1 Human Research Protection Program (HRPP)
1.3 Institutional Authority
1.5 Ethical Principles
1.6 Regulatory Compliance
1.7 Federalwide Assurance (FWA)
1.8 Institutional Official
1.9 Written Policies and Procedures
1.10 HRPP Organization
1.12.1 Institutional Audits and Compliance Reviews
1.12.2 Non-University Institutional Audits and Compliance Reviews
1.12.3 Reporting and Disposition
1.12.4 IRB Internal Compliance Reviews
1.12.5 IRB Internal Quality Improvement
Brown University fosters a research environment that promotes the respect for the rights and welfare of individuals recruited for, or participating in, research conducted by or under the auspices of the University. In the review and conduct of research, actions by the University will be guided by the principles (i.e., respect for persons, beneficence, and justice) set forth in the Ethical Principles and Guidelines for the Protection of Human Subjects of Research (often referred to as the Belmont Report). The actions of the University will also conform to all applicable federal, state, and local laws and regulations.
In order to fulfill this mission, the University has established a Human Research Protection Program (HRPP). The mission of the HRPP is to:
- safeguard and promote the health and welfare of human research participants by ensuring that their rights, safety, and well-being are protected;
- provide timely and high quality education, review and monitoring of human research projects; and
- facilitate excellence in human research.
The HRPP includes mechanisms to:
- Establish a formal process to monitor, evaluate and continually improve the protection of human participants
- Dedicate resources sufficient to do so
- Exercise oversight of research protection
- Educate investigators and research staff about their ethical responsibility to protect research participants
- When appropriate, intervene in research and respond directly to concerns of research participants
This Human Research Protection Program (HRPP) Policy is provided in an effort to give, to the members of the research community at Brown University, comprehensive information about the organization and focus of the HRPP.
Brown University has established an Institutional Review Board (IRB) to ensure the protection of participants in human research conducted under the auspices of the University. Human research not eligible for exemption, conducted under the auspices of the University, is reviewed and approved by the Brown University IRB prior to the initiation of the research. This review is based upon Department of Health and Human Services (DHHS) regulations, 45CFR46, and /or Federal Drug Administration (FDA) regulations, and the Belmont Report. The regulations provide a systematic means, based on established ethical principles, for protecting the rights and welfare of individuals who volunteer for Brown University research.
The IRB applies the ethical principles described in the Belmont Report and other international codes of ethics such as the Declaration of Helsinki to the conduct of human research conducted under the auspices of the University to ensure the ethically appropriate protection of research participants.
Researchers at Brown University will adhere to the standard operating procedures, for the conduct and review of all human research, found in the “Brown University Human Research Protection Program Policy and Procedure Manual.”
The following standard operating procedures (SOP) describe the authority, role, and procedures of the Brown University HRPP and IRB.
The Brown University Human Research Protection Program operates under the authority of the university policy “Human Research Protection Program (HRPP)” (section 1.2 – “Policy” above.) As stated in that policy, the operating procedures in this document serve as the governing procedures for the conduct and review of all human research conducted under the auspices of Brown University. The HRPP Policy and these operating procedures are made available to all Brown University investigators and research staff and are posted on the Research Protections Office (RPO) website.
Human participant. A human participant is a living individual about whom an investigator conducting research obtains data through intervention or interaction with the individual or through identifiable private information (45 CFR 46.102(f)). The definition provided in the Common Rule includes investigators, technicians, and others assisting investigators, when they serve in a "participant” role by being observed, manipulated, or sampled. As required by 45 CFR 46.102(f) an intervention includes all physical procedures by which data are gathered and all physical, psychological, or environmental manipulations that are performed for research purposes.
For research covered by FDA regulations (21 CFR 50 and 56), human participant means an individual who is or becomes a participant in a clinical investigation (as defined below), either as a recipient of the test article or as a control. A participant may be in normal health or may have a medical condition or disease. In the case of a medical device, a human subject/participant also means any individual on whose tissue specimen an investigational device is used or tested.
Note: The terms “subject” and “participant” are used interchangeably in this document and have the same definition.
Research. Research is defined as the testing of concepts by the scientific method of formulating a hypothesis or research question, systematically collecting and recording relevant data, and interpreting the results in terms of the hypothesis or question. The Common Rule (45 CFR 46) defines research as a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalized knowledge.
Under FDA regulations, the terms research and clinical investigation are deemed to be synonymous. For the purpose of this document, the term research includes clinical investigations as defined below.
Clinical investigation. A clinical investigation is defined as any experiment that involves a test article and one or more human participants and that, either must meet the requirements for prior submission to the Food and Drug Administration under section 505(i) or 520(g) of the act, or need not meet the requirements for prior submission to the Food and Drug Administration under these sections of the act; but the results of which are intended to be later submitted to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit. The term does not include experiments that must meet the provisions of part 58, regarding non-clinical laboratory studies. An experiment, as defined in 21 CFR 312, includes any use of a drug other than the use of a marketed (approved) drug in the course of medical practice.
Test article. A test article is a drug, device, or other article including a biological product used in clinical investigations involving human participants or their specimens.
Institutional Review Board (IRB). An IRB is a board established in accordance with, and for the purposes expressed in, the Common Rule [45 CFR 46.102(g).]
Institutional Official (IO). The President of Brown University has designated the Vice President for Research as the Institutional Official for carrying out the University’s human research protections program. The IO is the Brown University official responsible for ensuring that the HRPP has the resources and support necessary to comply with all federal regulations and guidelines that govern human research. The IO is legally authorized to represent the institution, is the signatory official for all Assurances, and assumes the obligations of the institution’s Assurance. The IO is the point of contact for correspondence addressing human research with OHRP, FDA, and other federal regulatory agencies.
Research under the auspices of the University. Research under the auspices of the institution is research conducted by or under the direction of any employee or agent of this institution (including students) in connection with his or her institutional responsibilities.
Protocol. The research protocol includes the complete packet of materials submitted to the IRB for review, including a description of the research design and methodology as well as a complete description of the procedures for the protection of human participants in the research.
Brown University is committed to conducting research with the highest regard for the welfare of human participants. It upholds, and adheres to, the principles of The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research by the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research (1979). These principles are:
- Respect for Persons, which is ensured by obtaining informed consent, consideration of privacy, confidentiality, and additional protections for vulnerable populations.
- Beneficence, which is assured by ensuring that possible benefits are maximized and possible risks are minimized to all participants.
- Justice, the equitable selection of participants.
The Brown University HRPP, in partnership with its research community, is responsible for ensuring the ethical and equitable treatment of all human participants in research conducted under its auspices.
The HRPP is responsible for ensuring compliance with federal regulations, state law, and institutional policies. All human research at Brown University is conducted in accordance with the policy and regulations found in 45 CFR 46 and 21 CFR 50 and 56. The actions of Brown University will also conform to all other applicable federal, state, and local laws and regulations.
The HRPP operates under the authority of its current Federalwide Assurance (FWA00004460) and provides support to an independent Institutional Review Board (IRB), which reviews all human research protocols.
The ultimate responsibility of the HRPP resides with the Vice President for Research (VPR), who serves as the Institutional Official (IO) of the program. The IO is responsible for ensuring the Brown University HRPP has the resources and support necessary to comply with all institutional policies and with federal regulations and guidelines that govern human research. The IO is legally authorized to represent Brown University. He/she is the signatory of the FWA and assumes the obligations of the FWA. The IO is the point of contact for correspondence addressing human research with the DHHS Office for Human Research Protections (OHRP), the Food and Drug Administration (FDA), and any other federal regulatory agencies.
The IO also holds ultimate responsibility for oversight of the Institutional Review Board (IRB) and all Brown University investigators; for assuring the IRB members are appropriately knowledgeable in accordance with ethical standards and applicable regulations; for assuring the investigators are appropriately knowledgeable to conduct research in accordance with ethical standards and applicable regulations; and for the development and implementation of an educational plan for IRB members, staff, and investigators.
The Brown University Human Research Protection Program Policy and Procedure Manual details the policies and regulations governing research with human participants and the requirements for submitting research protocols for review by the Brown University IRB.
The policies and procedures manual is not a static document. The policies and procedures are reviewed regularly and revised by the Director of the HRPP, the Institutional Review Board, and University counsel, as necessary. The Vice President for Research will approve all revisions of the policies and procedures.
The Research Protections Office (RPO) will keep the University research community apprised of new information that may affect the human research protection program, including laws, regulations, policies, procedures, and emerging ethical and scientific issues on its website and through campus electronic mailing lists. The policies and procedures will be available on the Brown University IRB website and copies will be available upon request.
The HRPP is a comprehensive system to ensure the protection of human participants in research. It consists of various individuals and committees such as: the Vice President for Research, the Associate Vice President for Research, the Research Protections Office, the IRB, other committees or subcommittees addressing human research protection (e.g., Biosafety, Radiation Safety, Conflict of Interest), investigators, research staff, and health and safety staff (e.g., Biosafety Officer, Radiation Safety Officer.) The objective of this system is to assist the institution in meeting ethical principles and regulatory requirements for the protection of human participants in research.
The following officials, administrative units, and individuals have primary responsibilities for implementing the HRPP:
As detailed above (Institutional Official of the HRPP), the ultimate responsibility of the HRPP resides with the Vice President for Research, who serves as the Institutional Official (IO) of the program. The responsibility for the HRPP at Brown University is delegated by the IO to the Director of the HRPP.
The Director of the HRPP (RPO Director) reports to the Associate Vice President for Research and is responsible for:
- Developing, managing, and evaluating policies and procedures that ensure compliance with all state and federal regulations governing research. This includes monitoring changes in regulations and policies that relate to human research protection and overseeing all aspects of the HRPP program.
- Advising the VPR on key matters regarding research at Brown University.
- Implementing the institution’s HRPP policy.
- Submitting, implementing, and maintaining an approved FWA through the Vice President for Research and the Department of Health and Human Services Office for Human Research Protection (OHRP).
- Managing the finances of the Brown University HRPP.
- Assisting investigators in their efforts to carry out the University’s research mission.
- Developing and implementing needed improvements and ensuring follow-up of actions, as appropriate, for the purpose of managing risk in the research program.
- Developing training requirements as required and as appropriate for investigators, committee members, and research staff, and ensuring that training is completed on a timely basis.
Brown University has one IRB, appointed by the Vice President for Research. The IRB prospectively reviews and makes decisions concerning all human research conducted by its employees or agents. The IRB discharges its duty by complying with the requirements of the Common Rule, state regulations, the FWA, and institutional policies. (See Section 2 for a detailed discussion of the IRB.)
The Brown University HRPP relies on the University Office of General Counsel for interpretations and applications of Rhode Island law and the laws of any other jurisdiction where research is conducted as they apply to human research.
The investigator is the ultimate protector of the individuals who participate in research. The investigator is expected to abide by the highest ethical standards and for developing a protocol that incorporates the principles of the Belmont Report. He/she is expected to conduct research in accordance with the approved research protocol and to oversee all aspects of the research by providing supervision of support staff, including oversight of the informed consent process. The investigator must establish and maintain an open line of communication with all research participants within his/her responsibility. In addition to complying with all the policies and standards of the governing regulatory bodies, the investigator must comply with institutional and administrative requirements for conducting research. The investigator is responsible for ensuring that all research staff completes appropriate training and must obtain all required approvals prior to initiating research. When investigational drugs or devices are used, the investigator is responsible for providing written procedures for their storage, security, dispensing, and disposal that may be coordinated through the appropriate pharmacist.
The IRB functions independently of, but in coordination with, other institutional regulatory committees. The IRB, however, makes its independent determination whether to approve or disapprove a protocol based upon whether or not human participants are adequately protected. The IRB has review jurisdiction over all research involving human participants conducted, supported, or otherwise subject to regulation, by any federal department or agency that has adopted the human research regulations.
The Research Compliance Network will meet to ensure a dialogue is maintained between the various compliance entities at the University. With the Associate Vice President for Research as chair, the committee will act in an advisory capacity to the Vice President for Research, monitoring the effectiveness of existing compliance programs, developing new or revised policies as changes in requirements occur, and disseminating updated compliance information to the research community.
Research that has been reviewed and approved by the IRB may be subject to review and disapproval by officials of the institution. However, those officials may NOT approve research if it has been disapproved by the IRB.
In addition to the leadership structure described previously, other support staff members for the HRPP may include coordinators, managers, administrative support staff, and the RPO assistant director.
The Brown University HRPP office, known as the Research Protections Office (RPO), reports directly to the Associate VPR and is supervised by the Director of RPO (Director). The Director has expert knowledge in regulatory issues regarding human research protections, serves as the Human Protections Administrator, and is the primary contact at Brown University for the Office for Human Research Protections, Department of Health and Human Services.
The Director of RPO has day-to-day responsibilities for the operation of the IRB. This includes responding to faculty, student, and staff questions about human research as well as organizing and documenting the review process. The Director works closely with the Chair of the IRB in the development of policy and procedures and is a voting member of the IRB. Additionally, the office is staffed by an assistant director, managers, coordinators, and a program support assistant. The duties and responsibilities for all staff are found in their respective job descriptions, and their performance is evaluated on an annual basis.
The IRB Manager is responsible for all aspects of the IRB throughout the review process of a research protocol involving human participants. This responsibility includes the initial review of documents and screening of research protocols prior to its review by the IRB, as well as serving as the liaison between the investigators and the IRB. The IRB Manager reviews the IRB minutes for accuracy and ensures proper documentation of discussions including controverted discussions and actions taken by IRB during convened meetings.
The IRB Coordinator is responsible for providing administrative and clerical support to the IRB Chair and IRB managers as well as scheduling and coordinating all IRB functions. The IRB Coordinator is also responsible for IRB record retention. The IRB Coordinator is responsible for maintaining complete IRB files, including records of all research protocols, IRB correspondence (including e-mails), and research credentialing file records of investigators.
RPO is equipped with all necessary office space, meeting space, storage space and equipment to perform the functions required for the HRPP. The adequacy of personnel and non-personnel resources of the HRPP program is assessed regularly by the Director with the RPO staff and are reviewed and approved by the IO.
The IO provides resources to the IRB and RPO, including adequate meeting and office space and staff for conducting IRB business. Office equipment and supplies, including technical support, file cabinets, computers, internet access, scanners, and copy machines, will be made available to the IRB and staff. The resources provided for the IRB and RPO will be reviewed during the annual budget review process.
Directed (“for cause”) audits and periodic compliance reviews (“not for cause”) will be conducted to assess investigator compliance with federal, state, and local law and University policies; to identify areas for improvement; and to suggest recommendations based on existing policies and procedures. Directed audits of IRB-approved research studies are in response to identified concerns. Periodic (“not for cause”) compliance reviews are conducted using a systematic method to review IRB-approved research on a regular basis. The results will be reported to the Director and the IRB Chair.
Activities of auditors during directed audits and periodic compliance reviews may include:
- requesting progress reports from researchers;
- examining investigator-held research records;
- contacting research participants;
- observing research sites where research involving human research participants and/or the informed consent process is being conducted;
- auditing advertisements and other recruiting materials as deemed appropriate by the IRB;
- reviewing projects to verify from sources other than the researcher that no unapproved changes have occurred since the previous review;
- monitoring conflict of interest concerns to assure the consent documents include the appropriate information and disclosures;
- conducting other monitoring or auditing activities as deemed appropriate by the IRB.
External directed (“for cause”) audits and compliance reviews may be conducted at non-University sites, where the University’s IRB serves as the “IRB of Record” to assess compliance with federal, state, and local law; participant safety; and IRB policies and procedures. These directed audits are implemented in response to identified concerns that require an IRB determination. These reviews may include items listed in Section 1.12.1 above.
The results are reported to the Director and the IRB Chair. Any noncompliance will be handled according to the procedures in Section 9 of this manual.
If an audit or review finds that participants in a research project have been exposed to unexpected serious harm, such findings will be promptly reported to the Director and the IRB Chair for immediate action.
Internal directed audits and random internal compliance reviews may be conducted. The results may impact current practices and may require additional educational activities, and will be reported to the Director. The RPO staff will:
- review the IRB minutes to determine that adequate documentation of the meeting discussion has occurred. This review will include assessing the documentation surrounding the discussion for protections of vulnerable populations as well as other risk/benefit ratio and consent issues that are included in the criteria for approval;
- assess the IRB minutes to assure that quorum was met and maintained;
- assess the current adverse event reporting process;
- assess that privacy provisions, as needed, have been adequately reviewed, discussed, and documented in the IRB minutes;
- evaluate the continuing review discussions to assure they are substantive and meaningful and that no lapse has occurred since the previous IRB review;
- observe IRB meetings or other related activities;
- review IRB files to assure retention of appropriate documentation and consistent organization of the IRB file according to current policies and procedures;
- review the IRB database to assure all fields are completed accurately;
- verification of IRB approvals for collaborating institutions or external performance sites, as necessary; and
- other monitoring or auditing activities deemed appropriate by the IRB.
The Director will review the results of internal compliance reviews with the IRB Chair and the IO. If any deficiencies are noted in the review, a corrective action plan will be developed by the Director and approved by the IO. The Director will have responsibility for implementing the corrective action plan, the results of which will be evaluated by the IO.
In the conduct of cooperative research projects, Brown University acknowledges that each institution is responsible for safeguarding the rights and welfare of research participants and for complying with applicable federal regulations. When a cooperative agreement exists, Brown University may enter into a joint review arrangement, rely on the review of another qualified IRB, or make similar arrangements for avoiding duplication of effort. A formal relationship must be established between the University and the other institution through either a Cooperative Agreement, a Memorandum of Understanding, or an IRB Authorization Agreement (IAA). This relationship must be formalized before the University will accept any human research proposals from the other institution or rely on the review of the other institution.
For collaborative research, the PI must identify all institutions participating in the research, the responsible IRB(s), and the procedures for dissemination of protocol information (IRB initial and continuing approvals, relevant reports of unanticipated problems, protocol modifications, and interim reports) between all participating institutions.
- When Brown University relies on another IRB, the RPO staff will ensure that the other organization has an active Assurance and appropriate policies in place.
- When Brown University reviews research conducted at another institution, the particular characteristics of each institution’s local research context must be considered, either (i) through knowledge of its local research context by the Brown University IRB or (ii) through subsequent review by appropriate designated institutional officials, such as the Chairperson and/or other IRB members.
The investigator is responsible for serving as the single liaison with outside regulatory agencies, with other participating facilities, and for all aspects of internal review and oversight procedures. The investigator is responsible for ensuring that all participating facilities obtain review and approval from their IRB of record and adopt all protocol modifications in a timely fashion. The investigator is responsible for ensuring that the research study is reviewed and approved by any other appropriate committees at the collaborating facility and at the participating facilities prior to enrollment of participants.