The purpose of this policy is to document the requirements and responsibilities associated with identifying and managing financial conflicts of interest to safeguard the integrity of Caeregen (the Company, formerly known as Retinal Solutions, LLC) research and to comply with federal regulations.
This policy has been developed to address and comply with federal Public Health Service (PHS) regulations (42 CFR Part 50 Subpart F and 45 CFR Part 94) on Promoting Objectivity in Research. These regulations describe the actions an individual and an organization must take in order to promote objectivity in PHS-funded research. The regulations apply to all PHS funded grants, cooperative agreements, research contracts (but not Phase 1 Small Business Innovation Research or Small Business Technology Transfer program grants), and subawards where the originating sponsor is PHS. An electronic version of the regulation is found at http://www.gpo.gov/fdsys/pkg/FR-2011-08-25/pdf/2011-21633.pdf.
SUMMARY OF PROCESS
Significant Financial Interests (SFI) (as defined below) shall be disclosed on the Significant Financial Interest Disclosure Form by an Investigator requesting government-sponsored or company-sponsored funds for a research project or by an Investigator when a Significant Financial Interest arises during the course of research. Regardless of whether a SFI exists, all Investigators and key personnel are required to submit a SFI Disclosure Form annually.
It is the Principal Investigator’s responsibility to ensure those with financial interests in research are identified and make the required disclosures in conjunction with submission of a research proposal or application for human subjects’ approval.
The Significant Financial Disclosure Form and supporting materials are forwarded to the Company President for review. The Finance Department will be responsible for evaluating and instituting a plan for managing any disclosed financial interests, for producing institutional reports and other required reports to external sponsors and governmental agencies, and for the general administration and enforcement of this policy.
Advance approval by the President or Finance Department is required prior to engaging in government-sponsored research. A SFI review must be completed before any expenses are incurred under an award.
Annual updates are required of all Investigators and key personnel participating in research. Any Investigator who has acquired a new or increased financial interest during the course of a research project shall report it immediately to the Finance Department. Annual updates and newly acquired interests are reported using the Significant Financial Interest Disclosure Form.
Each Investigator must complete training on the Company’s Financial Conflict of Interest Policy Applicable to an Award Issued by Public Health Services prior to engaging in research related to any NIH award and at least every four years, and immediately (as defined below) when any of the following circumstances apply:
1) Caeregen revises this Policy, or procedures related to this Policy, in any manner that affects the requirements of Investigators (training is to be completed within the timeframe specified in communications announcing such changes);
2) An Investigator is new to Company research under a NIH award (training is to be completed prior to his/her participation in the research); or
3) Caeregen finds that an Investigator is not in compliance with this Policy or a management plan issued under this Policy (training is to be completed within 30 days in the manner specified by the Finance Department).
In fulfillment of the training requirement, the Company requires its investigators to complete the National Institutes of Health’s Financial Conflict of Interest tutorial located at: http://grants.nih.gov/grants/policy/coi/tutorial2011/fcoi.htm in accordance with the requirements and expectations of this Policy. All investigators must print a certification of completion at the end of training and retain it for audit purposes.
The following definitions are provided as a reference and are considered key definitions in understanding the federal regulations of FCOI. A complete list of official definitions can be found at 42 CFR 50.603.
Financial conflict of interest (FCOI) – a significant financial interest that could directly and significantly affect the design, conduct, or reporting of PHS-funded research.
HHS – the Department of Health and Human Services
Institution – means any domestic or foreign, public or private, entity or organization (excluding a Federal agency) applying for, or receiving NIH research funding. Institution in this FCOI policy refers to Caeregen Therapeutics.
Investigator – means the project director or principal investigator and any other person, regardless of title or position, who is or will be responsible for the design, conduct, or reporting of research funded by the NIH, which may include, for example, collaborators or consultants.
Institutional Responsibilities – means an Investigator’s professional responsibilities on behalf of the Institution, and as defined by the Company, including but not limited to, activities such as research, research consultation, teaching, professional practice, institutional committee memberships, and service on panels such as Institutional Review Boards or Data and Safety Monitoring Boards.
Financial Interest – means anything of monetary value, whether or not the value is readily ascertainable.
Financial Conflict of Interest (FCOI) – means a significant financial interest that could directly and significantly affect the design, conduct, or reporting of NIH-funded research.
Manage – means taking action to address a financial conflict of interest, which can include reducing or eliminating the financial conflict of interest, to ensure, to the extent possible, that the design, conduct, and reporting of research will be free from bias.
PHS – 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).
NIH -the biomedical research agency of the PHS
Senior/Key Personnel – means the PD/PI and any other person identified as senior/key personnel by the Company in the grant application, progress report, or any other report submitted to the NIH by the Company under the regulation.
Significant Financial Interest (SFI) –
(1) 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 appear to be related to the Investigator’s institutional responsibilities on behalf of Caeregen:
i. 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 for the investigator, investigator’s spouse, and dependent children, 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;
ii. 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;
iii. With regard to intellectual property rights and interests (e.g., patents, copyrights), a significant financial interest exists upon receipt of income of greater than $5,000 related to such rights and interests.
(2) The term significant financial interest does not include the following types of financial interests:
i. Salary, royalties, or other remuneration paid by Caeregen to the Investigator if the Investigator is currently employed or otherwise appointed by Caeregen, including intellectual property rights assigned to Caeregen and agreements to share in royalties related to such rights;
ii. 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;
iii. Income from seminars, lectures, or teaching engagements sponsored by a federal, state, or local government agency located in the United States (U.S.), a U.S. Institution of higher education, an academic teaching hospital, a medical center, or a research institute that is affiliated with a U.S. Institution of higher education; or
iv. Income from service on advisory committees or review panels for a federal, state, or local government agency located in the U.S., a U.S. Institution of higher education, an academic teaching hospital, a medical center, or a research institute that is affiliated with a U.S. Institution of higher education.
(3) Investigators must disclose the occurrence of any foreign or domestic 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 the Investigator’s institutional responsibilities. The details of this disclosure will include at a minimum, the purpose of the trip, the identity of the sponsor/organizer, the destination, and the duration. The disclosure requirement does not apply to travel that is reimbursed or sponsored by the following:
Foreign Financial Interests – Investigators must disclose all foreign financial interests (which includes income from seminars, lectures, or teaching engagements, income from service on advisory committees or review panels, and reimbursed or sponsored travel) received from any foreign entity, including foreign Institutions of higher education or a foreign government (which includes local, provincial, or equivalent governments of another country) when such income meets the threshold for disclosure (e.g., income in excess of $5,000).
A. Disclosure: Prior to the submission of an application to the NIH Grantee for funding, the Principal Investigator, and all other Investigators at Caeregen must have disclosed to Caeregen’s Finance Department an up-to-date listing of their Significant Financial Interests [SFIs] (and those of their spouse and dependent children), as defined above. Any new Investigator, who, subsequent to the submission of an application to NIH for funding from NIH, or during the course of the research project, plans to participate in the project, must similarly disclose their SFI to the Finance Department promptly and prior to participation in the project.
B. Submission of the Significant Financial Interest Disclosure Form: Each Investigator who is participating in research under an NIH award must submit an updated disclosure of SFI at least annually, during the period of the award. Such disclosure must include any information that was not disclosed initially to the Company pursuant to this Policy, or in a subsequent disclosure of SFI (e.g., any financial conflict of interest identified on a NIH funded project directly as a NIH Grantee and/or indirectly through a subaward) that was transferred from another Institution), and must include updated information regarding any previously disclosed SFI (e.g., the updated value of a previously disclosed equity interest).
Each Investigator who is participating in research under an award from NIH must submit an updated disclosure of SFI (including reimbursed travel) within thirty (30) days of discovering or acquiring (e.g., through purchase, marriage, or inheritance) a new SFI that shall be submitted to the Finance Department.
C. Review of the Significant Financial Interest Disclosure Form: The President will conduct reviews of disclosures. The President will review any SFI that has been identified in a disclosure; these interests will be compared to each research award on which the Investigator is identified as responsible for the design, conduct, or reporting of the research to determine if the SFI is related to the award and, if so, whether the SFI creates a Financial Conflict of Interest (FCOI) related to that research award.
D. Determining “Relatedness” and Financial Conflict of Interest: The President will determine whether an Investigator’s SFI is related to the research under a NIH award and, if so, whether the SFI is a financial conflict of interest. An Investigator’s SFI is related to the research under the NIH award when the President reasonably determines that the SFI:
A financial conflict of interest exists when the President reasonably determines that the SFI could directly and significantly affect the design, conduct, or reporting of the NIH-funded research.
In determining if an Investigator’s SFI is related to the research under a NIH award, and if so, whether the relationship creates a FCOI, the President considers the role of the Investigator and the opportunity (if any), to bias the results, the nature of the research being proposed, and the value of the SFI in relation to the size and value of the entity. In addition, the President may also consider the following factors:
E. Management of Significant Financial Interests that Pose Financial Conflict(s) of Interest: If a conflict of interest exists, the President will determine by what means – such as the individual’s recusal from decisions affecting the conflicting entity, abstention from the external activity, modification of the activity, and/or monitoring of the activity by a subcommittee – the conflict should be avoided or managed in order to mitigate undue bias. In making those determinations, the President will be guided by the principles discussed in this Policy and the President will also take into consideration whether the Investigator’s ongoing role is necessary to continue advancing the research, based upon the factors such as the uniqueness of his or her expertise and qualifications.
Examples of conditions that might be imposed to manage a financial conflict of interest include, but are not limited to:
a. Public disclosure of financial conflicts of interest (e.g., when presenting or publishing the research, to research personnel working on the study, to the Institution Review Board, Institutional Animal Care and Use Committee, Data Safety and Monitoring Board, etc.);
b. For research projects involving human subjects research, disclosure of financial conflicts of interest directly to human participants in the informed consent document;
c. Appointment of an independent monitor capable of taking measures to protect the design, conduct, and reporting of the research against bias resulting from the financial conflict of interest;
d. Modification of the research plan;
e. Change of personnel or personnel responsibilities, or disqualification of personnel from participation in all or a portion of the research;
f. Reduction or elimination of the financial interest (e.g., sale of an equity interest);
g. Severance of relationships that create financial conflicts;
h. For research projects involving human subjects research, use of a data and safety monitoring board;
i. Double-blind conditions;
j. Provisions to conduct the work simultaneously at multiple sites;
k. Written disclosure of the conflict to all individuals working on the research project;
l. Annual reports on the research progress to the Finance Department.
m. Disclosure at any presentation of information related to the FCOI.
If the President determines that a conflict exists, he/she will communicate its determination and the means it has identified for eliminating or managing the conflict, in writing, to the individual, to the relevant Principal Investigator/Project Director, and the appropriate direct supervisor. The Finance Department will keep a record of the disclosure and other relevant information for at least three years. If the Finance Department prescribes monitoring of the activity, it will describe what monitoring shall be performed and what records are to be kept.
No expenditures on a NIH award will be permitted until the Investigator has complied with the Disclosure requirements of this Policy and has agreed, in writing, to comply with any plans determined by the Finance Department necessary to manage the Conflict of Interest. The President will communicate, in writing, with the NIH Grantee to notify it of the existence and the nature of a Financial Conflict of Interest and whether the conflict has been managed, reduced, or eliminated. No expenditures can be incurred until the NIH Grantee has reported the FCOI to NIH. The NIH Grantee will notify the Finance Department when it may incur expenditures.
The Finance Department will keep a record of Investigator disclosures of financial interests and the President’s review of, and response to, such disclosure and all actions under this policy. Such records will be maintained and kept for at least three years from the date the final expenditures reportis submitted or, where applicable, from other dates specified in 45 C.F.R. 75.361 for different situations.
F. Public Access to Information Related to Financial Conflicts of Interest: Prior to the expenditure of any funds under a NIH award, the Company will ensure public accessibility, by written response to any requestor within five business days of a request of information concerning any SFI disclosed that meets the following three criteria:
i. The SFI was disclosed and is still held by the senior/key personnel. Senior/key personnel are the PD/PI and any other person identified as senior key personnel by the Company in the award application, progress report or any other report submitted to the NIH Grantee;
ii. Caeregen has determined that the SFI is related to the research funded through an award; and
iii. Caeregen has determined that the SFI is a financial conflict of interest.
The Finance Department will provide public access to this policy via a publicly accessible page of the Company’s website www.caeregen.com, and in a written response to any requestor within five days of request which will include, at a minimum, the following:
i. The Investigator’s name;
ii. The Investigator’s title and role with respect to the research project;
iii. The name of the entity in which the Significant Financial Interest is held;
iv. The nature of the Significant Financial Interest; and
v. The approximate dollar value of the Significant Financial Interest in the following ranges: $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 reference to public prices or other reasonable measures of fair market value.
The information posted by Finance Department on the Company website to comply with the public disclosure requirements of the NIH regulations will be updated at least annually, and within sixty days of receipt or identification of: 1) information concerning any additional Significant Financial Interest of the senior/key personnel for the NIH-funded research project that had not been previously disclosed, or; 2) upon the disclosure of a Significant Financial Interest of senior/key personnel new to the NIH-funded research project, if it is determined by the President that the Significant Financial Interest is related to the research and is a financial conflict of interest.
Information concerning the SFI of an individual, as limited by this Policy, will remain available, for responses to written requests or for posting via the Company website, for at least three years from the date that the information was most recently updated.
Further information regarding Caeregen FCOI information is available via:
Director of Finance
Caeregen Therapeutics, LLC
510 Meadowmont Village Circle
Chapel Hill, NC 27517
G) Reporting of Financial Conflicts of Interest: Prior to the expenditure of any funds under an award funded by NIH, the Caeregen will provide to NIH a FCO report compliant with NIH regulations regarding any Investigator’s Significant Financial Interest found to be conflicting and will ensure that the Investigator has agreed to and implemented the corresponding management plan. While the award is ongoing (including any extensions with or without funds), the Company will provide to NIH an annual FCOI report that addresses the status of the FCOI and any changes in the management plan.
For any Significant Financial Interest that is identified as conflicting subsequent to an initial FCOI reportduring an ongoing NIH-funded research project (e.g., upon the participation of an Investigator who isnew to the research project), the Company will provide to NIH, within 60 days, an FCOI report regarding the financial conflict of interest and ensure that Finance Department has implemented a management plan and the Investigator has agreed to the relevant management plan.
(H) Violations of the Company’s Conflict-of-Interest Policy Applicable to PHS Funded Awards: When a FCOI is not identified or managed in a timely manner, including, failure by the Investigator to disclose a significant financial interest that is determined by the Institution to constitute a FCOI; failure by the Institution to review or manage such a FCOI; and failure by the Investigator to comply with a management plan; then CAEREGEN will within 120 days:
A. Complete a retrospective review of the Investigator’s activities and the research project to determine any bias in the design, conduct or reporting of research;
B. Document the retrospective review consistent with the regulation at 42 CFR 50.605(a)(3)(ii)(B);
C. Document the Company’s determination as to whether any research, or portion thereof, conducted during the period of time of the Investigator’s non-compliance with this Policy or a Financial Conflict of Interest management plan, was biased in the design, conduct, or reporting of such research;
If bias is found, the Company shall notify NIH promptly and submit a mitigation report to NIH via the eRA Commons FCOI Module that shall address the following:
Thereafter, Caeregen shall submit FCOI reports annually to NIH, in accordance with the regulation and terms and conditions of the award agreement. Depending on the nature of the Financial Conflict of Interest, the Company may determine that additional interim measures are necessary with regard to the Investigator’s participation in the research project between the date that the Financial Conflict of Interest is identified and the completion of the Company’s independent retrospective review.
I. Clinical Research: If HHS determines that one of its funded clinical research projects whose purpose is to evaluate the safety or effectiveness of a drug, medical device or treatment has been designed, conducted or reported by an Investigator with a Financial Conflict of Interest that was not managed or reported by Caeregen, the Company shall require the Investigator involved to disclose the Financial Conflict of Interest in each public presentation of the results of the research and to request an addendum to previously published presentations.
J. Subrecipient FCOI Compliance: A subrecipient relationship is established when federal funds flow down from or through Caeregen to another individual or entity and the subrecipient will be conducting a substantive portion of a PHS-funded research project and is accountable to the Company for programmatic outcomes and compliance matters. Subrecipients, who include but are not limited to collaborators, consortium members, consultants, contractors, subcontractors and sub-awardees, are subject to Caeregen’s terms and conditions, and as such, the Company will take reasonable steps to ensure that any subrecipient Investigator is in compliance with the federal FCOI regulation. Caeregen will incorporate, as part of a written agreement with the subrecipient, terms that establish whether the Company’s FCOI Policy or that of the subrecipient’s institution will apply to the subrecipient Investigator.
If the subrecipient’s FCOI policy applies to the subrecipient Investigator, the subrecipient institution will certify as part of the agreement with Caeregen that it is in compliance with the federal FCOI regulation, and that the institution’s portion of the project is in compliance with the FCOI policy. If the subrecipient cannot provide the certification, the agreement shall state that the subrecipient Investigator is subject to Caeregen’s FCOI Policy for disclosing SFI that are directly related to the subrecipient’s work for Caeregen. Caeregen will, if applicable, submit a FCOI report to the NIH through the eRA Commons FCOI Module for any FCOIs identified for a subrecipient Investigator.
If the subrecipient’s conflict of interest policy applies to the subrecipient Investigator, the agreement shall specify the time period for the subrecipient to report all identified FCOIs to Caeregen. Such time period must be sufficient to enable the Company to provide timely FCOI reports to the NIH as necessary, through the eRA Commons FCOI Module.
If the subrecipient Investigator is subject to Caeregen’s Investigator FCOI Policy, the agreement shall specify the time period for the subrecipient to submit all Investigator disclosures of SFI to THE COMPANY. Such time period shall be sufficient to enable Caeregen to comply with its review, management, and reporting obligations under the regulation. Caeregen will submit any NIH FCOI reports for a subrecipient Investigator through the eRA Commons FCOI Module.
K. Record Keeping: Records of all Investigator disclosures of financial interests including Investigator SFI Disclosure forms, and the Company’s review of, or response to, such disclosures (whether or not a disclosure resulted in the Company’s determination of a Financial Conflict of Interest), and all actions under the Company’s policy or retrospective review to manage actual or potential conflicts of interest, shall be retained by the Finance Department for at least three years from the date of submission of the final expenditures report or, where applicable, from other dates specified in 45 C.F.R. 75.361 for different situations. The Company will retain records for each competitive segment as provided in the regulation.
L. Compliance with This Policy: No expenditures of funds on an award supported by NIH will be permitted unless the Investigator has complied with the Disclosure requirements of this Policy and has agreed, in writing, to comply with any Company President or other Company designated official approved FCOI management plan.