Toward Evidence-Based Conflicts of Interest Training for Physician-Investigators

The Institute of Medicine defines a conflict of interest as “a set of circumstances that creates a risk that professional judgment or actions regarding a primary interest will be unduly influenced by a secondary interest.” Lo B. Field M. , eds., Conflict of Interest in Medical Research, Education, and Practice (Washington, D.C.: National Academies Press, 2009): At46. The primary interests of physician-investigators include advancing the scientific goals of their research and protecting the rights and well-being of research participants. Investigators may have a host of secondary interests as well, including career advancement, intellectual stimulation, and financial gain. Importantly, there is nothing inherently wrong with these secondary interests. As the IOM defines it, and as it is used here, the term “conflict of interest” does not equate to compromised judgment or action but to the risk of such compromisekk.

Ray Dorsey E. de Roulet J. Thompson J. P. Reminick J. I. Thai A. White-Stellato Z. Beck C. A. George B. P. Moses H. , “Funding of US Biomedical Research,” JAMA 303 (2010): 137–143, at 138–140 (explaining that they “used publicly available data, including those from trade organizations and firms' financial reports, to determine industry support”). Not all of these funds are directed to universities, academic medical centers, and physician-investigators; drug, device, and biotechnology firms also have internal research programs.

Id.

Bayh-Dole Act, 35 U.S.C. §§ 200–212.

Kesselheim A. S. , “An Empirical Review of Major Legislation Affecting Drug Development: Past Experiences, Effects, and Unintended Consequences,” Milbank Quarterly 89 (2011): 450–502, at.

Korenstein D. Keyhani S. Ross J. S. , “Physician Attitudes Toward Industry: A View Across the Specialties,” Archives of Surgery 145 (2010): 570–577, at 570 (“Most practicing physicians accept drug samples and gifts, most commonly food in the workplace, and smaller numbers of physicians accept larger payments, such as reimbursement of costs of educational meetings and conferences and speaking and consulting fees”).

See generally, Lessig L. , Republic Lost (New York: Hachette Book Group, 2011): At 21–29 looking at the effect of funding on research outcomes).

Harris G. Carey B. , “Researchers Fail to Reveal Full Drug Pay,” New York Times, June 8, 2008.

See also Gellene D. Maugh T. H. II , “Doctor Accused in Congress' Probe,” Los Angeles Times, October 4∼2008;

“Stanford Researcher, Accused of Conflicts, Steps Down as NIH Principal Investigator,” Chronicle of Higher Education, August 1, 2008.

See, e.g., Patient Protection and Affordable Care Act, Pub. L. No. 111–148, § 6002, 124 Stat. 119, 689 (codified as amended at 42 U.S.C. § 1320a-7h) (amending Part A of title XI of the Social Security Act by adding section 1128G) (2010) (requiring pharmaceutical and medical device manufacturers to disclose payments made to physicians and teaching hospitals for, among other things, conducting clinical research); California Health & Safety Code § 24173(c) (2006) (requiring disclosure to prospective research participants of “[t]he material financial stake or interest, if any, that the investigator or research institution has in the outcome of the medical experiment”).

Press Release, Department of Justice, “Minnesota-Based Medtronic Inc. Pays US $23.5 Million to Settle Claims That Company Paid Kickbacks to Physicians,” December 12, 2011, <http://www.justice.gov/opa/pr/2011/December/11-civ-1623.html> (last visited July 9, 2012) (announcing settlement to resolve allegations that device maker used post-market studies and device registries as vehicles to pay physician-investigators kickbacks to implant the company's pacemakers and defibrillators)

Press Release, Department of Justice, “Minnesota-Based St. Jude Medical Pays U.S. $16 Million to Settle Claims that Company Paid Kickbacks to Physicians,” January 20, 2011, available at <http://www.justice.gov/opa/pr/2011/January/11-civ-078.html> (last visited July 9, 2012) (same)

Murthy v. Abbott Labs., No. 4:11-cv-105, 2012 U.S. Dist. LEXIS 29683, at *24–25 (S.D. Tex. March 6, 2012) (declining to apply the learned intermediary doctrine as a matter of law where a physician-investigator was compensated by the defendant drug company because “[t]he doctrine is premised on the notion that the physician is an objective intermediary who will draw an independent judgment about the best course of treatment for his or her patient.”).

Responsibility of Applicants for Promoting Objectivity in Research for which Public Health Service Funding is Sought and Responsible Prospective Contractors, 76 Federal Register 53,256, 53,293 (August 25, 2011)(codified at 42 C.F.R. §§ 50.601–50.607) (adopting “changes that expand and add transparency to Investigators' disclosure of Significant Financial Interests (SFIs), enhance regulatory compliance and effective institutional oversight and management of Investigators' financial Conflicts of interests, as well as increase the Department of Health and Human Services' (HHS) compliance oversight”).

Rothman D. J. Chimonas S. , “Academic Medical Centers' Conflict of Interest Policies,” JAMA 304 (2010): 2294–2295, at 2295 (“During the past 4 years, a number of academic medical centers (AMCs) have taken the lead in implementing new policies that more strictly manage the relationships between physicians and industry.”).

Advanced Medical Technology Association, Code of Ethics on Interactions with Healthcare Professionals (2009)

International Federation of Pharmaceutical Manufacturers and Associations, Code of Practice (2012)

Pharmaceutical Research and Manufacturers of America, Code on Interactions with Healthcare Professionals (2008).

Lois Snyder for the American College of Physicians Ethics, Professionalism, and Human Rights Committee, “American College of Physicians Ethics Manual: Sixth Edition,” Annals of Internal Medicine 156 (2012): 73–104, at 88–89.

American Medical Association, Code of Medical Ethics, Opinion 8.031 (1999).

American Medical Association, Code of Medical Ethics, Opinion 8.0315 (2001).

American Medical Association, Code of Medical Ethics, Opinion 8.061 (1992).

See Korenstein , supra note 6, at 575.

Id., at 573.

Id.

See also Austad K. E. Avorn J. Kesselheim A. S. , “Medical Students Exposure to and Attitudes about the Pharmaceutical Industry: A Systematic Review,” PLoS Medicine 8, no. 5 (2011): 3 (“In most studies, almost two-thirds of students reported that they were immune to bias induced by promotion, gifts, or interactions with sales representatives in general. This perception of immunity to bias was prevalent in both the preclinical and clinical years. It appeared that students were more likely to report that fellow medical students or doctors are influenced by such encounters than they were personally.”).

Chimonas S. Brennan T. A. Rothman D. J. , “Physicians and Drug Representatives: Exploring the Dynamics of the Relationship,” Journal of General Internal Medicine 22 (2007): 184–190, at 184.

The centrality of internal motivations to comply has been noted in numerous areas of law. See, e.g., Kornhauser M. E. , “A Tax Morale Approach to Compliance: Recommendations for the IRS,” Florida Tax Review 8 (2007): 599–640, at 602 (discussing the importance of taxpayer attitudes and beliefs to tax law compliance).

May P. , “Compliance Motivations: Affirmative and Negative Bases,” Law & Society Review 38 (2004): 41–67, at 48–49 (finding that homebuilders' attitudes and beliefs, including their belief that the building code is necessary heavily influenced their motivation to comply with building code requirements).

Blair M. M. Stout L. M. , “Trust, Trustworthiness, and the Behavioral Foundations of Corporate Law,” University of Pennsylvania Law Review 149 (2001): 1735–1810, at 1780 (arguing that “[l]egal sanctions and market forces often cannot bind corporate participants tightly enough to restrain all opportunistic behavior (at least if one assumes that participants are rational and self-interested players)” because “[t]he information requirements are just too high and the business environment is too complex, opaque, and uncertain.”).

de Melo-Martin I. Palmer L. I. Fins J. J. , “Developing a Research Ethics Consultation Service to Foster Responsive and Responsible Clinical Research,” Academic Medicine 82 (2007): 900–904, at 900–901.

Id., at 901.

21 C.F.R. § 54.2(f).

Hall M. A. Weinfurt K. P. Lawlor J. S. Friedman J. Schulman K. A. Sugarman J. , “Community Hospital Oversight of Clinical Investigators' Financial Relationships,” IRB: Ethics & Human Research 31, no. 1 (2009): At 11.

See Cook A. F. Hoas H. , “Exploring the Obligation to Inform: Disclosing the Purpose and Benefits of Research in an Increasingly Commercial Research Environment,” AJOB Primary Research 2, no. 1 (2011): At 39 (finding that IRBs generally do not have access to “information about the study budget, levels of compensation provided to individuals and departments, and steps to assure that compensation provided to the researcher would not unduly influence their decisions to conduct the research or recruit research subjects[.]”).

Weissman J. S. Koski G. Vogeli C. Thiessen C. Campbell E. G. , “Opinions of IRB Members and Chairs Regarding Investigators' Relationships with Industry,” Journal of Empirical Research on Human Ethics 1, no. 1 (2008): At 7–8 (finding that less than half of the IRB members and administrators surveyed reported that their IRB always reviewed industry relationships).

See Hall , supra note 25, at 8, 10–11.

Id., at 10 (explaining that in general acute care and community hospitals financial relationships may be reviewed by staff with “a range of expertise, including expertise in legal and compliance matters, research administration, and financial and billing practices” and noting that “[a] primary focus in this review…is whether the organization receives adequate reimbursement for its participation in the study.”).

42 C.F.R. § 50.604 (requiring grantee institutions to “[i]nform each Investigator of the Institution's policy on financial Conflicts of interest, the Investigator's responsibilities regarding disclosure of significant financial interests, and of these regulations, and require each Investigator to complete training regarding the same prior to engaging in research related to any PHS-funded grant and at least every four years, and immediately when any of the following circumstances apply: (1) The Institution revises its financial conflict of interest policies or procedures in any manner that affects the requirements of Investigators; (2) An Investigator is new to an Institution; or (3) An Institution finds that an Investigator is not in compliance with the Institution's financial conflict of interest policy or management plan.”). Note that PHS has for many years required that recipients be trained in the responsible conduct of research. The American Medical Association also requires that medical residents be provided with instruction in medical ethics as applied to research.

Other possible methods to influence attitudes include the adoption of policies that limit contact between physician-investigators and pharmaceutical representatives. Similar policies have been shown to have lasting effects on medical residents' attitudes towards pharmaceutical sales representative-provided information. See, e.g., McCormick B. B. Tomlinson G. Brill-Edwards P. Detsky A. S. , “Effect of Restricting Contact between Pharmaceutical Company Representatives and Internal Medicine Residents on Posttraining Attitudes and Behavior,” JAMA 286 (2001): 1994–1999, at 1998.

Montague B. T. Fortin A. H. Rosenbaum J. , “A Systematic Review of Curricular on Relationships between Residents and the Pharmaceutical Industry,” Medical Education 42 (2008): 301–308, at 305 (finding that the scope of published curricula addressing relationships between residents and the pharmaceutical industry “was limited, largely addressing the acceptance of gifts and participation in pharmaceutical industry promotional activities.”).

See Austad, supra note 19, at 10 (“Our findings demonstrate a significant hole in the existing research, most notably the need for studies that can determine whether changes in student attitudes toward the pharmaceutical industry are caused by contact with industry sources, the influence of role models, institutional policies, or other factors.”). Cf.

Wasserstein A. G. Brennan P. J. Rubenstein A. H. , “Institutional Leadership and Faculty Response: Fostering Professionalism at the University of Pennsylvania School of Medicine,” Academic Medicine 82 (2007): 1049–1056, at 1051 (describing but not evaluating the effectiveness of “a mandatory online education program and certification for investigators who intend to do clinical research” that “includes intensive ethics and regulatory training.”).

Jacoby R. , “No–Employed Physicians Need Training, Too,” Journal of Health Care Compliance 7, no. 4 (2005): At 42.

See, e.g., Jones N. L. Pfeifer A. M. Lambros A. Eldridge J. C. , “Pr–Based Learning for Professionalism and Scientific Integrity Training of Biomedical Graduate Students: Process Evaluation,” Journal of Medical Ethics 36 (2010): 620–626, at 620.

Goldstein E. A. Maestas R. R. Fryer-Edwards K. Wenrich M. D. Amies Oelschlager A. M. Baernstein A. Kimball H. R. , “Professionalism in Medical Education: An Institutional Challenge,” Academic Medicine 81 (2006): 871–876, at 871.

Antes A. L. Wang X. Mumford M. D. Brown R. P. Connelly S. Devenport L. D. , “Evaluating the Effects that Existing Instruction on Responsible Conduct of Research Has on Ethical Decision Making,” Academic Medicine 85 (2010): 519–526, at 520.

Id.

Antes A. L. Murphy S. T. Waples E. P. Mumford M. D. Brown R. P. Connelly S. Devenport L. D. , “A Meta-Analysis of Ethics Instruction Effectiveness in the Sciences,” Ethics & Behavior 19 (2009): 379–402, at 380.

Id., at 390–91.

Id., at 393. Also potentially relevant were their findings that ethics instruction was more effective if it (1) focused on the need to think through and analyze complex ethical problems before responding, (2) covered reasoning errors, for example thinking in black-and-white terms, making hasty decisions, failing to weigh future consequences, and overlooking key causes, and (3) offered strategies for working through ethical problems, such as asking for help from someone with an outside perspective, considering the perspectives of others, managing one's own emotions, considering personal motivations, and anticipating consequences.

See Antes , supra note 34, at 519.

Id., at 521 (reporting that “the courses were typically semester-long, required courses aimed primarily at graduate students in biomedical fields.”).

Id., at 523.

Id.

See, e.g., McGee R. Almquist J. Keller J. L. Jacobsen S. J. , “Teaching and Learning Responsible Research Conduct,” Accountability in Research 15 (2008): 30–62, at 56–57. (2008) (finding, consistent with prior studies, that RCR course increased trainees' knowledge of but did not influence their attitudes towards potentially irresponsible or unethical behaviors).

Carroll A. E. Vreeman R. C. Buddenbaum J. Inui T. S. , “To What Extent Do Educational Interventions Impact Medical Trainees' Attitudes and Behaviors Regarding Industry-Trainee and Industry-Physician Relationships?” Pediatrics 120 (2007): e1528–e1535, at e1530.

Id., at e1532.

Id.

Id., at e1534.

Id., at e1533. Interestingly, the two classes from which trainees emerged with more positive attitudes towards industry and physician-industry relationships were developed in conjunction with pharmaceutical companies.

Id., at e1534.

Id.

See Montague , supra note 30, at 305.

Id., at 307.

Id.

Feldman Y. , “Five Models of Regulatory Compliance Motivation: Empirical Findings and Normative Implications,” in Levi-Faur D. , ed., Handbook on the Politics of Regulation (Cheltenham: Edward Elgar, 2011): At 336–339.

Id., at 336.

See May , supra note 21, at 43.

Tyler T. R. , “Legitimacy and Criminal Justice: The Benefits of Self-Regulation,” Ohio State Law Journal 7 (2009): 307–359, at 309.

See Feldman , supra note 54, at 336.

Id., at 337.

Tang H. Cowling D. W. Lloyd J. C. Rogers T. Koumjian K. L. Stevens C. M. Bal D. G. , “Changes of Attitudes and Patronage Behaviors in Response to a Smoke-Free Bar Law,” American Journal of Public Health 93 (2003): 611–617, at 616.

See Feldman , supra note 54, at 337.

Id.

Posner E. A. , “The Legal Construction of Norms: Law and Social Norms: The Case of Tax Compliance,” Virginia Law Review 86 (2000): 1781–1819, at 1785–1791.

Id.

Feldman Y. , “An Experimental Approach to the Study of Social Norms: The Allocation of Intellectual Property Rights in the Workplace,” Journal of Intellectual Property Law 10 (2002): 59–83, at 82–83.

Id., at 85, 91, and 110.

Id., at 91.

See Feldman , supra note 54, at 338.

Mazar N. Amir O. Ariely D. , “The Dishonesty of Honest People: A Theory of Self-Concept Maintenance,” Journal of Marketing Research 45 (2008): 633–644, at 634.

Id., at 636–37.

Sheppard B. Cushman F. , “Evaluating Norms: An Empirical Analysis of the Relationship between Norm-Content, Operator, and Charitable Behavior,” Vanderbilt Law Review 63 (2010): 55–103, at 80.

Id., at 83.

Id.

Id., at 63.

See Feldman , supra note 54, at 338.

Id.

Tyler T. Blader S. L. , “Can Businesses Effectively Regulate Employee Conduct? The Antecedents of Rule Following in Work Settings,” Academy of Management Journal 48 (2005): 1143–1158, at 1147.

Id., at 1152.

See Feldman , supra note 54, at 339.

See Antes , supra note 34, at 524.

Basken P. , “As He Worked to Strengthen Ethics Rules, NIMH Director Aided a Leading Transgressor,” Chronicle of Higher Education (June 6, 2010) (reporting that Dr. Charles Nemeroff, who failed to disclose $1.2 million in payments from drug and device companies, “has largely avoided NIH restrictions for [his] actions”).

Cf. Weber T. Ornstein C. , Doctors Avoid Penalties in Suits against Medical Firms, ProPublica, available at <http://www.propublica.org/article/doctors-avoid-penalties-in-suits-against-medical-firms> (last visited August 6, 2012).

21 C.F.R. § 54.2(e).

See Feldman , supra note 54, at 340.

Cain D. M. Loewenstein G. Moore D. A. , “The Dirt on Coming Clean: Perverse Effects of Disclosing Conflicts of Interest,” Journal of Legal Studies 34 (2005): 1–25, at 6.

See Feldman , supra note 54, at 337.

Campbell E. G. , “Physician Professionalism and Changes in Physician-Industry Relationships from 2004 to 2009,” Archives of Internal Medicine 170 (2010): 1820–1826, at 1820.

See Mazar , supra note 69, at 637.

Id.

While our focus is on the content of Conflicts of interest training, there are, of course, other issues related to training that academic medical centers will have to address including when and how often in the course of a physician's career it should occur, who should develop and conduct it, and how it should be funded.

See Feldman , supra note 54, at 336

Beresin E. V. Baldessarini R. J. Alpert J. Rosenbaum J. , “Teaching Ethics of Psychopharmacology Research in Psychiatric Residency Training Programs,” Psychopharmacology 171 (2003): 105–111, at 109 (“Simple multiple-choice tests can suffice for this purpose, and programs can devise their own methods of testing. …Another method of testing would be to give a sample protocol designed for submission to an IRB to residents and faculty to rate by the RePEAT protocol-assessment scheme, and perhaps discuss in a seminar, ideally with the principal investigator of the study present.”).

See Antes , supra note 34, at 525.

Id.

Merrill D. B. Girgis R. R. Bickford L. C. Vorel S. R. Lieberman J. A. , “Teaching Trainees to Negotiate Research Collaborations with Industry: A Mentorship Model,” American Journal of Psychiatry 167 (2010): 381–386, at 381.

Center for Health & Pharmaceutical Law & Policy, Seton Hall University School of Law, Conflicts of Interest in Clinical Trial Recruitment & Enrollment: A Call for Increased Oversight (2009): 1–55, at 25.