Stanford University Office of the Dean of Research
Human Research Protection Program (HRPP)
DOMAIN II: RESEARCH COMPLIANCE OFFICE, INCLUDING IRBs
Chapter 6: Structure and Composition of IRBs
The structure and composition of the STANFORD* Institutional Review Boards (IRBs) are appropriate to the amount and nature of the research reviewed. (AAHRPP Standard II-1.) The IRBs derive their authority from both federal regulatory and institutional sources. Institutional authority is conveyed by provisions of this Chapter 6 and the other chapters of the HRPP, through its approval by the Vice Provost and Dean of Research (Dean of Research), and a direct, written delegation of authority under an institutional Charge to IRB members (medical IRB and nonmedical IRB) from the Dean of Research, and Research Compliance Office (RCO) website when she appoints them. The Vice Provost in turn has the authority delegated to her from the Stanford University President. On a day-to-day basis, the IRBs report to the Dean of Research, through the RCO Director. However, any IRB Chair, member, or any convened IRB may refer a matter directly to the University President in those rare and extraordinary occasions when it may be deemed warranted.
The IRBs’ primary responsibility is to ensure that the rights and welfare of research participants are protected for all research involving human participants covered by the HRPP as defined in Chapters 1.1 and 1.3. In performing their review, the IRBs must ensure that the human research is conducted ethically and in compliance with federal regulations, the requirements of applicable state law, the relevant FWA and the HRPP and other applicable STANFORD policies and procedures.
The IRBs must prospectively review and make a decision concerning all human research. It must also conduct a continuing review of such research at intervals appropriate to the degree of risk, but not less than once per year, regardless of the source of funding. The IRBs may approve research protocols with or without modifications or may withhold approval of all or any portion of a protocol.
The IRBs have the statutory and institutional authority to take any action necessary to protect the rights and welfare of human research participants involved in research. The IRBs, for example, shall assess suspected or alleged protocol violations, subject complaints, or violations of external regulations or STANFORD policies. The IRBs have the authority to suspend or terminate the enrollment or ongoing involvement of research participants in research as it determines necessary for the protection of those participants. The IRBs also have the authority to observe or monitor any human research to whatever extent it considers necessary to protect research participants. (45 CFR 46.109, 46.112, and 46.113)
Upon request, the IRBs shall review and comment on proposed external regulations dealing with human research. When appropriate, the IRBs will formulate draft policies and procedures for approval by the appropriate STANFORD bodies and promulgation by the Dean of Research.
Decisions of the IRBs
IRB approval is always necessary before a research project involving research participants may begin. A human research project may not be approved by others at STANFORD if it has not been approved by the IRB. An IRB decision to disapprove a human research project, or require modifications, as a condition for approval, cannot be overturned by any STANFORD official or STANFORD committee.
Appeal of IRB Determinations
The IRBs must provide the investigator with a written statement of the reasons for disapproving or requiring modifications in proposed research and must give the investigator an opportunity to respond in person or in writing. The IRBs must carefully and fairly evaluate the investigator’s response in reaching a final determination.
If an investigator disputes a determination of the IRB (substantive or procedural), the investigator may appeal to the Dean of Research. An appeal must be in writing, state the decision being appealed and the basis of the appeal, and be filed within 30 calendar days of the decision. The Dean of Research may use his or her sole discretion to determine the process for the appeal and grant or deny the appeal, including:
· Notifying the IRB of the appeal and requesting a response and relevant information from its records before making a decision
· Submitting the appeal to mediation if the investigator agrees to participate
· Appointing a fact-finder to review the matter and report back
· Seeking assistance from consultants or internal administrative units such as the Office of Internal Audit or Office of the General Counsel
· Requesting that the IRB consider other factors, information or actions in relation to the decision under appeal.
The investigator is bound by the IRB decision prior to and during the appeal. The decision on an appeal by the Dean of Research is final, unless by its terms it indicates otherwise or unless it is a decision that may be appealed further to the Provost under Chapter 4.I of the Faculty Handbook of Stanford University, “Statement on Faculty Appeal Procedures”.
If the IRB decision is one that
(a) disapproves a protocol reviewed pursuant to its charge, or
(b) requires protocol modifications as a condition for approval
neither the Dean of Research, the Provost, nor any other STANFORD official or committee may overturn the IRB’s decision of disapproval, nor apply undue pressure on the IRB to reverse a decision.
Interactions with other STANFORD Programs
The IRBs are at times required to interact with other programs or research compliance committees. In some cases, the approval of another STANFORD body may be required prior to or in addition to IRB review. Such cases include the following:
1. Radiological Safety: If a study involves any radioisotopes or radiation-producing machines, a human research application is forwarded to Health Physics for their review. If it is determined by Health Physics that the Human Use Radiological Safety Committee review is required, the IRB will not issue approval until the Radiological Safety Committee issues its approval. The IRB Manager identifies protocols that involve radioisotopes or radiation-producing machines and assigns them to the Health Physics reviewer. The standard response time is expected to be within a week. When the regular reviewer is not available, arrangements have been made for two expert backup reviewers, so that the review is done in a timely manner. The reviewer may recommend approval, suggest language to be added to the consent document, or indicate that it needs to go to the Radiological Safety Committee meeting. If consent language is needed, the revised consent document containing the appropriate language is sent to the Health Physics reviewer to recommend for approval. If the Health Physics reviewer determines that a protocol must go to the Radiological Safety Committee meeting for review and approval, that meeting must be held prior to the IRB meeting, or the protocol must be moved to the next convened meeting of the IRB following the Radiological Safety Committee meeting (See also Chapter 5.4.).
2. Biosafety: Gene transfer studies and human subject protocols using biological agents must be approved by the Administrative Panel on Biosafety (APB) in addition to obtaining IRB approval. Protocol Directors (PDs) must submit an application using the combined Protocol Application Form for Human Subjects Investigation Using Biological Agents or Recombinant DNA Vectors. These protocols and reports on them are discussed at the APB meeting that is held three weeks prior to the IRB 1 meeting, the IRB that reviews all of the gene transfer studies and human subject protocols using biological agents. A protocol or report is not discussed at the IRB meeting until the protocol has been approved or the report has been accepted by the APB. The exception to this procedure is when a Continuing Review has missed the APB meeting and needs to go to the IRB meeting to avoid expiration of the protocol. In this situation, the Continuing Review is approved by the IRB contingent on APB approval. The APB meetings are attended by the RCO Director, who is a Non-voting Ex-officio Member, and the Sr. IRB Manager who is the IRB Manager for these protocols.
3. Conflict of Interest: The majority of PDs and Principal Investigators (PIs) are affiliated with Stanford University’s School of Medicine (SOM). The SOM has an annual requirement for disclosure of all personal financial interests related to STANFORD activities, regardless of dollar amount, for all faculty. In addition, the New Protocol Application requires disclosure of financial holdings for all personnel involved in the proposed research. The IRB Manager must provide notification to the Conflict of Interest Review Program (COIRP) at the time IRB reviewers are being assigned to review a protocol application reporting a financial interest. Whether a financial interest is discovered via the annual disclosure process or during individual protocol review, it must be reviewed by the COIRP in the SOM, and where warranted, satisfactorily managed prior to IRB approval of the research.
For research with PDs or PIs outside of the SOM, the IRB Manager must provide notification to the individual’s Department Chair and relevant Dean at the time IRB reviewers are being assigned to review a protocol application reporting a financial interest. The financial interest must be reviewed in accordance with the relevant School’s Conflict of Interest Policy, and where warranted satisfactorily managed, prior to IRB approval of the research.
The IRBs will conduct the review in parallel with the conflict of interest review but will not issue an approval until notified of the proposed management of the financial interest. The IRB shall be provided with sufficient information to determine whether any proposed plan sufficiently manages any conflict of interest so as to safeguard satisfactorily the rights, welfare, and safety of the research participants.
A full description of STANFORD processes is found in Chapter 3.7.
4. The Stanford General Clinical Research Center (GCRC): This NIH-funded facility currently supports over 150 active human research protocols, involving more than 100 faculty from 28 departments. The GCRC offers researchers 10 inpatient suites and two outpatient suites, a kitchen, laboratory, and computer center. Depending upon the nature of the research, any human research supported by the GCRC must be reviewed and approved by the GCRC Adult Protocol Review Committee, the GCRC Pediatric Protocol Review Committee, and a GCRC Safety Committee. Review by these committees is often conducted in parallel with IRB review. Both IRB and GCRC approvals are required to conduct research supported by the GCRC. See GCRC policies for SHC and LPCH.
5. The Stanford Comprehensive Cancer Center: The Comprehensive Cancer Center works with more than 500 PIs from 16 clinical and 11 basic science departments. Protocol review by the Cancer Center’s Scientific Review Committee (SRC) is conducted in parallel with IRB review. Both IRB and SRC approvals are required to conduct research supported by the Comprehensive Cancer Center.
6. The VA R&D Committee: Human research involving facilities or personnel of the Department of Veterans Affairs (VA) Palo Alto Health Care System (VAPAHCS) must be approved by the IRB prior to being placed on the agenda of the VAPAHCS Research and Development Committee for review and approval.
7. Human Embryonic Stem Cell Research Oversight (ESCRO) Body: The Vice Provost and Dean of Research will designate a Human ESCRO Panel, comprised of qualified individuals, to advise regarding issues related to the conduct of human embryonic stem cell research at or through Stanford University. This panel will be expected to report on its activities at least annually to the Dean of Research, and to other offices or entities within the University as directed. See RPH 10.7.
Reporting Obligations within STANFORD
The IRBs have a clear reporting line within STANFORD. All IRBs report to the President through the Office of the Dean of Research. The Dean of Research is the institutional official responsible for assuring compliance with STANFORD policies and external regulations on the use of human research participants. IRB Chairs prepare annual reports to the President, summarizing the nature and volume of the IRBs’ activities.
STANFORD IRBs are administered by the RCO, within the Office of the Dean of Research.
Responsibilities to Regulatory Agencies
The IRBs must comply with the requirements of all relevant federal regulatory and compliance enforcement agencies or offices, including OHRP and FDA, as well as relevant agencies of the State of California. For example, an IRB may need to tell the FDA directly, if it disagrees with a sponsor’s Non Significant Risk (NSR) determination.
IRBs’ Relationship to Industry Sponsors and Other IND/IDE Holders
Unless specifically required by the FDA or requested by the sponsor, the IRBs will not routinely provide written notification of IRB decisions to industry sponsors and other holders of INDs or IDEs (STANFORD sponsor-investigators excepted). For FDA regulated research, clinical investigators ordinarily serve as the link between the IRBs and the sponsor, and are required to do so by the FDA in compliance with their obligations as clinical investigators. Such linkage is agreed to by investigators when they sign FDA Form 1572 for drug and biologic studies or an investigator agreement for device studies.
There are occasions when direct communication between the IRB and the sponsor may facilitate resolution of concerns about study procedures or specific wording in an informed consent document. The IRB staff may engage in such direct communication on behalf of the IRBs when the IRB Chair or the RCO Director considers it desirable. The clinical investigator will be kept apprised of such communication.
The FDA requires direct communication between the sponsor and the IRB when an IRB does not accept a sponsor’s Non-Significant Risk (NSR) designation of a medical device under 21 CFR 812.2. Direct communication between the sponsor and the IRB is also required for the waiver of informed consent in planned emergency research under 21 CFR 50.24 relative to (a) the public disclosures required under 21 CFR 56.109(a)(7)(ii),(iii); or (b) disapproval of such a waiver under 21 CFR 50.24(e).
Administrative Review of Human Research Protection Activities
The Stanford University Internal Audit Department periodically reviews each IRB and the various schools and departments within STANFORD that conduct human research activities. A random selection of researchers’ human subject’s records and consent forms are reviewed during these audits. In addition, under Internal Audit's directive, the RCO audits three signed consent forms for three protocols per IRB and one IRB protocol file per IRB each month. Results are shared at the next relevant IRB meeting. If deviations from procedures are found, the IRB Chair will send a memo to the PD, and corrective action may be required.
During Continuing Review of protocols the IRB Associates select three protocols for which they request from the PD the last three signed consent forms for the “Consent Form Audit”. Whenever possible, one of the protocols selected is a VA protocol. A record of the RCO consent form audits entitled “Consent Form Audit File” is kept online on the server (rc-file1) under “IRB Coordination.” The IRB Associates enter their consent form audit information in this file. The VA consent form audit information is pulled from the “Consent Form Audit File” and kept in a separate file entitled “VA Audit” on the server under “IRB Coordination.” The Sr. IRB Manager forwards the VA Audit information to the VAPAHCS Associate Chief of Staff for Research and Development on a monthly basis.
Following each IRB meeting one protocol is audited jointly by the IRB Coordinator and the Sr. IRB Manager. A record of the RCO protocol audits entitled “Protocol Audit File” is kept online on the server (rc-file1) under “IRB Coordination.”
The IRB Chair may also designate IRB staff, or appoint subcommittees on an ad hoc basis, to perform non-review functions as needed, such as monitoring compliance with IRB regulations.
6.1 Scientific/Scholarly Expertise of IRB Members
Appointment of Members and Alternates, Length of Service, and Duties
IRB members are nominated from a variety of sources, including previous and current IRB members, division chiefs, department chairs, compliance administrators, Associated Students of Stanford University (ASSU), and various public groups. Consideration is given to race, gender, expertise, and cultural backgrounds. People with active licensure from various clinical disciplines are sought. A background knowledge of and current familiarity with affiliated institutional concerns (e.g., the VA) helps ensure that the local research context is brought into the evaluation. Also sensitivity to issues such as community attitudes and international dimensions is valued. During the three months prior to October 1st (the start date for the IRBs’ year) newly identified nominees are contacted by the Sr. IRB Manager about volunteering to serve on the IRB and their availability for the coming year. When a nominee agrees to serve on the IRB a copy of his/her CV is requested. The nominee’s CV and any relevant correspondence are reviewed by the RCO Director and Dean of Research. Nominees appointed to serve on the IRB receive a letter of appointment for one year signed by the Dean of Research.
OHRP guidance points out that officials who administer research programs may be in a position to influence programmatic and budgetary decisions and exert undue influence on IRBs or individual IRB members. To avoid such influence on IRB determinations, the Dean of Research, School Deans, and other Stanford University officers will not serve as voting members of the IRBs, unless there are compelling reasons to do so. Such reasons must be justified in writing, approved by the President of Stanford University, and include specific measures to manage any conflict of interest or the possibility of undue influence.
After an extensive review of their education, experience and other characteristics that might add diversity to the position, each individual is formally appointed to the IRB by the Dean of Research. Members serve 1-year renewable terms (from October 1 to September 30). At the conclusion of the IRB year, (and interim, if needed) members’ contributions are evaluated by the IRB Chair with the IRB Manager using the form for Evaluation of IRB Members. If their continued membership is mutually satisfactory, they are eligible for reappointment. At the conclusion of the IRB year (and interim, if needed) the IRB Chairs’ contributions are evaluated by the Dean of Research with the RCO Director using the form for Evaluation of IRB Chairs. If their continued membership is mutually satisfactory, they are eligible for reappointment.
Members are responsible for ensuring that the rights and welfare of research subjects are protected. Members vote to approve, require modifications in, disapprove, or defer research submitted to the IRB. Members are expected to attend IRB meetings on a regular basis, serve as primary reviewers for research within their areas of expertise, and serve as general reviewers on all research. Members may also be asked to participate in other subcommittees, audits, and education, as long as there is no conflict of interest with their IRB responsibilities or their other personal or professional roles.
The IRB Manager, in consultation with the IRB Chair where appropriate, assigns protocols to primary reviewers, who are expected to be present at the meeting, based on the individual’s scientific, scholarly, professional, or clinical expertise. Primary reviewers must have the relevant expertise to conduct an in-depth review of the protocols to which they are assigned. If the IRB manager cannot identify a primary reviewer with the appropriate scientific or scholarly expertise, the IRB manager arranges for expert consultation and will not place the protocol on an agenda until appropriate expertise is made available. Primary reviewers are expected to conduct an in-depth review, and it is the responsibility of primary reviewers to notify the IRB Chair should they feel unqualified or unable to do so. In such cases, the IRB Chair will assign primary review responsibilities to another member who is appropriately qualified or obtain consultation from one or more experts outside the IRB (see relevant section below).
The composition/membership of each IRB is evaluated annually by the RCO Director and the Dean of Research and is adjusted as needed to ensure appropriate knowledge of applicable regulatory and legal requirements; knowledge of professional standards and practices; knowledge of the local research context and research sites, and their capabilities and limitations; knowledge of community standards and attitudes; scientific, scholarly, clinical, and professional expertise; racial, ethnic, and cultural diversity; and representation of participants’ perspectives. Due to the increased complexity of human research protocols submitted, this often results in adding members. The composition of each IRB may change annually as needed.
Appointment of IRB Chair, Length of Service, and Duties
IRB Chairs are nominated from a variety of sources, including previous and current IRB members, division chiefs, senior deans, department chairs, and compliance administrators. In addition to the characteristics sought in an IRB member, these individuals possess demonstrated skills in leadership and group process. Typically, they have served on an IRB previously.
IRB Chairs are formally appointed by the Dean of Research. Chairs serve 1-year renewable terms (from October 1 to September 30). They may be reappointed, if their yearly evaluation is satisfactory.
In addition to the responsibilities of IRB membership, the Chair has primary responsibility for conducting IRB meetings and working with staff to ensure effective and efficient operation of the IRB within all applicable regulatory requirements. The IRB Chair works with IRB members, institutional officials, and investigators to ensure that the rights and welfare of research participants are adequately protected.
Compensation of IRB Members
IRB Chairs' departments receive a percentage of their salaries to offset 25% time dedicated to IRB duties. Other IRB members generally do not receive monetary compensation for their service on the IRB. However, it is acknowledged that service on the IRB requires a significant investment of time for all members. The Dean of Research, on an annual basis, does provide each IRB member and Chair with a formal letter describing the critical importance of their IRB service and Stanford University's gratitude for their service.
IRB members who are not otherwise affiliated with STANFORD or its collaborating institutions are compensated for their service by the issuance of an honorarium.
Alternate IRB Members
Alternates replace regular IRB members who are unable to attend convened meetings of the IRB. They are chosen with the same qualifications and characteristics of expertise and diversity in mind as the regular IRB members for whom they serve. When an alternate substitutes for a primary member, the IRB staff provides the alternate member the same material that the primary member received or would have received.
Alternate members are listed on the IRBs’ official membership rosters, which specify which member the alternate is qualified to replace. The backgrounds of alternate members are similar to the member they are replacing, or they are able to represent similar interests. Terms of appointment, length of service, and duties are exactly as for regular IRB members. Alternate members must adhere to the same conflict of interest standards and documentation requirements as regular IRB members.
Ad hoc substitutions for regular or alternate IRB members are not permitted.
Ex Officio Non-Voting Representatives to the IRB
“Ex Officio member” means that the individual is an automatic IRB member by virtue of the individual’s office and is not synonymous with a non-voting member. For example, if the chair of the radiation safety committee were an automatic IRB member and if the chair changed hands, the IRB membership would also change hands accordingly; thus, the chair of the radiation safety committee would be an ex officio member.
Medical IRBs accept permanent ex officio representatives (sometimes referred to as “ex officio” and sometimes also “non-voting” members) from the following areas:
The Non-medical IRB accepts permanent ex officio representatives (sometimes referred to as “ex officio” and sometimes also “non-voting” members) from the following areas:
Non-voting representatives (ex officio, non-voting members) may participate in the IRBs’ deliberations to provide information and expertise as requested by the IRB. Representatives are expected to adhere to the same conflict of interest standards and documentation requirements as are regular IRB members and alternates. Representatives may not vote on any IRB action or determination. IRBs may accept additional permanent non-voting representatives (ex officio, non-voting members) with the agreement of a majority of IRB members, the IRB Chair, and the RCO Director.
STANFORD IRBs have a process for obtaining additional expertise when needed for reviewing a specific protocol. (AAHRPP Element II.1.B) The IRB Chair will review the proposed agenda for meetings and determine whether the IRB has the required expertise to review the research. If not, the IRB Chair will invite individuals with competence in special areas to assist in evaluating issues that require expertise beyond or in addition to that available on the IRB. On an as-needed basis, an IRB primary reviewer may, at his/her discretion, invite individuals with competence in special areas to assist in evaluating issues that require expertise beyond or in addition to that available on the IRB.
When a consultant is used, that fact and the pertinent information gained, from the consultant’s assessment is documented at the time of the protocol discussion and recorded in the IRB minutes. IRB staff or the IRB Chair will make initial contact with a proposed consultant and notify the consultant of the IRB member conflict of interest policy. If the consultant has a conflict of interest as defined by this policy, the consultant will not be used and another will be sought. Consultants may not vote on any IRB action or determination. The IRB Manager and support staff can assist in making the consultation arrangements and in obtaining the required conflict of interest documentation.
Reasons for seeking additional or special competence from outside experts may include (but are not limited to) the need for additional scientific, clinical, or scholarly expertise; the need for particular knowledge and understanding about potentially vulnerable populations of subjects; and the desire to ensure appropriate consideration of race, gender, cultural backgrounds, and sensitivity to such issues as community attitudes, to promote enhanced respect for the IRBs’ advice and counsel in safeguarding the rights and welfare of research participants.
Frequently, needed expertise may be obtained through a member of another IRB or a faculty member at Stanford University. Regardless of whether consultants are internal or external to Stanford University, these individuals (as indicated above) are not IRB members and cannot vote with the IRB.
Potential consultant resources include individuals from Stanford University at large, or from various Schools and Departments within the University, such as:
· Medicine, Education, Business, and Law
· Office of Research Administration
· Stanford Center for Biomedical Ethics
· Academic Consortium for Excellence in Clinical Studies (ACCESS)
· Various specialty Clinical Departments at the affiliated institutions
· Stanford Comprehensive Cancer Center
· VA Palo Alto Health Care System (VAPAHCS), including the VAPAHCS Research and Development Office
· Experts from other institutions
· Representatives of the community
· Representatives of specific subject populations.
6.3 IRB Member and Consultant Conflicting Interest
The IRBs have the following written guidelines so that IRB members and consultants do not participate in the review of protocols in which they have a potential conflict of interest, except to provide information requested by the IRB. (AAHRPP Element II.1.C) (45 CFR 46.107(e); 21 CFR 56.107(e))
This policy requires any IRB member with a conflicting interest in a project to disclose that to the IRB Chair or RCO Director and to leave the room during the discussion of the project and the related vote, except if the member is providing information at the IRB’s request. The meeting minutes will document the recusal. The definition of conflicting interest extends to consultants, who are asked to review a project because of their expertise. This policy applies to all projects reviewed by the IRB, regardless of whether the project is exempt or considered during full, expedited, or continuing review.
Definition
Conflicting Interest: A conflicting interest generally includes participation in or supervision of a project, a financial interest, a personal relationship, or a fiduciary relationship, all as defined below. Certain other types of interests may also be conflicting interests, as explained below. A conflicting interest may arise because of an interest that the IRB member or consultant, or his/her immediate family, has; the aggregate interest of the IRB member or consultant, and his/her immediate family, is considered. “Immediate family” means the IRB member’s or consultant’s spouse or domestic partner and dependent children (as defined by the IRS).
Other examples of conflicting interest:
1. “Participation in a project” means the IRB member or consultant is listed as an investigator on the protocol or is a member of the research team.
2. “Supervision of a project” means the IRB member or consultant is a faculty sponsor of the Protocol Director (PD), or a situation in which any investigator must report to or is under the professional supervision of the IRB member or consultant.
3. A “financial interest” is a conflicting interest under this policy if it is one of the following situations: (a) receiving more than $10,000 annually as salary, consulting income, or other compensation from the sponsor of the project; (b) having an equity interest (including stock or stock options) that exceeds $10,000 or that represents more than 5% of the company sponsoring the research; (c) having an ownership interest (including patent, trademark, or copyright interest) in the drug/product/technology that is the subject of the research project; or (d) receiving or expecting to receive compensation with a value that may be affected by the outcome of the study.
4. “Personal relationship” means having an immediate family relationship or other close personal relationship with the investigator.
5. “Fiduciary relationship” means serving as an executive to a company sponsoring the research or serving on the company’s board of directors.
6. Other examples of conflicting interests include but are not limited to the following: (i) the IRB member or consultant has an interest that he/she believes conflicts with his/her ability to review a project objectively; or (ii) the IRB member or consultant is in direct competition with the investigators for limited resources, funding, sponsorship, or research subjects, or the IRB member or consultant is considered a personal or professional adversary of the investigators. (Since situations in (ii) may depend on the circumstances, the IRB member or consultant should raise such a situation as soon as possible with the IRB Chair or RCO Director, who will determine whether it is a conflicting interest. The standard used by the IRB Chair or RCO Director is whether an independent observer could reasonably question whether the individual’s actions or decisions would be based on factors other than the rights, welfare, and safety of the subjects.)
7. Any other reason for which the IRB member believes he or she has a conflicting interest with the research.
IRB Member’s Disclosure of a Conflicting Interest
When IRB members receive materials before a meeting, they must review the list of projects with the issue of conflicts in mind and disclose any conflicting interest to the IRB Chair or RCO Director before the meeting whenever possible. If the IRB member realizes at a meeting that he/she may have a conflicting interest in a given project, then that should be disclosed to the IRB Chair immediately, orally and in writing on the IRB Member Conflict of Interest Declaration.
The IRB Chair will begin each meeting with a reminder that proceedings are confidential. This is followed by a reminder of the requirement that each member must disclose any conflicting interest and recuse himself/herself from the discussion of and vote on the project by leaving the room, except if the member is providing information at the IRB’s request. Specifically, the IRB Chair reads the following statement on conflicting interests:
Any person having a conflicting interest in a protocol must leave the room during discussions and voting on the protocol.
“Conflicting interest” includes participating in or supervising the project, a financial interest, a personal or fiduciary relationship, or some other situation giving rise to a conflicting interest. Such situations are defined in the Guidelines on Conflicting Interest and related IRB policy.
A member who leaves the room for any reason will not be counted in the quorum for any vote that takes place while the member is out of the room.
The IRB Member Conflict of Interest Declaration should be signed after you have reviewed the agenda, and then updated as necessary during the meeting.
Procedure and Responsibility for Handling an IRB Member’s Conflicting Interest:
1. The IRB member with a conflicting interest on a specific protocol should not accept that protocol for review, and should return it to the RCO for assignment to another IRB reviewer. If there is no other regular or alternate member of the IRB qualified to perform the review, the RCO Director will reassign the protocol to another STANFORD IRB for review.
2. The IRB Chair is responsible for ensuring that an IRB member who discloses a conflicting interest does not participate in the deliberative discussion or vote on the protocol and leaves the room. The IRB Chair or his/her designee is responsible for ensuring that at each meeting, each IRB member submits a signed IRB Member Conflict of Interest Declaration form.
3. If other IRB members need to request information on the project from the IRB member with the conflicting interest, then the IRB member may remain in the meeting room during the presentation of the project. The IRB member must then leave the meeting room during IRB deliberative discussion and during voting on the protocol.
4. The IRB member with the conflicting interest will not be counted as part of the quorum for the review of the project. (Should the quorum fail, the IRB may not take further action or vote on the project.)
5. In the IRB Minutes, the name of the person leaving the room due to a conflicting interest must be recorded for each applicable vote. The IRB member will not be counted toward the quorum and will be recorded as recused.
Consultant’s Disclosure of a Conflicting Interest and Procedure:
The definition of conflicting interest above extends to a consultant who may be asked to review a protocol. The IRB Manager who contacts the consultant to inquire about review of a project is responsible for asking if the consultant has a conflicting interest in the project. If such an interest exists, then the protocol will not be assigned to the consultant. The Guidance for Obtaining Additional Expertise or an Expert Consultant addresses the use of consultants in further detail.
6.4 IRB Composition and Review of IRB Membership
In compliance with the DHSS regulations, FDA regulations, and STANFORD policies, IRBs must satisfy the following requirements:
1. Each IRB shall have at least five regular members.
2. IRB members shall possess varying professional backgrounds to promote adequate review of research activities and involvement of vulnerable populations in the research commonly, conducted at STANFORD.
3. IRB members shall be sufficiently diverse relative to race, gender, cultural background, and sensitivity to community attitudes so as to promote respect for the IRB’s advice and counsel in safeguarding the rights and welfare of research participants.
4. IRB members shall include persons able to ascertain the acceptability of proposed research in terms of institutional commitments, regulations, applicable law, and standards of professional conduct and practice.
5. Each IRB shall consist of qualified persons of both genders.
6. No IRB will consist entirely of members of one profession.
7. Each IRB shall include at least one member whose primary concerns are in scientific areas.
8. Each IRB shall have at least one member whose primary concerns are in non-scientific areas. A non-scientist’s primary concerns must be unambiguously in non-scientific areas. The individual may not have meaningful scientific or medical training or experience. Health professionals, regardless of discipline, may not be considered non-scientists. At least one unambiguous non-scientist IRB member must always be present to have a quorum. (See discussion of quorum in Chapter 6.5.)
9. Each IRB shall include at least one community (unaffiliated) member who is not otherwise affiliated with STANFORD and who is not part of the immediate family of a person who is affiliated with STANFORD.
10. Each IRB shall include one student when nominated by the ASSU Committee on Nominations who is either an upperclassman or preferably a graduate student with previous human research experience.
VA requirements: In compliance with national VA research standards, the IRBs must satisfy the following requirements:
1. Each IRB shall include two or more VA employees as voting members.
2. At least one of the VA representatives shall have scientific expertise.
3. The VA representatives shall serve as full members of the IRB and review non-VA research matters coming before the IRB.
4. At least one of the VA representatives on the IRB shall be present during the review of VA research.
5. VA representatives to the IRB shall be appointed by the VA Medical Center Director.
6. A licensed physician shall be included in the quorum in the review of research involving an FDA-regulated article.
7. VA Research and Development administration officials including, but not limited to, the Associate Chief of Staff for Research and Development and the Administrative Officer for Research and Development shall be prohibited from serving as voting members of the IRB.
8. The IRB membership shall include at least one member who is an expert in the area of the research for VA research that involves mentally disabled persons or persons with impaired decision-making capacity.
When the IRB reviews research that involves categories of participants vulnerable to coercion or undue influence, the review process includes one or more individuals who are knowledgeable about or experienced in working with these participants (children, pregnant women, and adults unable to consent, etc.). The IRB staff reviews each application to determine whether it involves participants vulnerable to coercion or undue influence and makes sure that at least one member will be present who is knowledgeable about or experienced in working with these participants.
Each IRB has a qualified Chair and members, and whose membership and composition are reviewed and adjusted annually by the RCO Director, and the Dean of Research. As indicated previously, this review ensures that the individual IRB Chairs and members have the knowledge, skills and abilities appropriate to their respective roles and are performing their responsibilities in an acceptable manner. (AAHRPP Element II.1.D) The review also ensures that collectively, each IRB is so constituted as to possess appropriate knowledge of applicable regulatory and legal requirements; knowledge of professional standards and practices; knowledge of the local research context and research sites, and their capabilities and limitations; knowledge of community standards and attitudes; scientific, scholarly, clinical, and professional expertise; racial, ethnic, and cultural diversity; and representation of participants’ perspectives.
Education of IRB Members
All IRB members receive initial training on the ethical principles, regulatory requirements, and institutional policies related to human research protection, as well as continuing education, and professional development activities concerning such issues from the RCO full-time IRB Training Specialist.
IRB members receive Orientation training regarding the responsibilities of IRB service. New members cannot participate in an IRB meeting unless the Orientation is complete. Completion of Orientation is mandatory because discussion and awareness of IRB member responsibility, including confidentiality, is integral to the initial Orientation training. The IRB Chairs receive additional education about their leadership roles and responsibilities.
Both IRB members and Chairs receive comprehensive reference materials necessary to review research from an ethical and regulatory perspective. All members complete the STANFORD Human Subjects Online Tutorial available from the RCO website, or comparable training approved by the RCO Director. New IRB members cannot review a research protocol until they have completed the tutorial or approved comparable training. Members are provided with monthly educational updates at IRB meetings, with quarterly IRB member and staff education sessions, and with other continuing education opportunities within Stanford University, the VA, or at neighboring institutions.
The Stanford University School of Medicine offers an online HIPAA tutorial for IRB members. The IRB Educational Specialist monitors and ensures that all members of the STANFORD Medical IRBs have completed HIPAA training.
Several Stanford University departments or programs work with the RCO to offer education to IRB members. These include the Office of Research Administration, the Stanford Center for Biomedical Ethics, and the Academic Consortium for Excellence in Clinical Studies. Resources are also made available each fiscal year for IRB members to attend national or regional human research protection conferences and meetings.
Education for IRB Chairs and members is discussed in detail in Chapter 4.
Coordination and Review of IRB Membership, Education, Activities and Functioning
To optimize the IRBs’ role in protecting human research participants, efforts are made on a continuing basis to incorporate input from the affiliated institutions. Thus, for example, the RCO Director ensures that periodic meetings of STANFORD personnel engaged in research are scheduled at least annually to update the administrators and clinical leaders as to the current STANFORD HRPP status.
Liability Coverage for IRB members
Stanford University provides liability coverage under its insurance programs for IRB members acting in good faith in the performance of their IRB duties. Stanford University's Office of Risk Management provides liability coverage of volunteer individuals, including community IRB members. All Stanford-University-related faculty, staff, and students are likewise covered in their capacity as employees and students.
Support of IRB Membership
The IRB has a qualified staff, whose membership and composition are reviewed at least annually by the RCO Director and the Dean of Research. The IRB staff has knowledge, skills and abilities appropriate to their respective roles. The following resources are provided by Stanford University to the IRBs to support their review and record keeping responsibilities:
The RCO Director oversees the RCO Deputy Director and the CQI Associate Director, and is responsible for the overall management of the RCO. See the RCO Organization Chart.
Initial Training, Continuing Education, and Professional Development of IRB Staff
The RCO maintains an educational program for human research protections for IRB staff. (See Chapter 4.) This program is led by the IRB Training Specialist. All IRB staff must complete the STANFORD Online Human Subjects Tutorial available from the RCO website, or comparable training approved by the RCO Director, to acquaint themselves with their responsibilities under the FWA.
Staff are regularly provided educational updates at IRB meetings, weekly staff meetings, quarterly IRB member and staff education sessions, periodic IRB newsletters, local and regional seminars, and other continuing educational opportunities within STANFORD.
The Stanford University School of Medicine offers an online HIPAA tutorial for IRB staff. The IRB Training Specialist monitors and ensures that all relevant staff have completed HIPAA training.
Additionally, IRB staff receive training appropriate to their roles. For example, a new IRB Manager will meet weekly with the IRB Training Specialist for training about federal regulations and weekly with a seasoned IRB Manager about the logistics of IRB support. This preparation period lasts for at least three months, at which time the Senior IRB Lead Manager evaluates the new staff person’s learning needs and accomplishments.
Several Stanford University departments and programs work with the RCO to offer education to IRB staff. These include the Office of Research Administration, the Stanford Center for Biomedical Ethics, and the Stanford/Packard Center for Translational Research in Medicine (SPCTRM). Resources are also made available each fiscal year for IRB staff to attend national or regional human subject protection meetings.
In order to ensure appropriate skill, abilities, knowledge, and performance, all IRB staff are evaluated at least annually by their supervisor and a second level review is conducted by either the RCO Director or RCO Deputy Director. Appropriate professional development is included in the performance plan of each IRB staff member. Professional staff are encouraged, and provided with resource support, to pursue certification as IRB professionals.
6.5 IRB Membership Appropriate for Each Protocol Review
The IRB membership rosters include sufficient information about members to permit appropriate representation at the meeting for each protocol under review. (AAHRPP Element II.1.E) A Master IRB Member Roster is used as the data source for all IRB member roster needs. All IRB membership rosters include the following information required under FDA and DHHS regulations and OHRP guidance:
· Names of IRB members
· Names of alternate members and the corresponding regular member(s) for whom each alternate may serve
· Gender
· Earned degrees of each member and alternate, where applicable
· Specific scientific qualifications (such as board certifications and licenses) or other relevant experience sufficient to describe each member’s chief anticipated contribution to IRB deliberations
· Scientific status of each member (i.e., scientist or non-scientist)
A Checklist for Determining if IRB Public Members are Unaffiliated (Document D.4.m.i.) will be used during recruitment and annual evaluation of IRB public members.
· The representative capacity of each member or alternate (e.g., children, pregnant women, prisoners, economically disadvantaged, educationally disadvantaged, cognitively impaired adults or Native Americans)
· Any employment or other relationship (e.g., current or former employee, consultant, Board of Directors, volunteer, trainee or student) between each member and Stanford University, Stanford Hospital and Clinics (SHC), Lucile Packard Children’s Hospital (LPCH), Veterans Affairs Palo Alto Health Care System (VAPAHCS), Palo Alto Institute for Research and Education (PAIRE), including both the relationship and the component with which the member has a relationship, or “none” if the IRB member has no affiliation.
· Affiliation status: A yes/no indication of whether the IRB member or any of the member’s immediate family is affiliated with STANFORD.
A Checklist for Determining if IRB Members are Nonscientists (Document D.4.m.ii.) will be used during recruitment and annual evaluation of IRB members.
Changes in IRB membership require reporting to OHRP. The RCO Director submits a revised IRB membership list to OHRP whenever membership changes occur, but at a minimum once a year. The RCO Director submits a new IRB membership list to OHRP whenever a new IRB is formed.
Each STANFORD IRB includes: one or more regular voting members who are unaffiliated with STANFORD (and whose immediate family members are unaffiliated with STANFORD) and one or more members who can represent the general perspective of participants. (AAHRPP Element II.1.E) Alternates are designated to fill-in for unaffiliated members, as needed. All IRBs have positions available for student members, filled when nominated by the ASSU.
Quorum Requirements and Voting at IRB Meetings
IRB Minutes shall include a statement of “Quorum Requirements” based on the following standards:
1. A majority of the (voting) members of the IRB (or their designated alternates), including at least one member whose primary concerns are in nonscientific areas, must be present to conduct a convened meeting. In order for research to be approved, it must receive the approval of a majority of such members present at the meeting.
2. Members may be present in person or through audio (telephone) or audio-visual teleconference. Members present via teleconference shall be noted as such in the meeting minutes, which shall also indicate that the members received all pertinent information prior to the meeting and were able to participate actively and equally in all discussions.
3. IRB minutes shall include documentation of quorum and votes for each IRB action and determination by recording votes as follows:
Total Number Voting ( )
Number for ( )
Number opposed ( )
Number abstaining ( )
Names of those abstaining.
4. Members leaving the meeting room due to a conflicting interest, or for any other reason, will not be recorded as part of the quorum for a particular protocol.
5. An individual who is not listed on the official IRB membership roster may not vote with the IRB.
6. A non-voting ex-officio member of, or representative to, a STANFORD IRB may not vote with the IRB.
7. Ad hoc consultants may not vote with the IRB.
8. A non-scientist must always be present for any vote to be taken.
9. When a member and his/her alternate both attend a meeting, only one person (generally the individual who performed the pre-review of protocols for that review cycle), may vote.
10. Voting by proxy is not permitted.
11. If the quorum fails during a meeting, such as due to lack of a majority of IRB members being present or an absence of a nonscientist member, the IRB cannot take any further actions or vote until the quorum is restored.
12. The IRB Manager is responsible for monitoring the members present at a convened IRB meeting to ensure that at the beginning of the meeting and for each subsequent vote the meeting is appropriately convened.
Additional quorum requirements:
1. When the IRB reviews research that involves participants vulnerable to coercion or undue influence, at least one member must be present who is knowledgeable about or experienced in working with these participants.
2. When the IRB reviews research that involves prisoners, a majority must have no association with the prison involved, apart from their membership on the IRB.
3. When the IRB reviews research that involves prisoners, at least one voting member at the IRB meeting must be a prisoner or a prisoner representative with appropriate background and experience to serve in that capacity.
4. When the IRB reviews VA research at least one of the VA members of the IRB must be present during the review of VA research.
5. When the IRB reviews VA research that involves an FDA-regulated article a licensed physician must be present.
6. When the IRB reviews VA research that involves mentally disabled persons or persons with impaired decision-making capacity, an IRB member who is an expert in the area of the research must be present.
6.6 Regular IRB Meeting with Timely Prior Review
The IRBs meet regularly and members have sufficient time to review materials prior to meeting. (AAHRPP Element II.1.F) Five of the Medical IRBs meet each month on a regular schedule and one meets on an ad hoc basis:
· IRB 1 meets the first Tuesday of the month.
· IRB 3 meets the second Tuesday of the month.
· IRB 4 meets the fourth Tuesday of the month.
· IRB 5 meets the third Tuesday of the month.
· IRB 6, which reviews Expedited and Exempt protocols and minor revisions, meets on an ad hoc basis as needed.
· IRB 7 meets the third Wednesday of the month.
The Nonmedical IRB (IRB 2) meets the last Friday of every month except August, when there is no scheduled meeting.
Individual meetings may be rescheduled, or additional meetings may be held, as needed by agreement of the IRB Chair and the RCO Director. Permanent changes to the meeting schedule may be made by agreement of a majority of IRB members, the IRB Chair, and the RCO Director.
The deadline for receipt of research proposals to the IRBs is the first working day of the month preceding an IRB meeting. For example, the deadline for the March meeting is February first. However, if there is room on the agenda of an upcoming IRB meeting, and sufficient time (generally, a minimum of 72 hours) for review of all relevant materials by the IRB members, research protocols can be placed on an earlier agenda, but only where determined necessary by the IRB Chair (e.g. to prevent serious harm to a specific or prospective patient-participant.)
Review preparation time
The RCO assigns one or more staff members to deliver protocol materials to the IRB members in sufficient time for them to be reviewed before the meeting. The timeframe for receipt by IRB members of the agenda and protocol materials for research to be reviewed or presented at an upcoming meeting is approximately five business days prior to the meeting. Such materials may be presented to IRB members less than 72 hours prior to a meeting only where determined necessary by the IRB Chair (e.g. to prevent serious harm to a specific or prospective patient-participant.)
The standard for members participating by audio or video conferencing is the same for those attending in person, giving all members the opportunity to participate fully in the IRB’s deliberations.