Stanford University Office of the Dean of Research

Human Research Protection Program (HRPP)

DOMAIN I:  ORGANIZATION

Chapter 1:  The Human Research Protection Program

The organizations (together referred to as “STANFORD”) covered by the Human Research Protection Program (HRPP) have a systematic and comprehensive program with appropriate leadership. (AAHRPP Standard I-1) 

STANFORD* has a written plan for its HRPP appropriate for the volume and nature of the research involving human participants conducted under its auspices. (AAHRPP Element I.1.A) 

The Stanford University Research Policy Handbook (RPH) 7.0 provides information about the organization, scope, authority and responsibilities associated with the Stanford University HRPP for the research community at Stanford University and its affiliates, and explains how the HRPP has been incorporated into one core document.

 

1.1  Organizations Covered by the HRPP

                                   

The five STANFORD affiliated organizations are:

·         Stanford University

·         Stanford Hospital and Clinics (SHC)

·         Lucile Packard Children’s Hospital at Stanford (LPCH)

·         Veterans Affairs Palo Alto Health Care System (VAPAHCS)

·         Palo Alto Institute for Research and Education (PAIRE). 

 

Any components of these organizations as listed in their Federalwide Assurances (FWAs) are considered part of that organization for purposes of the HRPP and are covered by this HRPP Manual.

SHC and LPCH are California non-profit corporations whose sole member is the Board of Trustees of Stanford University.  They provide hospital, clinic and physician services in affiliation with the Stanford University School of Medicine.  They each maintain a memorandum of understanding with Stanford University that retains and requires Stanford University to carry out the HRPP on their behalf.  This document also requires that they agree to cooperate with Stanford University and take all necessary actions to allow Stanford University to carry out the HRPP.  Both SHC and LPCH file a FWA appointing the Stanford University IRBs to review their human subject research.

VAPAHCS is operated by the US Department of Veterans Affairs to provide hospital, clinic and physician services in the region of Palo Alto and Stanford, California.  It is affiliated with Stanford University and its School of Medicine.  Many of its physicians and investigators are also faculty at the School of Medicine who conduct research at VAPAHCS facilities.  PAIRE is a non-profit corporation established and controlled by VAPAHCS pursuant to 38 USC 7361 and 7368.  Its purpose is to provide a flexible funding mechanism for the conduct of approved research (i.e., externally sponsored research) at VAPAHCS facilities and through VAPAHCS physicians and investigators. Both VAPAHCS and PAIRE file a FWA appointing the Stanford University IRBs to review their human subject research.  VAPAHCS and PAIRE also maintain a memorandum of understanding with Stanford University relating to the HRPP.  This document is similar to the agreement with SHC and LPCH, but provides that VAPAHCS “remains ultimately responsible for the maintenance of its overall institutional system to protect human subjects.”  This occurs through the VAPAHCS Research and Development Committee.  Additionally, the memorandum of understanding between VAPAHCS and Stanford University formally establishes the Stanford University IRBs as the Research Privacy Board for VAPAHCS and PAIRE.  

 

1.2     Goal and Objectives of the HRPP                                                      

The goal of the HRPP is to protect human research participants by ensuring that in all STANFORD research:

 

Objectives of the HRPP

The HRPP includes mechanisms to:

 

Written Plan for the HRPP

The written plan for the HRPP is comprised of policies, guidances, and supporting documents governing human subject research and the protection of participants. The HRPP is approved by the Vice Provost and Dean of Research.  The HRPP Manual is organized in 20 chapters, around the standards and elements of the Association for the Accreditation of Human Research Protection Programs (AAHRPP), with each chapter corresponding to one of the twenty standards of AAHRPP, as follows:

 

·         Organization

·         Chapters 1 – 5

·         Research Review Unit, Including IRBs

·         Chapters 6 – 13

·         Investigator

·         Chapters 14 – 15

·         Sponsored Research

·         Chapters 16 – 18

·         Participant Outreach

·         Chapters 19 – 20

1.3      Delegation of the Responsibility for HRPP Implementation to Stanford University 

STANFORD delegates responsibility for the HRPP to the Vice Provost and Dean of Research, Stanford University, who is an official with sufficient standing, authority, and independence to ensure implementation and maintenance of the program. (AAHRPP Element I.1.C) 

 

For the organizations covered by the HRPP, the President of Stanford University delegates the primary responsibility to the Vice Provost and Dean of Research to establish, maintain, and oversee the HRPP.  (See Delegation of Authority to Institutional Officer and Research Policy Handbook 7.0).

STANFORD considers the HRPP Manual to be a dynamic document, because the scientific developments, ethical issues, and regulatory circumstances that shape it are continuously evolving and improving.  The Research Compliance Office (RCO) maintains policies and procedures reflecting the current practices of the IRB in conducting reviews and approvals of human research.  As part of the RCO Continuous Quality Improvement (CQI) program, the RCO Director, in consultation with the HRPP Associate Director and the CQI Associate Director regularly reviews (i.e., at least annually) and refines the HRPP Manual and makes recommendations for modifications, or develops new policies and procedures as appropriate.  The Vice Provost and Dean of Research may approve a modification of any portion of the HRPP Manual.  The RCO Director may approve modifications to the HRPP Manual that relate to the day-to-day review and operational functions of the IRB; other modifications of the HRPP Manual must be approved by the Vice Provost and Dean of Research. 

The RCO is responsible for disseminating all modifications to the HRPP Manual and incorporating them into the relevant educational programs (discussed in Chapter 4). 

 

 

1.4         Research Covered by the HRPP

                                                                        

Types of human subject research at STANFORD

STANFORD conducts or oversees biomedical, social science and behavioral research.  Human subject research is covered as stated in the Federalwide Assurance for each STANFORD affiliated organization.  All research engaged in at STANFORD that involves human participants is covered by the HRPP.  

 

An activity is covered by the HRPP when:

·         It is considered “human subject research” - as defined in any one of the following: 

-   FDA regulations

-   DHHS regulations or other Common Rule regulations

-   VA regulations (VHA Handbook 1200.5 at http://www1.va.gov/visns/visn02/research/buf/f_/irb/guide/VHA_Handbook_1200_5_Protection_of_Human_Subjects.doc), or

-   Any other applicable state or local regulations, e.g. California State regulations

and

·         STANFORD (or its employees or agents) is engaged in the research – as defined by being involved in one or more of the following activities:

-   Receiving an HHS award for research

-   Intervening with participants for research purposes (invasive or noninvasive)

-   Manipulating the environment

-   Interacting with participants for research purposes

-   Obtaining identifiable private information or identifiable biological specimens from any source for research purposes,

 

according to the OHRP guidance Engagement of Institutions in Research at  http://www.hhs.gov/ohrp/humansubjects/guidance/engage08.html.

 

            Agents include all individuals performing institutionally designated activities or exercising institutionally delegated authority or responsibility, including students, faculty, staff, employees, visiting scholars.

 

See Chapter 3.3 for HRPP Manual policies and procedures for determining when studies meet the regulatory definitions of human subject research.

 

Approvals Required Before Human Subject Research Commences

IRB approval is required before research activities may commence.

In addition to approval from the IRB, depending on the funding source, either contract finalization or departmental approval is required before research involving human participants can commence, as follows:

·         Externally funded research (industry-sponsored clinical trials and other clinical research) undergoes a parallel review process by a combination of the following, depending on the funding source:

-   Research Management Group (RMG), who: develop and negotiate budget and payment schedules, route/ensure approvals,

-   Office of Sponsored Research (OSR), who: negotiate terms and conditions, sign contracts, issue notices of award (NOA) for industry-sponsored clinical trials

-   Industrial Contracts Office (ICO), who: handle Industry Research Agreements and Material Transfer Agreements (MTAs)

·         Other research (see Chapter 1.7) requires approval by a Division Chief, Department Chair, School Dean or designee, or a faculty sponsor as appropriate, confirming:

-   Scientific and scholarly validity

-   Adequacy of resources.

 

Some protocol-specific situations require additional review and approval by other organizational components, or must meet their standards (see Chapter 2.4).

 

 

1.5   Primary Officials, Administrative Units and Individuals of the HRPP

STANFORD Domain I:  Officials Responsible for the HRPP
The primary responsibility for the HRPP lies with Stanford University through the Vice Provost and Dean of Research.  See Research Policy Handbook RPH 7.0.  The President of Stanford University delegates this responsibility to the Vice Provost and Dean of Research.  The Board of Trustees of Stanford University, the governing body of Stanford University (as established by Jane and Leland Stanford in the 1885 Founding Grant), appoints the President.


Ann Arvin, M.D.:  In 2006 President John Hennessy appointed Ann Arvin, Lucile Salter Packard Professor of Pediatrics and Professor of Microbiology/Immunology, to the position of Vice Provost and Dean of Research. In this position she serves on the University's Executive Cabinet.  Dr. Arvin’s responsibilities and organization chart are given in Administrative Guide Memo 12.11.
        
As Stanford University’s Institutional Official, the Vice Provost and Dean of Research signs the Federalwide Assurance of Compliance (FWA) on behalf of the institution and is ultimately responsible for:

·         Creating, establishing and maintaining the policies and procedures for the HRPP and related research policies and procedures on behalf of Stanford University

·         Overseeing the protection of human participants, regulatory compliance, and the implementation of the HRPP for STANFORD

·         Ensuring that open channels of communication are maintained between the components of the HRPP

·         Overseeing research investigators and staff, and research management

·         Ensuring the independence of the IRB, including the authority to act without undue influence

·         Requiring periodic reviews of the HRPP

·         Ensuring that the HRPP is functional, adequately staffed and funded, involving:
       i). Annual review of the resources allocated to the HRPP
      ii).  Participation in the annual budget preparation for the HRPP and

      incorporation of the HRPP budget into the budget of Stanford University.

The day-to-day operational and oversight responsibility for the HRPP is delegated to the Research Compliance Director, a non-faculty, full-time administrator.  The Research Compliance Director reports to the Vice Provost and Dean of Research.

Kathy McClelland:  The Research Compliance Office (RCO) Director, Kathy McClelland, has day-to-day operational responsibility for the HRPP through the RCO.  She has over 25 years experience at Stanford dealing with aspects of research integrity and compliance.  She has served as Director for the last twelve years.  Before joining the Office of the Dean of Research, she held positions in the School of Medicine as an IRB manager; in the Office of Sponsored Research (OSR) as nonmedical IRB manager and Institutional Animal Care and Use Committee (IACUC) manager; and as Assistant Director of OSR in charge of compliance, as it pertained to research participants and animal welfare.  Among other functions as the RCO Director, she is administratively responsible for the operations of the IRBs, the Institutional Animal Care and Use Committee (IACUC), the Stem Cell Research Oversight (SCRO) Panel, and in conjunction with Environmental Health and Safety, assists the Biosafety and Radiological Safety Committees. 

VAPAHCS Research and Development Committee:  This committee is ultimately responsible for all human subject research which occurs at VAPAHCS.  Its membership, functions and responsibilities are described in the VAPAHCS Health Care System Memorandum No. 151-05-08, Research and Development Committee and Associated Subcommittees.

 

STANFORD Domain II:  Research Review Unit, including IRBs

IRBs: The Administrative Panels on Human Subjects in Medical Research and the Administrative Panel on Human Subjects in Non-Medical Research are the Institutional Review Boards (IRBs) and perform many of the core functions of the HRPP.  The Vice Provost and Dean of Research appoints the chairs and the members of the IRBs and assigns their authority and responsibility in the “charge” to the Chairs and members.  See Charge to the Administrative Panel on Human Subjects in Medical Research by the Vice Provost and Dean of Research, and Charge to the Administrative Panel on Human Subjects in Non-Medical Research by the Vice Provost and Dean of Research.  The charge emphasizes that the IRBs are functionally independent (e.g., of the individuals who are conducting the research) and have ready access to the highest officials of the covered organizations, if needed, to ensure protection for human research participants.

There are seven medical IRBs and one nonmedical IRB.  Their authority, membership requirements, and responsibilities are described in Chapter 6.  IRBs are responsible for the initial and continuing review, review of modifications, approval of all research subject to the HRPP, determining serious or continuing noncompliance, requiring modification (to secure approval), disapproving research, and applying applicable ethical standards.

Stanford University also participates in the Central Institutional Review Board (CIRB) Initiative of the National Cancer Institute (NCI).  A facilitated review process for local IRB review of adult and pediatric national multi-center cooperative oncology group cancer treatment trials is employed for selected protocols.   

IRB Staff in the Research Compliance Office:  The HRPP Associate Director is responsible for supporting the daily operations of the IRBs.  The IRB staff (Managers and Associates) review protocol applications for accuracy and completeness and act as liaisons between the Protocol Directors (PDs) and the IRB members.  The IRB Training Specialist and the HRPP Education Specialist are responsible for the training of all individuals who are affected by the Human Research Protection Program.  The Continuous Quality Improvement (CQI) Associate Director is responsible for the CQI plan and its implementation.  This plan ensures periodic evaluation and strengthening of the HRPP. 

Upon request, the RCO has responsibility for review and comment on proposed external regulations dealing with human research.  When appropriate, the RCO formulates and recommends draft policies and procedures for approval by the appropriate Stanford University bodies and promulgation by the Vice Provost and Dean of Research.

See Research Compliance Organization Chart.   

 

STANFORD Domain III:  Investigator

Principal Investigator/Protocol Director:  The STANFORD individual ultimately responsible for a protocol is the Protocol Director (PD).  Most (but not all PDs) have faculty appointments at Stanford University.  PD responsibilities are specified in the HRPP Manual and include ensuring that:

·         All STANFORD human subject research has received initial prospective review and approval by the IRB.

·         Continuing review and approval of the research has been accomplished within the time frame stipulated by the IRB.

·         The research is conducted at all times in compliance with all applicable regulatory requirements and the determinations of the IRB.

 

Other Members of the Research Team:  Every member of the research team is responsible for protecting human participants.  Co-investigators, study coordinators, nurses, research assistants, faculty sponsors, student/staff investigators, and all other research staff have the following strict obligations to:

·         Comply with all IRB determinations and procedures

·         Adhere rigorously to all protocol requirements

·         Inform the PD, and thus IRB, of unanticipated problems

·         Ensure the adequacy of the informed consent process

·         Take necessary measures to ensure adequate protection for study   

      participants.

 

Responsibilities and duties under the HRPP are described in more detail in Chapter 14 and Chapter 15.

 

 

STANFORD Domain IV:  Sponsored Research

Sponsors can be a company, institution, individual donor or organization responsible for the initiation, management, or financing of a research study.  Both the sponsor and STANFORD have obligations to protect research participants. 

 

STANFORD Domain V:  Participant Outreach

Participants in a research project also have responsibilities.  These include telling the truth, asking for clarification, following the protocol, notifying study personnel of their non-compliance, and telling investigators if they wish to withdraw from the study.

 

 

HRPP Organizational Components

In addition to the Vice Provost and Dean of Research and the Research Compliance Office, human research protection responsibilities are shared by these Stanford University HRPP components:

 

Cancer Clinical Trials Office (CCTO):  The CCTO provides administrative, research, and educational services to Cancer Center investigators conducting clinical trials. Programs serve to increase awareness and accrual to clinical trials as well as to improve the quality and efficiencies of conducting clinical trials in compliance with regulatory, documentation, and oversight requirements.  Its goals are to:

·         Facilitate clinical trials and translational research by providing administrative support to all Cancer Center investigators  

·         Enhance and facilitate data collection and reporting of clinical cancer research

·         Provide programs to contribute to quality assurance and the ongoing education of Cancer Center Clinical Research Personnel

·         Coordinate outreach efforts in the community to increase clinical trials awareness and accrual, and

·         Promote interdisciplinary collaborations and translational medical research.

 

All cancer-related studies are reviewed by the CCTO Scientific Review Committee (SRC), (except observational studies, retrospective chart reviews, compassionate use studies, and multiple program projects (MPPs)).  The Data Safety Monitoring Committee of the CCTO reviews adverse event reports and requires them, as appropriate, to be submitted to the IRB. (See Chapter 3.10).

 

Conflict of Interest Committee (COIC): The COIC of the School of Medicine (SOM) reviews CoI disclosures from all protocols (SOM and non-SOM) submitted to the IRB. The COIC considers the conflicting interests, determines or assesses any mitigation or management plan, and determines whether the conflict can be managed or needs to be eliminated.  If further review is appropriate, the case is examined by the Vice Provost and Dean of Research.  The decisions and actions of the COIC are reported to the IRB staff, and considered at an IRB convened meeting. See Chapter 3.7 for more information.

 

Environmental Health and Safety (EH&S):  EH&S provides and coordinates programs and services that minimize risks to safety and health, and environmental and regulatory risks to the Stanford University community in a manner consistent with responsible fiscal and environmental stewardship. EH&S works with investigators to promote safe and healthful laboratory environments that support the University's science and research mission. The Administrative Panel on Biosafety (APB) and Health Physics Radiation Safety are under the auspices of EH&S.  As appropriate:

·         Human subject research must have APB approval before research activities may commence;

·         The Protocol Application contains questions about radioisotopes and radiation 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 cannot be approved by the IRB, and must be tabled to a future convened meeting;

·         The Protocol Application instructs that patient related equipment, if used, must meet standards established by the Hospital Instrumentation and Electrical Safety Committee.

 

General Clinic Research Center (GCRC):  The GCRC is a major clinical research resource for Stanford University School of Medicine.  Its goals are to provide an optimal facility for the conduct of patient-oriented research, to translate basic scientific knowledge into better understanding and treatment of human diseases, and to train health professionals in clinical research.

 

HIPAA Council:  The HIPAA Council is convened by the Stanford University Privacy Officer to explore issues related to the implementation and enforcement of the Privacy and Security rules under HIPAA for the Stanford Affiliated Covered Entity.

 

Internal Audit and Institutional Compliance:  The Internal Audit Department periodically performs assessments of University operating units, such as the Research Compliance Office.  Additionally, the Director of Internal Audit and Institutional Compliance has oversight over:

·         Institutional Compliance Coordinating Committee (ICCC):  ICCC is part of the Stanford’s Institutional Compliance initiative and provides coordination and support to the offices at Stanford which have direct responsibility for complying with government regulations.

 

Office of the General Counsel (OGC):  The OGC is responsible for addressing all of the legal issues arising out of the activities of Stanford University, Stanford Hospital and Clinics and Lucile Salter Packard Children's Hospital at Stanford. A representative of the OGC serves as an ex-officio IRB member, and is available for consultation on issues regarding human subject research and participant protection.

 

Office of Research Administration (ORA):  The ORA manages the administrative processes related to Stanford’s sponsored research. Within ORA:

·         Office of Sponsored Research (OSR):  The OSR negotiates contract terms and conditions for industry-sponsored clinical trials, and provides pre-award and post-award administrative services for sponsored projects to ensure that Stanford is fully compliant with sponsor terms and conditions, University policies, and federal regulations. IRB approval is a prerequisite for OSR to sign a contract. 

·         Compliance Support Task Force (CSTF):  The CSTF is facilitated by ORA, and draws membership from the: School of Earth Sciences, Internal Audit, School of Engineering, Office of Research Administration, School of Humanities and Science, School of Medicine, Controllers Office, Vice Provost and Dean of Research, and Environmental Health and Safety. Its mission is to provide a forum to discuss University-wide research compliance issues, draw on the collective expertise available throughout the University, encourage dissemination of best practices, act in an advisory capacity to the Vice Provost and Dean of Research and to the Associate Vice President of the Office of Research Administration.

 

Office of Technology Licensing (OTL):  OTL is responsible for managing the intellectual property assets of Stanford University. The OTL charter is to help turn scientific progress into tangible products, while returning income to the inventor and to the University to support further research. OTL has signature authority on behalf of the University for license agreements, material transfer agreements, industrial contracts and other agreements that pertain to intellectual property.  Of particular relevance to human subject research protections are:

·         Clinical Technology Assessment Agreements (CTAA’s) - created when a sponsor provides an investigational drug or device for research; the protocol must have IRB approval, and, as appropriate an IND or IDE. 

·         Material Transfer Agreements (MTA’s) - these govern the use of tangible research materials distributed to other institutions. The Protocol Application asks whether tissues are to be distributed as part of such an agreement.

 

Research Management Group (RMG):  For School of Medicine research - Provides oversight and management of sponsored projects and ensures compliance with sponsor and University expectations for managing sponsored funds. RMG performs a parallel review to the IRB, and confirms IRB approval before routing sponsored project information to the Office of Sponsored Research (OSR) contracts office (see above). 

 

Stanford Center for Biomedical Ethics (SCBE):  The SCBE is dedicated to interdisciplinary research and education in biomedical ethics, and provides clinical and research ethics consultation. SCBE serves as a scholarly resource on emerging ethical issues raised by medicine and biomedical research, and is called upon for consultation by the IRB when needed.

 

Stanford/Packard Center for Translational Research in Medicine (SPCTRM): SPCTRM serves STANFORD faculty and clinical research personnel in the School of Medicine (SOM), Stanford University Medical Center, Lucile Packard Children's Hospital (LPCH) and Veterans Affairs Palo Alto Health Care System (VAPAHCS).  Its mission is to enhance the quality of clinical and translational research by:

IRB staff and SPCTRM collaborate to provide education to the research community, disseminate information about the HRPP, and to facilitate quality improvement activities such as compliance reviews.

 

Stanford University Schools:  Although human subject research (including undergraduate research programs) takes place within any of the seven Schools, most human subject research is performed by the Schools of Medicine, Education, and Humanities & Sciences, which includes the Department of Psychology.  All such research must receive IRB approval before research activities can commence.

 

 

1.6   Ethical and Legal Principles Governing Human Subject Research

 

STANFORD has the following written policies for working with research participants, sponsors, investigators, and the RCO, including IRBs, to uphold legal and ethical standards and practices in research involving human subjects. 

(AAHRPP Element I.1.D) 

 

Ethical Principles

The primary ethical principles applied to research covered by the HRPP, including protocols “exempt” under federal regulations pertaining to human subject research, are those set forth in The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (Belmont Report). 

The three main principles are:

1.    Respect for persons (e.g., applied by obtaining informed consent, giving consideration to privacy and confidentiality, and adding protections for vulnerable populations)

2.    Beneficence (e.g., applied by weighing risks and benefits)

3.    Justice (e.g., applied by the equitable selection of subjects)

All parties involved in the conduct of research are expected to also adhere to the principles of expertise (“competent to do the work”) and integrity (“faithfully adhere to professional principles”).  Ethical principles from other sources (e.g., International Conference on Harmonization) may also be applied to research covered by the HRPP, for example:

 

Investigator training on the ethical principles governing human subject research and investigator responsibilities is provided by the tutorial “Principal Investigator Responsibilities at Stanford University”. These principles are also covered in the CITI required tutorial for investigators, IRB Members, and IRB Staff, and in the orientation given to new IRB members.

With respect to sponsored research, Stanford University and PAIRE address the protection of research participants by including in their standard contract templates a provision that the sponsor acknowledges and understands that the STANFORD HRPP is applicable to all human participant research. See Chapter 16.

 

Legal Principles

The basic legal principles governing human subject research, covered by the HRPP and applicable to individual protocols are:

 

(These and other legal principles are addressed when applicable in the individual chapters of the HRPP Manual.)

 

 

1.7  Scientific and Scholarly Validity Review and Ethics Review                  

 

STANFORD has the following written policies and procedures for reviewing the scientific or scholarly validity of a proposed research study.  Such procedures are coordinated with the ethics review process. (AAHRPP Element I.1.B)

 

Scientific and Scholarly Validity Review

The IRB relies on the Scientific and scholarly validity review provided by different entities, as follows:

·         For federally sponsored research, including VA-funded research, the respective peer review process (e.g., NIH, NCI, DOD) provides scientific and scholarly review.

·         For research subject to FDA review, the FDA conducts a rigorous scientific design review during IND or IDE evaluation.   Most industry-sponsored research falls within this category.  An important exception is Non-Significant Risk device research.

·         For research occurring at VAPAHCS, the VA Research and Development Committee and subcommittees perform scientific review of all activities prior to initiation and at least annually thereafter, in order to evaluate the quality, design, desirability and feasibility of each new R&D proposal/application for funding, to assure maintenance of high scientific standards, protection of human research participants including privacy and confidentiality, and adequate safety measures.  The process is described in VAPAHCS Health Care System Memorandum No. 151-05-08, Research and Development Committee and Associated Subcommittees.

·         For research occurring in the General Clinical Research Center (GCRC) at SHC and LPCH, an internal review board provides scientific and ethical evaluation.  See the GCRC website page Research Protocol Approval and Continuing Scientific Review System.

·         The Cancer Center Scientific Review Committee (SRC) provides a peer review of local and national research protocols involving cancer patients treated at Stanford University Clinical Cancer Center and Lucile Packard Children's Hospital.  The review primarily focuses on the scientific merit of the study and applies to all phases of clinical therapeutic intervention, behavioral clinical trials, tissue and body fluid research, and diagnostic trials, which impact medical decision making for the treatment of cancer patients. The process is described in its “Stanford University Clinical Cancer Center, Scientific Review Committee, Policies and Procedures”.   SRC is not required for all cancer studies.  For a list of types of research for which SRC review is required, refer to the above Cancer Center website.

 

·         For research that has not otherwise gone through a scientific review as described above , for example:

-   research conducted by faculty without external sponsorship, or

-   for all research conducted by students, including student research that may undergo scientific review by an awarding entity,

then:

-   In the School of Medicine:  the Division Chief or Department Chair of the PD’s department, (or the School Dean or his designee when the Division Chief or Department Chair has a conflicting interest), or

-   In other schools:  the School Dean or designee

is responsible for confirming to the IRB that scientific review of the protocol has occurred. 

When the PD is a student, this confirmation may be provided by the Faculty Sponsor who is responsible for the scientific review (the Faculty Sponsor submits a Review of Scientific and Scholarly Validity, and Oversight [APP-9] to the IRB). When the protocol application indicates that the research has departmental funding, gift funding or no funding, the IRB requests that the PD have the Division Chief or Department Chair of the PD’s department in the School of Medicine (or the dean of other schools as appropriate), respond to the IRB, on the following (Review of Scientific and Scholarly Validity [APP-10]):

                        a.    Are the research procedures the least risky procedures that can be performed consistent with sound research design?

                        b.    Is the research likely to achieve its aims?

                        c.    Is the proposed research of sufficient scientific importance to justify the risks entailed?

                        d.    Are there adequate resources (e.g. facilities, qualified staff, access to participant population that will allow recruitment of the required number of participants) to complete the study?

For regular review protocols, the PD must answer the questions in the Scientific Review Protocol for Human Subjects Research [NOT-13].

For all research, the IRB evaluates, in accordance with federal research regulations [45 CFR 46.111(a) and 21 CFR 56.111(a)] whether the following requirements are satisfied:

        a.    Risks to participants (physical, psychological, social, legal and economic) are minimized (i) by using procedures which are consistent with sound research design and which do not unnecessarily expose participants to risk; and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.

        b.    Risks to participants are reasonable in relation to anticipated benefits, if any, to participants, and the importance of the knowledge that may be expected to result.

 

If the requirements noted above are not satisfied, the protocol may not be approved as written.  The IRB reviewer(s) may consider prior scientific reviews (e.g., NIH peer review, GCRC internal review board, SRC review) in their evaluation.  For protocols where the protocol design is unusual or novel, in addition to the protocol being assigned to primary reviewer(s) with relevant expertise, input from ad hoc consultants may also be obtained.  For further information, refer to guidance Evaluating Sound Study Design.

 

Ethics Review

The IRB review of the study procedures, risks and benefits includes the identification, evaluation and resolution of the ethics issues presented in the study in accordance with the ethical principles outlined in Chapter 1.4.  If necessary, the IRB may seek ad hoc assistance from ethical consultants, both internal and external (e.g., members of the hospital ethics committees of SHC, LPCH, or VAPAHCS, or members of Stanford University’s Center for Biomedical Ethics).

An ethics review (in addition to the scientific review) is also conducted by the internal review committees for research done in the General Clinical Research Center at SHC and LPCH, and in the Cancer Center at SHC and LPCH.