Date: May 2004
Investigators, IRB members and staff, institutions engaged in human subjects research and their officials, and other interested members of the research community
Laws and Regulations:
45 CFR part 46 – institutions performing HHS conducted or supported non-exempt research involving human subjects have the research reviewed and approved by an IRB whose goal is to help ensure that the rights and welfare of human subjects are protected
21 CFR parts 50, 56 – FDA regulated research involving human subjects is reviewed and approved by such an IRB
45 CFR 46.111(a)(1), 21 CFR 56.111(a)(1) – risks to subjects are minimized
45 CFR 46.111(a)(2), 21 CFR 56.111(a)(2) – risks to subjects are reasonable in relation to anticipated benefits to subjects
45 CFR 46.111(a)(3), 21 CFR 56.111(a)(3) – selection of subjects is equitable
45 CFR 46.111(a)(4), 21 CFR 56.111(a)(4) – informed consent will be sought from each prospective subject
45 CFR 46.116, 21 CFR 50.20 – the possibility of coercion or undue influence is minimized
45 CFR 46.109(b), 21 CFR 56.109(b) – additional information be given to subjects “when in the IRB’s judgment the information would meaningfully add to protection of the rights and welfare of subjects”
45 CFR 46.124 – the funding agency may impose additional conditions as necessary for the protection of human subjects
45 CFR 46.107(e), 21CFR 56.107 – “no IRB may have a member participate in the IRB’s initial or continuing review of any project in which the member has a conflicting interest, except to provide information requested by the IRB”
Institutions and individuals involved in human subjects research may establish financial relationships for research projects, such as payments for services, equity interests, or intellectual property rights. A financial interest related to a research study may be a conflicting financial interest and affect the rights and welfare of human subjects. This guidance provides some possible approaches to consider in assuring that human subjects are adequately protected.
Concerns have arisen that financial conflicts of interest in research may affect the rights and welfare of human subjects in research. Relationships between government, academia, industry and others often legitimately include financial relationships and may not cause conflicts of interest. However, when financial interests affect the rights and welfare of human subjects in research IRBs, institutions, and investigators need to consider what actions regarding financial interests may be necessary to protect those subjects.
In establishing and implementing methods to protect the rights and welfare of human subjects from conflicts of interest created by financial relationships of parties involved in research, the Department recommends that IRBs, institutions engaged in research, and investigators consider:
- Does the research involve financial relationships that could create potential or actual conflicts of interest? a) How is the research supported or financed? b) Where and by whom was the study designed? c) Where and by whom will the resulting data be analyzed?
- What interests are created by the financial relationships involved in the situation? a) Do individuals or institutions receive any compensation that may be affected by the study outcome? b) Do individuals or institutions involved in the research: have any proprietary interests in the product, including patents, trademarks, copyrights, or licensing agreements? have an equity interest in the research sponsor and, if so, is the sponsor a publicly held company or non-publicly held company? receive significant payments of other sorts (e.g., grants, compensation in the form of equipment, retainers for ongoing consultation, or honoraria)? receive payment per participant or incentive payments, and are those payments reasonable?
- Given the financial relationships involved, is the institution an appropriate site for the research?
- How should financial relationships that potentially create a conflict of interest be managed?
- Would the rights and welfare of human subjects be better protected by any or a combination of the following:
a) reduction of the financial interest? b) disclosure of the financial interest to prospective subjects? c) separation of responsibilities for financial decisions and research decisions? d) additional oversight or monitoring of the research? e) an independent data and safety monitoring committee or similar monitoring body? f) modification of role(s) of particular research staff or changes in location for certain research activities, e.g., a change of the person who seeks consent, or a change of investigator? g) elimination of the financial interest?
Institutions – Actions to Consider:
- Establishing the independence of institutional responsibility for research activities from the management of the institution’s financial interests.
- Establishing conflict of interest committees (COICs) or identifying other bodies or persons and procedures to a) deal with individuals’ or institutional financial interests in research or verify the absence of such interests and b) address institutional financial interests in research.
- Establishing criteria to determine what constitutes an institutional conflict of interest, including identifying leadership positions for which the individual’s financial interests are such that they may need to be treated as institutional financial interests.
- Establishing clear channels of communication between COICs and IRBs.
- Establishing policies on providing information, recommendations, or findings from COIC deliberations to IRBS.
- Establishing measures to foster the independence of IRBs and COICs.
- Determining whether particular individuals should report financial interests to the COIC. These individuals could include IRB members and staff and appropriate officials of the institutions, along with investigators, among those who report financial interests to COICs.
- Establishing procedures for disclosure of institutional financial relationships to COICs.
- Providing training to appropriate individuals regarding financial interest requirements.
- Using independent organizations to hold or administer the institution’s financial interest.
- Including individuals from outside the institution in the review and oversight of financial interests in research.
- Establishing policies regarding the types of financial relationships that may be held by parties involved in the research and circumstances under which those financial relationships and interests may or may not be held.
IRB Operations – Policies and Procedures to Consider:
- Reminding members of conflict of interest policies at each meeting and documenting any actions taken regarding IRB member conflicts of interest related to particular protocols.
- Developing educational materials for IRB members to ensure their awareness of federal regulations and institutional policies regarding financial relationships and interests in human subjects research.
IRB Review – Actions to Consider:
- Determining whether methods used for management of financial interests of parties involved in the research adequately protect the rights and welfare of human subjects.
- Determining whether other actions are necessary to minimize risks to subjects.
- Determining the kind, amount, and level of detail of information to be provided to research subjects regarding the source of funding, funding arrangements, financial interests of parties involved in the research, and any financial interest management techniques applied.
Investigators – Actions to Consider:
- Including information in the informed consent document, such as a) the source of funding and funding arrangements for the conduct and review of research, or b) information about a financial arrangement of an institution or an investigator and how it is being managed.
- Using special measures to modify the informed consent process when a potential or actual financial conflict exists, such as a) having another individual who does not have a potential or actual conflict of interest involved in the consent process, especially when a potential or actual conflict of interest could influence the tone, presentation, or type of information presented during the consent process.
- Using independent monitoring of the research.