The IRB has and follows written policies and procedures to conduct reviews by the convened IRB: (AAHRPP Element II.2.D)

  Element II.2.D.1. – Initial review

  Element II.2.D.2. – Continuing review

  Element II.2.D.3. – Review of proposed modifications to previously approved research

The IRB has and follows written policies and procedures to conduct reviews by an expedited procedure, if such procedure is used. (AAHRPP Element II.2.E)

  Element II.2.E.1. – Initial review

  Element II.2.E.2. – Continuing review

  Element II.2.E.3. – Review of proposed modifications to previously approved research

7.1      Protocol Review 

Section revised: 3/13/13  

All STANFORD new human research (as defined in Chapter 1.3) and modifications to approved research (except when the modification is necessary to eliminate apparent immediate hazards to participants) must be prospectively reviewed by the IRB.  In addition, no previously approved human subject research may be continued beyond the expiration date without prospective approval (continuing review). 

7.2      IRB Protocol Applications (eProtocol System)

Section revised: 01/12/16  

Most submissions to the IRB are via an online web-based system called “eProtocol".  Forms available for online submission include:

Š      Protocol applications for:

-       New protocols   

-       Modifications

-       Continuing Review

Š      Reports (of unanticipated problems and events and information requiring prompt reporting to the IRB)

Š      Final Reports

 

Protocol applications include the following sections that must be completed by the investigators, as applicable:  personnel, study location, funding, resources, collaboration/multi-site, participant population, purpose, procedures, background, use of radiation producing machines, use of drugs (investigational and commercial) and devices (non-significant risk and significant risk), recruitment methods and screening procedures, inclusion and exclusion criteria, inclusion of vulnerable populations, potential risks and benefits, procedures to protect privacy and maintain confidentiality of data, conflict of interest, consent and assent, and HIPAA.  A “check for completeness” feature requires that each question applicable to the study is answered before submission to the IRB is permitted.

Investigators must select a protocol review type (exempt, expedited or regular) and protocol form (medical or nonmedical). For expedited review, a Chart Review application is available for studies that only involve the use of data, documents or records (e.g., medical records); this form type may only be used for reviews of materials (data, documents, records) that have been collected for research or non-research purposes, or materials that will be collected for non-research purposes. However, if a study involves interaction or intervention with participants, evaluating the safety and effectiveness of a drug or device, or obtaining or analyzing specimens, it is submitted via the expedited or regular application.

Application form questions vary depending on the review type and protocol form selected. 

Protocol Application Form

Medical Protocols:  Protocols conducted by personnel within, or conducted through, the School of Medicine (SOM), the Veterans Affairs Palo Alto Health Care System (VAPAHCS), the Palo Alto Veterans Institute for Research (PAVIR), or otherwise involving any medical procedure or use of personally identifiable health information are submitted on the medical Protocol Application. 

Nonmedical Protocols:  Protocols for research not being conducted by personnel within, or conducted through, the School of Medicine or the hospitals (e.g., protocols from the Schools of Education, Engineering, Earth Sciences, Humanities and Sciences, Law and Business) are submitted on the nonmedical Protocol Application.  

Protocol Review Types (Exempt, Expedited or Regular)

Exempt: STANFORD requires protocols qualifying for exemption from applicable federal, state and local regulations to be submitted for IRB review and confirmation.

Exempt review is performed by IRB staff or IRB members who have the knowledge and authority to confirm exemption or refer the protocol for expedited or regular review. See Chapter 3.4, 3.5.

Expedited Review:  Protocols submitted for expedited review must meet the requirements set forth in 45 CFR 46.110, i.e., the research involves no more than minimal risk and falls within the categories published in the November 9, 1998, Federal Register 63 FR 60364-60367; 63 FR 60353-60356 DHHS-FDA list of research eligible for expedited IRB review. 

Regular Review: All protocols that do not qualify for exempt or expedited review are subject to regular review at a convened IRB meeting.

Other Research or Special Situations

VA Research:  For proposed research, investigators must complete and attach Required Questions-VA Research to the new Protocol Application. This supplemental form provides, for example, information pertinent to IRB determinations on whether participant medical records should be flagged; justification for the recruitment of non-veterans for VA research, etc.

Additional Requirements – Other Federal Agencies:  Depending on the source of support for research, regulations from other agencies such as DOD, etc. might apply.  See Other Federal Agencies - Additional Requirements [GUI-42] for these special considerations and for links to checklists to help ensure that all special considerations are met. IRB Managers, during pre-review, identify these requirements and confirm that they are documented.

Protocols Using Biological Agents or Recombinant DNA Vectors:  Investigators are required to submit a Protocol Application with a copy of Appendix M. This is a combined application for studies which include human participants and the use of biological agents or recombinant DNA vectors. It is reviewed by both the IRB and the Biosafety Panel.

 

Emergency Use of a Test Article: Chapter 5.8 describes the requirements for the emergency use of an investigational drug, device, or biologic under FDA regulations at 21 CFR 56.104(c), and materials which must be submitted to the IRB. 

The submitted material is assigned to a medical IRB.  If the IRB manager or the assigned reviewer has comments they are sent to the investigator for response.  Responses are reviewed and additional comments sent if needed.  The reviewer documents his/her findings on the Exemption from IRB Review: Emergency Use of a Test Article.  At the convened meeting the IRB notes the emergency use of the test article, which is reflected in the minutes.

7.3      Submission, Preliminary Review and Assignment to IRBs – New Protocols, Modifications, Continuing Review, Reports, Final Reports

Section revised: 04/15/16  

Submission and Preliminary Review - New Protocols

Nonmedical Protocols: New nonmedical protocols are received directly by the IRB manager for the Nonmedical IRB.  Nonmedical protocols subject to regular review are assigned to IRB 2 and nonmedical protocols subject to exempt and expedited review are assigned to IRB 2 and IRB 8.  The IRB manager performs the preliminary review for protocol completeness and confirms the review and protocol type selected by the PD as appropriate for the study.  

Medical Protocols:  Upon receipt of a new medical Protocol Application, the IRB intake staff reviews the application for completeness, including ensuring all required supplemental documents and information are provided.  The IRB intake staff also performs a preliminary review to confirm the PD’s selection of the protocol review type (Exempt, Expedited, or Regular) and protocol form type (medical or nonmedical). 

For both medical and nonmedical, protocols submitted for a review type determined not appropriate are converted to the appropriate review type by RCO staff.  If the change in review type requires additional information from the PD, the protocol is returned to the PD.  If the conversion does not require additional information, the protocol is assigned to an IRB.  If the nonmedical IRB manager receives a protocol that should be reviewed by a medical IRB the protocol is assigned to a medical IRB. 

Assignment to IRBs - New Protocols

Once a new medical Protocol Application is deemed complete, the protocol is assigned to a medical IRB for review.  To avoid any potential conflicting interest, new medical protocols are not assigned to an IRB where a member of that IRB is also an investigator on the research project.  After taking into consideration any conflicting interest issues, assignment of protocols to IRBs is based on the protocol review type, the order (by date) the protocol was submitted to the IRB, and for protocols subject to regular review the order of the monthly IRB meetings:

Medical protocols subject to expedited and exempt review are generally assigned to IRBs 6 and 8.  These IRBs do not generally have convened meetings.  IRB 6 reviews only medical protocols; IRB 8 reviews both medical and nonmedical protocols.

Medical protocols subject to regular review are assigned to IRBs 1, 3, 4, 5 and 7 with assignment to the next IRB starting after the preceding IRB has reached its protocol load for that meeting.

Nonmedical protocols subject to regular, expedited or exempt review are assigned to IRB 2 and IRB 8.

Special Assignment Considerations:

Protocols involving biological agents or recombinant DNA vectors (gene transfer) are assigned to IRB 1. Protocols involving prisoners are assigned to IRBs with a prisoner representative (IRBs 1, 2, and 7).

Generally, protocols involving both human subject and stem cell research are assigned to IRB 3.

Assignment to IRBs:

Modifications;

Continuing Review (except for exempt research);

Reports (unanticipated problems, events & information requiring prompt reporting);

Final Reports

All subsequent events submitted on approved protocols are received directly by the IRB that initially reviewed and approved the protocol.  When necessary, protocols may be moved to another panel with all related reviews and event history included.

 

7.4      Assignment of protocols to IRB members

Section revised: 6/1/13  

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)

Reviewer assignments are made with the objective of matching reviewer expertise and experience with protocol subject matter.  See Chapter 6.  “Nonscientific” members assigned to review protocols are valued for the community perspective they bring to the process of ensuring the protection of research participants.  For approved protocols an attempt is made to assign any subsequent protocol events to a member who was a primary reviewer when the study was first approved.

Protocols Subject to Regular Review – New, Modifications, Continuing Review and Reports

New Protocols: The medical and nonmedical IRBs utilize a primary reviewer system for protocols subject to regular review.  New protocols are assigned by the IRB manager to a minimum of two primary reviewers, with one of the primary reviewers assigned to present the protocol at the convened meeting.  The IRB manager assigns other expert reviewers to protocols when applicable, (e.g., Radiation Safety when a project involves radiation producing machines).

If there is not at least one person on the IRB with the appropriate scientific or scholarly expertise, or other expertise or knowledge, to conduct an in-depth review of the protocol, the IRB defers to another meeting or to another IRB, or obtains consultation.

The IRB Manager, primary IRB reviewer, or IRB Chair can determine whether a consultant is needed.  The process by which this is done is described in Chapter 6.5.

Modifications: The following modifications are subject to regular review and are assigned by the IRB manager to one reviewer who reviews and presents the protocol at the convened meeting:

Major (or “Substantive”) Modifications: A major (substantive) modification is one in which there is an increase in the level of risks to participants or a greater than minor modification in any of the following:

Š      The consent form

Š      Research design or methodology

Š      The subject population enrolled in the research

Š      The qualifications of the research team

Š      The facilities available to support safe conduct of the research

Š      Any other factor which would warrant review of the proposed changes by the convened IRB. 

Substantive modifications or clarifications: These are requested by the convened IRB, and are directly relevant to required IRB determinations.

Continuing Review: For all protocols initially subject to regular review, the continuing review application undergoes regular review, unless it meets the criteria for expedited review (see below).  Those which will undergo regular review are assigned to one reviewer who reviews and presents the protocol at the convened meeting.

Reports (unanticipated problems and events and information requiring prompt reporting):  See Chapter 3.10.

IRB notification to organizational offices and officials

The IRBs notify organizational offices and officials, in writing, of their findings and action and provide a copy of the minutes to the Vice Provost and Dean of Research.  The RCO Director reviews issues addressed in the minutes with the Vice Provost and Dean of Research during regularly scheduled meetings.

Protocols Subject to Expedited Review - New, Modifications, Continuing Review and Final Reports

See OHRP guidance Categories of Research That May Be Reviewed by the

Institutional Review Board (IRB) through an Expedited Review Procedure.

 

The IRB has and follows written policies and procedures for determining the risks to prospective participants who are vulnerable to coercion or undue influence and ensuring that additional protections are provided as required by applicable laws, regulations, codes, and guidance. (AAHRPP Element II.4.A)

Additional Requirements

Depending on the type of research project, or the source of support/funding for the study or institution at which the study will be conducted (e.g., Department of Defense), other additional requirements might apply.

See Other Federal Agencies - Additional Requirements [GUI-42].

 

Expedited reviews are assigned by the IRB manager either to the Chair of the IRB or to an IRB member designated by the Chair as qualified to conduct expedited review.  See Chapter 6 for reviewer qualifications, and the Evaluation of IRB Members which is completed annually.

 

New Protocols: Protocols subject to expedited review follow a single reviewer process and are assigned by the IRB manager either to the Chair of the IRB or to a qualified IRB member.

 

Modifications (Minor): A minor modification eligible for expedited review is one in which all of the following are true in the judgment of the IRB reviewer:

1.     Any increment in risk is less than minimal risk.

2.     All additional activities or procedures would have been eligible for expedited review had they been part of the initial protocol review.

3.     Either the research is minimal risk or the proposed changes do not alter the study design.

If the modification changes the review type appropriate for the study, the IRB staff will convert the protocol to the appropriate review type.  The IRB reviewer makes the final determination of whether changes to the protocol are “major” or “minor.”

 

Continuing Review (Protocols subject to regular review initially): For a protocol initially subject to regular review, the continuing review application undergoes expedited review:

  If (expedited category 8):

Š      (i) the research is permanently closed to enrollment of new subjects; (ii) all subjects have completed all research-related interventions; and (iii) the research remains active only for long term follow-up of subjects; or

Š      No subjects have been enrolled and no additional risks have been identified; or

Š      The remaining research activities are limited to data analysis,

 or (expedited category 9):

Š      For continuing review of research, not conducted under an investigational new drug application or investigational device exemption where categories two (2) through eight (8) do not apply but the IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk and no additional risks have been identified.

Protocols subject to expedited continuing review are assigned to one reviewer and are not presented at a convened meeting.

 

Continuing Review (Protocols subject to expedited review initially): For a protocol initially subject to expedited review, the continuing review application undergoes expedited review if:

Š      It does not include any modifications, or

Š      If modifications are included, the proposed modifications would have been eligible for expedited review had they been part of the initial protocol.

Protocols subject to expedited continuing review are assigned to one reviewer and are not presented at a convened meeting.

 

Protocols Qualifying for CIRB Review:  Stanford University, Stanford Hospital and Clinics and Lucile Packard Children’s Hospital participate in the independent (pilot) model of the National Cancer Institute (NCI) Central Institutional Review Board (CIRB) Initiative.  Under this model, the Adult and Pediatric CIRBs are the IRBs of record for certain adult and pediatric national multi-center cooperative oncology group cancer treatment trials. 

Currently, Stanford provides information about local context to the CIRBs.  The CIRBs assume responsibility for initial review, continuing review, modifications to approved research, unanticipated problems and non-compliance.  Stanford’s role in this process is to oversee the local conduct of the research.  This responsibility is shared with the Cancer Clinical Trials Office (CCTO).  The IRB maintains a current list of protocols reviewed by the CIRBs and provides support and resources to the CCTO.

 

Final Reports: Final Reports are subject to expedited review and are assigned by the IRB Associate to one reviewer and are not presented at a convened meeting. 

7.5      Protocol Review Material and Information

Section revised: 7/15/2015  

Upon protocol assignment, the reviewers and IRB staff have full access to all protocol information and materials submitted. Review materials always include the Protocol Application.  Depending on the protocol event under review, the Protocol Application will be supplemented with a Modification, Continuing Review (including a status report on the progress of the research), Report or Final Report setting forth the dispositive information supporting the event.    

In addition, reviewers have access to all documents submitted in support of the Protocol Application which may include as applicable:

Š      Informed consent and assent documents

Š      Recruitment materials, including advertisements

Š      Questionnaires and surveys

Š      Information sheets/brochures or other study related materials that participants receive

Š      Supporting protocol (e.g. industry sponsor or DHHS-approved protocol)

Š      DHHS-approved informed consent document

Š      Investigator’s brochure (drugs)

Š      Device manual or report of prior investigations (devices)

Š      Relevant federal grant application

Š      All relevant reports, including multi-center trial reports (at continuing review)

Additional information may be requested to complete the review of a protocol.

7.6      Protocol Review - Pre-Review Parallel Process

Section revised: 6/03/2016  

General Process for All Protocol Events

The medical and nonmedical IRBs utilize a parallel process of pre-review, which involves an interactive review process between reviewer(s), IRB staff, and investigators.  For protocols assigned to a convened meeting, this system allows all presented protocols to be fully reviewed by the reviewer(s), so that recommended changes to the protocols have been made and questions answered when the protocol is presented and considered by the convened members for approval.

The IRB notifies investigators and the institution in writing of its decision to approve proposed research activities.

Comment and Response Cycle(s)

During the parallel review of a protocol, the IRB staff and reviewer(s) enter any comments or questions or recommended changes to the protocol or associated documents (e.g. consent forms, advertisements) stemming from their review into the eProtocol Comments/Responses page.  After reviewing and editing all comments received for consistency and duplication, the IRB staff sends the comments to the investigators.  Investigators are notified via an auto-generated email that comments have been sent on the protocol.  All comments are sent without referencing the author of the comment, thus preserving their anonymity.  Comments are sent out with a request for response within three business days.

Upon return receipt of the investigators’ responses to the comments and recommended changes to the protocol and associated documents, the IRB staff review the responses and changes for completion then forward responses to the reviewers.  Comments and changes are reviewed by the reviewer.  If additional questions remain or changes need to be made, another round of comments is generated and sent to the investigators for responses.  This process is repeated as often as necessary, until all reviewer questions have been answered and requested changes to the protocol and documents have been made. 

Protocols may be moved for review to a subsequent meeting pending receipt of additional substantive information or if the comments and response cycles are not completed prior to the convened meeting.  The IRB manager notifies the PD that the protocol was moved and why it was moved.

 

Approval Criteria

All proposed research must meet STANFORD HRPP ethical standards governing the conduct of research (e.g., acceptable risk-benefit relationship, equitable selection, informed consent, protections of privacy, maintenance of confidentiality, and protections for vulnerable populations).  The reviewers consider the approval criteria set forth in 45 CFR 46 and 21 CFR 50 in reviewing and approving a new protocol, continuing review, or review of a modification when the modification affects a criterion for approval.  The IRB confirms that proposed Protocol Application, informed consent documents, and recruitment documents are accurate and complete. 

The reviewers consider the regulations in reviewing and approving a protocol.  They are aided in their consideration by regulatory guidance provided in the form of:

Š      Criteria for IRB Approval of Research

Š      General Requirements for Informed Consent

Š      Reviewer Checklist.

 

Review of Exempt Research

See Chapter 3.5.

 

Continuing Review

Submission of a protocol for continuing review is required on all non-exempt approved protocols where research activities are ongoing, including but not limited to continuing recruitment and enrollment of participants; research tests, procedures, and other interactions and interventions; review of identifiable information; data analysis; and follow-up of previously enrolled participants.

The IRB determines whether the protocol needs verification from sources other than the researchers that no material changes had occurred since previous IRB review.

Continuing review may stop only when:

Š      The research is permanently closed to the enrollment of new participants,

Š      All participants have completed all research-related interventions, and

Š      Collection and analysis of private identifiable information has been completed.

The continuing review of protocols that also include proposed modifications to a previously approved project, including supporting documents (e.g. consent forms, advertisements, sponsor protocol) or the addition of new documents must be accompanied by the new documents or the proposed revised versions of the previously approved or submitted documents.

Modifications

No modifications may be initiated without prior approval of the IRB, except where necessary to eliminate apparent immediate hazards to participants.  Investigators are required to complete a Modification application setting forth a summary of the proposed modification and indicate the change in the risks to participants associated with the modification (e.g. increase, decrease, no change).  Modifications involving changes to previously approved or submitted documents, (e.g. consent forms, advertisements, sponsor protocol) or the addition of new documents, must be accompanied by the new documents and/or the proposed revised versions of the previously approved or submitted documents.

In the rare situation where a modification is made without prior IRB approval because it is necessary to eliminate apparent immediate hazards to subjects, the investigator must report this change to the IRB, (see guidance Events and Information that Require Prompt Reporting to the IRB).  The IRB will determine whether the change was consistent with ensuring the participants’ continued welfare.  See Chapter 3.10.

Projects where completion is ‘premature’ (the study is ended before the originally anticipated completion point), should be submitted to the IRB as a modification for review prior to closing the study.

If significant new findings or information are submitted as part of a modification or continuing review, the IRB may require the reporting of this information to participants if the information could reasonably affect participants’ willingness to continue participation.

Final Reports

Upon completion of a research project investigators may be required to submit a Final Report notifying the IRB of the completion of the project. 

Final Reports are required for:

Š      Research that was subject to regular review and that enrolled participants,

 

Final Reports are not required for:

Š      Research subject to expedited or exempt review, or

Š      Research projects subject to regular review that never started or never enrolled participants at STANFORD. 

 

Additional Requirements: Federally-Supported Research Involving Surveys

See Other Federal Agencies - Additional Requirements [GUI-42] for other requirements, depending on the source of support/funding (e.g., Department of Defense, Department of the Navy).

 

Protocols Using Biological Agents or Recombinant DNA Vectors

The review processes described above for protocols subject to regular review are used for protocols using biological agents or recombinant DNA vectors, except for the following:

1.     Protocols using recombinant DNA vectors must first be submitted to the DHHS National Institutes of Health (NIH) Recombinant DNA Advisory Committee (RAC).  The RAC determines whether the protocol requires an in-depth review and public RAC discussion prior to submission to the Institutional Biosafety Committee (IBC) and Institutional Review Board (IRB).

2.     The protocols must be approved by the Biosafety Panel (IBC).  IRB approval is contingent on approval by the Biosafety Panel. (To prevent a protocol from expiring if it has missed the Biosafety Panel Meeting, the IRB may approve the continuation of the protocol at a convened IRB meeting pending Biosafety Panel approval.  No new research participants may be enrolled until Biosafety completes its continuing review.)

Protocols Using Radioactive Drugs

Protocols using radioactive drugs such as tracer or imaging compounds are reviewed by the local FDA-approved Radioactive Drug Research Committee (RDRC).  The determination of the RDRC is transmitted to the IRB through Radiation Safety reviewers.  The RDRC can only approve research with radioactive drugs in accordance with the regulations (21 CFR 361). The RDRC may recommend that a investigator obtain an IND from the FDA if the RDRC determines that it is outside its purview.

Range of Action for Decisions on Protocols Subject to Expedited Review

The reviewer(s) of protocols subject to expedited review act on behalf of the IRB and have the authority to approve, require modifications (to secure approval) or request full committee review of the protocols. The reviewers consider the approval criteria set forth in 45 CFR 46.111 and 21 CFR 56.111 in reviewing a protocol.  The IRB confirms that proposed Protocol Application Form, informed consent documents and recruitment documents are accurate and complete.  The possible decisions are:

1.     Approved with no changes: (or no additional changes).  After the reviewer(s) approve, the protocol is entered on a list that is circulated to all IRB members before the next meeting for the IRB and again at the convened meeting.  (Note IRBs 6 and 8 only review protocols subject to expedited and exempt review and do not have regularly scheduled meetings. The list of protocols is circulated to all members of the IRB.) 

2.     Modifications are required to secure approval:  The IRB Manager informs the PD in writing of any reviewer modifications, comments, questions, or concerns about the protocol and requests a reply within a specified time; the research may not proceed until the reviewer has reviewed and approved the answers.

3.     Moved to Regular Review:  The protocol raises questions that warrant regular review, PD does not agree to the modifications required for approval or if for research involving children, the children’s finding is that the research presents greater than minimal risk (greater than 45 CFR §46.404 (OHRP) or 21 CFR §50.51 (FDA)), the reviewer will request that the protocol be presented for regular review at the next convened IRB meeting. 

4.     Decision to not approve: A single IRB reviewer cannot reject or not approve a protocol; thus a reviewer using the expedited procedure may not disapprove research. A protocol can only be not approved (rejected) by a vote at a convened IRB meeting.

 

Protocols subject to regular review are presented and voted on at a convened IRB meeting with a quorum of reviewers present. 

7.7      Protocols Presented at a Convened Meeting

Section revised: 3/13/13  

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

Quorum

A quorum for IRB 1 and IRB 3 is six or more voting members, including a member whose primary concern is in a nonscientific area.  For all other IRBs, a quorum is five or more voting members, including a member whose primary concern is in a nonscientific area.  When the agenda for a specific meeting includes a protocol enrolling prisoners the prisoner representative must attend [and vote] on the prisoner protocol.  Expert reviewers are not required to attend the convened meeting, although they are sometimes invited to do so, and they do not vote.

Materials Available at Convened Meetings

Prior to the convened meeting, all scheduled voting IRB members, including non-primary reviewers, are notified of electronic access to all protocols to be presented.  This electronic access enables reviewers to see the entire protocol submission, including the application and any reports (e.g. modification, continuing review, reportable event), all comments and responses, assent and consent form(s) and all other documents associated with the protocol (e.g. telephone script, questionnaires or surveys, advertisements).  Reviewers are expected to review the information sufficiently to provide comments (if any) before the meeting and during the meeting.  All materials submitted supporting a protocol are also available to voting members during the meeting. 

In addition, all members are provided the Meeting Agenda, Agenda List of Protocols for Approval (all protocols reviewed for that meeting period, including protocols approved by expedited review and protocols reviewed by exempt review), educational and informational items being presented by the IRB Training Specialist, and color-coded laminated guidance documents (e.g. orange laminated sheet Additional Protections for the Inclusion of Children in Research (OHRP) for 45 CFR 46.404, 405, 406, 407 and 408; blue laminated sheet Regulations for Waiver or Alteration of Consent Requirements for 45 CFR 46.116, 117 ).  See Human Subjects Research website Guidances page.

Meeting Deliberations

The primary reviewers are considered the lead reviewers on the IRB for protocols assigned to them.  They are responsible for:

Š      Being thoroughly versed in all details of the research,

Š      Conducting an in-depth review of the research using the IRB reviewer forms and tools as guidance.

The primary reviewer designated as the presenter presents the protocol for discussion.  All IRB members are afforded full opportunity to discuss each research protocol during the convened IRB meeting.  The reviewers consider the approval criteria set forth in 45 CFR 46 and 21 CFR 50 in reviewing a protocol.  The IRB confirms the proposed protocol application, informed consent documents, and recruitment documents are accurate and complete.  Controverted issues that have not been resolved during the review prior to the convened IRB meeting are discussed.

Procedure for Special Findings When Approving a Protocol

The reviewers and voting members consider the following information and regulations to make any special findings in reviewing and approving a protocol. They are aided in their consideration by regulatory guidance provided in the form of color-coded laminated guidance documents, including:

Frequently referenced guidances    (laminates)

Laminate
color

Criteria for IRB Approval of Research

 

General Requirements for Informed Consent

Additional Protections for the Inclusion of Children in Research (OHRP)

When the protocol involves children as participants, the IRB considers all of the regulations of 45 CFR §46.404, 45 CFR §46.405, 45 CFR §46.406, 45 CFR §46.407, 45 CFR §46.408 to make the appropriate finding(s) under which the children may be included.     Wards: When the protocol involves children who are wards of the state the IRB considers all of the regulations of 45 CFR §46.406, 45 CFR §46.407 and 45 CFR §46.409(a) to make the appropriate finding(s).

 

Additional Protections for the Inclusion of Children in Clinical Investigations (FDA)

When the protocol involves children as participants, the IRB considers all of the regulations of FDA 21 CFR §50.51, FDA 21 CFR §50.52, FDA 21 CFR §50.53, FDA 21 CFR §50.54, and FDA 21 CFR §50.55 to make the appropriate finding(s) under which the children may be included.    Wards: When the protocol involves children who are wards of the state the IRB considers all of the regulations of FDA 21 CFR §50.53, FDA 21 CFR §50.54 and FDA 21 CFR §50.56(a) to make the appropriate finding(s).

 

Guidelines for IRB Members on Conflicting Interests

 

Regulations for Waiver or Alteration of Consent Requirements

When the investigator requests waiver or alteration of informed consent in the protocol application, the rationale for the waiver or alteration is considered by the IRB as it makes any finding of waiver or alteration of informed consent as required by 45 CFR §46.116(c) or 45 CFR §46.116(d).

 

 

Waiver of Documentation (Including Signature) of Consent

When the investigator requests waiver of consent documentation in the protocol application, the rationale presented for the waiver is considered by the IRB as it makes any finding of waiver of consent documentation under 45 CFR 46.117(c) and 21 CFR § 56.109(c).

 

Significant Risk and Non-significant Risk Medical Devices Studies When the protocol uses an investigational device that the investigator considers to be a non-significant risk, the rationale for non-significant risk is included in the protocol application.

 

Research Involving Pregnant Women, Fetuses, and Neonates

When a protocol involves pregnant women, human fetuses and neonates, the IRB considers the investigator’s response to the items in 45 CFR 46.204, as well as the IRB’s review of the items, and makes a finding under 45 CFR §46.204, 45 CFR §46.205, 45 CFR §46.206, and 45 CFR §46.207.

 

OHRP Guidance on the Involvement of Prisoners in Research

 

HIPAA and PHI

Waiver of HIPAA Authorization:  When the investigator requests waiver or alteration of HIPAA authorization for the study, or limited waiver of HIPAA authorization for activities such as recruitment, the IRB considers the rationale presented for the waiver(s) to determine if all of the requirements of 45 CFR 164.512(i)(2)(ii)(A), (B), and (C) are met, and if so, makes the required finding.

 

Emergency Use of a Test Article

 

Exempt Review Categories

 

Expedited Review Categories

 

What Qualifies as Human Subject Research

 

(1) Clinical Trials Terms (2) Commonly Used Acronyms

 

Additionally, for protocols involving fetal tissue transplantation, the IRB considers the investigator’s rationale and the risks involved in order to make any finding required by 42 USC §498A (b)(1) and (2).

Range of Actions on Regular Protocols at Convened Meetings

The IRBs must systematically evaluate each protocol to ensure the protection of research participants and reach a decision.  The possible decisions are:

Š      Approved with no changes:  (or no additional changes).  The research may proceed.  Approval requires an affirmative vote by a majority of the convened quorum.  If the protocol has been changed to an extent that it now qualifies for expedited review pursuant to expedited review category 9, the IRB will change the protocol review designation from regular to expedited.

Š      Contingent:  Approved at a convened IRB meeting contingent on the investigator making minor changes.  Such minor changes must be clearly delineated by the IRB at the meetings and approval is contingent on the PD accepting the IRB stipulations or making any verbatim changes to documents requested by the IRB.  The research may proceed after the IRB chairperson (or any other individual(s) designated by the IRB) has reviewed and accepted as satisfactory all changes to the protocol or informed consent documents, or any other responsive materials, required by the IRB from the investigator.   This review is carried out via the expedited process).

-       VA research: If the convened IRB approves the study contingent on specific minor modifications to the protocol or the informed consent form, the IRB Chair, or an experienced IRB voting member designated by the Chair, may use expedited review procedures to verify that the specific minor conditions were met.

If during the meeting the members decide major changes are required, the protocol is tabled.  

Š      Tabled:  Approvable with greater than minor changes to be reviewed by the convened IRB.  The research may proceed only after the IRB has reviewed and approved the required changes to the research at a convened IRB meeting. 

A protocol will be tabled until it is approved (or eventually not approved) by the voting members at a convened meeting.  If initial reviewers are not available at subsequent meetings where a tabled protocol is reviewed, additional reviewers will be assigned to review and present the protocol.

Š      Not approved:  The IRB has determined that the research cannot be conducted at STANFORD or under the auspices of STANFORD (e.g., the regulatory requirements, STANFORD HRPP standards, or other stipulations have not been satisfied).  The investigator is provided with a memorandum from the IRB Chair notifying him/her that the protocol was not approved by the IRB, explaining the reason(s) the protocol was not approved, and giving the investigator an opportunity to respond in person or in writing. (Not permissible for protocols undergoing to expedited review).

The minutes of the IRB meetings document the deliberations, actions, and votes for each protocol undergoing Regular Review. 

Approval Date and Determination of Expiration Date

The approval date for a protocol subject to regular review is the date of the IRB meeting where the protocol was approved.  The approval date of a protocol or protocol event (modification or continuing review) subject to expedited review is the date the reviewer recommends the protocol or event for approval.  Approval of a modification does not alter the expiration date. 

Protocols are approved for a period of no more than one year, except for nonfederally sponsored nonmedical research involving no more than minimal risk (see Chapter 7.8 below), and unless otherwise stipulated by the reviewers. The expiration date is the last day the protocol is approved (e.g. A protocol approved on January 1, 2010 will expire at midnight on January 1, 2011).

The IRB can approve a protocol for a shorter period if warranted by the risks presented to participants.  The IRB may approve a study for 6 months or may stipulate the approval on further IRB review after a defined number of participants have been enrolled (e.g., review after the first three subjects receive a Phase I drug that has never been tested in humans).  If any of the following are true, the IRB may perform review more often than annually: (a) novel high-risk study using new therapeutic modality; (b) phase I studies of a new drug or biologic that has never been tested in humans; (c) studies involving a novel significant risk medical device that has never been tested in humans; and (d) other high-risk studies as IRB members deem appropriate (this includes research for which the IRB determines that reports to the IRB of monitoring data should be more frequent than annually).

 

Triennial review: Qualifying non-federally sponsored research protocols involving no more than minimal risk (as defined by 45 CFR 46.102) are reviewed once every three years, as long as certain conditions are met.  Certain changes in these studies may change the triennial IRB review requirement to annual review.  See Chapter 7.8.

 

Approval contingent on minor conditions: The protocol initial approval date is recorded as the date the convened IRB approved the study contingent on minor conditions being addressed. However, the “effective” date of initial approval is the date on which the IRB chairperson (or designee) has reviewed and accepted as satisfactory any documents or any other responsive materials required by the IRB; IRB Approval Letters are not ‘released’ until contingencies have been met. No research study activities involving human subjects may be initiated until the conditions have been satisfied in the manner set forth by the IRB and the approval becomes effective. The expiration date is determined in reference to the date the study was approved by the convened IRB contingent on minor conditions being addressed.  

 

Research that continues after the approval period expires is considered research conducted without IRB approval. If investigators fail to apply for continuing review prior to the expiration date, the designated IRB must notify the PDs that research activities -- including but not limited to recruitment, advertisement, enrollment, interventions, interactions, data collection, and data analysis -- are unapproved and must stop, unless the IRB determines that continued involvement is in the best interest of enrolled subjects who are still receiving study-related interventions.  (The IRBs do not consider this a suspension or termination under Chapter 9.3, since it is not activity under an “approved” protocol.)  

In such a situation, the IRB will notify investigators, through the Notice of Protocol Expiration to submit immediately a list of participants for whom stopping research activities would cause harm.  The IRB will determine whether the continued involvement is in the best interests of each individual participant. 

VA research: In the case of VA research, the IRB or IRB Chair will consult with the VA Chief of Staff in making this determination.  The IRB Chair or designee will provide a written determination to the investigator following consideration of this issue.  The IRB also will instruct the investigator on relevant reporting requirements, including promptly reporting the expiration of approval to the sponsoring agency or private sponsor if any.

 

7.8 Extended Approval Period - Triennial Review

Section revised: 3/13/13  

Stanford University has chosen to limit the scope of its Federalwide Assurance (FWA) to federally sponsored research by “unchecking the box” on its FWA on 1/31/2011.  This has allowed an appropriate degree of flexibility by extending the approval period for non-federally sponsored research, involving no more than minimal risk (as defined by 45 CFR 46.102), to researchers conducting:

Š      Nonmedical studies, (policy effective on 10/1/201),

Š      Medical human subject chart review studies, (policy effective on 3/1/2013.)

Research projects reviewed under the Extended Approval Policy will be afforded protections commensurate with risk as determined by the IRB.  

All human research projects conducted or supported at Stanford remain subject to Stanford IRB policies and review, whether they are reviewed under this policy or not.  When questions of applicability arise, studies will be reviewed on a case by case basis.

Inclusion/exclusion of any research project will be at the discretion of the Stanford Research Compliance Office. 

Policy

This policy extends IRB approvals to a (3) three-year approval period for:

Š      Nonmedical human subject research,

Š      Medical human subject chart review studies, (policy effective on 3/1/2013)

involving no more than minimal risk, and that has no federal sponsor.  The policy does not apply to exempt research, which has an approval period for the life of the project.

These research projects will be processed according to 45 CFR 46.110, except approval will be valid for three (3) years, rather than one (1) as stated in the federal regulations.

Š      Annually, a notice will be sent to PDs asking whether any of the following have occurred: 

-       increase in risks;

-       adverse events that have not yet been reported to the IRB; or

-       addition of federal sponsor(s). 

Š      If none of the aforementioned have occurred, no reply or submission to the IRB is required and the protocol can continue.  If one or more of the above have occurred, a Continuing Review application must be submitted and approved in order for the protocol to continue.

Š      Changes that do not involve added risks or added federal sponsor(s) should continue to be submitted on a Modification application, as needed, during the 3 year approval period.

Š      If the protocol is no longer active, the PD will be asked to close the protocol.

The IRB reserves the right to make exceptions to this policy.  Projects that are federally sponsored, in whole or in part, or that involve greater than minimal risk, are subject to the full terms of the Stanford FWA and cannot be reviewed under this policy.

Examples of exclusions from this Policy are:

Š      Federally sponsored projects, including federal training  and program project grants

Š      Student projects when the academic sponsor uses federal funding for the student’s project

Š      Federal no-cost extensions

Š      Studies with clinical interventions or FDA-regulated components

Š      Studies with contractual obligations or restrictions that preclude eligibility in this policy, i.e. the nonfederal sponsor or funder of the research requires annual review.

Š      Studies seeking or obtaining Certificates of Confidentiality

It is the responsibility of the PD to report to the IRB changes in funding or sponsoring status that involve federal agencies.

Monitoring

A random sample of studies processed under this policy will be reviewed periodically to confirm that the funding status has not changed to federally sponsored, the level of risk has not increased to more than minimal, and that any changes made to the protocol have been reported to the IRB prior to implementation.

Notices will be sent out annually to researchers requesting that they address whether changes have occurred regarding study procedures, increase in risks, adverse events, or addition of a federal sponsor.

 

Reporting Requirements

Research projects outside the scope of the FWA are not subject to federal reporting requirements.  For projects conducted under the Extended Approval Policy, the Stanford IRB follows internal reporting requirements for serious or continuing non-compliance, suspensions or terminations, or reporting of unanticipated problems involving risks to participants or others, as described in Chapter 3.9 – 3.11.