As we mentioned earlier this week, Richard A. Epstein, a visiting scholar at the Manhattan Institute, examined “How Conflict-of-Interest Rules Endanger Medical Progress and Cures.” The published report was part of the Manhattan Institute’s “Project FDA,” which is a committee of physician-scientists, economists, medical ethicists, and policy experts, which examines the current framework and direction of federal and state regulation to help promote the development of a robust medical innovation pipeline.
Epstein organizes his report into five separate parts. Part I introduces readers to a definition of conflicts of interest (COI). Part II looks at the nature of COI regulations in general. Part III discusses COI in government work. Part IV analyzes COI regulations in university-industry collaboration. Part V discusses conflict of interest (COI) regulations in drug and device marketing. This article will discuss Epstein’s analysis of COI regulations in general, and more specifically in government work and university-industry collaboration.
Definition of COI
There is no universal definition of what constitutes a conflict of interest. Having different understandings of what signifies a “conflict of interest” is one of the problems with COI regulations. Since institutions, agencies, journals, academic medical centers, and professional organizations all use different definitions the meaning of COI varies. Epstein uses the example of the COI policy from Harvard Medical School, which states that "A Faculty Member is considered to have a conflict of interest when he/she, any of his/her Family, or any Associated Entity possesses a Financial Interest in an activity which involves his/her responsibilities as a member of the Faculty of Medicine.”
COI regulation is typically used “before something improper occurs or when sanctions are triggered by the occurrence of some wrongful action (i.e. fudging data).” While regulations that operate prior to the commission of any wrongdoing help prevent “messy scandals,” Epstein points out that they can also impose heavy costs on research projects and development, which result in delay of medical care and denial of medical care. Delay in care can lead to loss of life, and significant time delays for getting products into each stage of drug design, testing, and commercialization.
Epstein asserts that a better way to go about COI regulation is to let the pre and post policies work together in a synergistic fashion. He explains that this approach often “requires a system of using a set of widely circulated and highly publicized announcements to warn individuals of the adverse consequences of conflicts of interest, should they materialize.” Instead of listing all the possible COIs, he notes that “it is better to follow a simple program calling for the release of all experimental data and the disclosure of all funding sources.” Similar to how product warnings have a few clear cautions on the label, but a comprehensive list in the FDA package insert, Epstein states that “simple remedies for complex processes should never be disparaged when they actually alter behavior for the better.”
He also recognizes that strict COI policies, which force disclosures of financial COIs, has markedly diminished the “willingness of governing authorities to issue waivers” for government or institutional researchers. This has the impact of “fewer good people to sit on these committees” and leads to their exclusion from participation in key projects. Such policies run “the high cost of impeding or even stopping the orderly transfer of information among experts at all points in any complex distribution system.”
While disqualification is proper in certain instances, Epstein acknowledges that a total ban on particular persons “should be invoked only when alternative modes of communication and investigation are abundant and secure.” Instead, he asserted that where “only imperfect substitutes are available, continued participation in a given venture should be encouraged, subject to various forms of cooperation, supervision, and oversight by persons who do not labor under the same direct conflict of interest.”
For Epstein, this analysis shows that the new trend of COI regulations “pushes in the wrong direction at key stages of the drug-production cycle.” He recognizes that the “contemporary one-two punch—adopt a broad definition of a conflict of interest, and then impose stiff sanctions for a violation of the conflict-of-interest rules—can block the easy flow of information needed at every stage in the drug-development process.”
COI in Government Work
COI regulations in government agencies such as the NIH and FDA are beginning to block those very channels needed for an easy flow of information needed at every stage in the drug-development process. In Epstein’s detailed analysis of the historical progression of COI policies at the NIH, what is important to take away is that although incidents of serious lapses in judgment have occurred, they “do not suggest a serious institutional breakdown in the applicable scientific norms.” He also notes that incidents involving senior scientists not filing required forms do not suggest “a need for new rules to plug the gap.” Instead, Epstein asserts that these events “suggest only that the rules already on the books should be diligently enforced. Problems with NIH policies include:
Senior scientists and family members having to divest holdings in private companies, making recruitment difficult and would delay treatment and important decisions about products and research.
Encouraging NIH employees to advance science and stay on the cutting edge of research, but not allowing them to interact with scientists in industry, whose applied research could be expedited by contact with the NIH’s basic scientists.
The Office of Technology places heavy barriers in the path of fruitful collaborations between basic scientists and their counterparts in private industry based on the “risk” of some conflict of interest.
A clear bias against industry by preventing NIH scientists from engaging in public health activities and genuine teaching opportunities such as vaccine programs or speaking with a company’s research group.
The clear problem with government policies is that “strict separation that prevents conflicts of interest also prevents cooperation” and collaboration. Institutions depend on collaboration to “encourage scientific interactions that facilitate the cross-pollination of ideas with outside scientists.” As Epstein points out, NIH regulations that go overboard in an effort to hinder such cooperation are unnecessary since “many of these potential exchanges do not pose the slightest risk of inappropriate influence.”
Similarly, the COI policies at the FDA also “tend to eliminate the most valuable advisory committee members” due to the risk of COI. The 49 FDA Advisory Committees are essential for every stage of drug development as well because they review key submissions of the various drug companies. However, FDA’s recent change to more stringent COI policies are causing significant problems for the agency given that over 200 seats on the 49 Advisory Committees are vacant. Not only is this troublesome for the sake of speed and reliability for companies to have their products considered, but the new FDA policies used misguided reasoning.
FDA tightened its COI policies in “response to academic warnings of runaway conflicts of interest.” Policy changes at academic medical centers (AMCs) sprung from the Wazana study, which did not use patient outcomes. Moreover, Epstein noted that claims made in the Wazana study about “differences in apparent patterns of behavior is a far cry from presenting evidence of any newly found dangers in physician care.” Moreover, a study in JAMA showed that the impact of COI on meetings was modest, which means adjustments to practices should be modest.
Given the obvious problems of COI policies in government, Epstein asserted that a “wholesale revision of the basic NIH policy is needed.” He recognized that it “is critical that the NIH treat collaboration as the main objective and conflicts of interest simply as an important side constraint.” In addition, NIH should seek not only to “remove barriers to cooperation but to open additional possibilities to it by sponsoring workshops and conferences that bring together scientists from government and universities to work together on joint projects whenever possible.”
With respect to the FDA, Epstein acknowledged the need for policies to enable the agency to fill seats, instead of placing additional obstacles in the path of that objective. He warned that with stricter rules, “the likely result of this will be to narrow the pool of qualified applicants, which will lead to “additional delay, weaker committees, and more dubious decisions.
Universities have also handled the COI policy problem in a counterproductive manner. Academic scientists address scientific problems until a “proof of principle” is established; then private firms take over the task of commercialization. In the process of taking over commercialization of a product, private firms and “individuals who developed the basic theory often realize that academic scientists are in the best position to aid in its rapid and effective commercialization.” As Epstein explains, that is “why it is commonplace today for many basic scientists in universities to work on outside ventures of a commercial nature, in which they take an ownership or a patent position.”
Recently enacted policies by academic medical centers (AMCs) hinder this relationship by preventing those individuals who know about the field of research from providing valuable information to industry. As Epstein asserts, “to impose an absolute ban on these collaborations would be to force major scientists to take up residence in one camp or the other, in ways that could impoverish both.”
Industry-academic collaboration should be championed, not prohibited. Epstein asks why it is bad that Bayh-Dole does direct research to commercial ends. The reality is, “a project that produces commercial gains benefits individuals, often desperately sick individuals, outside the academic community. Indirectly, it generates tax revenues for the government, some of which can be used to fund further research, and it offers proof that individuals outside the tight circle of academia have gained from the research, for they purchase only those products and services whose value to them exceeds their costs.”
As a result, Epstein recognizes that showing “these tangible benefits could easily affect public support for basic research. Tangible inventions and therapies enable people to see what their tax dollars have bought. If we adopted that view, we would quickly dismiss the universal, if unsubstantiated, fear that the successful commercialization of basic research will sap the public’s confidence in the entire academic enterprise.” This kind of public support is crucial as many “universities today are short on resources to conduct basic research.” Accordingly, Epstein asserts that a proper balance of industry-academic collaboration is needed because blocking out industry support “is deadly to scientific advancement.”
Accordingly, Epstein’s analysis of government and university COI policies makes a clear case for why agencies, institutions, and academic medical centers should not adopt strict COI policies. As Epstein asserts, the government or a private body should not adopt the “ban-first, think-later approach because it could effectively block all formal and informal means of communication” between researchers and industry.
What institutions and policymakers at agencies should take away from Epstein’s recommendations is the need to reassess COI regulations. Extreme responses through strict regulation are not justified from rare exceptions and modest mistakes. The most important tasks that government agencies and AMCs must now address is the need to put collaboration and innovation with industry first, and management of COI second, so that barriers to information are removed and successful progress that our country has enjoyed in medicine the past decade can continue unhindered.
There is no widespread abuse of COI in AMCs or the government, at least not in medicine or scientific research. Instead, there is a natural tendency and desire among industry, physicians, and researchers to seek out the best sources of information to ensure the continued advancement of health and wellness in Americans.