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:

• The rights and welfare of human research participants are adequately protected.
• Such research is guided by the ethical principles of respect for persons, beneficence, and justice as set forth in the Belmont Report, and is conducted with the highest level of expertise and integrity.
• Such research complies with applicable laws.

Objectives of the HRPP

The HRPP includes mechanisms to:

• Establish a formal process to monitor, evaluate, and continually improve the protection of human research participants and dedicate resources sufficient to do so
• Exercise oversight of research protection
• Educate investigators and research staff about their ethical responsibility to protect research participants
• When appropriate, intervene in research and respond directly to concerns of research participants.

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/assurance/engage.htm.

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