6.1            Scope of IRB Authority

Section revised: 8/10/2015  

The IRB derives its authority from both federal regulatory and institutional sources.  Institutional authority is conveyed by the Vice Provost and Dean of Research through approval of this chapter and other chapters of the HRPP Policy Manual. Additionally, the Vice Provost and Dean of Research issues a direct, written delegation of authority under an institutional Charge to IRB members upon their appointment to the IRB (see Charge to IRB members (medical and nonmedical).  The Vice Provost and Dean of Research in turn has the authority delegated to him or her from the President of Stanford University (President).  On a day-to-day basis, the IRB reports to the Vice Provost and Dean of Research, through the RCO Director.  However, the IRB Chair, an IRB member, or the convened IRB may refer a matter directly to the President on those extraordinary occasions when it may be deemed warranted.

The IRB has the statutory and institutional authority to take any action necessary to protect the rights and welfare of human research participants involved in research.  For example, the IRB assesses suspected or alleged protocol deviations, participant complaints, or violations of external regulations or STANFORD policies.  The IRB has the authority to suspend or terminate the enrolment or ongoing involvement of research participants in research as it determines necessary for the protection of those participants.  The IRB also has 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 IRB shall review and comment on proposed external regulations dealing with human research.  When appropriate, the IRB will formulate draft policies and procedures for approval by the appropriate STANFORD bodies and promulgation by the Vice Provost and Dean of Research.

Decisions of the IRB 

IRB approval is always necessary before a research project involving research participants may begin. An IRB decision to not approve a human research project, or require modifications as a condition for approval, cannot be overturned by any STANFORD official or STANFORD committee.

The IRB must provide the investigator with a written statement of the reasons for not approving proposed research and must give the investigator an opportunity to respond in person or in writing.  The IRB must carefully and fairly evaluate the investigatorŐs response in reaching a final determination. 

If an investigator has concerns with respect to procedures or decisions of the IRB, the investigator may discuss his/her concerns with the Vice Provost and Dean of Research with the understanding that neither the Vice Provost and Dean of Research, the Provost, nor any other STANFORD official or committee may approve a protocol that has not been approved by the decision of one of the Panels, nor apply undue pressure on the Panel to reverse a decision.  

At the time an investigator seeks to discuss his or her concerns with the Vice Provost and Dean of Research, those concern(s) must be in writing, and the Vice Provost and Dean of Research will use his or her sole discretion to determine the process for responding to the concern, included but not limited to:

á      Notifying the IRB of the concern and requesting a response and relevant information from its records

á      Appointing a fact-finder to review the matter and report back to the Vice Provost and Dean of Research

á      Seeking assistance from consultants or internal administrative units such as the Office of Audit, Compliance and Privacy or Office of the General Counsel.

However, all such reviews are subject to the fundamental principle that no one at Stanford can approve a human subjects protocol that has not been approved by an IRB Panel, nor apply pressure on the Panel to reverse a decision.  Thus, all policies clearly state that no other review or person at Stanford can overturn the decision of an IRB Panel.

Reporting Obligations within STANFORD

The IRB is administered by the RCO and reports to the Office of the Vice Provost and Dean of Research.  The Vice Provost and Dean of Research is the institutional official responsible for assuring compliance with STANFORD policies and external regulations on the use of human research participants, and is the head of the STANFORD HRPP. IRB Chairs prepare annual reports to the Vice Provost and Dean of Research, summarizing the nature and volume of the IRB activities and resources needed for the new academic year.   

Responsibilities to Regulatory Agencies      

The IRB 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. 

6.2            Relationships between the IRB and Others

Section revised: 12/7/2015  

The IRB is required at times to participate with other programs or research compliance committees at STANFORD that also have responsibility for the ethical oversight of research within the HRPP.  In some cases, the approval of another STANFORD body may be required prior to or in addition to IRB review.  Such cases include:

Radiological Safety:  If a study involves any radioisotopes or radiation-producing machines, The Radiation Safety Committee must certify that it has reviewed a protocol using radioisotopes or radiation machines and recommends it for approval. Without this approval, a study which employs these modalities will either be tabled to a future convened meeting, or will be approved contingent on Radiation Safety Committee recommendation for approval.  If a modification involves review by Radiation Safety, the IRB will hold its approval until Radiation Safety forwards its approval to the IRB.  Radiation Safety is given access to the protocol information by the IRB. 

Protocols involving biosafety materials and requiring review by the Biosafety Panel must be reviewed by this Panel and receive an approval letter in addition to review by the IRB.  A new protocol generally will not be presented at an IRB convened meeting until the Biosafety Panel has approved it.  If a modification or continuing review involves review by Biosafety, the IRB will hold its approval until Biosafety forwards its approval to the IRB.  The HRPP Associate Director, and the Senior IRB Manager are ex-officio members of the Biosafety Panel.  A senior member of the IRB staff attends the Biosafety Panel meetings and receives communications directly from the Panel regarding submitted protocols.  The Biosafety Officer and Biosafety Specialist (from the Environmental Health & Safety department) are ex officio members of the medical IRBs and IRB/SCRO and attend medical IRB and IRB/SCRO Panel meetings.

Investigator Conflict of Interest disclosures:  All investigator conflicting interest is managed via the Conflict of Interest Review Program (COIRP) and its associated Conflict of Interest Committee (COIC).  The IRB will not approve a protocol until any disclosed COI has been reviewed and resolved by the COIRP/COIC, and as appropriate, a plan or strategy to adequately eliminate, mitigate, or manage the conflict has been determined by the COIRP/COIC.  See Chapters 3.7, 6.3, and 14.1.

Clinical and Translational Research Unit (CTRU):  Depending upon the nature of the research, for any human research supported by the CTRU, in addition to IRB approval, CTRU approval must be obtained prior to enrolling participants in the study.   

The Stanford Cancer Institute:  Protocol review by the Stanford Cancer CenterŐs Scientific Review Committee (SRC) is conducted in parallel with IRB review.  Both IRB and SRC approvals are required to conduct research supported by the Stanford Cancer Institute.

The Veterans Affairs Research and Development (R&D) Committee:  Human research involving facilities or personnel of the Department of Veterans Affairs Palo Alto Health Care System (VAPAHCS) must be approved by the IRB prior to being placed on the agenda of the VAPAHCS R&D Committee for review and approval (VA Memorandum 151-15-11).

Stem Cell Research Oversight:  Any human research involving human stem cells must be reviewed by the Stem Cell Research Oversight Panel (SCRO) as well as the IRB.

See RPH 5.8 Human Stem Cell Research.

 

Relationships with Industry Sponsors and Other IND or IDE Holders 

Unless specifically required by the FDA or requested by the sponsor, the IRB 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 generally serve as the link between the IRB and the sponsor, and are required to do so by the FDA in compliance with their obligations as clinical investigators.  This relationship 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 IRB when the IRB Chair or the RCO Director considers it desirable.  The clinical investigator will be kept apprised of such communication.

The FDA indicates that direct communication between the sponsor and the IRB may be appropriate when the IRB does not accept a sponsorŐs Nonsignificant Risk (NSR) designation of a medical device (21 CFR 812.66).  Direct communication between the sponsor and the IRB is required for the waiver of informed consent in planned emergency research 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).

See Chapter 5.11.

6.3            IRB Composition and Membership

Section revised: 6/03/2016  

The IRB has qualified leadership (e.g., chair and vice chair) and qualified members and staff. Membership and composition of the IRB are periodically reviewed and adjusted as appropriate. (AAHRPP Element II.1.B)

Each IRB has a qualified Chair, members and staff whose membership and composition is reviewed and adjusted annually by the RCO Director and the Vice Provost and Dean of Research.  This review ensures that individual IRB Chairs and members have the knowledge, skills and abilities appropriate to their respective roles and perform their responsibilities in an acceptable manner.

Stanford policy requires that the IRB be constructed according to DHHS regulations and FDA regulations (45 CFR 46.107 and 21 CFR 56.107). Additionally,

á      The IRB shall include a nonscientific IRB member, educated and with experience in unambiguously nonscientific areas, (see Checklist for Determining if IRB Members are Nonscientists.)  These individuals may not have meaningful scientific or medical training or experience.  Health professionals, regardless of discipline, may not be considered nonscientists.  At least one nonscientist IRB member must always be present to have a quorum. (See discussion of quorum in Chapter 6.8.)

á      The IRB shall include student(s), when nominated by the ASSU Committee on Nominations, who are either upperclassmen or preferably graduate students with previous human research experience.

Furthermore, in compliance with national VA research standards, (VHA Handbook 1200.05), the IRB must satisfy the following requirements:

á      Each IRB reviewing VA research shall include two or more VA employees as voting members.

á      At least one of the VA representatives shall have scientific expertise.

á      The VA representatives shall serve as full members of the IRB and review non-VA research matters coming before the IRB.

á      At least one of the VA representatives on the IRB shall be present during the review of VA research.

á      VA representatives to the IRB shall be appointed by the VA Medical Center Director.

á      A licensed physician shall be included in the quorum in the review of research involving an FDA-regulated article.

á      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.

á      When VA research involves persons with impaired decision-making capacity, the IRB membership shall include at least one member who is an expert in this area of the research.

Appointment of Members and Alternates, Length of Service, and Duties

IRB members are nominated from a variety of sources, including previous IRB members, division chiefs, department chairs, compliance administrators, faculty, hospital pharmacy and nursing staff, research laboratories, senior administrative IRB staff, Associated Students of Stanford University (ASSU), and various public groups.  Consideration is given to balancing 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, LPCH, SHC) helps ensure that the local research context is brought to IRB deliberations.  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 IRB year) newly identified nominees are contacted by the HRPP Associate Director (or delegate) about their willingness to voluntarily serve on the IRB and their availability for the coming year.  When a nominee agrees to serve on the IRB, his or her CV and any relevant correspondence are reviewed by the RCO Director and Vice Provost and Dean of Research. 

STANFORD has and follows written policies and procedures to separate competing business interests from ethics review functions. (AAHRPP Element II.1.C)

To avoid any possible conflicting interests or influence on IRB determinations due to competing business interests, individuals who are responsible for development activities (including raising funds), or are in a position to influence programmatic and budgetary decisions may not serve as IRB Members. See Chapter 6.6.1.

After an extensive review of a potential memberŐs education, experience and other characteristics that might add diversity to the IRB, a new IRB member is formally appointed by the Vice Provost and Dean of Research.  Members serve one-year renewable terms (from October 1 to September 30). Members who are VA representatives are appointed by the VA facility Director (the IO) for a period of up to 3 years. They may be re-appointed to new terms of up to 3 years without a lapse in service at the end of each term.   At the conclusion of the IRB year (and interim, if needed), membersŐ contributions are evaluated by the IRB Chair with the IRB manager (See Chapter 4). If their service is satisfactory, and continued membership is mutually desired, they are eligible for reappointment.  All members may be re-appointed at the end of their terms without lapse in service.  An IRB member may be removed at the discretion of the Vice Provost and Dean of Research in consultation with the Chair of the Panel and the Director of RCO.

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 subcommittees, audits, and education, as long as there is no conflict of interest with their IRB responsibilities or their other personal or professional roles.

Qualification to Perform Expedited Review

An IRB member may perform protocol review according to the expedited procedure when the IRB Chair, in consultation with the IRB manager and IRB Training Specialist, determines that the member is "experienced" with regard to this purpose. There are several ways a member may achieve sufficient experience, including attendance at IRB meetings, targeted education, working with a mentor, independent study, and previous IRB service.  See Chapter 7 for more information.

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 Vice Provost and Dean of Research. Chairs serve one-year renewable terms (from October 1 to September 30).  At the conclusion of the IRB year (and interim, if needed) the IRB ChairsŐ contributions are evaluated by the Vice Provost and Dean of Research with the RCO Director (See Chapter 4).  If their service is satisfactory, and their continued service is mutually desired, they are eligible for reappointment.  An IRB Chair may be removed at the discretion of the Vice Provost and Dean of Research in consultation with the Director of RCO.

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 the time dedicated to IRB duties. IRB members generally do not receive monetary compensation for their service on the IRB.  However, it is recognized that service on the IRB requires a significant investment of time for all members. 

IRB members who are not otherwise affiliated with STANFORD or its collaborating institutions are compensated for their service by the issuance of an honorarium.  As stated in OHRP guidance, compensating unaffiliated members in this way does not create an affiliation or cause a conflict of interest.

Alternate IRB Members

Alternates replace regular IRB members who are unable to attend convened meetings of the IRB.  They are required to have the same qualifications and characteristics of expertise and diversity as the regular IRB members for whom they substitute.  When an alternate substitutes for a regular member, the IRB staff provides the alternate member the same material that the regular member received or would have received.

IRB membership rosters specify which regular member each alternate member is qualified to replace.  The expertise or qualifications of alternate members are similar to those of the regular member they replace, and in some case, alternate members are able to represent similar interests or a specific vulnerable population.  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.

If an alternate member attends a convened meeting at which his or her regular member is in attendance, one of them does not vote.  Ad hoc substitutions for regular or alternate IRB members are not permitted.

Ex Officio IRB Members 

An ex officio member is designated as an IRB member by virtue of that individualŐs office. For example, if the chair of the Administrative Panel on Radiological Safety changes hands, that ex officio IRB membership changes hands accordingly and does not remain with the individual who has left that office. Some ex officio members serve on other STANFORD compliance panels and may provide expertise to IRB members. Ex officio members may participate in the IRB deliberations to provide information and expertise as requested by the IRB.  Ex officio members are expected to adhere to the same conflict of interest standards and documentation requirements as regular IRB members and alternates.  Ex officio members may not vote on any IRB action or determination, and for this reason are sometimes referred to as Ňnon-votingÓ members.

The medical IRBs accept permanent ex officio representatives from the following areas:

á      Office of the Vice Provost and Dean of Research

á      Office of the General Counsel

á      Biosafety Panel

á      Radiological Safety Panel

á      Research Management Group

á      VAPAHCS Research and Development Office

á      Palo Alto Veterans Institute for Research (PAVIR)

á      Institutional Animal Care and Use Committee (IACUC/APLAC)

The nonmedical IRB accepts permanent ex officio representatives from the following areas:

á      Office of the Vice Provost and Dean of Research

á      Office of the General Counsel

The IRB may accept additional permanent ex officio members with the agreement of the IRB Chair and the RCO Director.

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.  The Stanford University 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, dedicated to supporting the IRB in its mission to protect human participants in research. The IRB staff teams are reviewed at least annually by the RCO Director and the Vice Provost and Dean of Research to ensure they continue to provide sufficient resources to the IRB.  The IRB staff has knowledge, skills and abilities appropriate to their respective roles.  The RCO Director oversees the RCO Deputy Director and the HRPP Associate Director, and is responsible for the overall management of the RCO. See the RCO Organization Chart

For policies on qualifications, education and periodic evaluation of RCO staff, see Chapter 4.

6.4            Scientific and Scholarly Expertise of IRB Members

Section revised: 3/13/13  

Wide-ranging scientific or scholarly expertise among IRB members allows the IRB to review the broad variety of research in which STANFORD investigators are engaged.  These policies and procedures require IRB members to be knowledgeable about all relevant regulatory requirements, and to strive to remain impartial and objective during protocol review, deliberation and voting.  The IRB includes several members who are particularly knowledgeable about research ethics and the vulnerable research participants included in STANFORD research.    

The IRB uses a Ňprimary reviewerÓ system.  The IRB manager, in consultation with the IRB Chair where appropriate, assigns protocols to primary reviewers, based on each individualŐs 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 or IRB staff 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 below).

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, adults unable to consent, students, etc.).  The IRB staff reviews each application to determine whether it involves participants vulnerable to coercion or undue influence, and considers the participant population when assigning reviewers.

The IRB is constituted to possess and make use of collective 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 participantsŐ perspectives. 

6.5            Obtaining Additional Expertise

Section revised: 6/03/2016  

The IRB Chair or IRB staff reviews the proposed convened meeting agenda and determines whether the IRB has the required expertise to review upcoming research.  If not:

á      The IRB Manager, in consultation with the IRB Chair, will invite individuals with competence in the specific areas needed to assist in evaluating issues that require expertise beyond or in addition to that available on the IRB.  

á      On an as-needed basis, an IRB primary reviewer may invite individuals with competence in special areas to assist in evaluating specific issues.

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; the desire to ensure appropriate consideration of race, gender, language, cultural background, and sensitivity to such issues as community attitudes.

Additional expertise may be obtained through a member of another IRB, or individuals from various Schools and Departments within Stanford University, such as:

á      Medicine, Education, Business, and Law

á      Office of Research Administration

á      Stanford Center for Biomedical Ethics

á      Stanford Center for Clinical and Translational Research and Education (Spectrum)

á      Various specialty Clinical Departments at the affiliated institutions

á      Stanford Cancer Institute

or from:

á      VA Palo Alto Health Care System (VAPAHCS), including the VAPAHCS Research and Development Office

á      Experts from other institutions

á      Representatives of the community

á      Representatives of specific subject populations

The IRB Manager or the IRB Chair makes initial contact with a proposed consultant and notifies the consultant of the IRB member conflict of interest policy (See Chapter 6.6). When a consultant is used, that fact and the pertinent information gained from the consultantŐs assessment is documented at the time of the protocol discussion, and recorded in the IRB minutes.  In some cases, a consultant may provide the IRB with a written report of his or her assessment which is kept with the protocol file.  The IRB staff can assist in making the consultation arrangements and in obtaining the required conflict of interest documentation.

All consultants, internal or external to Stanford University, must comply with the IRB conflict of interest policy. They are not considered ad hoc IRB members, and cannot vote with the IRB.

The Guidance for Obtaining Additional Expertise or an Expert Consultant addresses the use of consultants in further detail.

6.6            IRB Member, IRB Staff, and Consultant Conflicting Interest

Section revised: 3/13/13  

The IRB has and follows written policies and procedures so that members and consultants do not participate in the review of research protocols or plans in which they have a conflict of interest, except to provide information requested by the IRB. (AAHRPP Element II.1.D)

See 45 CFR 46.107(e); 21 CFR 56.107(e).

Guidelines for IRB Members on Conflicting Interest includes definitions of conflicting interest and outlines procedures for recusal. This policy applies:

á      When protocols and reports are first received by members assigned to review

á      During discussion and voting in convened meetings

á      When consultants are asked to advise the IRB

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. This policy also applies to reviews of non-compliance reports and unanticipated problems involving risks to participants or others.

IRB Intake procedures take into account conflicts of interest when assigning new protocols to an IRB, such as when any IRB member is named in the research protocol or has a spousal relationship with any research personnel.

IRB MemberŐs Disclosure of a Conflicting Interest

IRB members who realize they have a conflicting interest when they are first assigned a protocol or report for review must notify the IRB staff or IRB Chair immediately so that the protocol can be reassigned.

IRB members review the draft Agenda List before a convened meeting with the issue of conflicts in mind. Any conflicting interest for protocols to be voted on must be reported to the IRB Chair or RCO Director before the meeting whenever possible. 

The IRB Chair begins 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 him or herself from the discussion of and vote on the project by leaving the room, except if the member is providing information at the IRBŐs request.  If an IRB member realizes at a meeting that he or 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.

ConsultantŐs Disclosure of a Conflicting Interest

The definition of conflicting interest as defined in the Guidelines for IRB Members on Conflicting Interest extends to any consultant who may be asked to review a protocol.  The IRB Manager who contacts a consultant to enquire 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.  If no COI is declared, the consultant is asked to complete a Consultant Conflict of Interest Declaration for inclusion with the minutes of the meeting.

If a consultant with a conflicting interest is the only appropriate resource for the IRB, (e.g., is the only scientist with sufficient technical understanding of the project) and if that consultant has been asked to provide information to the IRB, then the conflict of interest must be disclosed to the IRB members reviewing the protocol or present in the convened meeting where the information is presented.  Such a consultant is excluded from discussion except to provide information requested by the IRB, and must leave the meeting room during discussion and voting.

IRB Staff and Conflicting Interest

IRB Staff must not participate in the review of research protocols, and must not make exempt determinations for research protocols in which they have a conflict of interest. IRB staff who realize they have a conflicting interest when they are first assigned a protocol or report for review must notify their supervisor immediately so that the protocol can be reassigned.

The Stanford Staff Policy on Conflict of Commitment and Interest (Administrative Guide Memo 1.5.2) is distributed annually to IRB Staff who are involved in protocol review.

6.6.1  Separating Competing Business Interests from Ethics Review Functions

Section revised: 3/13/13  

STANFORD has and follows written policies and procedures to separate competing business interests from ethics review functions. (AAHRPP Element II.1.C)

STANFORD recognizes that officials who administer research programs, and individuals who are responsible for development activities (including raising funds), may represent competing business interests, or 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 Vice Provost and 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.

Research Policy Handbook RPH 4.7 Institutional Conflict of Interest in Research Involving Human Subjects describes principles and procedures designed to ensure that research involving human subjects at Stanford University is conducted without untoward influence resulting from either the University's financial investments or holdings or the personal financial interests or holdings of key institutional leaders (which  can include the President, the Provost, the Vice Provost and Dean of Research, School Deans, Senior Associate Deans, Department Chairs, Division Chiefs, and Institute and Center Directors.) 

As stated in RPH 4.7 Institutional Conflict of Interest in Research Involving Human Subjects, Department chairs are required to review and sign off on all research proposals being submitted by faculty in their departments, divisions or institutes, including those involving human subjects research.  This review occurs when the proposal is submitted for funding to an extramural sponsor (as part of the electronic submission of the Proposal Development & Routing Form, PDRF) or in meeting their obligation to provide scientific evaluation when internal funds are used to support a human subjects research project.  In carrying out these duties, the chair must identify any personal financial conflict of interest, regardless of value, that he or she has in the research sponsor or in an entity that owns or controls the investigational product that is the subject of the research.

Thus, the institutional leaders, as described above, do not:

á      Serve as members on the IRB.

á      Carry out day-to-day operations of the review process except as noted above.

As stated in the charges to the IRBs, ŇÉneither the Vice Provost and Dean of Research, nor the Provost, nor any other STANFORD official or committee may approve a protocol that has not been approved by the decision of one of the Panels, nor apply undue pressure on the Panel to reverse a decision (as further provided in Chapter 3 of the HRPP Policy Manual).Ó  See:

á      Charge to the Administrative Panels on Human Subjects in Medical Research

á      Charge to the Administrative Panel on Human Subjects in Non-Medical Research

á      Charge to the Administrative Panel on Human Subjects in Medical Research (IRB/SCRO).

6.7            Assessment and Evaluation of the IRB

Section revised: 3/13/13  

The IRB has qualified leadership (e.g., chair and vice chair) and qualified members and staff. Membership and composition of the IRB are periodically reviewed and adjusted as appropriate. (AAHRPP Element II.1.B)

The composition and membership of each IRB is evaluated annually by the RCO Director and the Vice Provost and 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; knowledge of community standards and attitudes; scientific, scholarly, clinical, and professional expertise; racial, ethnic, and cultural diversity; and representation of participantsŐ 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.

Education, training and periodic evaluation of IRB members, IRB Chairs, and IRB staff is discussed in Chapter 4.

6.8            IRB Roster and Quorum Requirements

Section revised: 12/7/2015  

The IRB membership permits appropriate representation at the meeting for the types of research under review, and this is reflected on the IRB roster. The IRB has one or more unaffiliated members; one or more members who represent the general perspective of participants; one or more members who do not have scientific expertise; one or more members who have scientific or scholarly expertise; and, when the IRB regularly reviews research that involves vulnerable participants, one or more members who are knowledgeable about or experienced in working with such participants. (AAHRPP Element II.1.A)

The IRB has and follows written policies and procedures requiring research protocols or plans to be reviewed by individuals with appropriate scientific or scholarly expertise and other expertise or knowledge as required to review the research protocol or plan.

 (AAHRPP Element II.1.E)

IRB Rosters are constituted to meet the requirements of 45 CFR 46.107 and 108; 21 CFR 56.107 and 108.  In addition, membership of those IRBs which review VA research includes two VA employees as voting members, (at least one of whom has scientific expertise), and comply with the requirements of 38 CFR 16.103(b),108(b) and VHA Handbook 1200.05 (Sections 3,5, and 7).

An IRB Member database is maintained by the RCO and used as the data source for all IRB membership roster needs.  The IRB Member database includes all information required under FDA and DHHS regulations and OHRP guidance (45 CFR 46.107 and 108; 21 CFR 56.107 and 108) including:

á      Names of members

á      Names of alternate members (and regular members for whom they substitute )

á      Gender

á      Earned degrees

á      Scientific status

á      Representative capacity

á      Affiliation

Representative capacity is presented in enough detail to indicate which appropriate participants can be represented by each member (e.g., children, pregnant women, prisoners). When research protocols include vulnerable participants, a member who is knowledgeable about that population, or who has experience working with similar participants, should be assigned to the protocol review.

Scientific status, (including the designation of ŇnonscientistÓ – see Chapter 6.3), is determined during recruitment and annually upon evaluation of IRB members.  Scientific status and area of scientific expertise (e.g., pediatrician, radiologist, psychologist, anthropologist, pharmacist) are presented in sufficient detail to allow appropriate protocol assignment and in-depth protocol review.

Affiliation is determined during recruitment and annually upon evaluation of IRB members.  An IRB member is considered affiliated if he or she, or any member of his or her immediate family, has any employment or other relationship (e.g., current employee, consultant, Board of Directors, current volunteer, trainee or student) with any of the STANFORD affiliated entities:

á      Stanford University

á      Stanford Hospital and Clinics (SHC)

á      Lucile Packard ChildrenŐs Hospital (LPCH)

á      Veterans Affairs Palo Alto Health Care System (VAPAHCS)

á      Palo Alto Veterans Institute for Research (PAVIR)

The role of unaffiliated members is to represent the general perspective of participants; the Checklist for Determining if IRB Members are Unaffiliated [CHK-12] is used to determine if members meet the criteria for serving as unaffiliated.

Changes in IRB membership require reporting to OHRP.  The HRPP Associate Director (or delegate) submits a revised IRB membership list to OHRP whenever membership changes occur, but at a minimum once a year and whenever a new IRB is formed.

VA Requirements: The HRPP must maintain accurate membership rosters for their designated IRB(s) of Record and submit the roster(s) to ORO whenever membership changes occur, but at a minimum once a year or whenever a new IRB is formed (as required by VHA Handbook 1058.03).

The IRB has positions available for student members, filled when nominated by the ASSU. Student members represent the perspective of participants in much nonmedical research.  Senior IRB administrative staff may also be appointed as nonscientist alternate members of the IRBs.

Quorum Requirements and Voting at IRB Meetings

The IRB has and follows written policies and procedures for conducting meetings by the convened IRB. (AAHRPP Element II.2.C)

The IRB Chair is a voting member of the IRB. The Chair determines that quorum is established and maintained, chairs the meeting discussions, and calls for votes as appropriate.

Maintenance of quorum and voting at convened meetings is 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.

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 IRB deliberations.

3.     IRB minutes shall include documentation of quorum and votes for each IRB action and determination by recording votes as follows:

á      Total number voting

á      Number for

á      Number opposed

á      Number abstaining

á      Names of those abstaining

á      Names of those recusing.

Votes are indicated by voice vote or show of hands.

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 nonscientist must always be present for any vote to be taken.

9.     Regular attendance of unaffiliated members is strongly encouraged. Individual members of the IRB may satisfy more than one required type of member (i.e. a nonscientific member may also be the unaffiliated member).

10.  When a member and their alternate both attend a meeting, either person (but not both) may vote on each protocol.

Generally if one of these individuals was the primary reviewer of a given protocol for that review cycle, that person votes on the protocol at the convened meeting.

11.  Voting by proxy is not permitted.

12.  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.

13.  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.

14.  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.

15.  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.

16.  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.

17.  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.

18.  When the IRB reviews VA research that involves an FDA-regulated article a licensed physician must be present.

See Chapter 8.3 for information about convened meeting minutes.

 

 

6.9            Meeting Times and Materials

Section revised: 10/27/2015  

The IRB has and follows written policies and procedures for conducting meetings by the convened IRB. (AAHRPP Element II.2.C)

Each IRB meets each month according to a regular schedule.  Some IRB members, who review protocols according to the expedited review procedure and confirm exemptions meet on an ad hoc basis as needed.

Individual meetings may be rescheduled, or additional meetings may be held, as needed by agreement of 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, as deemed necessary by the IRB Chair or IRB staff.

Protocol materials are available online, via the web-based ŇeProtocolÓ system:  all IRB Members in attendance at a convened meeting are provided individual laptop computers to access eProtocol, and pertinent material is also projected.  A hardcopy set of the most commonly referenced guidances is provided for each IRB member.

Review and Preparation Time

Protocol Materials

The RCO staff assigns protocols in sufficient time for them to be reviewed before the meeting, generally two to four weeks, but not later than 72 hours before an upcoming meeting.  Assignment is done via the eProtocol system; this immediately makes available all necessary protocol materials to the primary reviewers.  All other IRB members are granted view access to the presented protocol materials, generally 5-7 days prior to the convened meeting. 

Materials necessary for review may be presented to IRB members less than 72 hours prior to a meeting only where determined necessary by the IRB Chair or HRPP Associate Director.

For protocol materials provided to members, see Chapter 7.5 and 7.7.

Meeting Documents

Approximately five days prior to the IRB convened meeting, all members receive the:

á      Agenda List for the coming meeting, typically containing:

-        a statement on confidentiality of meetings,

-        conflict of interest statement(s),

-        vote on previous meeting minutes,

-        education and information items (including reports to be discussed)

á      Minutes from the previous meeting.

á      The Agenda, distributed at the beginning of the convened meeting, details:

á      Protocols which will be presented at the meeting,

á      Protocols (new, minor modifications, or continuing reviews) which, since the previous convened meeting for this IRB, have been reviewed by the expedited process and recommended for approval, and do not need to be presented at a convened meeting.

á      Other items (such as findings on Reports which have not required presentation at the convened meeting).