Collaborative Research and Conflicts of Interest Delia Y. Wolf, MD, JD, MSCI Associate Dean, Regulatory Affairs & Research Compliance Harvard School of Public Health Email: [email protected] Website: www.hsph.harvard.edu/ohra February 28, 2014
Jan 04, 2016
Collaborative Research and Conflicts of Interest
Delia Y. Wolf, MD, JD, MSCI
Associate Dean, Regulatory Affairs & Research Compliance Harvard School of Public Health
Email: [email protected]
Website: www.hsph.harvard.edu/ohra
February 28, 2014
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Topics to be Covered
Collaborative Research
Conflicts of interest
What is COI
Regulatory requirements
Institutional policies
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Collaborative Research
Types of collaborative research
Points to consider before, during and
after collaboration
Case studies
Types of Collaborative Research
Within institution
With institutions/hospitals
Multicenter – within the US
Multicenter – transnational
Collaborations with industry
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Points to Consider Before any work is undertaken
Clear understanding of the nature of the collaboration Roles and responsibilities
Sufficient resources Time, space
Written agreement (between/among collaborators) Who does what Who owns what Criteria to identify and rank contributing authors
Necessary review and approval from institution Grants/contracts Technology transfer IRB/IACUC
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Points to Consider (cont.) During the course of collaboration
Following research plan/study protocol Communication
Report Progress Share findings Discuss problems
Documentation If it is not documented, it is not done!
Training and supervision Verification Good record keeping
Time and effort
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Points to Consider (cont.) After the completion of a collaborative
research project Submit final report/closure to relevant
offices at researcher’s institution IRB office
Be aware of record keeping requirements Institutional requirements Sponsor requirements Government agency requirements
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Case A Dr. D is a biostatistician from HSPH. He is the
PI for a data coordinating center that oversees and analyzes all data collected from a multi-canter clinical trial involving 12 sites in the US and 10 sites outside of the US. What are Dr. D’s responsibilities in terms of meeting
regulatory requirement? Obtaining IRB approval Overseeing of research conduct Reporting obligations
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Case B Dr. M is the overall PI for a multi-center Vitamin
A supplementation clinical trial that is sponsored by NIH. She is a faculty member at HSPH, but no study activities will be conducted in the US. There are a total of three sites in India, Tanzania and Botswana. Does Dr. M need to get HSPH IRB approval to work on
the study? Which country’s rules should be followed for
regulatory oversight? Since she only visits each site once a year, how can
she fulfill her responsibility as a PI?
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Case C Amber, Ben and Carol have just received funding from a small
pharmaceutical company to test one of its imaging agent. Amber is a neuro-radiologist at BIDMC, who will be the PI, as
well as the IND holder, Ben is a psychiatrist at MGH, and Carol is a biostatistician at HSPH. Ben and Carol will serve as co-investigators.
Study is going to be conducted at BIDMC. Both Amber and Ben will be interact with research participants; Carol will not have direct contact with participants, but will have access to participants’ identifiable information. Which office(s) will they have to deal with Do all three need to get IRB approval from each of his/her
institution? Do they need an agreement among themselves? If so, what should
be included in the agreement?
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What is a Conflict of Interest
Many definitions, only some consensus One possible working definition: an
individual or institution has a primary interest or duty (e.g., scientific integrity and objectivity, protection of subjects) that may be affected or undermined by a competing interest (e.g., financial reward, professional advancement, etc.)
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Types of Potential Conflicts
Individual financial interest, examples Equity interests: ownership of stock and stock options in a
company sponsoring research Royalty: when an investigator is conducting a research
project for a company that is developing the technology, of which the investigator is also the inventor
Consulting fees, over-scale honoraria and gifts, or other monetary compensation from companies whose products are affected by investigators’ research results
Recruitment bonus or milestone payments from sponsoring company to investigators in order to “accelerate” research process
Finder’s fees
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Significant Financial Interest according to PHS include: An equity interest which when aggregated for
the investigator and his/her spouse and dependent children (a) exceed $5,000 in value and/or (b) represents more than five percent (5%) ownership in any single entity
Salary, royalties or other payments for service that when aggregated, investigator and his/her spouse and dependent children, over twelve months period, is reasonably expected to exceed $5,000
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Significant Financial Interest (SFI)
Financial Interests Disclosure
Financial interests meet De minimis threshold of $5000 (SFI)
ALL SFI related to the investigator's institutional responsibilities (note: the 1995 regulations required “only those SFI the investigator deems related to the PHS-funded research”)
Travel reimbursements and sponsored travel (De minimis threshold does not apply)
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Excluded from Disclosure Income from lectures, seminars, or teaching
engagements sponsored by public or nonprofit entities; a federal, state, or local government agency, an Institution of higher education, an academic teaching hospital, a medical center, or a research institute that is affiliated with an Institution of higher education.
Income from investment vehicles, such as mutual funds and retirement accounts, as long as the investigator does not directly control the investment decisions
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Conflicts of Commitment Competing demands on researchers’ time
Working on one or more funded projects Teaching and advising students Attending professional meetings and giving lectures Serving as a peer reviewer
Allocation of time Time and effort reporting – seek advice if unsure
whether a particular commitment of time is allowed under an institution's or funding agency’s policy
Use of resource Equipment purchased with public funds cannot be used
for private research
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Examples of potential COI
An academic researcher in a NIH study section reviews a grant application from a competitor in the same field
A clinical investigator receives $3,000 for each patient she recruits into a clinical trial
A university’s IRB reviews a research proposal sponsored by a company that has recently given $10 million to the university
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Examples of potential COI (cont.)
A university holds stock in a chemical plant but also hires employees to monitor its emissions.
A university president owns stock in a company that sponsors research on campus and has made large gifts to the campus
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Impact of Financial Interests
Existing evidence suggests an impact on science doe to financial relationships: Industry-sponsored studies that are published
are more likely to reach pro-industry conclusions (Bekelman et al., 2003)
Gifts change physicians’ prescribing behaviors (to the benefit of the gift-giver)
In one survey, 15.5% of 3,247 scientists surveyed reported that they had changed the design, methodology or results of a study in response to pressure from a funding source (Martinson et al., 2005)
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How COI is identified/judged
Conflicts usually judged in retrospect Hard to “prove” causative effect
(conflict bias) Often only an issue in the wake of an
adverse event and compounds the problem for investigators and/or institutions
Public perception/media focus
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Regulatory Requirements
FDA Regulations (21 CFR Parts 54; 312.53; 812.43) Investigators must disclose certain financial
interests to sponsors; sponsors then disclose to FDA
FDA may take action if it determines that the financial interests of an investigator raise a serious question about data integrity
PHS Regulations 42 CFR Parts 50 and 94 (1995) Revised final rule public August 2011
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University-wide Policy
Harvard University policy on individual financial conflicts of interest policy can be found at: http://vpr.harvard.edu/content/conflicts-interest
Approved by the President and Fellows of Harvard College on May 26, 2010
Applies to holders of faculty and teaching appointments at the Schools
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Responses to COI Concerns
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Common themes in existing responses: DISCLOSURE
Information gathering IDENTIFICATION
Defining what constitutes a COI MANAGEMENT
Disclosure component (transparency) Reducing impact of conflicted investigator
Managing Financial COI
Disclosure to the IRB Protocol-specific $1 threshold at Harvard Catalyst institutions
Following management plan such as: Disclosure to potential research participants Refrain from recruitment activities Refrain from interpretation of data Appoint another investigator to be the
principal investigator (PI)
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Limitations of disclosure to subjects: Can subjects make meaningful use of that
information? Evidence that some patients view their
doctors’ financial interests positively: Demonstrates knowledge and that they are on
cutting edge If physicians are more vested they will work
harder
Managing Financial COI (cont.)
COI in International Research
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Globalization of research/clinical trials Increased outsourcing of research by
industry This has resulted in the outsourcing of COIs as
well (Gatter, R.) Drug company payments to health
professionals in resource-poor countries can double or triple their annual incomes (Washington Post, Dec. 2000)
COI in International Research (cont.)
Reliance on industry funding Many countries want to be viewed positively
to industry as a good place to site trials Trials bring funding for research as well as
access to investigational therapies and, for resource-poor countries, often additional capacity-building for the institution and/or nation that goes beyond the research study (e.g., access to standard of care therapy for all patients, funds to improve facilities, etc.)
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COI in International Research (cont.)
Government involvement In many countries, regional and/or national
approval of research is required
Governments may have incentives either to
ensure research happens (reflects positively
on country, financing is dependent on it) or
block it (if anticipated results may damage
country’s reputation)
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