Conflicts of Interest(In Clinical Research) Multidisciplinary Clinical Research Career Development Program University of Maryland February 28, 2008
Some Things to Think About • Which aspects of a given situation constitute CoI? Which are directly financial and which are not? • How can CoI affect the conduct of research? Of the scientific record? • What are the ramifications of CoI for scientists as researchers? As consumers of scientific information?
Some More Things to Think About • What can scientists do to avoid the ramifications of CoI? • What regulations apply to CoI in research? • How is CoI in research routinely managed? • How should CoI in research be managed?
Conflict of Interest Situation in which the integrity of academic activity, especially research, may be, or may be perceived to be, compromised by financial or other interests.
Perceived Actual vs Conflicts of Interest
Baltimore Sun December 8, 2006 By Matthew Dolan Government Scientist Pleads Guilty Senior Alzheimer’s Researcher Admits Taking $285,000 In Fees, Expenses A senior government scientist working in Alzheimer’s disease research pleaded guilty today to accepting $285,000 in consulting fees and travel expenses from the world’s largest drug manufacturer without proper approval from his bosses. As part of his agreement with federal prosecutors, Pearson “Trey” Sunderland III, chief of the geriatric psychiatry branch of the National Institute of Mental Health, which is part of the National Institutes of Health, will be sentenced to two years of supervised probation and must forfeit $300,000.
Conflicts of Interest • Most are financially based • Some are just accepted • Owning an hypothesis • Research results as proprietary information pending publication • Continuing research support • Developing intellectual property R P Taleyarkhan Woo Suk Hwang
Roles Entrepreneur Scientist Produces data which may be built upon Uses the scientific method Rules out alternatives to an idea Avoids risky approaches to a problem Produces something marketable Uses business development models Develops support for an idea Is comfortable accepting and managing risk
Similarities Scientist Entrepreneur Reputation is a key asset It’s all about gaining acceptance of a new idea Passion for the enterprise is essential
Sources of Potential Conflict • Consultant • Speaker • Stock or Other Equity • Management Position • Income from Royalties or Licensing Fees • Board or Scientific Advisory Board Member • Gift • Relationship with Competitor • Loans (To or From) • Family Member has Relationship Institutional vs Invididual CoI
Does conflict of interestpresent a legitimate concern? Financial interests steer the academic activity to the point where it is compromised Financial interest gives the appearance that the academic activity may be compromised Maintaining full academic integrity would compromise the business plan and/or require excess resources
Science Gone Wrong What’s the worst that could happen?
Examples of What We are Guarding Against Deciding not to publish research results which would be harmful to the entity Agreeing to develop a research protocol to the entity’s specifications Falsifying or fabricating research results which would be beneficial to the entity Conducting research which poses significant risk in order to develop a technology licensed by the University
Relationship betweenFunding Source and Conclusion amongNutrition-Related Scientific Articles • 111 of 206 articles declared financial sponsorship • 22% had all industry funding • 47% had no industry funding • 32% had mixed funding • Funding source was significantly related to conclusions for all article types (p=0.037) • Odds ratio of favorable to unfavorable conclusions for all industry funding vs no industry funding was 7.61 • Interventional studies • 0% unfavorable conclusions for all industry funding • 37% unfavorable conclusions for no industry funding Data from Lesser, et al. PLoS Medicine, Jan 2007, pp 0001-0006
Leaky Labs From Hopkins Magazine (Fall, 2006)
Spectrum of Conflicts minor major $$$ or Equity Influence Complexity Sensitivity
Applicable Policies and Procedures USM Policy On Conflicts of Interest In Research or Development www.umaryland.edu/hrpolicies/section3/t30111sa.html UMB Procedures Implementing Board of Regents Policy on COI… www.ord.umaryland.edu/researchers/policies/umproceed.php
Maryland Public Ethics Law Code of Maryland Regulations 15-501 and 15-523
Applicable Policies and Procedures(cont’d) UMB IRB Policies and Procedures 6c: Investigator and Study Personnel Conflicts of Interest http://medschool.umaryland.edu/orags/hrpo/HRPP_Policies.pdf
NIH Objectivity In Science http://grants1.nih.gov/grants/compliance/42_CFR_50_subpart_F.htm
Reporting Requirements • Internal to UMB • As required in provisions • Annually • Whenever a significant change occurs • External to UMB • Chancellor • State Ethics Commission • Public Record • Research Sponsors, where applicable
Exemption Provisions/Conditions(examples) Conflict of Commitment Insider Trading
Case Study #1 • A clinical researcher receives $4,500 per patient from a pharmaceutical firm to enroll patients in a clinical trial of a new hypertension medication. The money covers patient care and administrative costs and includes a $200 finder’s fee. After the initial screening and enrollment, participants will make a total of eleven 15-minute office visits during the study. At each visit, nurses will take blood, record vital signs, and ask them questions about their hypertension. The clinical researcher will do a physical exam.
Case Study #2 • A clinical researcher has partial ownership of a patent on a new gene therapy technique. Her work is being funded by a biotech company, which owns the other part of the patent. She also has stock in the company. She plans to use her patented technique in clinical trials for gene therapy to treat breast cancer.
Case Study #3 A junior scientist at a university discovered a new prostate cancer drug. With the help of the University’s Office of Research and Development, he applied for a patent and established an agreement that splits the profits between him and the university. Using venture capital, the university formed a start-up company based on the technology. The scientist and his department chair were on the board of directors. Other board members included several university administrators and a few employees of the venture capital company. The patent was awarded a few years later. The company still has not realized any profit, but is very close to marketing the drug.
Case Study #3 (cont’d) The scientist, while at a conference, heard that a researcher at another university has come up with a drug very close in chemical structure to his, but one that is much more effective and has fewer side effects. Another group of venture capitalists has formed a company to manufacture the new drug as quickly as possible. The junior scientist, with prodding from his original company, is now thinking about challenging the new company with a lawsuit on the basis of patent infringement.
National Lung Cancer Screening Trial An example