Conflicts of Interest in Research

Eric Cottington, Ph.D.

Vice President

Research and Technology Management

Memorial Sloan-Kettering Cancer Center

October 7, 2008

Objectives

What is conflict of interest?

Why is it in the spotlight?

What are the policies, regulations and guidelines in this area?

Case studies

What is Individual Financial COI?

“Situations in which financial considerations may compromise, or have the appearance of compromising, an investigator’s professional judgement in conducting or reporting research”

AAU Report on Individual and Institutional Financial Conflict of Interest, Oct. 2001

Significant Financial Interest

Salary or other payments for services, e.g., consulting fees or honoraria expected to exceed $10,000 in the next twelve months (when aggregated for you, your spouse and dependent children);Equity interest, e.g., stock, stock options, etc., with a fair market value over $10,000 or which represents more than a 5% ownership in any single publicly-held entity (when aggregated for you, your spouse, and dependent children);Any equity interest, e.g., stock, stock options, etc., in a privately-held entity (when aggregated for you, your spouse, and dependent children);Officer in a company, e.g., CEO, board of directors, chief scientific officerIntellectual property rights (e.g., patents, copyrights and royalties from the rights)

What is Institutional Conflict of Interest?

“An institutional financial conflict of interest may occur when the institution, any of its senior management or trustees, or a department, school or other sub-unit, or an affiliated foundation or organization, has an external relationship or financial interest in a company that itself has a financial interest in a faculty research project”

AAU Report on Individual and Institutional Financial Conflict of Interest, Oct. 2001

Situations that can create an institutional conflict of interest

• Institution is entitled to receive royalties from sale of product that is the subject of the research

• Institution has an equity interest in research sponsor or licensee of technology that is the subject of the research

• Institutional official holds significant financial interest in a research sponsor or licensee of technology that is the subject of the research

• Institution receives gift from research sponsor or licensee of technology that is the subject of the research

• Major procurement or purchasing decisions involving research sponsor made by investigator, research administrator, or institutional official with research oversight authority

Why is COI in the spotlight?

• Growth in research funded by industry

• University interest in technology transfer

• Evidence that COI influences research results

• Negative publicity

Growth in Industry Research

R&D Funding:1953-2006(source: NSF)

0

50

100

150

200

250

19531957

19611965

19691973

19771981

19851989

19931997

20012005

Constant 2000Dollars (billions)

industry

federal govt

other

Growth in Industry Research

Industry Funding for Universities: 1993 to 2006(source: National Science Foundation)

0.0

0.5

1.0

1.5

2.0

2.5

Billions of Dollars

University Interest in Technology Transfer

• Bayh-Dole Act passed in 1980• University-generated patent applications have

increased from 250 per year prior to 1980 to more then 7,900 in 2003

• In Fiscal Year 2003, U.S. universities executed 4,516 technology licenses and options, received $1.310 billion in gross license income, and held equity in 251, or 67 percent, of the 374 start-up companies that were formed around university-licensed technology.

Authors with Financial Relationships with Pharmaceutical Manufacturers (Stelfox et al, NEJM, 1998)

Manufacturer Supportive Authors (n=24)

N (%)

Neutral Authors (n=15)

N (%)

Critical Authors (n=30)

N (%)

Chi-Square for Linear

Trend

P Value for Trend

Manufacturer of Calcium-Channel Antagonist

23 (96) 9 (60) 11 (37) 22.02 <.001

Manufacturer of Competing Product

21 (88) 8 (53) 11 (37) 14.84 <.001

Any Manufacturer

24 (100) 10 (67) 13 (43) 22.68 <.001

Reported Study Outcomes Among Original Manuscripts by Conflict of Interest Criteria and Study Focus - NEJM and JAMA (2001) (Friedman and Richter, J. Gen. Intern. Med., 2004)

All Positive n (%)

Mixed

n (%)

Negative

n (%)

Other

n (%)

P Value

ICMJE Criterion for COI

Drug treatment studies with COI

46 36 (78.3) 9 (19.6) 1 (2.2) 0 (0.0)

Drug treatment studies without COI

73 39 (53.4) 7 (9.6) 21 (28.8) 6 (8.2) < .001

All treatment studies with COI

57 45 (78.9) 10 (17.5) 2 (3.5) 0 (0.0)

All treatment studies without COI

117 69 (59.0) 14 (12.0) 27 (23.1) 7 (6.0) < .01

Negative Publicity

Recent Responses to COI concerns

• Inquires and investigations by congressional committees focusing on consulting by NIH intramural scientists, oversight of COI in NIH extramural program, and COI among NIH funded researchers themselves

• NIH requests and reviews information about COI policies at grantees

• NIH announces new business process for reporting an identified financial conflict of interest through eRA Commons

• FASEB COI Toolkit• Journals strengthen COI disclosure requirements • Forum on Conflict of Interest (FOCI) Academe – AAMC

sponsored working group of major academic research institutions expands

Policies, Regulations and GuidelinesFederal Policies:

• OBJECTIVITY IN RESEARCH NIH GUIDE, Volume 24, Number 25, July 14, 1995 http://grants.nih.gov/grants/guide/notice-files/not95-179.html

NIH Guidance Documents on COIhttp://grants.nih.gov/grants/policy/coi/index.htm

NSF Conflict of Interest Policyhttp://www.nsf.gov/pubs/manuals/gpm05_131/gpm5.jsp#510

Institutional Policy and Procedures

• Every institution funded by NIH should have a COI policy• Institutional policy should define significant financial interest, conflict of interest, and

describe procedures for reporting, review and management of COI

Policies, Regulations and Guidelines

Report on Individual and Institutional Conflict of Interest, Association of American Universities; Oct. 2001

HHS Direction Needed to Address Financial Conflicts of Interest, US General Accounting Office; Nov. 2001

Policy and Guidelines for the Oversight of Individual Financial Interests in Human Subjects Research; Association of American Medical Colleges; Dec. 2001

Protecting Subjects, Preserving Trust, Promoting Progress II: Principles and Recommendations for Oversight of an Institution’s Financial Interests in Human Subjects Research; Association of American Medical Colleges, October 2002

University Research: Most Federal Agencies Need to Better Protect against Financial Conflicts of Interest; US General Accounting Office, November 2003

Shared Responsibility, Individual Integrity: Scientists Addressing Conflicts Of Interest In Biomedical Research; The Federation of American Societies for Experimental Biology (FASEB), March 2006

Summary of Recommendations from Recent Reports/Guidelines

• Expand definition of significant financial interest• Treat research consistently, regardless of funding source• Disclosures should be made by more than just faculty• Research involving human subjects requires special scrutiny• Disclosures should be made to various constituencies, as needed• Use a Conflict of Interest Committee

Policies, Regulations and Guidelines

A cure for public distrust “Disclosure is nothing more than an excuse to continue business as usual. The cure for public distrust is to employ people who have opted not to be compromised by money. We must find ways of rewarding academic physicians who decide that patient care and personal integrity is more important than a $10,000 infusion into their bank accounts. One cure is to reward physicians by recruiting those without financial ties to write the review articles and to serve on panels that recommend what devices we use and what drugs we take. Maybe then many will opt not to be bought.”

Dr. Jerome P. Kassirer, Boston Globe, July 26, 2006

Policies, Regulations and Guidelines

What's Wrong With Money in Science? “Over the past two decades, private biotechnology firms and other drug companies have increasingly played a major role in cutting-edge medical research. These companies have built relationships with many of the best and brightest academic scientists, helping to bring about huge advances in medical treatment, including powerful new hormones and anti-cancer drugs as well as new devices that repair heart damage. But they have also drawn scrutiny from those who believe that, with so much money at stake, corruption must surely be present. Instead of assuming that scientists would want, above all, to protect their reputations and their research, critics have assumed the worst -- and have underestimated the positive impact of relationships between university researchers and companies.”

Thomas Stossel and David Shawitz, Washington Post, July 2, 2006

How Do/Should Academic Institutions Handle COI?

Reporting:Significant financial interests are defined by PHS regulation and incorporate recent recommendations from AAMC/AAU. These interests are disclosed by all investigators annually, with each sponsored project and IRB application, and as financial interests change.Review:Disclosures reviewed initially by COI Administrator and then by COI Committee. COI Committee composed of faculty and administrators and, in some cases, external members.COI Committee may identify individuals who need to be interviewed about their COI in order to collect additional information and to jointly develop a COI management plan. Management:Management plan approved by COI Committee and signed by investigator.Monitoring:COI administrator or COI Committee follows up at least annually on high-risk management plans and a sample of others to ensure that the plans are being followed.

Strategies for COI Management

• Broad disclosure is generally the sole management strategy for non-human subject research

• For human subject research, usually also require recusal as PI• If human subject research is viewed as a feasibility study, then

conflicted individual may participate in a limited fashion if expertise is critical. Independent review (data, safety) generally required.

• If institutional COI present, additional safeguards include independent DSMB and in some cases, independent IRB review

COI Monitoring

• Identify previously approved COI management plans to monitor

• Interview investigator, update information about financial interests and sponsored research

• Solicit copies of publications and presentations to confirm disclosure

• Require additional COI management actions in light of new requirements, e.g., notify graduate students and staff, independent DSMB reports

Case Study

Dr. Smith is a consultant to several drug companies and is compensated quite well for this (>$10,000 per year per company). He is the principal investigator on an NIH sponsored multi-center clinical trial that is testing the efficacy of several drugs including one from a company that he serves as a consultant. Is this a conflict of interest? If so, what should be done to address it?

Case Study

A university has licensed sensor technology invented by one of its professors, Mary Nobel, to a company called Remote Sensors, Inc. Remote Sensors would like to fund research at the university in Prof. Nobel’s lab to further develop the technology. Is this a conflict of interest? If so, why; and what if anything should the university do about it? Would the situation change if the company was founded by Dr. Nobel and she had equity in the company? Would the situation change if the university had equity in the company?

Case Study

Professor Morley has developed a device that could potentially restore function to certain areas of the brain in stroke patients. Professor Morley is both a neurosurgeon and biomedical engineer. He has patented this technology through his university and it has been licensed to a small start-up company in which both the university and Professor Morley have equity. Professor Morley has received funding from NIH to conduct a feasibility study of the device in humans at the hospital affiliated with the university. This feasibility study will be done in a small number of subjects and the device will not need to be implanted (no invasive surgery required). Is this a conflict of interest, and if so, what can be done to address it?

Ongoing Areas of Concern

• How can we make sure that those who need to disclose are doing so and that their disclosure is complete?

• Can or should conflict of interest (either individual or institutional) be eliminated? If so, when?

• What is an acceptable conflict of interest management plan for investigators with financial conflicts of interest who are conducting human subjects research? How should the plan change if there is also institutional conflict of interest?

• How does one coordinate the activities of the Conflict of Interest Committee with the IRB, IACUC, and sponsored project office?

• What is a reasonable and effective approach to monitoring conflict of interest management plans? How often? What is monitored and how?