Guidance: Financial Conflict of Interest (linked to printable document in forms list)
E&I recognizes that objectivity is a key factor for successful communication of study risks, data monitoring and reporting, as well as subject selection and proper gathering of informed consent.
Although there are many kinds of conflicting interests that may occur and are considered as part of an IRB’s overall review, a financial conflict of interest (FCOI) requires specific regulatory consideration that must be addressed.
Identification, disclosure and management of a significant financial interest is a vital part of the review and approval process, necessary to assure an appropriate balance among all competing interests that have the potential to produce bias in the design, conduct or reporting of research.
This guidance is intended to assist investigators and research staff in understanding the purpose, practice and expectations of financial disclsoure, E&I's thresholds, determinations of conflicts and acceptable mitigation plans.
Applicable Regulations and Guidance (external links):
There are four basic steps to how E&I will manage financial conflicts of interest:
Step 1: Identification The first step is to identify if any financial interests even exist that might lead to a possible conflict of interest that could create bias.
Each of the E&I investigator application forms (most commonly 30A PI Clinical Biomed and 30B PI Social Behavior) contain a multi-faceted screening question related to the possible existence of financial interests or relationships, which hold the potential to present a conflict with the investigator’s study related responsibilities. The question applies to the investigator, including their immediate family or dependents, as well as any other key personnel who share responsibility for study design, conduct, consent, subject interaction, data management and reporting, or who are listed on the FDA form 1572.
The act of identification begins when an investigator seeks initial approval, but continues to be sought throughout the life of the study through screening disclosure questions being asked again on the PI continuing review application (most commonly forms 42A PI Continuing Review BioMed and 42B PI Continuing Review SBER.) Further, investigators are reminded of their obligation to report any changes in their (including family / key personnel) acquisition of interests to the IRB within 30 days of such acquisition or discovery, in the stipulations section of their approval document, and in initial application form itself.
If this screening question shows a financial interest exists, the submitter moves on to step 2.
Step 2: Disclose & Screen The second step is for the submitter to formally disclose their financial interests for consideration by the IRB as part of their review.
If the application form reveals that a financial interest exists, a completed copy of Investigator Supplement E&I Form 31 Conflict of Interest is required with the investigator’s submission packet for each and every member of the study team, for whom a financial interest exits. This form takes the applicant through a process of full disclosure and requires submission of their intended management plan to assure that any conflict created by the financial interest does not interfere with their ability to properly execute their responsibilities objectively.
Although there are different regulatory criteria for the determination of ‘significant financial interests’ each with their own unique remuneration levels, E&I has elected to use a single level for disclosure of ‘significant’, regardless of the funder or regulatory authority. The following criteria define E&I’s test to determine “significant financial interest” requiring disclosure.
Note: All financial interests will take into consideration the person disclosing and their family (as defined above) and will be considered in aggregate (combined total) over the previous 12 months prior to disclosure, unless otherwise stated.
The interests are in companies that are involved in development of the test article, or the conduct or the analysis of the study and to direct competitors of those companies.
Disclosure is required for
- Financial support or grants from the same institute or corporation or from a competing corporation, in an amount that its loss would significantly impact the member.
- Ownership interest: A "significant" equity position in the sponsor company or a direct competitor of that company. Ownership interest, stock, stock options, or other financial interest
- Greater than $5,000 or greater than 5% of any single entity;
- Whose value cannot be referenced to publicly traded prices;
- Whose value will be affected by the outcome of the research; or
- Whose value cannot readily be determined.
- Income or Compensation: Receipt or expectation of receiving compensation related to the research (lectures, seminars, teaching committees, review panels or public or nonprofit entities) including salary (consulting fees, honoraria, paid authorship, etc.), royalties, or other payments related to the research for the prior year and following 1 year exclusive of the cost of conducting the study:
- With value that may be affected by the outcome of the study; or
- Greater than $5,000 per year.
- Proprietary interest related to the research including but not limited to
- A patent, trademark, copyright or licensing agreement;
- Membership on the board, director or officer or other executive position, regardless of compensation.
- Reimbursed or sponsored travel (including travel for industry not paid by employer, or travel paid by non-profit or professional society.) Do not include travel paid for by federal, state or local government agencies, any institution of higher education or academic teaching hospitals.
- Any paid for by a third party where the amount is unknown; or
- Any reimbursed travel totaling greater than $5,000.
- FDA specific for investigators: any holdings that would generate need for a Form 3455.
Any changes in financial interests, or relationships must be reported to E&I within 30 days of acquisition, or discovery.
Upon receipt of the completed E&I Form 31, the administrative staff will screen the form to ensure that all requested information is provided, that it appears to meet the level of significant financial interest, requiring consideration by the board and will include the disclosure in the reviewer (and/or full board’s) meeting packet permitting consideration during review.
The administrative staff will also monitor all submission documents with COI screening questions during the data entry stage and again during QA of the investigator submission to ensure identification of any reported changes to existing or possibly new potential financial conflicts and to require full disclosure through submission of a completed Form #31.
Upon receipt of completed Form #31, the E&I administration notes the disclosure in the database, permitting easy generation of ongoing reports and follow-up.
Step 3: Review and Evaluate Upon receipt of a disclosure (E&I Form 31) the IRB will review the submitter’s identified interests, their presented evaluation of the potential conflict and any relatedness, to determine if a conflict, or financial conflict of interests exists and if so, if the proposed mitigation plan is acceptable.
Once it is established that a significant financial interest exists, the IRB will evaluate if that SFI presents a conflict. Reviewing the submitter’s disclosure, the reviewer (or full board) will establish:
- If the interest is related to the research
Relatedness (for purpose of this guidance): An Investigator’s significant financial interest is related to research if that significant financial interest could be affected by the research or is an entity whose financial interest could be affected by the research.
- If the significant financial interest being disclosed creates a financial conflict of interest
Financial Conflict of Interest (for purpose of this guidance): A financial conflict of interest exists when the significant financial interest could directly and significantly affect the design, conduct or reporting of the research.
E&I Form #31, section D requires the submitter to provide a personal evaluation of the potentially conflicted interests. This assessment should present the submitter’s opinion, in their own words, on whether or not their interest(s) present any risk to the study or subjects. If it is found that a FCOI exists, the reviewer/board will take into consideration the submitter’s comments as part of their evaluation to determine if a management plan is required, although ultimately it is the IRB that will decide if a conflict exists and, when necessary, the need for and acceptability of a management plan. As part of their review, consideration of the FCOI will be given to:
- Whether the financial interest will adversely affect the protection of participants (in terms of the criteria for IRB approval) or
- Whether the financial interest will adversely affect the integrity of the research.
As part of their review, it is not the objective of the IRB to make a judgment about the Investigator or research team’s motives, intentions, or personal character.
Step 4: Mitigate and Manage If it is determined that a mitigation plan is necessary to assist in managing the conflict and the potential for negative effects that could occur, the reviewer/board will consider the plan and its application as part of their review and criteria for approval.
E&I Form #31, section E requires the submitter to provide a written management plan including any intent to disclose the conflict in the consent language.
The following are examples of conditions or restrictions that could be applied to a research plan to help manage, reduce, or eliminate conflicts of interest. This is not intended to be a comprehensive list, but to give ideas on how to reduce risk caused by the conflicted interest(s.)
- Disclosure of significant business or financial interests to subjects;
- Disclosure of conflicts of interest in each public presentation of the results of the research;
- Monitoring of research by independent reviewers;
- Separate data analysis for site;
- Modification of the research plan;
- More objective endpoints;
- An election to reassign oversight of the portion of the research that could affect the significant business or financial interest;
- Use of other personnel for specific activities;
- Divestiture of significant business or financial interests; or
- Severance of relationships that create conflicts.
The reviewer/board will consider the plan as part of their review and consideration of approval, again paying particular attention to:
- Whether the financial interest will adversely affect the protection of participants; and
- Whether the financial interest will adversely affect the integrity of the research.
If it is determined that the research, with inclusion of the management plan can be approved, the plan will be put into record as part of the study and the Principal Investigator will be held responsible for adherence and related reporting.
If the plan is not found to be sufficient, the reviewer/board may suggest additional changes to the plan, or disapprove the research.
Once a management plan has been accepted by the IRB, the investigator remains responsible for ongoing reporting of any changes in their interests, or those of their research staff that would affect their disclosure. They are also responsible for including information about the mitigation plan in their progress reports at each continuing review.
Additional guidance is available by contacting E&I.
CONFLICT OF INTEREST (COI) A convergence of an investigator’s private interests with his or her research interests such that an independent observer might reasonably question whether the investigator’s professional actions or decisions were improperly influenced by considerations of personal gain.
An individual or a group with interests that conflict in such a way that a study could be biased or an inappropriate subject could be enrolled.
Any test for conflict of interest applies to the person and to the family.
FAMILY: (As used in conflict of interest) Includes at a minimum, the investigator and the immediate family. Immediate includes spouse or domestic partner and dependent children. There is no requirement to include those who are dependent on the PI or on whom he or she is dependent.
KEY PERSONNEL: Those who are responsible for design, consent, subject interaction, data management, and reporting. Those people listed on the grant or on the 1572.
SIGNIFICANT FINANCIAL INTEREST (SFI): Defined by regulation, SFI is established by specific, separate criteria identified by each regulatory authority. E&I elects to apply a single level (using the most restrictive regulation) of criteria to define SFI in our process and policy.
SFI is determined based on all financial interests that have monetary value, whether or not the value is readily ascertainable.