Source: https://www.federalregister.gov/documents/2004/05/12/04-10849/financial-relationships-and-interests-in-research-involving-human-subjects-guidance-for-human
Timestamp: 2017-08-22 06:34:28
Document Index: 359235947

Matched Legal Cases: ['art 46', 'arts 50', 'art 50', 'art 94', 'art 54', 'art 46', 'arts 50', 'art 50', 'art 94', 'art 54', 'art 54', 'art 54']

Federal Register :: Financial Relationships and Interests in Research Involving Human Subjects: Guidance for Human Subject Protection
Financial Relationships and Interests in Research Involving Human Subjects: Guidance for Human Subject Protection
A Notice by the Health and Human Services Department on 05/12/2004
The guidance is effective as of the date of publication.
69 FR 26393
26393-26397 (5 pages)
04-10849
SUPPLEMENTARY INFORMATION:Start Printed Page 26394
https://www.federalregister.gov/d/04-10849 https://www.federalregister.gov/d/04-10849
The Office of Public Health and Science (OPHS), Department of Health and Human Services (HHS) announces a final guidance document for Institutional Review Boards (IRBs), investigators, research institutions, and other interested parties, entitled “Financial Relationships and Interests in Research Involving Human Subjects: Guidance for Human Subject Protection.” This guidance document raises points to consider in determining whether specific financial interests in research could affect the rights and welfare of human subjects, and if so, what actions could be considered to protect those subjects. This guidance applies to human subjects research conducted or supported by HHS or regulated by the Food and Drug Administration.
Office for Human Research Protections, The Tower Building, 1101 Wootton Parkway, Suite 200, Rockville, MD 20852, (301) 402-4994, facsimile (301) 402-2071.
Submit requests for single copies of the guidance document to the address identified below for further information. Requests may be made by mail or e-mail. Persons with access to the Internet also may obtain the document at http://ohrp.osophs.dhhs.gov/​humansubjects/​finreltn/​finreltn.htm. Glen Drew, Office for Human Research Protections, Office of Public Health and Science, The Tower Building, 1101 Wootton Parkway, Suite 200, Rockville, MD 20852, (301) 402-4994, facsimile (301) 402-2071; e-mail gdrew@osophs.dhhs.gov.
In the March 31, 2003, Federal Register, (68 FR 15456) OPHS published a notice seeking comments on the HHS draft guidance for IRBs, investigators, and research institutions, entitled “Financial Relationships and Interests in Research Involving Human Subjects: Guidance for Human Subject Protection.” The Department has considered the 40 comments that were submitted and has made appropriate changes in the guidance.
The guidance recommends consideration of approaches and methods for dealing with issues of financial interests that could affect HHS human research subject protections in research subject to 45 CFR part 46 for HHS conducted or support research and 21 CFR parts 50 and 56 for FDA regulated clinical investigations. The guidance expressly does not address regulatory requirements designed to enhance data integrity and objectivity in research found in 42 CFR part 50, subpart F, 45 CFR part 94, and 21 CFR part 54.
The guidance recommends that, in particular, IRBs, institutions engaged in research, and investigators consider whether specific financial relationships create financial interests in research studies that may adversely affect the rights and welfare of subjects. The guidance poses general considerations in evaluating financial relationships and their possible effects on human subjects. More detailed points for consideration are also offered for institutions, IRBs, and investigators.
This document replaces the “HHS Draft Interim Guidance: Financial Relationships in Clinical Research: Issues for Institutions, Clinical Investigators, and IRBs to Consider when Dealing with Issues of Financial Interests and Human Subject Protection” dated January 10, 2001. This document is intended to provide guidance. It does not create or confer rights for or on any person and does not operate to bind the Department of Health and Human Services (HHS, or the Department), including the Food and Drug Administration (FDA), or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations.
In this guidance document, HHS raises points to consider in determining whether specific financial interests in research affect the rights and welfare of human subjects [1] and if so, what actions could be considered to protect those subjects. This guidance applies to human subjects research conducted or supported by HHS or regulated by the FDA. The consideration of financial relationships, as discussed in this document relates to human subject protection in research conducted under the HHS or FDA regulations (45 CFR part 46, 21 CFR parts 50, 56).[2] This document is nonbinding and does not change any existing regulations or requirements, and does not impose any new requirements.
Institutions and individuals involved in human subjects research may establish financial relationships related to or separate from particular research projects. Those financial relationships may create financial interests of monetary value, 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. The Department recognizes that some conflicting financial interests in research may affect the rights and welfare of human subjects. This document provides some possible approaches to consider in assuring that human subjects are adequately protected. Institutional review boards (IRBs), institutions, and investigators engaged in human subjects research each have appropriate roles in ensuring that financial interests do not compromise the protection of research subjects.[3]
The regulations protecting human research subjects are based on the ethical principles described in the Belmont report: [4] respect for persons, beneficence, and justice. The Belmont principles should not be compromised by financial relationships. Openness and honesty are indicators of respect for persons, characteristics that promote Start Printed Page 26395ethical research and can only strengthen the research process.
What procedures would be helpful, including those to Start Printed Page 26396
Does the research involve financial relationships that could create potential or actual conflicts of interest?
—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?
Establishing the independence of institutional responsibility for research activities from the management of the institution's financial interests.
Establishing conflict of interest committees (COICs)[7] or identifying other bodies or persons and procedures to
The Department recommends that institutions engaged in human subjects research and IRBs that review HHS conducted or supported human subjects research or FDA regulated human subjects research consider whether establishing policies and procedures addressing IRB member potential and actual conflicts of interest as part of overall IRB policies and procedures would help ensure that financial interests do not compromise the rights and welfare of human research subjects. As noted, 45 CFR 46.107(e) and 21 CFR 56.107(e) prohibit an IRB member with a conflicting interest in a project from participating in the IRB's initial or continuing review, except to provide information as requested by the IRB.
Reminding members of conflict of interest policies at each meeting and documenting any actions taken Start Printed Page 26397regarding IRB member conflicts of interest related to particular protocols.
1. Under the Public Health Service Act and other applicable law, HHS has authority to regulate institutions engaged in HHS conducted or supported research involving human subjects. For a description of what is meant by institutions engaged in research see the Office for Human Research Protections (OHRP) engagement policy at http://ohrp.osophs.dhhs.gov/​humansubjects/​assurance/​engage.htm. Under the Federal Food, Drug, and Cosmetic Act, FDA has the authority to regulate Institutional Review Boards (IRBs) and investigators involved in the review or conduct of FDA-regulated research.
2. This document does not address HHS Public Health Service regulatory requirements that cover institutional management of the financial interests of individual investigators who conduct Public Health Service (PHS) supported research (42 CFR part 50, subpart F, and 45 CFR part 94). This document also does not address FDA regulatory requirements that place responsibilities on sponsors to disclose certain financial interests of investigators to FDA in marketing applications (21 CFR part 54). Guidelines interpreting the application of the PHS regulations to research conducted or supported by the National Institutes of Health (NIH) that involve human subjects are available at http://grants.nihgov/​grants/​guide/​notice-files/​NOT-OD-00-040.html. Guidance interpreting the provisions of the FDA regulations appears at http://www.fda.gov/​oc/​guidance/​financialdis.html.
Sponsors are required to disclose certain financial interests of clinical investigators to FDA in marketing approval applications under the Federal Food, Drug and Cosmetic Act (FD&C Act) (21 CFR part 54). FDA regulations at 21 CFR part 54 address requirements for the disclosure of certain financial interests held by clinical investigators. The purpose of these regulations is to provide additional information to allow FDA to assess the reliability of the clinical data (21 CFR 54.1). The FDA regulations require sponsors seeking marketing approval for products to certify that investigators do not have certain financial interests, or to disclose those interests to FDA (21 CFR 54.4). These regulations require sponsors to report (1) financial arrangements between the sponsor and the investigator whereby the value of the investigator's compensation could be influenced by the outcome of the trial; (2) any proprietary interest in the product studied held by the investigator; (3) significant payments of other sorts over $25,000 beyond costs of the study; or (4) any significant equity interest in the sponsor of a covered study (21 CFR 54.4).
3. The Department recognizes that some non-financial conflicting interests related to research also may affect the rights and welfare of human subjects. However, non-financial interests are beyond the scope of this guidance document.
5. http://ohrp.osophs.dhhs.gov/​humansubjects/​finreltn/​finguid.htm.
The National Bioethics Advisory Commission (NBAC), in a comprehensive examination of the “Ethical and Policy Issues in Research Involving Human Participants,” in Chapter 3 recommended development of federal, institutional, and sponsor policies and guidance to ensure that research subjects' rights and welfare are protected from the effects of conflicts of interest (http://www.georgetown.edu/​research/​nrcbl/​nbac/​human/​overvol1.pdf).
The HHS Office of the Inspector General (OIG) has issued a series of reports examining regulation and activities of IRBs. A June 2000 OIG report addressed recruitment practices and found that about one-quarter of the surveyed IRBs consider financial arrangements with sponsors of research as part of their protocol review (http://oig.hhs.gov/​oei/​reports/​oei-01-97-00195.pdf).
The National Human Research Protections Advisory Committee (NHRPAC) offered advice to HHS regarding the content and finalization of the HHS Draft Interim Guidance in August, 2001 (http://ohrp.osophs.dhhs.gov/​nhrpac/​documents/​aug01a.pdf).
A number of nongovernmental organizations recently have addressed financial interests in reports and issued new or updated policies or guidelines of varying scope and specificity, including the Association of American Universities, October 2001 (http://www.aau.edu/​research/​COI.01.pdf), the Association of American Medical Colleges, December 2001 and October 2002 (http://www.aamc.org/​members/​coitf/​firstreport.pdf and http://www.aamc.org/​members/​coitf/​2002coireport.pdf), the International Committee of Medical Journal Editors October 2001 (http://www.icmje.org/​sponsor.htm), the American Medical Association, January 2002 (http://jama.ama-assn.org/​cgi/​content/​short/​287/​1/​78), and opinions E-8.0315 Managing Conflicts of Interest in the Conduct of Clinical Trials (http://www.ama-assn.org/​ama/​pub/​category/​8471.html) and E-8031 Conflicts of Interest: Biomedical Research (http://www.ama-assn.org/​ama/​pub/​category/​8470.html), the American Society of Gene Therapy, April 2000 (http://www.asgt.org/​policy/​index.html), the American Society of Clinical Oncology, June 2003 (http://www.jco.org/​cgi/​content/​full/​21/​12/​2394), and the Institute of Medicine, October 2002, report “Responsible Research: A Systems Approach to Protecting Research Participants” (http://www.nap.edu/​books/​0309084881/​html/​).
Two accrediting bodies for human subject protection programs have included elements addressing individual and institutional conflicts of interest in their accreditation evaluations, the Association for the Accreditation of Human Research Protection Programs (http://www.aahrpp.org/​images/​Evaluation_​Instrument_​1.pdf) and the National Committee for Quality Assurance, (http://www.ncqa.org/​Programs/​QSG/​VAHRPAP/​vahrpapfindstds.pdf).Internationally, the World Medical Association's revision in 2000 of the Declaration of Helsinki, (http://www.wma.net/​e/​policy/​17-c_​e.html) principle 22, includes “sources of funding” among the items of information to be provided to subjects. A number of individual institutions also have developed policies for their own situations, as noted in the NIH Guide Notice issued in June 2000 (http://grants.nih.grants/​guide/​notice-files/​NOT-OD-00-040.html). Some of these policies involve conflicts of interest management methods and address institutional financial interests as well as individual interests.
[FR Doc. 04-10849 Filed 5-11-04; 8:45 am]