Guidance for Clinical Investigators
- Introduction
- Clinical Research and Trials: Special Considerations
- Considerations in the Review
- Measures to Manage a Potential Conflict
- Questions about the Review Process and Criteria?
Introduction
University and State of California policies require an institutional review when a Principal Investigator or Co-Principal Investigator has a financial interest in the sponsor of an award (gift, grant, contract, or clinical trial). In addition, the UCI Institutional Review Board (IRB) has instigated a Policy on Disclosure of Conflicts of Interest in Human Subject Research. At UCI, the Conflict of Interest Oversight Committee (COIOC), which is advisory to the Vice Chancellor for Research, conducts these reviews.
Under the State of California policy, financial interests to be disclosed by the Principal Investigator for studies sponsored by a non-exempt, non-governmental entity are:
- A direct or indirect investment in the sponsor or stock options equal to or greater than $2000
- Position as director, officer, partner, trustee, employee or other management position
- Income within the prior 12 months or the promise of income equal to or greater than $500
- Gift from the sponsor/donor with the value equal to or greater than $50
- Ownership directly, indirectly or beneficially in any business entity or trust with a financial interest in sponsor greater than 10%
- Loan from sponsor/donor with balance exceeding $500 in past 12 months
- Travel and related expenses paid for by sponsor/donor
For studies sponsored by PHS or NSF involving human subjects, disclosure is required by the Lead Researcher and all individuals responsible for the design, conduct or reporting of the research. Disclosure is to include all significant and related financial interests, consistent with the definitions in the federal regulations and UC policy.
In addition, the IRB COI policy requires financial disclosure from all research personnel. Disclosing individuals shall report for themselves, their spouses and dependent children the following disclosable financial interests:
- Ownership interest, stock, stock options, or other financial interest related to the research, unless it meets all four tests:
- Less than $10,000 when aggregated for the immediate family and
- Publicly traded on a stock exchange and
- Value will not be affected by the outcome of the research and
- Less than 5% interest in any one single entity.
- Compensation related to the research, including salary, consultant payments, honoraria, royalty payments, dividends, loans, or any other payments or consideration with value, including payments made to the University Health Sciences Compensation Plan, unless it meets both of the following tests:
- Less than $10,000 in the past year when aggregated for the immediate family and
- The Amount will not be affected by the outcome of the research.
- Proprietary interest related to the research including, but not limited to, a patent, trademark, copyright or licensing agreement.
- Board or executive relationship (e.g., director, officer, partner, or trustee) related to the research, regardless of compensation. This review of potential conflict of interest is separate from, and additional to, the review conducted by the Institutional Review Board, which ensures that the benefits to the research subject and/or population sufficiently outweigh any potential risks to the research subject.
Clinical Research and Trials: Special Considerations
Clinical research and clinical trials pose special situations that require close scrutiny for several reasons. The University is responsible for ensuring that human subjects are fully informed and not placed at additional risk because of financial interests on the part of the investigator(s). In addition, the University and the company sponsoring a clinical trial are obligated to ensure that the results are free from a harmful conflict of interest (or any appearance thereof); otherwise, approval by the FDA may be jeopardized. Campus policy, effective January 1, 2000, requires the informed consent document presented to potential research subjects to advise them whether or not the PI or LR has a financial interest in the sponsor of the trial, in a supplier of drugs and/or other materials to be used in the study, or in other entities that would be interested in the study results. Suggested language is included in the consent template for medical studies and for social and behavioral studies.
Considerations in the Review
The COIOC will consider the research project according to traditionally held principles of ethical conduct and academic freedom. The COIOC will evaluate whether: there is sufficient separation of University and private interests, the proposed research is appropriate to the University, the teaching and research environment is open, freedom to publish and to disseminate research results is preserved, the University's rights are protected, the University's facilities and resources are used appropriately, and that the University receives proper compensation for their use.
In conducting its review, the COIOC refers to the disclosure documents including the addendum provided by the investigator, as well as other relevant information. The Committee considers multiple factors in weighing the benefits of a specific project and potential associated risks when the principal investigator has disclosed a financial interest in the sponsor or other interested entity. The following is intended to be a guide to clinical investigators who have (or are contemplating) a management/financial relationship with a private company.
- Study Design: Blinding or masking, prospective randomization of subjects to treatment and control groups, and/or multi-center studies help to minimize any potential bias or perceived conflict of interest resulting from the investigator's financial interest in the outside entity. The COIOC considers such design features important in reducing the perceived risks of financial interests for clinical studies. If such measures are not possible, and especially if the trial is to be open-label, the investigator should provide in the supplemental questionnaire a clear explanation and justification of why the particular design was necessary and what other design characteristics may mitigate this aspect of the trial.
- Financial Impact: The extent to which the outcome of a clinical study can affect the company's and/or the investigator's near-term fortunes can be a factor. Of particular concern are companies that are small, not publicly traded, and/or have few marketable products (either currently or in the near future).
- Type of Financial Interest: Some forms of financial interest are viewed as potentially more problematic than others. Substantial equity holding (stock or stock options) can create an unmanageable conflict due to the possible intrusion of bias, subtle or unconscious, into the study. A position of management with an outside entity (such as director, officer, partner, or trustee) can blur an investigator's responsibilities to the entity and the University. Service on a scientific advisory board or its equivalent is usually viewed as acceptable if the investigator does not participate in the final discussion and decision to fund his/her own research. Income can be derived from several activities, such as lectures, seminars, and/or consulting. Clearly, if an investigator has financial interests in several categories, this heightens the risk of a potential conflict of interest, which is especially problematic when human subjects are involved.
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Investigators are urged to attach explanatory notes to the addendum that address such concerns as: Is the consulting for a single activity or long-term? Is the consulting activity specifically related to the drug or device under investigation in the UCI study? How is the investigator keeping his/her outside obligations separate so that there is little or no impact on the design, conduct, analysis, or reporting of the study?
- Publication Rights: Clinical studies sponsored by private companies routinely impose publication delays that differ for single-site trials and multi-center trials. Particularly if students are involved in the study, it is important that access to data and publication of research results will not be unduly impeded, and that an open environment, relatively free of confidential information, can be maintained. On the other hand, if students' thesis or dissertation research is in a related, but distinct area, so that publication is not impacted, that should be noted on the addendum.
- Intellectual Property: In general, Investigators are discouraged from testing their own inventions, including drugs, devices, or tangible research products.
- University Resources: University resources and facilities should be used appropriately and compensated by payment of direct and indirect costs by the sponsor.
- Human Subjects: The COIOC must consider the effect of the disclosed financial interests on the rights and welfare of the participants. The COIOC must consider whether the rights of the participants would be better protected by reduction or disclosure of a financial interest, separation of responsibilities for financial and research decisions, additional oversight, elimination of a financial interest, implementation of an independent data and monitoring committee, modification of roles in research staff, or any other mechanism which would mitigate effects of the financial interest.
Measures to Manage a Potential Conflict
If the COIOC perceives a potentially harmful conflict of interest, it will recommend to the Vice Chancellor of Research that measures be implemented to mitigate or manage the conflict. Management options include: semi-annual or annual reports to the COIOC on measures for assuring separation of interests; public disclosure during presentations and in publications; appointment of a third party to monitor and report periodically; project oversight by an ad hoc committee; modification of the research plan; disqualification from all or part of the protocol; reduction or divestiture of the related financial interest; and severance of the relationships that create actual or potential conflicts. The final decision for approval, management, or disapproval of the project rests with the Vice Chancellor for Research.
For clinical studies, the COIOC must consider the effect of the disclosed financial interests on the rights and welfare of the participants. The COIOC must consider whether the rights of the participants would be better protected by reduction or disclosure of a financial interest, separation of responsibilities for financial and research decisions, additional oversight, elimination of a financial interest, implementation of an independent data and monitoring committee, modification of roles in research staff, or any other mechanism which would mitigate effects of the financial interest.
Questions about the Review Process and Criteria?
Faculty engaging in relationships with outside companies are encouraged to refer to Guidance to Principal Investigators for Disclosure and Review of Financial Interest in Non-Governmental Sponsors of Research for more detailed information. Or contact the COI Staff: Administrator, Grace J. Park at 824-7218 or parkgj@uci.edu.
