It is important to maintain public confidence in the integrity and credibility of the Sentinel Initiative and its findings by avoiding Conflicts of Interest (“COI”) by the individuals conducting Sentinel Initiative medical product assessments. A COI exists when, because of other interests, activities, or relationships with other persons or organizations, an individual conducting Sentinel Initiative medical product assessments is unable or potentially unable to render impartial assistance or advice to the FDA, the individual’s objectivity in performing the Sentinel medical product assessment is or might be otherwise impaired, or the individual has or might acquire an unfair competitive advantage. A COI may arise not only from financial interests, but also from non-financial engagements with or commitments to other organizations with interests related to the subject matter being addressed by specific Sentinel activities. This COI policy includes steps to identify and minimize bias in the design, conduct, and reporting of a Sentinel project where a COI exists.
The Sentinel COI policy applies to assessments of FDA-regulated medical products (“Studies”) that involve development of project-specific protocols or use of the Sentinel Active Risk Identification and Analysis (ARIA) System to perform analyses that have been designated by FDA as a “safety assessment.” The FDA reserves the right to extend this policy to additional Sentinel projects as deemed appropriate by the Agency.
Individuals who are responsible for the design, conduct, or reporting of a Study are required to submit attestations of no conflicts or disclose financial and other interests specified by this COI policy. These individuals include scientific leads and co-leads. For the purposes of this policy, such individuals are referred to as “Covered Persons.”
This COI policy does not apply to analysts, programmers, project managers, research assistants, support personnel, or persons whose only role is to execute or run an algorithm, query or software code because any interests of these individuals will not affect the design, conduct, or reporting of a Sentinel Study.
Covered Persons must disclose their interests in the following types of entities (“Relevant Companies”):
- Manufacturer of the product being studied;
- Manufacturer(s) of generic equivalents of the product being studied (if any);
- Manufacturer(s) of comparator product(s) used in the Study (if any); and
- Other companies providing funding or material support for the Study (if any). Material support could include providing products or equipment without charge or at discounted rates for the Study.
Covered Persons must disclose the following interests and activities:
- Any financial interest of the Covered Person that is one or more of the following:
- Any remuneration received by the Covered Person from a Relevant Company (including reimbursed or sponsored travel) within the last 12 months;
- Any equity interest in a Relevant Company (e.g., stock, stock options, or other ownership interest) (except that, for publicly traded Relevant Companies, this does not include mutual funds that include the Relevant Company’s stock as long as the Covered Person does not directly control the investment decisions made in the mutual fund);
- Intellectual property rights and financial interests (e.g., patents, copyrights) in the product being studied;
- Any financial arrangement entered into between the Relevant Company and the Covered Person, whereby the value of the compensation to the Covered Person could be influenced by the outcome of the Study; and
- Payments of more than $25,000 made by the Relevant Company to the Covered Person’s institution/employer during the Study and for one year after the Study is completed, specifically to support activities of the Covered Person, such as grants or other funding for equipment, materials, lab space or staff resources, retainers or honoraria for the Covered Person, or travel or entertainment provided to the Covered Person. This would not include payment to the institution/employer for the costs of conducting the Study or other research.
- Leadership or related activities, including serving on a scientific advisory board for a Relevant Company or serving as a corporate officer or member of the board of directors of a Relevant Company.
- Any Study involving former employers, or their representatives, for whom the Covered Person worked within the past one-year period prior to starting work on the Study.
In disclosing a potential COI, a Covered Person must include interests of the following family members of the Covered Person: spouse, dependent children, a member of their household, and any relative with whom they have a close personal relationship (collectively (“family members”).
Each Covered Person must submit an Absence of Individual Conflicts of Interest Attestation or complete a Financial Interests Disclosure Form for each Relevant Company.
For each Study that proposes to include Covered Persons unable to submit Absence of Individual Conflicts of Interest Attestations, the SOC will prepare a Cover Memorandum that provides a project-specific list of companies and products for which individual financial and non-financial interests must be disclosed. FDA will verify the Cover Memorandum after the statement of work is approved and before workgroup participants are selected.
Each Covered Person involved in a Study who is unable to complete an Absence of Individual Conflicts of Interest Attestation must complete a Financial Interests Disclosure Form for each Relevant Company identified in the Cover Memorandum:
- Before beginning work on a particular Study;
- Annually thereafter until completion of the work on the Study and for one year thereafter;
- Promptly upon discovering or acquiring a new financial or non-financial interest that would change the answers on the Financial Interests Disclosure Form; and
- Promptly if a Relevant Company changes during the course of the Study (e.g., through acquisition or merger) or if a new comparator product is added to the Study; the Covered Person then will update their Financial Interests Disclosure Form relevant to the new Relevant Company.
Collection of Forms and Initial Review
The SOC will ensure that a Cover Memorandum is prepared for each relevant Study and that all Covered Persons have completed either Absence of Individual Conflicts of Interest Attestations or Financial Interests Disclosure Forms before starting work on the Study. The SOC will designate an independent evaluator (the “COI Official”), who will review the Financial Interests Disclosure Forms to determine whether the forms indicate a COI and, if needed, will gather any additional details from the Covered Person where materially relevant to determining whether a COI exists. The SOC will designate a second independent evaluator to function as back-up to the COI Official when the COI Official is not available to perform these functions.
Financial COI disclosure forms provided by Covered Persons to their places of employment may be substituted for Sentinel disclosure forms if accepted by the COI Evaluator.
COI Management Plan
If a COI is identified by the COI Official, and they make an initial determination that a COI management plan would appropriately mitigate the COI, the COI Official will prepare a draft COI management plan. The guidelines below will be followed when determining whether a COI exists and/or drafting a COI management plan. If the COI Official concludes that a COI management plan is not necessary (i.e., that the interest disclosed does not meet the minimum threshold requiring a COI management plan), that decision and the rationale will be documented and kept in the SOC files.
Interests Requiring a COI Management Plan
A COI management plan will be required:
- If the value of any remuneration received by the covered person from the Relevant Company within the last 12 months exceeds $5,000;
- With regard to a publicly traded Relevant Company, if the value of any equity interest, when aggregated, exceeds $5,000 (excluding holding in mutual funds as long as the Covered Person does not directly control the investment decisions made by the mutual fund);
- With regard to a non-publicly traded Relevant Company, if the Covered Person holds any equity or ownership interest (regardless of amount);
- If the Covered Person holds any intellectual property rights (e.g., patents, copyrights) in the product being studied;
- If the Covered Person will receive compensation from the Relevant Company that could be influenced by the outcome of the Study (regardless of the amount);
- If the Relevant Company has made payments of more than $25,000 to the Covered Person's institution/employer during the Study and for one year after the Study is completed, to support activities of the Covered Person, such as grants or other funding for equipment, materials, lab space or staff resources, retainers or honoraria for the Covered Person, or travel or entertainment provided to the Covered Person (not including payments to the institution/employer for the costs of conducting the Study or other research);
- If the Covered Person serves on a scientific advisory board for the Relevant Company or serves as a corporate officer or member of the board of directors of the Relevant Company; or
- The Study involves former employers or their representatives, for whom the Covered Person worked within the past one-year period before starting work on the Study.
Elements of a COI Management Plan
A COI management plan will contain the following elements:
- Role and principal duties of the conflicted Covered Person in the Study;
- Conditions of the management plan appropriate to eliminate or mitigate the COI, which would vary according to type of conflict and its seriousness. These conditions might include one or more of the following:
- Public disclosure of the COI (e.g., when presenting or publishing the research);
- Appointment of an independent monitor capable of taking measures to protect the design, conduct, and reporting of the research against bias from the COI;
- Modification of the Study plan to protect the design, conduct, and reporting of the Study;
- Change of personnel or personnel responsibilities, or disqualification of the Covered Person from participation in all or a portion of the Study;
- Reduction or elimination of the COI (e.g., sale of an equity interest); or
- Severance of relationships that create financial conflicts.
- How the COI management plan is designed to safeguard objectivity in the Study;
- Confirmation of the Covered Person’s agreement to the management plan; and
- How the COI management plan will be monitored to ensure the Covered Person’s compliance.
Review and Approval of COI Management Plan
The COI Official will submit any proposed COI Management Plan and accompanying documentation to the FDA for review and approval. If the FDA does not object nor indicate the need for more time to consider within ten (10) business days, the individual COI management plan is considered approved by the FDA. If the FDA does not approve the COI management plan, the COI Official will work with the FDA to determine whether an alternative COI management plan would be approved.
The Covered Person may not begin work on the Study until the COI Official informs the Covered Person they are cleared for work on the Study.
Covered Persons may not work on activities concerning the same medical product for both a Sentinel assessment and an industry sponsored project at the same time without explicit permission from FDA.
The SOC will provide quarterly written reports to the FDA’s Sentinel Core Team delineating all industry sponsored activities on which Covered Persons are currently or have recently been engaged for up to one year following completion of the industry funded activity. The COI Evaluator will assess industry funded projects semi-annually for conformance to the policy and will review the annual report prior to submission to the FDA.
A project conducted solely for developing or improving query methods, code, or analytic functions is considered as having no Relevant Company, regardless of funding source. Such a project is exempt from the COI disclosure process because there is no potential bias as long as the results of the project will be applied across all studies regardless of the particular medical product involved. The SOC will document this determination for a particular project and keep that documentation according to the retention requirements in this policy.
ARIA assessments that have not been designated as a “Safety Assessment” by FDA are exempt from the disclosure process.
Covered Persons may participate in activities funded by the following sources: U.S. federal, state or local governmental agencies; U.S. institutions of higher education; U.S. research institutes affiliated with institutions of higher education, academic teaching hospitals, and medical centers; the Reagan-Udall Foundation for the Food and Drug Administration (RUF-FDA); the Patient-Centered Outcomes Research Institute (PCORI); the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC). Projects funded by these sources are exempt from the COI disclosure process.
Additional information about select funding organizations that do not pose conflicts is provided below.
The Reagan-Udall Foundation for the Food and Drug Administration (RUF-FDA)
The RUF-FDA is an independent 501(c)(3) not-for-profit organization created in the Food and Drug Administration Amendments Act (FDAAA) of 2007. It is the only organization specifically established by the United States Congress to provide a framework for public-private partnerships intended to advance regulatory science on behalf of the Agency. As a result, it can be expected to receive funding from groups other than U.S. federal, state or local governmental agencies; U.S. institutions of higher education; U.S. research institutes affiliated with institutions of higher education, or academic teaching hospitals or medical centers. Covered Persons who participate as decision-makers in assessments covered by the Sentinel COI policy may participate in activities funded by the RUF-FDA’s Innovation in Medical Evidence Development and Surveillance (IMEDS) Program. The Foundation has established governance procedures for IMEDS that address scientific and technical issues, stakeholder access, and appropriate reporting, and these governance procedures have been endorsed by FDA.
The Patient-Centered Outcomes Research Institute (PCORI)
The PCORI is an independent 501(c)(1) not-for-profit organization created by Congress in 2010 to fund research to help patients and those who care for them make better-informed decisions about healthcare choices. PCORI is funded through the Patient-Centered Outcomes Research Trust Fund (PCORTF), which was established by Congress through the Patient Protection and Affordable Care Act of 2010. The PCORTF receives income from three funding streams: appropriations from the general fund of the Treasury, transfers from the Centers for Medicare and Medicaid trust funds, and a fee assessed on private insurance and self-insured health plans (the PCOR fee). Covered Persons who participate as decision-makers in in assessments covered by the Sentinel COI policy may participate in activities funded by PCORI.
The Biologics and Biosimilars Collective Intelligence Consortium (BBCIC)
The BBCIC, affiliated with the Academy of Managed Care Pharmacy (AMCP), is a not-for-profit, scientific public service initiative established in 2015 to monitor and generate post-market evidence for novel biologics, their corresponding biosimilars, and other related products regarding effectiveness and safety. The BBCIC is the only research network dedicated to monitoring biosimilars, draws on large sets of de-identified medical and pharmacy data (100 million lives), and harnesses cutting-edge distributed research network and surveillance methods. Managed care and integrated delivery organizations have devoted significant resources to develop an infrastructure that makes possible active surveillance of biosimilars and novel in distributed research networks (DRNs). The BBCIC marshals these resources for the important public health benefit inherent in monitoring biosimilar safety and effectiveness, using ongoing sequential analyses to compare biosimilars to their innovator product. Projects are jointly funded by pharmaceutical companies and overseen by independent scientific committees. An FDA liaison sits on the BBCIC Planning Board. The BBCIC requires that BBCIC Research Reports be submitted for publication within six months after the completion of the Research Report. When published, the publication will be posted on the BBCIC.org site. If six months have elapsed after the publication submission and the publication does not give a publication date or a release, the BBCIC Science Committee may release such results at its discretion on the BBCIC.org site.1 Covered Persons who participate as decision-makers in assessments covered by the Sentinel COI policy may participate in activities funded by BBCIC.
All Absence of Individual Conflicts of Interest Attestations, Cover Memoranda, Financial Interests Disclosure Forms, additional financial interest documentation, COI management plans, COI Official evaluations, FDA approvals and/or communications about COI, and related supporting documentation will be stored by the SOC or the COI Evaluator for at least three years after the Study is completed. The SOC will keep a list of Covered Persons who have COI management plans. The SOC or the COI Evaluator will make available to the FDA, on demand, all disclosures of Covered Persons performing work under the Sentinel contract.
Covered Persons will not be permitted to participate in work on a Sentinel Study until they have provided the disclosures or attestations required in this COI policy and, if a financial disclosure is declared, until they are cleared to work by the COI Official. Covered Persons who fail to comply with the requirements of this COI policy may be banned from continued engagement in Sentinel activities.
This Sentinel COI policy shall be made available to all SOC employees and employees of all Collaborating Institutions, including HPHC subcontractors and consultants working on Sentinel activities. The SOC will provide instruction concerning the Sentinel COI policy when a Covered Person is newly assigned to work on a Sentinel Study and annually thereafter. The COI training shall include the basics of COI, a review of the COI policy, and any changes to the COI policy made during the period since the last training. The SOC may periodically disseminate COI information and materials to Covered Persons performing work on Sentinel Studies.