Collaborative Research and Conflicts of Interest

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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