4. Harvard University Institutional Review Boards

4 Harvard University Institutional Review Boards

4.1 Authority of the Committee on the Use of Human Subjects

4.2 CUHS Relationships

4.3 Roles and Responsibilities

4.3.1 Chair of the CUHS

4.3.2 Acting Chair of the CUHS

4.3.3 CUHS Executive Officer

4.3.4 Subcommittees of the CUHS

4.4 Resources for CUHS

4.5 Conduct of Quality Assurance/Quality Improvement Activities for CUHS Operation

4 Harvard University Institutional Review Boards 

The University Area IRB, Medical School IRB, and School of Public Health IRB are administrative bodies established to protect the rights and welfare of human research subjects recruited to participate in research activities conducted under the auspices of this institution. 

Harvard University’s Provost reviews the activity of the three IRBs on a continuing basis so as to determine, in consultation with the Deans of the relevant Harvard faculties, the appropriate number of IRBs for the University. 

4.1 Authority of the Committee on the Use of Human Subjects 

The CUHS reviews and has the authority to approve, require modifications in, or disapprove all research activities conducted under the auspices of the University-Area institutions. The CUHS is required to ensure that the rights and welfare of research subjects are appropriately safeguarded. In fulfilling these responsibilities, the CUHS reviews all the research documents and activities that bear directly on the rights and welfare of the subjects of proposed research, for example, the protocol, the consent/assent document(s), questionnaires or interview or survey instruments, and, for studies conducted under the Investigational New Drug (IND) regulations, the investigator's brochure. The CUHS must also review the methods and material that investigators propose to use to recruit subjects. 

Before any human subject is involved in research in the University-Area institutions, the CUHS will give proper consideration to: 

1. the risks to the subjects 

2. the anticipated benefits to the subjects and to others 

3. the importance of the knowledge that may reasonably be expected to result 

4. the informed consent process to be employed 

The CUHS has the authority to suspend, place restrictions on, or terminate approval of research activities that fall within its jurisdiction and that are not being conducted in accordance with its requirements or that have been associated with unexpected adverse events. The CUHS has the authority to observe or have a third party observe the consent process and the research if the CUHS determines that such observation is indicated. 

4.2 CUHS Relationships 

Although it may coordinate with other institutional regulatory committees, the CUHS functions independently. The CUHS’s independent determination as to whether to approve or disapprove a protocol based upon whether or not human subjects are adequately protected may not be overruled except by a subsequent decision of the CUHS itself. 

The University Human Subjects Research Committee (HSRC) meets regularly to ensure a dialogue is maintained among the various entities involved with human research protections at the University. HSRC membership is comprised of the chairs and staff of CUHS and the other two Harvard University IRBs, a Risk Management & Audit Services officer, and other institutional officials. An attorney from the Office of General Counsel advices the HSRC and representatives from some of the Harvard-affiliated teaching hospitals are regular guests. Currently the HSRC is chaired by a Professor at the Medical School. The committee acts in an advisory capacity to the Provost, 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 CUHS may be subject to review and disapproval by officials of the relevant University Area institution. However, those officials may NOT approve human subject research if it has NOT been approved by the CUHS. 

If a CUHS chair, Officer, member, or staff person feels that the CUHS has been unduly influenced by any party, they shall make a confidential report to the Associate Provost for Research Policy and Institutional Compliance or to the Dean of the relevant institution. and/or the Dean of the Faculty of Arts and Sciences, depending on the circumstances, who shall investigate the allegations. Where warranted, corrective action will be taken to prevent additional occurrences. 

Relationships with other institutions: Harvard University may choose, on a case-by-case basis, to provide human research protection oversight for another institution, or to delegate responsibility for human research protection oversight to another institution. In each case, a formal relationship must be established between the University and the other institution through either an Institutional Authorization Agreement or a Memorandum of Understanding. This relationship must be formalized before the University will accept any human research proposals from the other institution, or delegate responsibility for IRB review to another institution. 

In the conduct of cooperative research projects, Harvard University acknowledges that each institution is responsible for safeguarding the rights and welfare of human subjects and for complying with applicable federal regulations. When an Institutional Authorization Agreement exists, Harvard 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. When doing so, Harvard University will ensure that the review arrangement is approved, in writing, by the appropriate officials of the institutions involved, and the particular characteristics of its local research context are considered, either (i) through knowledge of its local research context by the relevant Harvard University IRB or (ii) through subsequent review by appropriate designated institutional officials, such as the Chair and/or other IRB members. 

When a University Area institution is the coordinating center for a multi-center protocol, the CUHS will require the PI to ensure that IRB approval has been obtained at each participating site prior to initiation of the research at that site. At the time of initial review, the CUHS will assess the procedures for dissemination of protocol information (e.g., unanticipated problems involving risks to participants or others, protocol modifications, interim findings) to all participating research sites. 

4.3 Roles and Responsibilities 

4.3.1 Chair of the CUHS 

The Dean of the Faculty of Arts and Sciences, in consultation with the Provost, and the CUHS Executive Officer, appoints a Chair of the CUHS to serve for renewable three-year terms. Any change in appointment, including reappointment or removal, requires written notification to OHRP. 

The CUHS Chair should be a highly respected individual from within the University, fully capable of managing the CUHS and the matters brought before it with fairness and impartiality. The task of making the CUHS a respected part of the institutional community is the joint responsibility of the Chair and the Executive Officer. The CUHS must be perceived to be fair, impartial, and immune to pressure by the institution's administration, the investigators whose protocols are brought before it, and other professional and nonprofessional sources. 

The CUHS Chair is responsible for conducting the meetings of the CUHS. 

The CUHS Chair may designate the CUHS Officers and staff, and other CUHS members, to perform duties as appropriate including review, signature authority, and other CUHS functions. 

The CUHS Chair, in consultation with the Executive Officer, advises the Institutional Official and the Dean of the Faculty of Arts and Sciences about IRB member performance and competence. 

The performance of the CUHS Chair will be reviewed on an annual basis by the Institutional Official and the Dean of the Faculty of Arts and Sciences. If the Chair is not acting in accordance with the CUHS’s mission, is not following these policies and procedures, has an undue number of absences, or is not fulfilling the responsibilities of the Chair, he/she will be replaced. 

4.3.2 Acting Chair of the CUHS 

The CUHS Chair, in consultation with the Executive Officer, may appoint another CUHS member to serve as Acting Chair of the CUHS in the absence of the Chair. The Acting Chair will have the same authority and duties as Chair and will be selected based on his/her qualifications and ability to fulfill the duties of Chair of the CUHS. 

4.3.3 CUHS Executive Officer 

The CUHS Executive Officer shall be qualified, by training and experience, to direct the administrative operation of the CUHS. S/he shall have a firm understanding of relevant regulations, law, and University policies that affect the conduct of research involving human subjects. The Executive Officer shall ensure the coordination of CUHS activities with other University academic and administrative offices; s/he shall be responsible for presenting staffing and/or budgetary needs to School and University administration to ensure that the CUHS has access to sufficient resources to fulfill its obligations. Other duties and responsibilities of the Executive Officer are referenced throughout these Policies and Procedures. 

The Executive Officer shall be a voting member of the CUHS, unless s/he has other responsibilities that could be viewed as presenting a conflict of interest (such as, administrative responsibilities relating to the review, submission, or administration of sponsored research proposals), in which case s/he shall be a non-voting member of the CUHS. 

Since the CUHS is a Standing Committee of the Faculty of Arts and Sciences, appointment of the Executive Officer shall be made by the Dean of the Faculty of Arts and Sciences in consultation with the office of the Executive Dean and with the concurrence of the Institutional Official. The performance of the Executive Officer is reviewed on an annual basis by the office of the Executive Dean. 

4.3.4 Subcommittees of the CUHS 

The Chair and the Executive Officer of the CUHS, may designate a subcommittee of one or more other CUHS members to perform duties, as appropriate, including review, signature authority, and other CUHS functions. 

Duties of a subcommittee may include the following: 

1. Serve as designees by the CUHS Chair for the expedited review of new or continuing protocols, and/or modifications of continuing protocols. The subcommittee member(s) must be experienced, and must have expertise, acquired through education, training and/or experience on the CUHS, appropriate to the nature of protocols to be reviewed. 

2. Review and approve protocol revisions where a protocol has been given provisional (“Contingent”) approval by the convened CUHS and the revisions are not substantive changes that are directly relevant to the determinations the committee must make to approve research, 45 CFR 46.111, see Section 8 below. 

3. Review allegations of noncompliance. A subcommittee is appointed consisting of CUHS members (and non-members if appropriate) to review allegations of non-compliance. The subcommittee is given a charge by the CUHS, to determine whether the allegation has a basis in fact, and may do any or all of the following: 

a. Review of protocol(s) in question; 

b. Review of any relevant documentation, including consent documents, case report forms, subject's investigational and/or medical files, investigator’s files, etc., as they relate to the investigator's execution of her/his study involving human subjects; 

c. Review of FDA audit report of the investigator, if appropriate; 

d. Interview of appropriate personnel if necessary; 

e. Preparation of either a written or oral report of the findings, which is presented to the full CUHS at its next meeting; 

f. Recommend actions if appropriate. 

4. Review findings of noncompliance. A subcommittee is appointed consisting of CUHS members (and non-members if appropriate) to review allegations of non-compliance. The subcommittee is given a charge by the CUHS to determine whether the finding of non-compliance is serious or continuing, and may do any or all of the following 

a. Review of protocol(s) in question; 

b. Review of any relevant documentation, including consent documents, case report forms, subject's investigational and/or medical files, investigator’s files, etc., as they relate to the investigator's execution of her/his study involving human subjects; 

c. Review of FDA audit report of the investigator, if appropriate; 

d. Interview of appropriate personnel if necessary; 

e. Preparation of either a written or oral report of the findings, which is presented to the full CUHS at its next meeting; 

f. Recommend actions if appropriate. 

5. Conduct on-site review. Determination of the review interval and the need for additional supervision and/or participation is made by the CUHS on a protocol-by-protocol basis. For example, for an investigator who is performing particularly risky research, or for an investigator who has recently had a protocol suspended by the CUHS due to regulatory concerns, an on-site review by a CUHS subcommittee might occur, and/or approval might be subject to an audit of study performance after a few months of enrollment, or after enrollment of the first several subjects. 

4.4 Resources for CUHS 

The Dean of the Faculty of Arts and Sciences provides resources to the CUHS and CUHS Office, including adequate meeting and office space, and staff for conducting CUHS business. Office equipment and supplies, including technical support, furnishings, computers, printers, internet access, and fax and copy machines, plus books, journal subscriptions, and conference and training expenses are also made available to the CUHS and staff. 

On a calendar-year basis, the CUHS reviews its direct personnel and non-personnel expenses and calculates the share of such expenses attributable to projects from each of the University-area institutions other than the Faculty of Arts and Sciences submitting proposals to the CUHS. Each institution is invoiced for its share of the expenses and the funds are reimbursed to the Faculty of Arts and Sciences. In addition, the office of the Provost provides support for some activities that benefit all HRPPs at the University. The resources provided for the CUHS and CUHS office are reviewed each year during the annual budget process. 

4.4.1 Annual Report 

The CUHS summarizes its actions and operations in an Annual Report that is distributed to the Institutional Official and relevant University Area administrators. Following distribution of the Annual Report, the CUHS Executive Officer and Chair confer regarding the capacity of the organization to accomplish IRB reviews in a thorough and timely manner, and make recommendations to the Institutional Official about any changes they deem appropriate. 

4.5 Conduct of Quality Assurance/Quality Improvement Activities for CUHS Operation 

The HSRC will coordinate regular review of the activities of all IRBs and HRPPs at the University. (See Section 11 for a detailed discussion of investigations and audits.) CUHS staff will conduct investigations and reviews of ongoing research when the CUHS directs a review to be conducted or when a complaint or allegation of non-compliance is received and requires an investigation. In addition, the staff will conduct “not for cause” reviews of research.