DEPARTMENTOFRESEARCH

LBH IRB Guide #6: Conflict of Interest Guidelines for Clinical Research Page 1 of 6

Version 3, 08-28-2012

Administrative & Institutional Review Board

Conflict of Interest Guidelines for Clinical Research

The following policies and procedures apply to allhuman subjects research regardless of funding source.

  1. Annual Disclosure: All investigators involved in the conduct of clinical research must report any significant financial interest associated with a research study in their initial Administrative Review Board (ARB) and initial and continuing Institutional Review Board (IRB) applications. A significant financial interest is defined as any interest that could directly and significantly affect the design, conduct, or reporting of a research project. If a significant financial interest does exist, a LifeBridge Health (LBH)Financial Interest Disclosure Form must be submitted at the time of ARB and IRB review. Only covered parties declaring a financial interest greater than $5,000 must submit a Financial Interest Disclosure Form along with their ARB and IRB applications. Individual investigators are also responsible for filing an updated form anytime there is a relevant change in a significant financial interest.
  2. Administrative Review Board (ARB) Review of Conflict of Interest: Based on the information provided by investigators, the ARB will determine whether or not any of the disclosed relationships constitute a real or potential conflict of interest. This initial determination will be based on guidelines described below and in the LBH Department of Research Policy on Conflict of Interest in Research (IRB Guide #5).
  1. Disclosure and ARB Determinations Required Before Institutional Review Board (IRB) Review: All investigators and key personnel having a significant financial interest in a clinical research study must submit a Financial Interest Disclosure Formannually. Furthermore, a conflict of interest determination by the ARB MUST be rendered and on file for the principal investigator and all key personnel BEFORE the IRB can complete an initial review of any human subjects protocol.To avoid possible delays in protocol review, all investigators with either real or perceived conflicts of interest should submit a Financial Interest Disclosure Formalong with their ARB/IRB applications, and update it whenever their reportable financial interests change.
  1. Categories and Management Conditions: The ARB will initially assess whether real or potential conflicts of interest exist, evaluate their magnitude and recommend to the IRB what management conditions, if any, should be put in place in order to ensure that any conflict of interest issues are appropriately managed. Written recommendations will be forwarded to the appropriate LBH IRB for consideration and final resolution.

In addition to standard management conditions applicable to all investigators, additional management conditions will apply to investigators conducting human subjects research based on whether their significant financial interests are judged to be of either Moderate or Higher Risk as described below.

  1. Conflict of Interest – Minimal Risk:

Individuals who report having no significant financial interests or financial interests below the thresholds established for Moderate Risk situations (Table I) will be classified in the Minimal Risk category. Minimal Risk situations do not require specific management terms.

  1. Conflict of Interest – Moderate Risk:

Significant Financial Interest (SFI) thresholds used to define Moderate Riskconflicts are summarized in Table I. Individuals satisfying these thresholds will automatically be assigned to the Moderate Risk category and will be subject to the standardmanagement conditions described in Table I. Depending on the nature of the relationship between an investigator and any specific Outside Entity with which they hold a significant financial interest additional management conditions may be imposed by the IRB.

TABLE I: Thresholds and Standard Management Conditions for Conflict of Interest
Category / SFI Thresholds / Management Conditions
Moderate
Risk /
  1. Involved in clinical research
    AND
  2. Receive more than $5,000 from a Financially Interested Company
/
  1. Can serve as Principal Investigator (PI) or key personnel on clinical studies sponsored by a Financially Interested Company with which they have a SFI satisfying Moderate Risk thresholds
  2. Can recruit patients to such studies
  3. Must disclose the relationship in publications, seminars etc.
  4. Must disclose the relationship to trainees, fellows, etc. involved in the study
  5. Cannot receive any personal (including immediate family) incentives (recruitment and/or performance incentives, research support other than direct support for sponsored clinical study, fellowships, lectureships, etc.) related to such studies.

c. Conflict of Interest – Higher Risk:

Certain financial interests and relationships between investigators and potential sponsors of research represent a much greater risk with respect to conflicts of interest. The thresholds summarized in Table II define these potentially higher risk situations.

TABLE II: Thresholds and Standard Management Conditions for Conflict of Interest
Category / SFI Thresholds / Management Conditions
Higher Risk /
  1. Involved in clinical research
    And
  2. Receive more than $5,000 annually from a sponsoring Financially Interested Company
    And
  3. Significant ownership of stock or intellectual property or any other ownership interest in the sponsoring Business Entity
    Or
4. Leadership role or service as an officer or director for the sponsoring Financially Interested Company (directorship, scientific board, Board of Directors) /
  1. The investigatormust disclose the relationship in publications, abstracts and oral presentations
  2. Depending on the circumstances, the investigator may not::
a) serve as PI (protocol chair, study director) of any clinical study sponsored by the Financially Interested Company
b)serve as “key personnel” on any clinical study sponsored by the Financially Interested Company
c) recruit patients to the particular study in question
3. If a conflict develops or is discovered after initiation of a study, the investigator must notify the ARB/IRB and disclose the relationship to trainees, fellows, and staff involved with the study .
4. Cannot receive any personal (including immediate family) incentives (capitated payments, research support, fellowships, etc.) directly related to such studies

In all cases in which these threshold conditions are met or exceeded the full ARB will review the particulars of the involved relationship(s) and will classify the relationship(s) as Moderate or Higher Risk. In addition to standard management conditions applicable to all investigators, additional management conditions summarized in Table II may apply in situations designated by the IRB as Higher Risk.

The major difference between management of Moderate and Higher Risk conflicts is that individuals found to have Higher Risk conflicts maynot serve as PI for that clinical research, may not participate in any other key personnel capacity, and may not recruit patients to studies sponsored by the Outside Entity with which they have significant financial interests.

  1. Possible Management Strategies:

a. The conflicted investigator may be excluded from contract negotiationswith the outside entity.

b. The conflicted investigator should disclose his/her financial relationship with the company in allpublications, abstracts and oral presentations that report on research related to the commercialinterests of the company and/or its competitors. Such conflict must also be reported in grantapplications pertaining to research of interest to the company.

c. The conflicted Investigator should request and submit a declaration of COI from the sponsor summarizing the existing financial conflict the sponsor currently has with the investigator and the sponsor’s plans for management of the perceived/potential conflict at that site.

d.The conflicted investigator may be prohibited from serving asPrincipal Investigator (PI) on the research study. Where possible, the alternative PI selected shouldnot be one who reports administratively to the conflicted investigator. In those cases where thissituation cannot be avoided, a different individual should be responsible for conducting thealternative PI’s annual performance evaluations. The conflicted Investigator may be permittedto serve as a co-investigator on the research study.

e. In some cases, although not a requirement, the conflicted Investigator may be prohibited fromserving as a researcher on the study and may be required to remove himself from all aspects of theproject.

f. An Oversight Committee comprised of qualified faculty (not all from the same department) may beconstituted to assure the LBH community that an individual’s financial relationship with acompany will not compromise the integrity of LBH research. The Oversight Committeeshould meet with the conflicted investigator on a periodic basis (at least annually) and recordits conclusions in a written report. The report should be provided to those who requested thecreation of such Committee.

g. The conflicted investigator could be excluded from, or not be the sole individual responsiblefor, designing the study and recording, analyzing, and reporting research data. All research resultsshall be published, regardless of whether the results are favorable or unfavorable to the interests ofany sponsor or to the outside interests of the conflicted investigator.

h. Request a declaration of COI from the sponsor summarizing the existing financial conflict the sponsor currently has with the principal investigator and their plans for management at the site level of this perceived/potential conflict.

i. A researcher with outside financial interests could be required to complete the NIH Tutorial on Financial Conflict of Interest (FCOI) Requirements for NIH-Supported Institutions (

j.LBH may decline to enter into a research agreement if a conflict of interest cannot bemanaged effectively

  1. Exceptions to Higher Risk management conditions 1, 2 and 3 under Compelling Circumstances: In the event of compelling circumstances, an individual holding significant financial interests in a Financially Interested Company sponsoring a specific clinical study may be permitted to serve in the role of PI or other key personnel for the study and may be permitted to recruit patients to the study.

Whether the circumstances are deemed compelling will depend in each case upon the nature of the clinical research, the nature of the significant financial interest(s), how closely the interest(s) is related to the clinical research, and the degree to which the interest may be affected by the outcome of the clinical research. When the significant financial interest is directly related to the clinical research and may be substantially affected by it (e.g., an equity interest in a start-up company that manufactures the investigational product) the risk is greatest and the bar must be high. However, even direct and potentially lucrative financial interests may be justified in some circumstances. For example, when the individual holding such interests is uniquely qualified by virtue of expertise or experience and the clinical research could not otherwise be conducted as safely or effectively without that individual, he or she should be permitted the opportunity to rebut prohibition against participation (e.g. serving as PI; key personnel; recruiting patients) by demonstrating these facts in writing to the satisfaction of the IRB. The IRB may then approve the involvement of such an individual in the clinical research, subject to conditions that ensure effective management of the conflict and credible oversight of the clinical research.

If the IRB grants exceptions for any particular protocol, the following information MUST be provided in the corresponding human subjects research consent form:

  1. Source of funding for the study
  2. The nature of the PI’s relationship with the study sponsor
  3. Any payments the PI receives from the sponsor
  4. Provisions for ensuring subject’s protection
  5. Contact information for the IRB

When the IRB agrees to grant an exception under compelling circumstances, the committee will prepare a report summarizing the IRB’s recommendation and transmit it to the ARB.

  1. Prohibition on Payments for Results: Payments from LBH or the research sponsor to an investigator are prohibited if such payments are conditioned upon a particular research result or are linked to successful research outcomes. Payments for subject enrollment or for the referral of patients to clinical studies are only permitted when such payments:
  1. Are reasonably related to costs incurred, as specified in research agreements between the sponsor and LBH;
  2. Reflect the fair market value of services performed; and
  3. Are commensurate with the efforts of the individual(s) performing the research.
  1. Publication Policy: Under no circumstances may a sponsor of clinical research limit the rights of the principal investigator to receive, analyze or interpret any data generated as part of the sponsored research project, nor restrict publication of the results, regardless of the outcome of the research. A sponsor may request that publication be delayed as much as 90 days for the purpose of pre-publication review, or for a period of time that is agreed to by both parties. The only exception to this policy is a federally sponsored multi-center study in which the clinical trial agreement prohibits the investigator from publishing his or her own results before completion and publication of the multi-center study.
  1. Protection of students/residents/trainees: Significant financial interests may give rise to conflicts with an investigator’s responsibility to foster the academic development of students, residents and/or trainees. An investigator’s financial relationship with an Outside Entity may not place restrictions on the activities of students/residents/trainees. Investigators judged to have Moderate or Higher Risk conflicts must disclose the details of the relevant relationship(s) to all students/residents/traineesprior to their involvement in the clinical research.
  1. Disclosure to IRBs: Each time a clinical protocol is submitted to the IRB for review, each investigator will be asked to:
  1. Declare if they have significant financial interests with any sponsor of the study, and if so
  2. Attest that they have a current financial disclosure form on file with the ARB and submit a copy of that form along with the IRB application,
  3. Disclose the risk level assigned to the relationship by the ARB, and
  4. Acknowledge that they have read and agree to comply with LBH ARB/IRB policies.

The ARB will share information about individual ARB determinations with the LBH IRBs. IRBs have the ultimate responsibility and authority to evaluate how any particular conflict of interest determinations impact specific research protocols involving human subjects. Thus, IRBs may impose additional terms, conditions, limitations or other management elements they believe are necessary to ensure the protection of human subjects when approving any research protocol.

  1. Sanctions for Non-compliance: The LBH IRB will not review a protocol unless a) all key personnel listed on the protocol have declared their status of financial interest as indicated in the ARB/IRB application forms, b) all required annual financial disclosure forms are submitted, and c) the ARB has rendered a decision concerning the potential for conflicts for each key personnel. Deliberate misrepresentation of information provided to the ARB/IRB or failure to comply with the terms of this policy may result in sanctions up to and including loss of investigator status.

LBH IRB Guide #6: Conflict of Interest Guidelines for Clinical Research Page 1 of 6

Version 3, 08-28-2012