Policy

1. Purpose. 

The U.S. Department of Health and Human Services issued a Final Rule for identifying and managing investigator’s financial conflicts of interest (FCOI). The 2011 revised FCOI regulation, 42 CFR Part 50, Subpart F (grants and cooperative agreements), promotes objectivity in research by establishing standards that provide a reasonable expectation that the design, conduct, and reporting of research funded under Public Health Service (PHS) grants or cooperative agreements will be free from bias resulting from Investigator’s financial conflict of interest. The detail of the Final Rule can be found on the NIH website (https://grants.nih.gov/grants/FCOI_Final_Rule_inspection_Desk.pdf). 

The goal of this Policy is to establish standards for EarlyDiagnostics Inc. (“EarlyDx”) to ensure compliance with the Final Rule, to protect the integrity of Research and to maintain public trust in EarlyDx and its employees. 

 

2. Definitions. 

Disclosure of significant financial interests means an Investigator’s disclosure of significant financial interests to an Institution. 

PHS means the Public Health Service of the U.S. Department of Health and Human Services, and any components of the PHS to which the authority involved may be delegated, including the National Institutes of Health (NIH). 

Investigator means the project director or principal Investigator and any other person, regardless of title or position, who is responsible for the design, conduct, or reporting of research funded by the PHS, or proposed for such funding, which may include, for example, collaborators or consultants. 

PD/PI means a project director or principal Investigator of a PHS-funded research project; the PD/PI is included in the definitions of senior/key personnel and Investigator. 

Senior/Key Personnel means the PD/PI and any other person identified as senior/key personnel by EarlyDx in the grant application, progress report, or any other report submitted to the PHS by EarlyDx under the regulation. 

Designated Officials (“FCOI Official”) means one or more persons designated by EarlyDx as having responsibilities and authority under this Policy. 

Immediate Family Member means a person’s spouse, domestic partner, parent, grandparent, grandchild, sibling, child, or anyone who qualifies as the person’s dependent under the U.S. Internal Revenue Code. 

Entity means any domestic or foreign, public or private, for profit or not-for-profit legal entity or organization other than EarlyDx or the federal government. 

Equity means any interest in the profits of or other ownership interest in any commercial or non-profit enterprise, including common stock and other equity securities, and any right to acquire any of the foregoing such as an option, warrant or other security convertible into an equity security. 

Intellectual Property means the rights comprising a patent, trademark, copyright, trade secret, know-how or other similar intangible property right, including but not limited to, inventorship or authorship. 

Institutional responsibilities means an Investigator’s professional responsibilities on behalf of EarlyDx, including research, research consultation, institutional committee memberships, and service on panels such as Institutional Review Boards or Data and Safety Monitoring Boards. 

Research means a systematic investigation, study or experiment designed to develop or contribute to generalizable knowledge relating broadly to public health, including behavioral and social-sciences research. The term encompasses basic and applied research (e.g., a published article, book or book chapter) and product development (e.g., a diagnostic test or drug). As used in the subpart (“42 CFR Part 50, Subpart F”), the term includes any such activity for which research funding is available from a PHS Awarding Component through a grant or cooperative agreement, whether authorized under the PHS Act or other statutory authority, such as a research grant, career development award, center grant, individual fellowship award, infrastructure award, institutional training grant, program project, or research resources award. 

PHS-Funded Research means any Research or sponsored activity for which funding is available from a PHS awarding component through a grant or cooperative agreement, however authorized, such as a research grant, career development award, center grant, individual fellowship award, infrastructure award, institutional training grant, program project, or research resources award. Notwithstanding the foregoing, PHS-Funded Research does not include any Phase I SBIR Program application or award. 

Significant Financial Interest (SFI) means a financial interest consisting of one or more of the following interests of the Investigator (and those of the Investigator’s spouse and dependent children) that reasonably appears to be related to the Investigator’s institutional responsibilities:

• With regard to any publicly traded entity, a significant financial interest exists if the value of any remuneration received from the entity in the twelve months preceding the disclosure and the value of any equity interest in the entity as of the date of disclosure, when aggregated, exceeds $5,000.  For purposes of this definition, remuneration includes salary and any payment for services not otherwise identified as salary (e.g., consulting fees, honoraria, paid authorship); equity interest includes any stock, stock option, or other ownership interest, as determined through reference to public prices or other reasonable measures of fair market value;
• With regard to any non-publicly traded entity, a significant financial interest exists if the value of any remuneration received from the entity in the twelve months preceding the disclosure, when aggregated, exceeds $5,000, or when the Investigator (or the Investigator’s spouse or dependent children) holds any equity interest (e.g., stock, stock option, or other ownership interest); or
• Intellectual property rights and interests (e.g., patents, copyrights), upon receipt of income related to such rights and interests.

Investigators also must disclose the occurrence of any reimbursed or sponsored travel (i.e., that which is paid on behalf of the Investigator and not reimbursed to the Investigator so that the exact monetary value may not be readily available), related to their institutional responsibilities, provided, however, that this disclosure requirement does not apply to travel that is reimbursed or sponsored by a Federal, state, or local government agency, an Institution of higher education as defined at 20 U.S.C. 1001(a), an academic teaching hospital, a medical center, or a research institute that is affiliated with an Institution of higher education.

Certain types of financial interests are not included in the term of significant financial interest:

• Salary royalties, or other remuneration paid by EarlyDx to the Investigator if the Investigator is currently employed or otherwise appointed by EarlyDx;
• Intellectual Property Rights assigned to EarlyDx and agreements to share in royalties related to such rights;
• Any ownership interest in EarlyDx held by the Investigator;
• Income from investment vehicles, such as mutual funds and retirement accounts, as long as the Investigator does not directly control the investment decisions made in these vehicles;
• Income from seminars, lectures, or teaching engagements sponsored by a federal, state or local government agency, an Institution of higher education as defined at 20 U.S.C. 1001(a), an academic teaching hospital, a medical center, or a research institute that is affiliated with an Institution of higher education; or
• Income from service on advisory committees or review panels for a federal, state or local government agency, Institution of higher education as defined at 20 U.S.C. 1001(a), an academic teaching hospital, a medical center, or a research institute that is affiliated with an Institution of higher education. 

Financial Conflict of Interest (FCOI) means an SFI that could directly and significantly affect the design, conduct, or reporting of NIH-funded research. 

Small Business Innovation Research means the extramural research program for small businesses that is established by the Awarding Components of the Public Health Service and certain other Federal agencies under Public Law 97–219, the Small Business Innovation Development Act, as amended. For purposes of this subpart, the term SBIR Program also includes the Small Business Technology Transfer (STTR) Program, which was established by Public Law 102–564. 

 

3. Procedures 

A. Training for Investigators Participating in PHS-funded research 

Each Investigator must complete FCOI training with respect to this Policy and the then-current federal regulations (https://grants.nih.gov/grants/policy/coi):

• Prior to engaging in research related to any NIH funded project;
• At least every four years, and
• Immediately when any of the following circumstances apply: i) EarlyDx revises its policy in a manner that affects the Investigator; ii) when an investigator is new to EarlyDx; or iii) when EarlyDx finds an Investigator is not in compliance with EarlyDx’s policy or management plan.

B. Disclosure, Review and Monitoring

B.1) Responsibilities of designated EarlyDx FCOI Official

EarlyDx’s Designated FCOI Official’s responsibilities include:

·         Take necessary actions to manage FCOIs of EarlyDx’s Investigators, including those of subrecipient Investigators.

·         Inform EarlyDx Investigator of PHS regulations regarding Financial Conflicts of Interest, 42 Code of Federal Regulations Part 50, Subpart F.

·         Inform Investigator of EarlyDx’s policy on FCOI.

·         Inform Investigator of responsibilities regarding disclosure of SFIs.

·         Solicit & review disclosure statements from each Investigator planning to participate in, or is participating in, PHS/NIH-funded research.

·         Provide guidelines to identify conflicting interests related to proposed or PHS/NIH-funded research.

·         Develop management plans and monitor compliance that specify the actions that have been, and shall be, taken to manage FCOI.

·         Certify in each application for funding that EarlyDx: (i) Has in effect an up-to-date written, and enforced administrative process to identify and manage FCOIs related to all PHS research projects; (ii) Promotes and enforces Investigator compliance with the regulations pertaining to disclosure of SFIs; (iii) Manages FCOIs and provides initial and ongoing FCOI reports to PHS/NIH; (iv) Agrees to make information available upon request relating to any Investigator disclosure of financial interest and the Institution’s review of, and response to, such disclosure, whether or not the disclosure resulted in the Institution’s determination of an FCOI; (v) Fully complies with the requirements of the regulation. 

·         If the designated FCOI Official identifies an SFI that was not disclosed or reviewed in a timely manner, the designated official shall within sixty (60) days review the SFI, determine if an FCOI exists and implement an interim management plan, if needed.

·         In cases of noncompliance, complete a retrospective review and submit a Mitigation Report if bias is found. 

B.2) Disclosure of SFIs 

Each Investigator must disclose SFIs:

·    At time of Application: Each Investigator, including subrecipient Investigators, if applicable, planning to participate in PHS/NIH-funded research, must disclose to the designated official(s) at time of application.

·        Annually: Each Investigator, including subrecipient Investigator, if applicable, must submit an updated disclosure of SFI annually, during the period of the award.

·      Within 30 days: Each Investigator, including subrecipient Investigator, if applicable, who is participating in the NIH-funded research to submit an updated disclosure of SFI within thirty days of discovering or acquiring (e.g., through purchase, marriage, or inheritance) a new SFI. 

B.3) Review, determination and management of FCOI 

When a written SFI disclosure is received by the designated FCOI official, the FCOI official shall complete the review within thirty days. The investigator having an SFI disclosure shall not participate in Research activities before the review is completed. The FCOI official will determine whether the disclosed SFI is related to the Research and constitute a FCOI which must be managed, reduced, or eliminated. If an FCOI cannot be managed, reduced, or eliminated, the Research will not be allowed to proceed.

If the FCOI Official determines that an SFI Disclosure constitutes an FCOI and the FCOI can be managed, the FCOI Official will develop and implement an FCOI Management Plan to manage, reduce, or eliminate the effects of the FCOI. The SFI disclosure review, determination, and management plan development shall be done prior to EarlyDx’s expenditure of funds. The management plan shall consider various factors, e.g., type/amount of SFI, the nature of the Research, the role of the Investigator, and may include one or more of the following:

• Requiring the divestiture and termination of an Investigator’s SFI; 
• Restricting participation in activities (e.g., recruitment or consent of human subjects, data analysis) that may affect Research;
• Disclosures of FCOIs to the public, e.g., all investigators and research personnel, study participants, publishers, conference organizers and audience;
• Oversight of Research by independent co-researchers and EarlyDx executives;
• Maintaining copies and performing independent analysis of Research data by a third party;

 B.4) Monitor Investigator’s compliance with management plan

 The FCOI official shall audit and monitor compliance with FCOI Management Plan on a weekly basis, including obtaining regular reports from the investigator having the FCOI and from independent co-researchers with oversight responsibilities, discussing with EarlyDx executive members for further actions.     

C. Reporting to NIH 

The designated FCOI Official’s responsibilities include:

·         Provide initial, ongoing and revised FCOI reports to NIH: i) prior to the expenditure of funds; ii) during the period of award within 60 days of identifying a new FCOI; iii) annually to report on the status of FCOI and any changes in management plan, which is due at the same time that EarlyDx submits its annual progress report, including multi-year progress report, or at the time of extension.

·         All FCOI reports are submitted to NIH through the eRA Commons FCOI Module.

 

The elements of an FCOI report shall include:

·         Grant number;

·         PD/PI or contact PD/PI;

·         Name of Investigator with the FCOI;

·         Name of the entity with which the Investigator has an FCOI;

·         Nature of FCOI (e.g., equity, consulting fees, travel reimbursement, honoraria);

·         Value of the financial interest $0-4,999; $5K-9,999; $10K-19,999; amounts between $20K-100K by increments of $20K; amounts above $100K by increments of $50K or a statement that a value cannot be readily determined;

·         A description of how the financial interest relates to NIH-funded research and the basis for EarlyDx’s determination that the financial interest conflicts with such research; and

·         Key elements of EarlyDx’s management plan, including (i) Role and principal duties of the conflicted Investigator in the research project; (ii) Conditions of the management plan; (iii) How the management plan is designed to safeguard objectivity in the research project; (iv) Confirmation of the Investigator’s agreement to the management plan; (v) How the management plan will be monitored to ensure Investigator compliance. 

If results of a retrospective review warrant it, the designated FCOI official shall update previously submitted FCOI report to specify the actions that have been taken to manage the FCOI going forward. If bias is found through retrospective review, the NIH Awarding Component will be promptly notified (through the eRA Commons) and a Mitigation Report will be submitted.

 Mitigation Report. The Mitigation Report shall include:

·         Key elements documented in retrospective review;

·         Description of the impact of the bias on the research project;

·         Plan of action(s) to eliminate or mitigate the effect of the bias;

·         Notify NIH promptly and submit a Mitigation Report when bias is found. 

D. Maintenance of Records 

The Designated FCOI Official shall maintain records of all Investigator disclosures of financial interests and EarlyDx’s review of, and response to, such disclosures (whether or not a disclosure resulted in EarlyDx’s determination of FCOI) and all actions under EarlyDx’s policy or retrospective review, if applicable, (i) for at least three years from the date of submission of the final expenditures report or, where applicable, (ii) from other dates specified in 45 C.F.R. 74.53(b) and 92.42 (b) for different situations. 

E. Enforcement Mechanisms and Remedies and Noncompliance 

Investigators failing to comply with the FCOI Policy shall be subject to enforcement mechanisms including termination of the participation in the Research, restriction in applying for further PHS funding, and other applicable disciplinary actions.  

Whenever an FCOI is not identified or managed in a timely manner, including failure by the Investigator to disclose an SFI, failure by EarlyDx to review or manage an FCOI, or failure to comply with the management plan, EarlyDx shall within 120 days of the determination of noncompliance, complete a retrospective review of the Investigator’s activities and the project to determine bias in the design, conduct or reporting of such research. The following key elements shall be documented in the retrospective review:

·         Project number;

·         Project title; 

·         PD/PI or contact PD/PI if a multiple PD/PI model is used;

·         Name of the Investigator with the FCOI;

·         Name of the entity with which the Investigator has an FCOI;

·         Reason(s) for the retrospective review;

·         Detailed methodology used for the retrospective review (e.g., methodology of the review process, composition of the review panel, documents reviewed);

·         Findings and conclusions of the review. 

F. Subrecipient 

The subrecipient must

·         Comply with EarlyDx FCOI policy or provide written certification to EarlyDx that subrecipient’s FCOI policy complies with all applicable PHS and federal FCOI regulations.

·         Subrecipient Institutions who rely on their FCOI policy must report identified FCOIs to EarlyDx in sufficient time to allow EarlyDx to report the FCOI to the PHS/NIH Awarding Component (i.e., to NIH through the eRA Commons FCOI Module) to meet FCOI reporting obligations. 

G. Public Accessibility 

Prior to expenditure of funds, EarlyDx shall make certain information concerning FCOIs held by senior/key personnel publicly accessible via company website and provide written response within five business days of a request. EarlyDx is responsible for updating the website annually and within 60 days of identifying any new FCOIs when posting FCOIs to the website and retaining information for three years. Information to be made publicly available on the company’s website includes the following:

(1) Investigator’s name;

(2) Investigator’s title and role with respect to the research project;

(3) Name of the entity in which the SFI is held;

(4) Nature of the SFI; and

(5) Approximate dollar value of the SFI (dollar ranges are permissible:  $0-$4,999; $5,000-$9,999; $10,000-$19,999; amounts between $20,000-$100,000 by increments of $20,000; amounts above $100,000 by increments of $50,000), or a statement that the interest is one whose value cannot be readily determined through references to public prices or other reasonable measures of fair market value.