Continuing Harvard University’s lecture series on Institutional Corruption at the Edmond J. Sarfa Foundation Center for Ethics, David Korn, M.D., recently lectured the participants about “Financial Conflicts of Interest in Academic Medicine: Whence They Came, Where They Went, Why They Vex Us So.” As the second speaker in the field of medicine to address institutional corruption, Dr. Korn professed to be a “moderate” between Dr. Angell and Dr. Stossel.
Dr. Korn, who attended Harvard for undergraduate and medical school, began teaching and researching in the late 1960s, and eventually went on to become the Dean of Stanford’s Medical School. He was also a professor of pathology and vice provost of research.
Conflict of Interest (COI)
In beginning of his lecture, Dr. Korn framed the definition of COI by using the Institute of Medicine (IOM) report from April 28, 2009, which stated that:
“A COI is a set of circumstances that creates a risk that professional judgments or actions regarding a primary interest will be unduly influenced by a secondary interest.”
Dr. Korn further explained that a COI describes a situation and is not per se a judgment about the character or actions of an individual. Instead, a COI is a set of circumstances that either exist or don’t exist. Looking at it from the behavioral economic perspective, George Loewenstein observed that:
Traditional economics assumes that professionalism and COIs are asymmetric motives in influencing behavior, and that persons who confront COIs are equipped to deal with them rationally.
Behavioral economics posits a more complex model of decision-making, one that includes unconscious motives and other factors outside the control of a purely rational process; biases are viewed as unconscious.
History of COI
Dr. Korn then traced the history of COI back to the late 1970s and 1980s when there were financial COIs with flagrant scientific misconduct that gathered significant major media coverage. In response to this publicity, Congressional hearings were held between the 1980s and 1991, the outcome of which produced a House Committee on Government Operations report titled: “Are Scientific Misconduct and Conflicts of Interest Hazardous to Your Health?”
While investigations were taking place, Congress also directed the Public Health Services (PHS) in 1985 to begin regulating scientific misconduct. (It should be noted the problem was largely limited to government supported research). This regulation eventually led to PHS issuing formal regulations of scientific misconduct in 1988. This was the first time congress asked the government to regulate conduct of federally funded research. Previously, conduct had been left to oversight of academic institutions.
The outcome of these regulations was to prevent fabrication, falsification, and plagiarism in the conduct of federally funded research. He said that such light handed regulations were what academia wanted. In other words, if the government was going to be involved, academia wanted to limit their involvement.
Also occurring in 1988, Congress directed the PHS to regulate financial COIs. These regulations were eventually issued in a 1995 PHS report on financial COIs called, “To Ensure the Objectivity of Research.” Dr. Korn noted that the regulations from this report are still in place today. Dr. Korn called these regulations “light handed” because it only requires institutions that receive federal money to have policies in place and enforce these policies to detect financial COIs in individuals who are going to receive federal funding. Dr. Korn’s issue with this regulation is that there is no requirement to say what the conflict is, what kind of conflict, or how much it is. The regulation states that you only have to identify it and take care of it.
What members of academia feared then, and most continue to be afraid of now, is the political interference with academic and scientific matters the government would have.
If the issue is being managed or resolved in accordance with an institutions policy, and the management of the COI has been reported to the federal agency, why do we need more government oversight?
1995 – 2000
Dr. Korn’s lecture then progresses to what he refers to as “scathing reports” and the President’s Commission, which focused on institutional review boards (IRBs) who had conducted military experiments in WWII that nobody knew about. Since these reports were coming from DHHS, OIG and GAO the focus on COIs moved from individual to institutional, and people began to ask how can we trust an IRB if the institution itself has a financial investment in the research itself?
In response to this concern, the National Bioethics Advisory Commission (NBAC) was formed during the Clinton Administration, headed by Harold Shapiro, with a focus on human subjects research (HSR). NBAC Called for enhanced institutional management of institutional, IRB and individual financial COIs.
Another problem that brought attention to COIs took place when three research subjects died in two clinical experiments, which were physiological trials, not drug trials. One was an interventional trial. The deaths increased calls for enhanced federal oversight, which resulted in the Office for Protection from Research Risks (OPRR) shutting down and suspending human subject research (HSR) in major research universities, which also drew attention.
In addition, the Association for the Accreditation of Human Research Protection Programs (AAHRPP) was also created in response to negative attention, with the responsibility of accrediting human research programs. There was also the formation of the Association of American Medical Colleges (AAMC) Task Force, which Dr. Korn believed helped to “lower the temperature in Washington.” He also added that the creation of these entities during these events helped avoid some serious speculation.
The first AAMC Task force, which Dr. Korn was a member of, issued a report titled: “Policy and Guidelines for the Oversight of Individual Financial Interest in Human Subject Research: Protecting Subjects, Preserving Trust, Promoting Progress (December 2001). Dr. Korn believed the report was very influential, and was directed to medical schools and teaching universities.
The Task Force did not use an absolute prohibition on pursuing HSR research in which one has a financial stake. Instead, the report established a rebuttable presumption, and stated that research may be pursued if the researcher can establish “compelling circumstances.” Among the relevant considerations that make circumstances “compelling” are the nature, magnitude, and “relatedness” of the interest, and the risk to human subjects and to the scientific integrity of the research that these interests pose. The report also noted that circumstances may be compelling if the research could not otherwise be conducted as safely or as effectively. Dr. Korn argued, if that were the standard of compelling, there would probably be fewer financially conflicted individuals.
In October 2002, the same Task Force created: “Principles and Recommendations for Oversight of an Institution’s Financial Interests in Human Subjects Research: Protecting Subjects, Preserving Trust, Promoting Progress II.” This task force defined an Institutional COI (ICOI) to exist whenever the financial interests of the institution, or of an institutional official or committee, create a risk of unduly influencing institutional processes for the review, conduct, or oversight of [human subjects] research.
Dr. Korn acknowledged that a core management principle of institutional COIs is a separation of functions. Specifically, institutional administrative functions and responsibilities related to the oversight of [human subjects] research should be cleanly separated from those related to investment management and technology licensing. He recognized that most major research institutions have this kind of separation.
He then referred to the “partnership,” wherein the university community, protective of academic freedom and institutional autonomy, got the federal government to agree to delegate to the universities major responsibilities for the oversight of federally funded research. He called this the “assurance mechanism,” which he noted is still in use today. Since this assurance is based on a relationship of trust, Dr. Korn noted that institutional COIs are so vexing because when they occur they “shake the assumption of the trustworthiness of the institution.”
21st Century
Moving into the first decade of the 21st century, Dr. Korn highlighted cases of financial COIs such as GSK for suppressing negative clinical trial results of antidepressants; and NIH’s year of embarrassment and draconian regulations in 2004-05 in response to senior scientists engaged in transactions with industry.
NIH responded to their COIs by barring all interactions of NIH researches with industry. This then led to members of Congress to ask “if this is good enough for members of the NIH, why should it not be good for awardees of NIH grants?” That question is still active in Congress, Dr. Korn noted.
He also brought up the 2006 NIH report of its Targeted Site Reviews (TSRs) at 18 awardee institutions, public and private, which identified that the definition of “investigator” was too narrow; required reports to NIH were submitted erratically, if at all; and subrecipient monitoring was poor.
OIG issued a severely critical report of NIH, and Senator Charles Grassley (R-IA) followed-up OIGs report by requesting information regarding certain reports from NIH TSRs. There was also a letter from House Members Dingell and Stupack concerning the National Cancer Institute (NCI) lung cancer trial testing value of CT chest scans, in which the principal investigator had 12 patents on technology related to the research.
Subsequent to these developments, another letter was sent to NIH in February 2008 to 19 institutions requesting detailed information about COIs reported to NIH. There was also former US Attorney Christopher Christie (NJ) who subpoenaed records of payments to physicians from orthopedic device manufacturers that led to a multi-hundred million dollar penalty and agreement to post all such payments on their company websites. Then Senators Grassley and Kohl sent letters to university and hospital presidents alleging failures of Key Opinion Leader (KOL) physician scientists to fully and accurately disclose payments from industry vendors.
In a seemingly rapid response to such investigations, Dr. Korn noted that increasingly, vendor companies are now disclosing payments to physicians, sometimes voluntarily, sometimes as a result of settlements with the DOJ, for example:
- 2008 Cephalon; $425 Million Corporate Integrity Agreement (CIA);
- 2008 Eli Lilly, $1.4 Billion CIA;
- 2009, Pfizer, $2.3 Billion CIA; and
- Voluntary: Merck, J&J, GSK, AstraZeneca.
Dr. Korn also mentioned an AAMC-AAU Workshop in September 2005, which highlighted a lack of consistency in policies and practices across institutions; and a conflict of public expectations. Specifically, the public wanted to see more and more results and tangible benefits, and at same time want researches and institutions to be as pure as possible. He noted this as a conflict for institutions and faculty to manage because by interacting with industry, and commercializing there discoveries, they are realizing one benefit but still have to remain “clean.” He also discussed the AAMC-AAU Advisory Committee in 2006-08, which put together a “How to Do It Manual,” for implementing effective and comprehensive COI programs.
Medical Education
Dr. Korn then shifted to the AAMC Task force study on: “Industry Funding of Medical Education.” He noted the report to find concerns associated with industry funding of Medical Education such as:
- Conflicts of Interest;
- Compromise of objectivity;
- Integrity of professional decision-making;
- Blurring of marketing and scientific evidence;
- Distortions in prescribing or in formulating practice guidelines;
- Hidden curriculum for students and trainees;
- Growing body of scientific evidence about reciprocity and influence; and inadequacy of disclosure as safeguard.
He tried justifying such concerns from presentations given at a symposium on “The Scientific Basis of Influence and Reciprocity” organized by the AAMC. There, speakers discussed the typical MRI imaging studies (that we have dismissed since they use no clinical data), and the idea that people grant themselves moral “wiggle room” within which they can behave deviantly without letting this impair their self-image.
Using this highly controversial research, Dr. Korn raised a number of questions about the proper institutional response to COIs: Should management of COIs be based on a weighing of risks, or should it be formulaic, drawing “bright lines” that may not be crossed? In addition to these questions, he also discussed NIH’s ANPRM in the spring of 2009, and OIG’s November 2009 report, which requested detailed COI information from 41 awardee institutions. The report found:
- 90% of awardees rely “solely on researchers’ discretion to determine which financial relationships should be reported;”
- Less than 50% of awardees to not require specific values;
- No routine verification of information provided;
- Lack of management documentation; and
- Awardees not required to report their own financial interests with outside; research-related entities
As a result, OIG recommended that awardees:
- Report COI details to NIH and collect information on all SFIs held by researchers;
- Develop methods to verify reported financial interests;
- Ensure proper documentation and appropriate awardee enforcement;
- Require NIH to increase oversight; and
- Develop new regulations that address institutional COIs (process is underway).
Conclusion
Interestingly, since Dr. Korn noted that today it might be impossible to find uninvested experts because of the prevalence of industry relations, who can carry out federally funded research that has the right expertise and experience?
If “it’s important for academic scientists to contract with industries that make their work useful for the public, and since those relationships can be managed through institutional policies that are enforced,” as Dr. Korn states, what is the need then for extra oversight? There is no need to respond extremely to recent cases since industry and institutions are doing so on their own.
Accordingly, because duties have become more difficult to live up to as demands for tangible results in research (made by both universities and public funding bodies) have put pressure on physicians commitments to institutional and individual integrity, a more common sense approach is needed. This kind of perspective is important because COIs are particularly troubling because they threaten the long-standing partnership between universities and the government. As a result, Dr. Korn’s recommendation to use guidance by judgment rather than overregulation, will achieve the best balance for managing COIs without hurting patients or relations with physicians and industry.
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Oleg V. Anokhin
http://WWW.APPLY.COM.UA