illness. She goes on to discuss in vivid terms the insidious downside of these conflicts and the great efforts made by industry to involve prominent physicians in supporting their drugs.
Calfee, J. E. (2001). "Pharmaceutical Price Controls and Patient Welfare." Ann Intern Med 134(11): 1060-
He argues forcefully against price controls for drugs as inhibiting innovation and eliminating the risk capitol necessary to bring new ideas to market by killing incentive.
Campbell, E. G., J. S. Weissman, et al. (2001). "Market Competition and Patient-oriented Research: The Results of a National Survey of Medical School Faculty." Acad Med 76(11): 1119-1126. They tried to determine the impact of carrying out clinical care in a competitive environment on research productivity by surveying research faculty (2336 responses). They found that both basic and clinical research productivity was adversely affected by the need to do more clinical care in the most competitive markets. Good study demonstrating the impact of changing priorities for survival.
Cech, T. and J. Leonard (2001). "Science and business. Conflicts of interest--moving beyond disclosure." Science 291(5506): 989. As director of the Howard Hughes Institute the author makes his point about conflicts of interest in research and indicates a strong position in avoiding them.
Cho, M., R. Shohara, et al. (2000). "Policies on faculty conflicts of interest at US universities." JAMA 284(17): 2203-8. This excellent study has become somewhat dated because of the impacts of studies and changing policies secondary to various forces acting on universities. It reviewed COI policies of 89/100 polled Institutions. They found that there was great variability in types of relationships that were controlled, the financial limits, and the disclosures required. They recommended much more specific and consistent rules throughout the country.
Coyle, S. L. (2002). "Physician-Industry Relations. Part 1: Individual Physicians." Ann Intern Med 136(5): 396-402. This is part 1 of a 2-part paper on ethics in physician-industry relationships. Part 1 offers advice to individual physicians; gives recommendations to medical education providers and medical professional societies. While physicians and commerce share an interest in advancing medical knowledge they diverge in that the former is a fiduciary for the patient and the latter has responsibility primarily toward its investors. This can lead to conflicts of interest, biased reporting and issues with appropriate experimental design. While physicians and trainees think they are impervious to Drug Company blandishments, the companies know better. So physicians have to decide for themselves what gifts raise no problems and which do. A general guideline is inexpensive and no strings attached. But, in our society, the very act of accepting a gift creates an obligation. Other financial ties between physicians and industry include honorariums for speaking or writing and payment for doing clinical research. These also can influence a physician's beliefs and practices. The paper goes into considerable detail.
Coyle, S. L. (2002). "Physician-Industry Relations. Part 2: Organizational Issues." Ann Intern Med 136(5): 403-406. This is part 2 of a 2-part paper on ethics and physician-industry relationsips. Part 1 offers advice to individual physicians; part 2 considers medical education providers and medical professional societies. While industry develops advances in medicine it also plays a key role in disseminating up-to-date medical information. The problem is bias and providers of the education must protect against that bias by presenting objective and balanced information. To do that, they must be careful of conditions under which money is collected to carry out their programs. They should insist on control of the content and conditions of the learning process Disclosure of industry sponsorship to students, faculty, and continuing medical education trainees is mandatory. This also applies to medical societies.
Dana, J and G. Lowenstein (2003). "A social science perspective on gifts to physicians from industry." JAMA 290(2): 252-5.
Friedberg, M., B. Saffran, et al. (1999). "Evaluation of Conflict of Interest in Economic Analyses of New Drugs Used in Oncology." JAMA 282(15): 1453-1457. Recent studies have found that when investigators have financial relationships with pharmaceutical or product manufacturers, they are less likely to criticize the safety or efficacy of these agents. In this study of a number of oncology drugs of different kinds, when comparing company vs non- profit supported studies, it was found that overstatement of positive results were less of a problem than a reduced likelihood of reporting unfavorable qualitative conclusions.
Friedman, P. J. (2002). "The Impact of Conflict of Interest on Trust in Science." Sci Eng Ethics 8(3): 413-
This paper is a deep analysis of the corrosive effects of conflicts of interest on trust in schience, with the public and even among investigators. This lack of trust can have an adverse effect on the scientific record as well. Disclosure, our major method of dealing with COIs is really inadequate even if it were well- and completely carried out. We need new rules and new approaches and the author discusses some possibilities. He points out that managing COIs is not institutions of learning’s best suite and that institutions can get into COI problems themselves.
Gelijns, A. C. and S. O. Thier (2002). "Medical Innovation and Institutional Interdependence: Rethinking University-Industry Connections." JAMA 287(1): 72-77. The authors attempt to present a balanced account of the great benefits associated with Industry- Academic collaborations in research and development and the negative impacts of the relationships. This paper reviews institutional patterns of innovations and suggests organizational and public policy implications. This is important reading because many of the papers in this area deal with the negative aspects of university-industry relations and do not deal with the importance of these collaborations for advances.
Hahn, R. (2002). "Conflicts of Interest and the False Comfort of "Full Disclosure"." Professional Ethics Report 15(4). The concept that revealing conflicts of interest in all presentations and publications eliminates their insidious effects on research. Not true, this article claims. The problem is that other mechanisms of control severely limit the incomes of successful scientists.
Hall, S. S. (2001). Claritin and Schering-Plough: A Prescription for Profit. The New York Times. New York. March 11, 2001. This article purports to show that Schering used inadequate science to demonstrate that a mediocre antihistamine was less soporific than the older variety and therefore supplanted the older versions at great cost to society. Ironically, branded clariton sells well as an over-the –counter antihistamine even though it is expensive.
Hart, D. (2002). "The "Corporatization" of Science." Science 295: 439. This letter reviews the history of the support of basic research after WWII and reviews the changes in the scientific community that supported Bayh-Dole and indicated the importance of continuing attention to the new relationships developing as a result.
Horton, R. (2004). "The Dawn of McScience." The New York Review. This review of Seldon Krimsky’s book Science in the Private Interest: Has the Lure of Profits Corrupted Biomedical Research? The reviewer indicates that Krimsky produced a polemic indicating that declaring conflicts of interest will not solve the problems but that the separation of science from industry never truly existed and that, to some extent, the moral requirement to tell the truth in science was always blemished when it related to practical products. The Nancy Oliveri case, as well as the purchase of investigators and physicians by gift giving of pharmaceutical houses, are thoroughly discussed. I think that we are moving in the direction of balance by now, but my naivete may be showing.
Johns, M. M. E., M. Barnes, et al. (2003). "Restoring Balance to Industry-Academia Relationships in an Era of Institutional Financial Conflicts of Interest: Promoting Research While Maintaining Trust." JAMA 289(6): 741-746. This paper deals with University-Industry relationships from the point of view of the research managers and other leaders at academic institutions. The authors discuss divestiture, firewalls and other methods to ensure that industrial affiliations do not corrupt the activities of the university and adversely affect the public trust.
Johnston, J. (2004). "Outing the Conflicted: Et Tu, NIH?" Science 303(5664): 1610b-. This report outlines the findings on NIH senior investigator and administrator conflicts of interest and their potentially serious consequences.
Kaiser, J. (2004). "BIOMEDICAL RESEARCH: Feeling the Heat, NIH Tightens Conflict-of-Interest Rules." Science 305(5680): 25-26. This news article describes the first responses of NIH administration to revelations about intramural conflicts of interest.
Kaiser, J. (2004). "NATIONAL INSTITUTES OF HEALTH: Paid Consulting: Good for the Staff, Not for the Chiefs." Science 304(5673): 936a-937. A news report on the extent of NIH staff involvement in conflicts of interest.
Kaiser, J. (2005). "CONFLICT OF INTEREST: NIH Chief Clamps Down on Consulting and Stock Ownership." Science 307(5711): 824-825. A news report on the NIH ruling on conflicts of interest among its employees.
Kassirer, J. P. and M. Angell (1993). "Financial Conflicts of Interest in Biomedical Research." N Engl J Med 329(8): 570-571. An early voice indicating the growing involvement of with industry and the conflicts of interest and of commitment they engender. Worthwhile reading.
Kassirer, J. P. and M. Angell (1997). "The High Price of Product Endorsement." N Engl J Med 337(10): 700-. Product endorsement by a professional or scientific organization raises serious ethical problems. The endorsement is worth a lot to the product’s company and it is willing to pay well for it. The question is whether the organization has done the comparative testing to determine whether this is a superior product worth endorsing. Organizations take risks to their credibility and financial risks when they endorse a product.
Kjaergard, L. L. and B. Als-Nielsen (2002). "Association between competing interests zand authors' conclusions: epidemiological study of randomized clinical trials published in the BMJ." BMJ 325(7358): 249-. To assess the association between competing interests and authors' conclusions in randomized clinical trials the authors conducted an epidemiological study of randomized clinical trials published in the BMJ from January 1997 to June 2001. Financial competing interests were defined as funding by for profit organizations and other competing interests as personal, academic, or political. They reviewed159 trials from 12 medical specialties.. Authors' conclusions were significantly more positive towards the experimental intervention in trials funded by for profit organizations alone compared with trials without competing interests, trials funded by both for profit and non-profit organizations, and trials with other competing interests. The authors' conclusions were that randomized clinical trials significantly favored
federal agencies in order to analyze their policies on conflicts of interest. There was a very high response rate.. Fifteen of the 250 institutions (6 percent)--5 medical schools and 10 other research institutions-- reported that they had no policy on conflicts of interest. Among the institutions that had policies, there was marked variation in the definition and management of conflicts. They concluded that there is substantial variation among policies on conflicts of interest at medical schools and other research institutions. This variation, combined with the fact that many scientific journals and funding agencies do not require disclosure of conflicts of interest, suggests that the current standards may not be adequate to maintain a high level of scientific integrity.
Moses, H., III, E. Braunwald, et al. (2002). "Collaborating with Industry -- Choices for the Academic Medical Center." N Engl J Med 347(17): 1371-1375. This is a core paper that defines the issues in the various relationships between industry and academic medical centers. They take a drastic step in outlawing (at Harvard) most conflicts of interest with industry.
U. S. G AO (2003). University Research: Most Federal Agencies Need to Better Protect against Financial Conflicts of Interest. G. A. Office. This extensive study of Federal agencies and universities indicated that at the time of the report protection against conflicts of interest was inadequate. Among Federal agencies only the NIH and NSF had policies requiring review and reporting of conflicts of interest related to research support.
Orlowski, J. and L. Wateska (1992). "The effects of pharmaceutical firm enticements on physician prescribing patterns. There's no such thing as a free lunch."Chest 102(1): 270-3. They examined the impact on physician prescribing patterns of pharmaceutical firms offering all- expenses-paid trips to popular sunbelt vacation sites to attend symposia sponsored by a pharmaceutical company. Drug usage patterns were tracked for 22 months preceding each symposium and for 17 months after each symposium. Ten physicians invited to each symposium were interviewed about the likelihood that such an enticement would affect their prescribing patterns. A significant increase in the prescribing pattern of both drugs occurred following the symposia. These changed prescribing patterns were also significantly different from the national usage patterns of the two drugs by hospitals with more than 500 beds and major medical centers over the same period of time. These alterations in prescribing patterns occurred even though the majority of physicians who attended the symposia believed that such enticements would not alter their prescribing patterns.
Patricia, B., D. Jocelyn, et al. (2002). "MEDICINE: Clinical Trials and Industry." Science 297(5590): 2211-.
Royal Australasian College of Physicians (2000). Ethical Guidelines in the Relationship Between Physicians and the Pharmaceutical Industry. The Australians were able to agree on a set of ethical guidelines related to physicians and the pharmaceutical industry. They were opposed to most forms of gifts and proposed a skeptical position. It was not clear the extent to which these guidelines penetrated the profession..
Psaty, B. M., C. D. Furberg, et al. (2004). "Potential for Conflict of Interest in the Evaluation of Suspected Adverse Drug Reactions: Use of Cerivastatin and Risk of Rhabdomyolysis." JAMA 292(21): 2622-2631. In recent years, US patients have increasingly been the first to receive new medications, some of which are subsequently discovered to have suspected adverse drug reactions (SADRs). As a result, the challenge of early detection has largely shifted to the US postmarketing systems. They sought to review the association between the use of cerivastatin sodium and the risk of rhabdomyolysis in an effort to illustrate the operation and limitations of the current US postmarketing safety-surveillance system. In the published literature, cerivastatin was associated with much larger risks of rhabdomyolysis than other statins. Analyses suggested that compared with atorvastatin calcium, cerivastatin monotherapy substantially increased the risk of rhabdomyolysis. To our knowledge, these findings were not disseminated or published. The company continued to conduct safety studies, some of them inadequately designed to assess the risk of rhabdomyolysis, until cerivastatin was removed from the market in August 2001. They concluded that
despite limitations of the available data, the asymmetry between the information available to the company and the information available to patients and physicians seems striking. A subjective element is present in the effort to infer whether or not the occurrence of untoward outcomes in users of a particular drug was actually the consequence of the use of that drug, and, under the current system, a pharmaceutical company's appraisal of SADRs may be influenced by economic considerations. Such an appraisal would best be made by an independent group. They claim US Congress should mandate and provide adequate support for independent reviews and analysis of postmarketing data.
Psaty, B. M. and D. Rennie (2003). "Stopping Medical Research to Save Money: A Broken Pact With Researchers and Patients." JAMA 289(16): 2128-2131. This report documents a case in which a drug company decided that its cancer drug was no longer worth developing and stopped a trial even though they had promised a longer trial in writing. Both the company and the institution were sued.
Ramsay, S. (2001). "Online database reveals researchers' industry ties." The Lancet 357(9269): 1977. This neat idea reveals the great extent to which those conducting clinical research have industry income associated with that activity. The list proceeds apace.
Roberts, T. G., Jr. and B. A. Chabner (2004). "Beyond Fast Track for Drug Approvals." N Engl J Med 351(5): 501-505. Clinical Trials. Deals with fast track mechanism and the importance of selecting probable responses to each new drug. Proposes "selective approval mechanism."
Scherer, F. M. (2004). "The Pharmaceutical Industry -- Prices and Progress." N Engl J Med 351(9): 927-
This report examines the cost and pricing structures of pharmaceutical companies and tries to deal constructively with the demands for lower prices while at the same time supporting costly research. It is a very wor thwhile read.
Schulman, K. A., D. M. Seils, et al. (2002). "A National Survey of Provisions in Clinical-Trial Agreements between Medical Schools and Industry Sponsors." N Engl J Med 347(17): 1335-1341. Concerned about threats to the integrity of clinical trials in a research environment increasingly controlled by private interests, the International Committee of Medical Journal Editors (ICMJE) has issued revised guidelines for investigators' participation in the study design, access to data, and control over publication. It is unclear whether research conducted at academic institutions adheres to these new standards. From November 2001 through January 2002, they interviewed officials at U.S. medical schools about provisions in their institutions' agreements with industry sponsors of multicenter clinical trials. The results demonstrated limited adherence to the standards embodied in the new ICMJE guidelines. Scores for coordinating-center agreements were somewhat higher for most survey items. They suggest that a reevaluation of the process of contracting for clinical research is urgently needed.
Univ. of California Senate. (2004). Report of the University Committee on Research Policy: Problematic Restrictive Clauses in Contracts, Grants and Gifts for Research, University Committee on Research Policy.
Steinbrook, R. (2004). "Conflicts of Interest at the NIH -- Resolving the Problem." N Engl J Med 351(10): 955-957. This intermediate report discusses the various ideas that were considered at the NIH in an attempt to silence criticism while maintaining leeway for extra income for investigators.
The, Editor. (2004). "Publishing Commentary by Authors with Potential Conflicts of Interest: When, Why, and How." Ann Intern Med 141(1): 73-74. This describes their policies at the time.
Weiss, R. (2004). NIH Bans Collaboration With Outside Companies. Washington Post. September 24,
common practices. They propose a policy for academic medical centers to take the lead in eliminating these conflicts of interest that impair patient care.
Stossel, T. (2005). Mere Magazines. The Wall Street Journal. Washington, DC: A16. December 30, 2005. In this brief article Dr. Stossel raises important questions about the arrogance of major medical journals and their persistent negative attitude towards the companies that are responsible for all the advances in medicine that we have seen over the past half-century. Whether or not you end up agreeing with the arguments, this is a refreshing contrast with the uniformity of the beating big Pharma has been taking in the medical literature and the media.
(2004). Financial Relationships and Interests in Research Involving Human Subjects: Guidance for Human Subject Protection. DHHS. Services, Federal Register. 69 (92): 26393-7. This federal guideline asks IRBs and institutions to consider a variety of means to eliminate, document, disclose, and manage conflicts of interest. It is not overly prescriptive but it expects institutions to actively and effectively deal with conflicts of interest both of individual investigators and of IRB members. Conflict of interest committees distinct from IRBs are expected to be developed. Required reading for research administrators.
Brody, B., C. Anderson, et al. (2003). "Expanding Disclosure of Conflicts of Interest: Views of Stakeholders." IRB Ethics and Human Research 25 (1): 1-8.
Kim, S. Y. H., R. W. Millard, et al. (2004). "Potential research participants' views regarding researcher and institutional financial conflicts of interest." J Med Ethics 30 (1): 73-79. This empirical study of the attitudes of potential research subjects towards the revelation of financial conflicts of interest and their existence gave strong evidence that subjects wanted to know. Some would be less inclined to participate in the proposed study knowing of the conflicts of interest. A very nice study. http://jme.bmjjournals.com/cgi/content/full/30/1/
Taylor, R. and J. Giles (2005). "Cash interests taint drug advice." Nature 437 (7062): 1070. This paper and the accompanying editorial deal with groups empanelled by professional societies primarily to write "evidence based" clinical practice guidelines. A study by Materal found that substantial number of the panel members receive income or own stock in companies whose products are under consideration. The influence of these companies may be indirect in promoting drug use in the filed or to encourage use of a specific product. Better methods of developing guidelines are suggested. http://www.nature.com/nature/journal/v437/n7062/full/4371070a.html
Brody, H. and F. G. Miller (2003). "The clinician-investigator: unavoidable but manageable tension." Kennedy Institute of Ethics J 13 (4): 329-46. This paper addresses the two roles of the Clinician-Investigator as scientist and caregiver. The authors indicate that research is very different from care and thus there is ethical tension in doing both (the difference position). Those that argue that the physician's role is similar in both circumstances (similarity position) are claimed to be in error because the position denies the ethical tension. A very worthwhile read.
Mello, M. M., B. R. Clarridge, et al. (2005). "Academic Medical Centers' Standards for Clinical-Trial Agreements with Industry." N Engl J Med 352 (21): 2202-2210. This critical paper delineates the weaknesses of academic institutions in writing contracts that protect data and investigators from bias. This is very important reading. http://content.nejm.org/cgi/content/abstract/352/21/
(2003). "American Society of Clinical Oncology: Background for Update of Conflict of Interest Policy." J Clin Oncol 21 (12): 2387-2393.
The new version of their conflict of interest policy that is based on complete disclosure and a number of prohibitions. A good set of rules that others could emulate. http://www.jco.org/cgi/content/full/21/12/
Bentley, J. P. and P. G. Thacker (2004). "The influence of risk and monetary payment on the research participation decision making process." J Med Ethics 30 (3): 293-298. This questionnaire study attempted to determine the impact of various levels of payment on willingness to participate in a trial. Knowledge of the characteristics of a trial and whether it would lead to behavior damaging the quality of the study. Money was an incentive. The other effects did not seem to be present. http://jme.bmjjournals.com/cgi/content/full/30/3/
Miller, F. G. and A. F. Shorr (2002). "Ethical Assessment of Industry-Sponsored Clinical Trials*: A Case Analysis." Chest 121 (4): 1337-1342. These authors review a single randomized control trial of asthma therapy in children for its ethical characteristics and find it faulty. This is worthwhile reading. http://www.chestjournal.org/cgi/content/abstract/121/4/
Schroter, S., J. Morris, et al. (2004). "Does the type of competing interest statement affect readers' perceptions of the credibility of research? Randomised trial." BMJ 328 (7442): 742-743. http://bmj.bmjjournals.com/cgi/content/full/328/7442/ An empirical study noting a competing financial interest on receiving research support on various aspects of a study. Believability and relevance were both significantly reduced in the presence of a financial conflict. All in all, a weak paper, but provocative. Resnik, D. (2004). "Disclosing conflicts of interest to research subjects: an ethical and legal analysis." Accountability in Research 11 (2): 141-59. The author makes the case that investigators have an ethical and now a legal obligation to disclose their conflicts of interest in a manner such that the study participants will have enough information to sign an informed consent. He argues that disclosure of conflicts of interest should be required in informed consent documents. Campbell, E., B. Moy, et al. (2004). "Institutional academic industry relationships: results of interviews with university leaders." Accountability in Research 11 (2): 103-18. The investigators conducted interviews of university leaders to get their viewpoints on academic- industry relationships. Generally, there were many such relationships and these were generally thought to be constructive. There was understanding that conflicts of interest were pervasive and sometimes risky. Holmes, D. R., B. G. Firth, et al. (2004). "Conflict of interest." American Heart Journal 147 (2): 228. This report of an expert meeting reviews conflict of interest issues from the level of the investigator on to the FDA. It has become somewhat dated because of the recent NIH revelations and rule development and progress in registering clinical trials.
Bernstein, M. (2003). "Conflict of interest: It is ethical for an investigator to also be the primary care-giver in a clinical trial." Journal of Neuro-Oncology 63 (2): 107. The author addresses one of the issues of the day. He comes down in opposition to the AAME report on individual conflicts of interest in clinical research, as supporting such research in many instances. http://www.springerlink.com/openurl.asp?genre=article&id=doi:10.1023/A:
Komesaroff, P. (2005). "Ethical issues in the relationships with industry: an ongoing challenge. New Guidelines open for public comment." J Paediatr Child Health 41 (11): 558-60. In this paper the author explains the extent to which medical decision-making in Australia is influenced by industry. He provides guidelines to Australian physicians as to their behaviors, including the rejection of gifts, subsidized attendance at meeting, and samples. They should not endorse specific products. Clinicians should also avoid recruiting their patients into studies in which they are investigators, as well as only doing studies in which there is a commitment to make the results public. This should be followed by an empirical study on compliance.