1360 Human Research Protection
This policy applies to all University personnel who conduct research involving human subjects and to the members and staff supporting the Yale University Institutional Review Boards.
The University maintains an integrated human research protection program (HRPP) under the oversight of the Associate Vice President for Research Administration to ensure the protection of human subjects who participate in research projects conducted under the auspices of the University. The program ensures that (1) the rights and welfare of the research subjects are protected effectively, (2) the risks to subjects are reasonable when considering the potential benefits of the research, (3) the selection of subjects is equitable, and (4) informed consent will be obtained and, when appropriate, documented. Further, the program assures compliance with federal regulations and with ethical standards for research involving human subjects.
University personnel involved in human research are required to submit research protocols for review and approval to the relevant Institutional Review Board (IRB). Human research protocols cannot commence without approval or exemption determination by the IRB.
The University recognizes, however, that the protection of human subjects participating in research transcends traditional department jurisdictions and is not the sole responsibility of the IRB. The University therefore extends the HRPP to incorporate compliance, education, and informatics components of the HRPP office as well as investigator and departmental oversight responsibilities to allow for an integrated program for research subject protection initiatives as they relate to the individual and the unit’s core function in supporting the research enterprise. Other institutional offices and committees involved in research oversight and administration may include, but are not limited to, Office of Sponsored Projects, Office of the Provost, Office of Research Compliance, University Conflict of Interest and Conflict of Commitment Committee, the Yale Center for Clinical Investigation, the Yale Cancer Center, the Pediatric Protocol Review Committees, the Biological Safety Committee, Yale University (YU) and Yale New Haven Health (YNHH) Radiation Safety Committees, the Radioactive Drug Research Committee and departmental representatives.
Reason for the Policy
- To ensure that the rights and welfare of human research participants are protected in all research conducted under the auspices of Yale University.
- To define the responsibilities of University investigators in conducting research involving human subjects in accordance with state and local laws, federal guidance and regulations, the University’s Federalwide assurance and other University policies on ethical conduct of research.
- To define the review, approval and oversight responsibilities and authority of the University Institutional Review Boards (IRBs), the Human Subjects Protection Administrator (HPA) and the Institutional Official (IO) for the ethical conduct of research involving human subjects which the University has included in its human research protection program.
- To define the responsibilities of the HRPP compliance, education, and informatics components
- To define the human subject protection responsibilities of other University departments, committees or individuals charged with research oversight and/or administration.
A systematic investigation, including research and development, testing and evaluation, designed to develop or contribute to generalizable knowledge.
Activities that meet applicable regulatory definitions, including, but not limited to, the HHS definition of research set forth in 45 CFR § 46.102(l) and involve human subjects as set forth in 45 CFR § 46.102(e)(1), as adopted by any federal agency, department or entity that has taken appropriate administrative action to make 45 CFR 46 or an identical regulation applicable to its human subjects research, or activities that meet the FDA definitions set forth at 21 CFR § 50.3(c) and § 56.102(c) that involve human subjects as set forth at 21 CFR § 50.3(g), §103(e), §312.3(b).
- HHS regulations: “Human Subjects means a living individual about whom an investigator (whether professional or student) conducting research: (i) Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or (ii) Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.”
- FDA regulations: “An individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy human or a patient.”
Institutional Review Board
A committee established in accordance with applicable regulations to protect the rights and welfare of human research subjects who participate in research.
The Yale University Human Research Protection Program (HRPP) involves the cooperative interaction of offices and individuals within the University which are involved in research involving human subjects.
The Associate Vice President for Research Administration is the Institutional Official (IO) responsible for oversight of the human research protection program and serves as the signatory official on the Yale Federalwide Assurance filed with the Department of Health and Human Services Office of Human Research Protection (OHRP). The Institutional Official appoints members of the IRBs and ensures that the IRBs retain autonomy and remain free from undue influence on their decision making. The Institutional Official must be informed of any allegation of undue influence on the IRB or its staff. Upon learning of the allegation, the Institutional Official will assign an appropriate person, based on the nature of the allegation, to investigate and make recommendations for resolution or corrective action.
The Institutional Official maintains regular communication with the IRBs, including reports of serious or continuing non-compliance with IRB requirements and any other emergent issues. The Institutional Official shall ensure that adequate resources are provided to the components of the HRPP to perform their respective functions.
The Human Protections Administrator (HPA) is responsible for oversight and day-to-day management of the HRPP. The HPA ensures that IRB policies, procedures and practices are compliant with applicable laws, regulations, guidelines, and other human research standards. The HPA provides guidance to the IRBs on emergent issues and ensures consistency across the University IRBs.
The University maintains Institutional Review Boards (IRBs) which are charged with the review and continuing oversight of research involving human subjects, in accordance with University policies and applicable laws, regulations, and other human research standards. The IRBs have the authority to:
- grant exemptions from IRB review;
- determine when projects are not considered to require IRB review;
- approve, disapprove, or require modifications to research protocols;
- monitor or observe the consent process and/or conduct of the research to ensure that the rights and welfare of research participants are adequately protected; and
- suspend or terminate approval of research not being conducted in accordance with the IRB’s requirements or research that is associated with unexpected serious harm to research participants.
Approval by other institutional bodies cannot substitute for IRB approval. IRB disapprovals may not be superseded by other institutional authorities although studies which receive IRB approval may be deemed inappropriate for conduct at the University by other institutional authorities.
IRB membership and practices are described in the University’s HRPP policies and procedures.
University faculty, staff, fellows, students, and trainees involved in the design, conduct or analysis of human research are responsible for ensuring adequate subject protection in the course of their interactions with subjects and/or their data. Investigators must submit human research protocols to the IRB for approval or other determination pursuant to IRB policies and/or procedures prior to commencing the research.
Investigators shall maintain IRB approval for the lifespan of the project and shall submit continuing review documents to the IRB as necessary to maintain the approval. Research staff shall adhere to the approved protocol except when nonadherence is necessary to minimize a threat to the health and safety of the participants. Performing human research in violation of the approved protocol or without IRB approval is a serious breach of conduct and is subject to disciplinary action up to and including termination.
Other offices or committees that oversee University research are responsible for considering the rights and welfare of human subjects participating in Yale studies when developing and carrying out their core functions supporting the research, including their own compliance responsibilities. These entities are responsible for integrating their core business processes and/or responsibilities into the University’s human subject protection program.
The HRPP Compliance and Education components will conduct oversight and supporting activities to ensure that all individuals involved in the conduct of human research understand their responsibilities and adhere to University policies related to the conduct of human research. The HRPP Informatics component is responsible for the development and maintenance of systems and processes to facilitate human research record keeping and reporting requirements.
Roles & Responsibilities
Office of Research Administration
- Oversees and disseminates University requirements related to the human subjects protections program. Appoints the Chair and members of the IRBs, serves as the Institutional Official for University Federalwide Assurance and ensures that resources are appropriately allocated to the IRBs to carry out their responsibilities and authorities.
- Ensures compliance with ethical principles and federal laws and guidance, state and local laws and University policy through interpretation and advice on regulatory requirements.
Office of the Provost
- Provides counsel to the HRPP regarding policies, emergent issues and other matters related to academic activities and the protection of research volunteers.
IRB Leadership Committee
- Provides oversight and guidance to the IRBs. Reviews and approves institution-wide IRB policies, procedures, and practices. Assists in determining appropriate University responses or positions to emergent IRB issues.
Office of General Counsel
- Interprets human subjects protection regulations and assists in ensuring that agreements between Yale and parties external to the University, which involve human subjects, require the ethical conduct of human subject research.
Office of Research Compliance (ORC)
- Provides support to the Office of Research Administration (ORA) and its mission. Ensures University compliance with federal regulations, state and local laws, and University policy through assessments. Provides interpretation and advice on regulatory requirements, develops policy and provides educational opportunities for the community addressing sponsored project requirements.
Office of Sponsored Projects
- Structures relationships and agreements with external parties which fund research at the University, such as federal agencies, foundations, and for-profit corporations. Ensures agreements are consistent with University requirements related to the ethical conduct of research. Ensures that research grant and contract funds are not expended for human subjects research which has not been approved by one of the Yale University IRBs. Ensures that the terms of the clinical trials agreements do not conflict with the IRB approved protocols.
Institutional Review Boards (HIC, HSC)
- Reviews, approves, and provides continuing oversight of research involving human subjects. Ensures the protection of human subjects in the design and conduct of human subject research through dissemination of guidance, training, and monitoring activities.
- Develop and submit research protocols involving human subjects to the IRB for review. Adhere to IRB requirements, federal, state, and institutional rules and regulations related to research involving humans and, if applicable, to the Good Clinical Practice Guidelines as adopted by the Food and Drug Administration (FDA) for the conduct of human subjects research.
Information Security Office (ISO)
- Assures appropriate technical, physical, and administrative policies and safeguards are implemented to secure the creation, access, transmission, and receipt of protected or restricted information, including electronic PHI. The ISO provides guidance to the research community related to compliance with University IT and HIPAA security policies.
Biological Safety Committee (Institutional Biosafety Committee, IBC)
- Reviews scientific and safety aspects of research involving gene transfers, human pathogens, and other biologic agents.
YNHH and YU Radiation Safety Committees (YNHH RSC and YU RSC)
- Reviews scientific and safety aspects of research involving radioactive materials and/or subject exposure to external sources of radiation. Ensures compliance with appropriate radioactive material use licenses and radiation producing equipment permits and registrations.
Radioactive Drug Research Committee (RDRC)
- Operates under federal regulation 21 CFR 361.1, which permits review and monitoring of basic research using radioactive drugs in humans without an IND when the drug is administered under specific conditions. The RDRC ensures that both the pharmacological dose to be administered to subjects and the radiation dose received by subjects are within limits set by the FDA. The research that requires YU RIDC review is typically conducted at the Yale University PET Center under Yale University’s NRC medical use license.
Radioactive Investigational Drug Committee (RIDC)
- All human subject research protocols involving the use of investigational radioactive drugs with an IND, amended IND, or an FDA allowed IND exemption (as well as the use of FDA-approved radiopharmaceuticals) are reviewed by the YU RIDC. The research that requires YU RIDC review is typically conducted at the Yale University PET Center under Yale University’s NRC medical use license. Subject to the IRB final approval, the YU RIDC, has the authority to approve, disapprove or require modifications to the protocol as it relates to the use of radiopharmaceuticals in human subjects for research.
Pediatric Protocol Review Committee (PPRC)
- Reviews the scientific aspects of all research conducted at the Yale School of Medicine that involves children with the exception of Pediatric Oncology, which is reviewed by the Protocol Review Committee noted below.
Protocol Review Committee (PRC)
- Reviews the scientific aspects of oncology or cancer-related research trials that are conducted by researchers from the School of Medicine and, as appropriate, from the School of Nursing.
Yale Center for Clinical Investigation (YCCI)
- Participates in the review of research that is fully or partially supported with YCCI funds. The scientific aspects of research supported by the YCCI may be reviewed by the YCCI’s Science and Safety Committee (SSC).
Committee on Conflict of Interest and Conflict of Commitment
- Collaborates with the IRB in review of protocol-specific conflict of interest disclosures to ensure that conflicts are either reduced, managed, or eliminated.
Departmental Research Administrators
- Responsible for departmental adherence to University policies related to human subject research and adherence to funding agency requirements.