Advancing Clinical Research While Maintaining Trust: Managing Conflicts of Interests

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Advancing Clinical Research While Maintaining
Trust Managing Conflicts of Interests

• Elizabeth Boyd, PhD
• University of California, San Francisco
• Project support NIH/ NINDS NS42398-02
• Soros Foundation Grant

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Questions

• What is a conflict of interest?
• Why are conflicts of interest of concern?
• Is there evidence that conflicts of interest
  threaten the integrity of clinical research?

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What is a Conflict of Interest?

• A situation in which an investigators primary
  interests compete with secondary interests
• Those secondary interests may or may appear to
  influence the investigators judgment
• This situation may lead to adverse outcomes.
• From Mildred Cho, Stanford University

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What is conflict of interest?

• 1 INTEREST/DUTY
• Research integrity
• Patient welfare
• Education

• 2 INTEREST
• Financial gain
• Recognition

JUDGEMENT
UNDUE INFLUENCE
ADVERSE OUTCOME
Slide courtesy of Mildred Cho, Stanfod University
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Why are conflicts of interest of concern?

• Trust in science and medicine is fundamental to
• Funding of research
• Success of clinical studies
• Doctor-patient relationship
• Public support for advancements in science and
  medicine

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Public perceptions matter
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Underlying assumptions

• Taken for granted that
• Physicians act in the patients best interest
• Scientific evidence is sound, unbiased, and free
  from external influence
• Institutions supporting scientific research are
  disinterested and dedicated to knowledge for the
  public good

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What Do We Know?

• Competing interests increasingly challenge these
  underlying principles
• Financial interests
• Career interests
• Personal interests

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Is there evidence to suggest that conflicts of
interest are a problem for clinical research?

• Answer Some evidence suggests that industry
  sponsorship and financial ties contribute to
  biased outcomes.

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Whats the evidence?

• Anecdotal evidence
• GlaxoSmithKline
• Boots Pharmaceuticals

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The Evidence Studies of industry sponsorship

• Suppression of results
• Secrecy among researchers
• Bypassing the peer review system
• Influence over study design and interpretation of
  data

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Study design and interpretation

• Patients not representative
• Non-random allocation
• Choice of comparison group (drug,dose)
• Lack of masking
• Inappropriate choice of outcome measures
• Misleading data analysis or presentation

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The Evidence Studies of financial ties of
investigators

• Bias toward favorable results

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What can be done to manage conflicts of interest?

• Federal, state, and institutional policies
  regulating individual investigators
• Federal and professional guidelines for
  institutional relationships

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Federal Regulatory Policy

• 1995 PHS "Objectivity in Research," Code of
  Federal Regulations (42CFR Part 50 and 45 CFR
  Part 94)
• PI, Co-PI and key personnel must disclose"all
  significant financial interests" to their
  institutions
• Income gt 10000/annually
• Equity holdings gt5
• Management position
• In a company whose work is "reasonably" related
  to the sponsored project

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Regulatory Policy in California

• 1974 Fair Political Practices Act
• A PI must disclose to the institution
• Annual income over 500 (originally 250)
• Equity ownershipgt 1000
• Management position
• Gifts and loans
• From the company sponsoring the research

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Institutional Policies

• UCSF "Faculty who have or participate in a
  sponsored clinical study shall not concurrently
  receive any compensation from the sponsor,
  including honoraria and consulting fees or have
  any investments or a decision-making
  relationship, during the course of the study."

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Institutional COI

• What happens when institutions -- as well as or
  instead of investigators -- stand to gain
  financially from the outcome of clinical
  research?

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AAMC 2002

• Human subjects research should not be conducted
  at institutions where human subjects research
  oversight and institutional investments are not
  separated
• Such institutions should not be the coordinating
  center for multi-center trials

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AAMC 2002

• Institutional officials with individual COI
  should divest themselves from financial interests
  if possible
• Institutional officials with individual COI
  should recuse themselves from COI management
  decisions if divestiture is not possible

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AAMC 2002

• Oversight should be used to monitor trials where
  the conflicted institution is conducting a
  single-site trial or is the primary site of a
  multi-center trial
• Institutions should consider using an external
  IRB in situations where a conflicted
  institutional official has authority over the
  internal IRB

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Institutional policies - NIH

• Intramural scientists conducting human subjects
  research should not be allowed to have financial
  interests except in special circumstances
• Outside activities should not be compensated by
  stock options or equities

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Institutional policies - NIH

• NIH employees may not be members of corporate
  boards
• Senior management and employees responsible for
  extramural funding decisions should not consult
• Oct 1, 2004 One-year ban on paid consulting

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Do these policies work?

• In many instances, yes.
• In UC study, COI committees regularly evaluated
  financial disclosures for
• Nature of the scientific work
• Separation of paid activities from research
• Protection of graduate students and trainees
• Independence of PI from company influence

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Management strategies

• No conflict, no management (74 of disclosures)
• Require disclosure of financial ties
• Appoint an oversight committee
• Eliminate / reduce the financial tie
• Deny / ban the funding

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Do policies influence attitudes?

• While many investigators are concerned about the
  influence of industry sponsorship and coi
• Many investigators do not see the relevance of
  coi to their work and believe in the power of the
  individual to overcome temptation

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Attitudes No need to know policies

• Irrelevance of policies
• I do not know the details of what is/is not
  allowed at the university level as I have no
  conflicts and have not bothered to learn the
  details.

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AttitudesBelief in self-determination

• Individuals can and should monitor their own
  behavior and use common sense to ensure unbiased
  research
• It really depends on the individual to adhere
  to these ethics.
• I use my common sense and ethical honesty.

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Conflict of Interest?

• "I have never been bought, I cannot be bought. I
  am an icon, and I have a reputation for honesty
  and integrity, and let the chips fall where they
  may. It is true that there are people in my
  profession who could not receive a million-dollar
  grant and stay objective. But I do.
• Slide courtesy No Free Lunch website

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Conclusions and questions

• Is self-regulation effective?
• Is disclosure effective?
• Who needs to know what and when?
• Do current policies adequately protect the
  integrity of clinical research?