Human Research Protection Program

SECTION: Office of the Director Policies and Procedures
SUBCATEGORY: Research
DEPARTMENT: Director's Office 

CONTENTS:

Policy Statement

It is the policy of Fred Hutchinson Cancer Research Center (“Fred Hutch”) that the rights and welfare of human subjects participating in research engaged in by Fred Hutch must be adequately protected. All such research, whether conducted at Fred Hutch or at its affiliate sites within the United States, or internationally at sites operated by a Fred Hutch component entity, must satisfy each of the following requirements:

1. It must be guided by applicable ethical principles including respect for persons, beneficence and justice as described 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 Behavioral Research (“Belmont Report”);
2. It must comply with applicable laws and regulations;
3. It must be conducted by persons with appropriate expertise and training;
4. It must have appropriate scientific or scholarly merit;
5. It must be reviewed and approved by a properly constituted institutional review board that functions independently of other Fred Hutch managerial or scientific units with respect to protecting the rights and welfare of human research. This requirement may be satisfied through an expedited IRB review process if permitted under applicable law and Fred Hutch policy.
6. Research subject to the HRPP may not proceed without IRB approval even if it has been approved by other Fred Hutch departments or officials. However, Fred Hutch officials may disapprove the conduct of research that has been approved by the reviewing IRB.

The ability to effectively protect the rights and welfare of human subjects participating in Fred Hutch research depends on the willingness of those involved in such research to personally adhere to the standards described in this policy and to report suspected noncompliance with this policy. Principal investigators and others who design, conduct or report Fred Hutch research involving human subjects are expected to be familiar with this policy and Fred Hutch’s human research protection program (“HRPP”), acquire appropriate training and education for the responsible conduct of research involving human subjects, and accept continuing responsibility for compliance with this policy and the HRPP through all stages of the research process. It is the obligation of all Fred Hutch employees to report any suspected or confirmed noncompliance with the HRPP to Fred Hutch’s Institutional Review Office (“IRO”), the Institutional Official ("IO"), the Office of the Associate Vice President and Chief Ethics and Compliance Officer, the Office of the General Counsel (“OGC”), or through other normal organizational channels.

Reason for Policy

The purpose of this policy is to ensure the protection and welfare of human subjects participating in research engaged in by Fred Hutch through the development, implementation and maintenance of a systematic and comprehensive human research protection program with appropriate leadership and monitoring.

Overview

Fred Hutch recognizes that the ability to conduct research involving human subjects is a privilege that imposes an obligation to adequately protect the rights and welfare of human subjects participating in that research. To ensure that the rights and welfare of human subjects are adequately protected, Fred Hutch is committed to developing, implementing and maintaining a systematic and comprehensive human research protection program with appropriate leadership and monitoring.

The Associate Vice President and Chief Ethics and Compliance Officer (“CECO”) in close coordination with the IO have overall responsibility for Fred Hutch’s HRPP. In further recognition of the importance of protecting the rights and welfare of human subjects, the Board of Trustees of Fred Hutch has established the Audit and Compliance Committee (“ACC”), which is responsible for oversight of Fred Hutch’s policies and practices pertaining to research involving human subjects including, without limitation, its policies and practices relating to institutional review of proposed new protocols, informed consent, protocol data and safety monitoring, management of financial conflicts and financial disclosure.

This policy describes the following essential elements of Fred Hutch’s plan for implementing, maintaining and monitoring the HRPP:

1. The scope of the HRPP including the types of activities to which it applies and the conditions of its application;
2. The ethical and legal principles applied to research governed by the HRPP;
3. The process for scientific or scholarly review of research governed by the HRPP;
4. A description of the essential components of Fred Hutch that participate in the HRPP and their respective roles and responsibilities; and
5. The essential elements of the plan for maximizing compliance with the HRPP.

Unless otherwise stated, responsibility for developing and maintaining specific policies and procedures consistent with this policy is delegated to the Director of Fred Hutch’s IRO. Any such policy or procedure that is inconsistent with this policy requires the prior approval of the CECO.

Procedures

1. Scope of Fred Hutch’s HRPP.

a. Activities to which the HRPP Applies.

Fred Hutch’s HRPP applies to all research involving human subjects engaged in by Fred Hutch. Research shall be considered human subjects research if it satisfies any one or more of the following criteria:

(i.) It is a “clinical investigation” involving “human subjects” as defined in United States Food and Drug Administration (“FDA”) regulations (21 CFR Section 50.3);
(ii.) It is “research” involving “human subjects” as defined in United States Department of Health and Human Services (“DHHS”) regulations or other Common Rule regulations (45 CFR Section 46.102);
(iii.) It is funded by the Department of Defense and DOD regulations for the protection of human subjects (32 CFR Part 219) apply;
(iv.) It is research involving “health care information” of a “patient” under the Washington Uniform Healthcare Information Act (see Revised Code of Washington (“RCW”) Chapter 70.02); or
(v.) It is research involving human subjects under any other applicable state or local laws or regulations.

b. Conditions for Application of HRPP.

Human subjects research becomes subject to the HRPP whenever one or more of the following conditions occurs:

(i.) Fred Hutch’s employees or agents intervene or interact with human subjects for purposes of research conducted or supported by Fred Hutch;
(ii.) Fred Hutch’s employees or agents obtain individually identifiable private information about human subjects for purposes of research conducted or supported by Fred Hutch;
(iii.) Fred Hutch receives a direct award from any source to conduct research involving human subjects, even where all activities involving human subjects are carried out by a subcontractor or collaborator;
(iv.) The research involves human subjects and the researchers recruit those subjects from Fred Hutch, including using Fred Hutch’s non-public information to identify and contact potential research subjects, or uses any of its property or facilities;
(v.) There is an emergency use of an investigational drug, device or biologic under FDA regulations by an employee or agent of Fred Hutch; or,
(vi.) Fred Hutch’s IRB is the IRB of record for the research even though conducted or supported by another institution.

c. Procedures for Implementation.

The IRO is responsible for developing appropriate procedures consistent with this policy for determining when an activity is research involving human subjects and when it is governed by the HRPP including appropriate procedures for (i) implementing federal guidance on when a researcher is “engaged in research”, (ii) determining when a researcher is acting as an agent of Fred Hutch and (iii) determining when research involving human subjects is exempt from review.

2. Ethical and Legal Principles Governing Research Subject to the HRPP.

a. Ethical Principles. The primary ethical principles applied to research governed by the HRPP are those stated in the Belmont Report. The three main principles are:

(i.) Respect for persons (including obtaining informed consent, giving consideration to privacy and confidentiality and adding protections for vulnerable populations);
(ii.) Beneficence (applied by weighing risks and benefit); and
(iii.) Justice (applied by the equitable selection of subjects).

Other appropriate ethical standards may be applied to research governed by the HRPP in certain circumstances if they are recognized by the federal or other funding source or the state or country where the research will occur. For example, clinical trials that require adherence to the ICH GCP (E6) guideline, will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with good clinical practice and the applicable regulatory requirements.

b. Legal Principles and Guidelines. The basic legal principles governing research governed by the HRPP are:

(i.) The federal policy for protection of human subjects (“Common Rule”) in 45 CFR Part 46;
(ii.) FDA regulations for the protection of human subjects in 21 CFR Parts 50 and 56;
(iii.) Standards for privacy of individually identifiable health information (“HIPAA Privacy Rule”) in (a) 45 CFR Parts 160 and 164 (Fred Hutch is not a covered entity under HIPAA) and (b) applicable state laws including RCW Chapter 70.02 (Washington Uniform Healthcare Information Act), RCW Chapter 71.05 (mental illness), RCW Chapter 71.34 (mental health services for minors). RCW Chapter 70.24 (sexually transmitted diseases); 
(iv.) Other applicable state and local laws including RCW 70.54.230 et seq. (state cancer registry) and RCW, 7.70.065 (persons authorized to provide informed consent for incompetent patients), and, with respect to international trials, applicable laws of foreign countries; and
(v.) ICH GCP (E6) guidelines, when applicable

c. Procedures for Implementation. The IRO is responsible for developing appropriate procedures consistent with this policy for the application of ethical and legal principles to research governed by the HRPP. When there are conflicts between applicable laws and regulations, the most protective approach applies.

3. Scientific or Scholarly Review of Research.

Fred Hutch’s institutional review boards (“IRBs”) have the ultimate responsibility for determining whether the risks to participants have been appropriately minimized through the use of sound research design and whether those risks are reasonable in light of the anticipated benefits to the participants and the importance of the research. An IRBs review of research subject to the HRPP should consider (a) whether the research is consistent with sound research design, (b) whether the research design is sound enough to reasonably expect the research to answer its proposed question and (c) the importance of the knowledge expected to result from this research.

For Fred Hutch/University of Washington Cancer Consortium ("Cancer Consortium") research, scientific review is conducted by the Scientific Review Committee (see Section 4.g. below). The results of the Scientific Review Committee must be communicated to the appropriate IRB. The IRB may reasonably rely on the scientific review conducted by the Scientific Review Committee. If, in the discretion of the IRB, there has not been sufficient scientific or scholarly review of specific research, and the IRB lacks the expertise itself to evaluate the research for this purpose, the IRB may use an internal or external consultant to assist with its evaluation. No research subject to the HRPP may proceed without IRB approval or a proper waiver of approval even if it has been reviewed and approved by the Scientific Review Committee or any additional scientific or scholarly review procedures established by the Senior Vice President and Division Director ("Division Director").

4. Essential HRPP Components and their Roles and Responsibilities.

a. Principal Investigators. Principal investigators who conduct research subject to the HRPP are ultimately responsible for all aspects of that research including the safety of human subjects participating in that research and ensuring that such research does not proceed without necessary IRB and regulatory approvals. Principal investigators are expected to be familiar with this policy and the HRPP, acquire appropriate training and education for the responsible and ethical conduct of research involving human subjects, and accept continuing responsibility for compliance with this policy and the HRPP through all stages of the research process.
Fred Hutch employees with a faculty appointment of Member, Associate Member, or Assistant Member or Professor, Associate Professor or Assistant Professor (see Fred Hutch Academic Policies for Faculty and Scientific Staff section 2.1) at Fred Hutch may serve as Principal Investigators. Fred Hutch employees, or Affiliate Investigators, without a faculty appointment at Fred Hutch may serve as Principal Investigator with the approval of the IO and the Fred Hutch President and Director, or his/her designee. If approved, non-faculty employees, or Affiliate Investigators must have appropriate training and oversight.
Fred Hutch employees with no affiliation with a scientific division, may not serve as Principal Investigator without the approval of the IO and the Fred Hutch President and Director, or his/her designee.
Cancer Consortium Members (“Consortium Members”) may serve as Principal Investigators if authorized by their home institution (i.e., UW Medicine or Seattle Children’s Hospital) in accordance with their standard policies and procedures.

b. Audit and Compliance Committee. The ACC is a committee of the Fred Hutch Board of Trustees, responsible for overseeing Fred Hutch’s policies and practices pertaining to research involving human subjects including, without limitation, Fred Hutch’s policies and practices relating to institutional review of proposed new protocols, informed consent, protocol data and safety monitoring, and management of financial conflicts and financial disclosures. The ACC receives regular reports from Fred Hutch management concerning audits conducted by Fred Hutch or any government or outside agency pertaining to the protection of human subjects and also receives immediate notification of any issue resulting from any such audit that could materially and adversely impact patient safety or Fred Hutch operations. The ACC reports to and makes recommendations to the Executive Committee of the Board of Trustees and/or the Board of Trustees from time to time concerning Fred Hutch’s policies and practices pertaining to research involving human subjects. The ACC may from time to time require external reviews of Fred Hutch processes relating to the protection of human subjects participating in research engaged in by Fred Hutch.

c. Office of the Associate Vice President and Chief Ethics and Compliance Officer (”CECO”).

(i.) Associate Vice President and Chief Ethics and Compliance Officer. The CECO has overall responsibility for Fred Hutch’s HRPP including the following primary responsibilities:

(a) Overseeing the creation, implementation and maintenance of the HRPP and ensuring that the importance of protecting human subjects is properly understood within Fred Hutch’s research community;
(b) Working in close coordination with the IO who is responsible for signing Fred Hutch’s Federalwide Assurance (“FWA”);
(c) Ensuring that there are open channels of communication between the components of the HRPP and between Fred Hutch and its affiliated organizations with respect to the protection of human subjects participating in research governed by the HRPP;
(d) Ensuring the independence of Fred Hutch’s IRBs and their ability to act without undue influence and that no research subject to the HRPP may proceed unless it is reviewed and approved by one of Fred Hutch’s IRBs unless such research is exempt or review is properly waived under applicable laws and Fred Hutch policies;
(e) Evaluating through Fred Hutch’s annual budgeting process that the HRPP has sufficient resources to function properly including adequate funding for the IRO, OGC, and space and personnel to support the HRPP.
(f) Ensuring that there is appropriate review and monitoring of the HRPP and that appropriate disciplinary action is taken with respect to non-compliance with this policy, the HRPP or requirements or determinations of the IRB;
(g) Working in close coordination with the IO in his/her appointment of the members and chairs of Fred Hutch’s IRBs; and,
(h) Reviewing and approving conflict management plans as required by Fred Hutch’s Conflict of Interest Policy.

The CECO works in close coordination with the Vice President for Clinical Research who leads the Clinical Research Support Office of the Cancer Consortium (“CRS”) including oversight and execution of the Cancer Consortium Protocol Review and Monitoring System (“PRMS”) and the Consortium Data and Safety Monitoring Plan (“DSMP”). The CECO also has responsibility for reviewing and approving the budget related to the IRO and the IRBs and for ensuring that those budgets are adequate to carry out the HRPP.

d. Senior Vice President & Division Director. Each Division Director oversees the activities of one of the scientific divisions at Fred Hutch. The primary responsibilities of each Division Director with respect to the HRPP include:

(i.) Assisting the CECO in ensuring that the HRPP is understood and respected within that division;
(ii.) Working with the CECO to ensure that appropriate disciplinary action is taken with respect to non-compliance with the HRPP by persons in that division;
(iii.) Ensuring that there is appropriate communication and cooperation between investigators and research staff within that division and the IRB and IRO concerning research conducted within that division;
(iv.) Ensuring that any serious concerns about the HRPP or noncompliance with the HRPP of which they are aware are communicated to the CECO.

e. Institutional Review Boards. The IRBs perform the principal review functions of the HRPP. No research subject to the HRPP may proceed without review and approval by one of the IRBs even if it has been approved by some other Fred Hutch department or official. This requirement may be satisfied through an expedited IRB review process if permitted under applicable law and Fred Hutch policy.

The primary responsibilities of the IRBs include, and the IRBs are granted authority to do, the following:

(i.) Reviewing all research governed by the HRPP, including those research studies identified as exempt, to determine if the research meets applicable ethical standards and other requirements of this policy and the HRPP, and based on its review, approving, requiring modifications to secure approval of, or disapproving such research;
(ii.) Reviewing (a) serious or continuing noncompliance with the HRPP and the requirements and determinations of the IRB and (b) unanticipated problems that involve risks to human subjects or others and requiring suspension or termination of its approval of or modifications to research that is not being conducted in accordance with the requirements and determinations of the IRB or the HRPP or which is causing unexpected problems placing subjects or others at a greater risk of harm than was previously known or recognized;
(iii.) Ensuring that the CECO and the IO, or their designees, are advised of (a) any serious or continuing noncompliance with the HRPP or requirements and determinations of the IRB, (b) any concerns about the independent functioning, undue influence or coercion of the IRBs or any of their members relating to their role in the HRPP, or (c) any other serious concerns about the ability of the IRBs to effectively carry out their responsibilities under the HRPP;
(iv.) At the discretion of the IRB, observing or having a third party observe the consent process or any research subject to IRB review; and
(v.) Reviewing proposed conflict management plans and having the final authority to determine whether the management plan is appropriate to approve the research.

Each IRB shall have at least five members, with varying backgrounds to promote complete and adequate review of research activities commonly conducted by Fred Hutch. The IRBs shall be sufficiently qualified through the experience, expertise and diversity of their members to promote respect for their advice and counsel in safeguarding the rights and welfare of human subject, shall possess the professional competence necessary to review specific research activities and shall be able to ascertain the acceptability of proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice. IRB members will be selected based on their qualifications. No IRB member will be selected based on gender although nondiscriminatory efforts will be made to ensure that no IRB consists entirely of men or women. No IRB may consist entirely of members of one profession.

The IRB will include members who are knowledgeable about and experienced working with subjects vulnerable to coercion or undue influence (e.g., children, prisoners, pregnant women, individuals with impaired decision-making capacity, or economically or educationally disadvantaged persons) that are regularly included in the research under its review.

Each IRB shall include (a) at least one member who is not otherwise affiliated with the institution and who is not part of the family of a person who is affiliated with the institution, (b) at least one member whose primary concerns are in scientific areas, (c) at least one member whose primary concerns are in nonscientific areas, and (d) at least one member who represents the perspective of research participants.

Individuals from the Fred Hutch Office of Sponsored Research, the Business Development & Strategy office, the Office of the Vice President for Research Administration, the Office of the Associate Vice President and Chief Ethics and Compliance Office including IRO, cannot serve as voting IRB members.

In carrying out their responsibilities, the IRBs may use the expertise of established Fred Hutch committees and the scientific and administrative divisions. If an IRB reasonably determines that appropriate expertise necessary for its review does not exist within Fred Hutch or on the IRB, the IRB is authorized to hire consultants to provide that expertise. The IRBs may reasonably rely on the expertise provided by outside consultants or internal components of the HRPP in connection with their determination as to whether or not to approve research subject to the HRPP; provided, however, that the IRB remains ultimately responsible for determining whether or not the research satisfies the requirements of this policy and the HRPP including the determination of whether the risks to participants have been appropriately minimized and whether the risks are reasonable in light of the anticipated benefits and the importance of the research.

Except for reasonable reliance on expertise as described in the preceding paragraph, review by the IRB must be independent of other components of the HRPP and must be free from any undue influence or other coercion. Concerns about undue influence, coercion or lack of independence of the IRBs should be reported promptly to the CECO or IO.

The IRB may establish subcommittees to evaluate specific issues of concern and make recommendations to the IRBs. The IRBs may also observe or have a third party observe the consent process or any part of the conduct of any research subject to the HRPP.

f. The Institutional Review Office is managed by the Director of the Institutional Review Office (“IRO Director”). The IRO Director reports to the CECO and is accountable to the CECO and IO for the effective operation of the HRPP and Fred Hutch’s compliance with its FWA. The primary responsibilities of the IRO Director are:

(i.) Managing the IRO and ensuring that the IRO is providing appropriate administrative support to the IRBs;
(ii.) Developing policies and procedures relating to implementation of the HRPP particularly with regard to the operations of the IRBs and for reporting non-compliance with the HRPP or the requirements and determinations of the IRBs;
(iii.) Developing and implementing training programs for persons engaged in research governed by the HRPP including members of the IRB, IRB staff, investigators and research staff;
(iv.) Ensuring that appropriate government agencies are notified of (a) serious or continuing noncompliance with the requirements or determinations of the IRBs, (b) unanticipated problems involving risks to research participants or others or (c) study terminations or suspensions required by the IRB;
(v.) Ensuring that the CECO and IO are advised of (a) any serious or continuing noncompliance with the HRPP or the requirements or determinations of the IRBs, (b) unanticipated problems involving risks to research participants or others, (c) study terminations or suspensions required by the IRB, (d) any concerns about the independent functioning, undue influence or coercion of the IRBs or any of their members relating to their role in the HRPP, or (e) any other serious concerns about the ability of the IRBs to effectively carry out their responsibilities under the HRPP;
(vi.) Providing the CECO and IO with the minutes of all IRB meetings and an annual report on the operations of the IRBs and IRO including an assessment of the adequacy of resources available to effectively carry out their responsibilities under the HRPP;
(vii.) Preparing and presenting the annual budget for the IRO to the CECO for inclusion in Fred Hutch’s annual budget to ensure that the IRO has sufficient resources to function properly including resources to support HRPP education, community outreach and quality improvement;
(viii.) Acting as a liaison between the IRBs, other components of the HRPP and Fred Hutch’s affiliated entities to ensure effective communication among components of the HRPP, effective operation of the HRPP and that no research subject to the HRPP proceeds without the necessary IRB approval;
(ix.) Developing policies and procedures for the disclosure and management of financial conflicts of IRB members as required by the Institutional Conflict of Interest Policy; and
(x.) Ensuring that there are appropriate means for research participants to report questions or concerns about research in which they are participating and that any such questions or concerns are responded to promptly and appropriately.

g. Scientific Review Committee. The Scientific Review Committee (“SRC”) is part of the Protocol Review and Monitoring System (“PRMS”) and provides the formal internal peer review process required of the Cancer Consortium as an NIH comprehensive cancer center.

The SRC has a defined membership representing all of the major clinical research areas of the Consortium, including oncology specialties, laboratory research, biostatistics, population science, pharmacy, and nursing. SRC members are appointed by the Consortium Principal Investigator (Fred Hutch President and Director) for a term of 3 years and may serve additional, consecutive terms.

The SRCs primary responsibilities with respect to the HRPP are:

(i.) Reviewing all interventional clinical trials that meet PRMS review criteria to ensure research is: a) scientifically important; statistically sound; b) designed appropriately without excluding special populations for non-scientific reason; c) feasible, with reasonably attainable accrual targets given the available patient population; and d) supportive of the research mission of the Consortium and providing approval, conditional approval or disapproving the clinical trial reviewed;
(ii.) Providing oversight of SRC-approved trials open to enrollment to ensure (a) the scientific rationale for the protocol has remained relevant and that (b) accrual is sufficient to meet the scientific aims of the trial; and
(iii.) Ensuring that the results of its reviews and any action taken by it with respect to any Consortium research are communicated to the appropriate IRB and the IRO. The SRC has authority to close a study to further accrual with treatment, intervention, and patient follow up continuing, with expedited notification to the IRB.

h. Data and Safety Monitoring Committee. The Consortium Data and Safety Monitoring Committee (“DSMC”) reviews interventional clinical trials that were subject to SRC review and if the intervention involves a drug, device, or biologic. The highest level of review is given to investigator-initiated studies without a data and safety monitoring board (“DSMB”). The DSMC does not routinely oversee clinical trials monitored by another entity including national cooperative group trials and industry-sponsored clinical trials. For applicable trials, the DSMC annually reviews the following:

(i.) For studies without a DSMB, the DSMC will review the following current information: Number of subjects, Unanticipated Problems, Serious Adverse Events, stopping rules, if applicable, list of dose-limiting toxicities and responses that have occurred in the specified timeframe, premature terminations of investigational treatment and any other observations related to subject safety, and a cumulative tabulation of adverse events by type and grade, including deaths, as described by the protocol DSMP.
(ii.) For studies with a DSMB, the DSMC will review: number of subjects, Unanticipated problems, Serious Adverse Events, the DSMB report will be reviewed with regard to accrual, stopping rules, if applicable, adherence to the protocol DSMP and scheduled reviews, together with any recommendations by the DSMB.

DSMC outcomes include the following: Full Approval: Accrual may continue, no changes required; Conditional Approval: Accrual may continue, but protocol changes or other actions are required to improve or assure subject safety; or Suspension: Accrual must stop.
If the DSMC finds that a study is continuing accrual in violation of the study design or the recommendation of a DSMB, the DSMC may suspend trial accrual. If a trial is suspended by the DSMC, expedited notice of the suspension is forwarded to the IRB and to the Clinical Research Oversight Committee (“CROC”) (see Section 4.j.). The outcome of any DSMC review is communicated promptly to the Principal Investigator and the IRB. The PI may respond to any concerns of the DSMC. Such responses are reviewed by the DSMC at its next meeting.

DSMC Compliance Sub-Committee. The quality assurance responsibilities are managed by the CRS Regulatory Affairs and Compliance group and overseen by the Compliance Sub-Committee, which functions under the direction of the CROC. The Compliance Sub-Committee operates under a strict confidentiality agreement.

The Compliance Sub-Committee has two primary responsibilities: 1) identification of significant compliance issues and 2) ensuring adequacy of the monitoring plan for external performance sites associated with Consortium investigator-initiated trials. The group is composed of the CRS Medical Director, the Vice President of CRS, and the Director of Regulatory Affairs and Compliance.

i. CRS Regulatory Affairs and Compliance. CRS Regulatory Affairs and Compliance reviews all monitoring and auditing reports. If issues impacting subject safety or serious, persistent non-compliance are identified these issues are escalated to the DSMC’s Compliance Sub-Committee. Depending on the gravity of the issue, escalation may occur directly to the CROC (see Section 4j below). In addition, CRS Regulatory Affairs and Compliance conducts a prospective review of all monitoring plans for external performance sites and monitors the protocol regulatory file during the conduct of the study to determine compliance with the approved plan.

j. Clinical Research Oversight Committee. The CROC ensures that all aspects of the clinical research process are conducted according to applicable law, Consortium policies, and best practices. The CROC has the following responsibilities:

(i.) Review and enforce all Consortium policies and procedures related to clinical research;
(ii.) Oversee all cancer clinical trials conducted by the Consortium;
(iii.) Advise the Consortium Principal Investigator (Fred Hutch President and Director) on appointments to the Scientific Review Committee and the Data and Safety Monitoring Committee. Provide regular updates to leaders and staff of the Consortium member institutions.

The CROC does not review SRC decisions nor does it review clinical trials for scientific merit or accrual.

k. Clinical Research Support. The implementation and oversight of the Consortium DSMP is provided by CRS. The Vice President of CRS works in partnership with the CRS Medical Director to ensure implementation of this plan. Responsibilities are as follows:

(i.) Provide administrative support to the SRC and the DSMC.
(ii.) Monitor Consortium investigator-initiated trials that are not externally monitored, according to trial size and risk level.
(iii.) Perform routine and focused audits of clinical trials.
(iv.) Review the data and safety monitoring plan of all new investigator-initiated protocols for consistency with the Consortium DSMP.
(v.) Ensure that, where appropriate, protocols have a study-specific DSMB.
(vi.) Train investigators and clinical trial staff in the development and conduct of clinical research.
(vii.) Recommend Consortium-wide policies and procedures for clinical trials and develop strategies for implementation of those policies with oversight and support from the CROC.

l. Office of the General Counsel. OGC is managed by the Vice President & General Counsel of Fred Hutch (“General Counsel”). The Vice President & General Counsel reports to the Executive Vice President and COO (“COO”). The primary responsibilities of the General Counsel with respect to the HRPP are:

(i.) Providing legal advice through the OGC or through outside counsel to all components of the HRPP; and
(ii.) Ensuring that the CECO is advised of the following of which the OGC becomes aware (a) any serious or continuing noncompliance with the HRPP, (b) any concerns about the independent functioning, undue influence or coercion of the IRBs or any of their members relating to their role in the HRPP or (c) any other serious concerns about the ability of the IRBs to effectively carry out their responsibilities under the HRPP.

m. Office of Sponsored Research. The Office of Sponsored Research (“OSR”) is managed by the Senior Director of the OSR, who reports to the Vice President & Chief Financial Officer of Fred Hutch. The primary responsibilities of the OSR with respect to the HRPP are:

(i.) Disbursing funding for research sponsored by government agencies and private foundations to principal investigators to permit the conduct of the sponsored research; and
(ii.) Working with CRS, IRO and OGC to develop and implement policies and procedures to ensure that funding for research governed by the HRPP is not available to principal investigators or their research staffs until all necessary institutional approvals including approval by the IRB are received.

n. Environmental Health and Safety Committees. Fred Hutch’s Environmental Health and Safety Department (“EH&S”) is responsible for the formation and administration of the Radiation Safety Committee (“RSC”) and the Institutional Biosafety Committee (“IBC”). The Director of the EH&S reports to Fred Hutch’s Deputy Chief Operating Officer and is responsible for hiring the radiation safety officer and the biosafety officer.

(i.) Institutional Biosafety Committee. The IBC together with the biosafety officer, EH&S, and IRO is responsible for the development of appropriate policies and procedures to ensure that all research conducted at Fred Hutch facilities and utilizing recombinant DNA and recombinant RNA and synthetic DNA is reviewed and approved as required by applicable government regulations and guidelines including NIH guidelines for research involving recombinant DNA molecules. Fred Hutch’s IBC is responsible for communicating the results of its reviews to the IRB and IRO in appropriate cases, and for providing additional information to the IRB as requested. The IRB will not approve participant accrual for research requiring IBC approval under NIH Guidelines until it has received confirmation of IBC approval. However, the IRB may disapprove or require modifications to research notwithstanding IBC approval if, in the IRBs sole discretion, such action is appropriate to ensure compliance with the HRPP.

(ii.) Radiation Safety Committee. RSC together with the radiation safety officer and EH&S is responsible for the development of appropriate policies and procedures for reviewing and approving the use of radioactive material within Fred Hutch facilities and for helping to ensure that Fred Hutch research utilizing radioactive materials is conducted in accordance with applicable laws and regulations on the use of radioactive materials. Fred Hutch’s Radiation Safety Officer, upon request from the IRB, will review and evaluate the risk to study participants due to the use of radioactive materials or radiation generating equipment in Fred Hutch research involving human subjects and compare this risk to the consent form language. The RSO communicates in writing the results of his or her review to the IRB and IRO and provides additional information to the IRB as requested. The RSO review is not an approval process but a subject matter consultation to provide the IRB and IRO with information and guidance to be considered during their review process. The IRB may disapprove or require modifications to research notwithstanding the results of the RSO review if, in the IRBs sole discretion, such action is appropriate to ensure compliance with the HRPP.

o. Therapeutic Products Program. The Therapeutic Products Program (“TPP”) reports to the Vice President for Research Administration ("VPRA"). TPP is a centralized core within Fred Hutch that provides manufacturing facilities and services for the development and production of a variety of both biologics and cell therapy-related products. Of most relevance to the HRPP are the Biologics Production Facility (“BPF”) and the Cellular Processing Facility (“CPF”). The BPF provides support for the production and purification of antibodies and other cell culture derived products. The BPF is designed to produce two types of monoclonal antibodies from established cell lines: (1) clinical grade, intended for intravenous administration in humans and (2) non-clinical grade for use in research models. Manufacture and purification of products are performed in dedicated clinical and non-clinical areas in compliance with regulatory standards. The CPF provides support for reproducible production of human hematopoietic or immuno-competent cells under stringent quality control and safety conditions required for therapeutic studies, including cGMP requirements. The primary responsibilities of the VPRA with respect to the HRPP are:

(i.) Working with the OGC, CRS and the CECO to ensure that the TPP operates in accordance with applicable laws and regulations;
(ii.) Developing and implementing policies and procedures to ensure that materials manufactured by the TPP are not released until all necessary regulatory and Fred Hutch approvals, including IRB approval, are obtained;
(iii.) Ensuring that the TPP staff as well as investigators using the resources provided TPP have been properly trained and educated to use the relevant resources;
(iv.) Ensuring that there is appropriate communication by TPP with other components of the HRPP, including the IRB and the CECO.

5. Compliance.

Maximizing compliance with the HRPP requires training and education of participants in the HRPP, regular monitoring and evaluation of HRPP operations and an appropriate system for reporting, investigating and addressing noncompliance. In general, each person that manages one of the HRPP essential components is responsible for ensuring that (a) the persons working under him or her are properly trained and educated to carry out their responsibilities under the HRPP, (b) the component is effectively carrying out its responsibilities under the HRPP and impediments to effective operation of the component are addressed if possible or reported to his or her supervisor and (c) matters of noncompliance with the HRPP are reported to either the IRO, the IO, the CECO or OGC or through other normal organizational channels. In addition, the following specific requirements apply:

a. Training and Education. All persons involved in the design, conduct or reporting of research governed by the HRPP must be properly trained, and must be familiar with this policy and applicable laws and regulations relating to such research. Each principal investigator involved in research governed by the HRPP is responsible for ensuring that all persons conducting such research under his or her direction are properly trained and supervised. The IRO Director and the IRO are responsible for developing, implementing and monitoring a training and education program on Fred Hutch policies and procedures and laws and regulations governing research involving human subjects, which will be available to Fred Hutch employees and others participating in research governed by the HRPP.

The Vice President of CRS and staff are responsible for developing, a training and education program on applicable FDA requirements and good clinical practice (GCP).

b. Monitoring. To help ensure appropriate monitoring and oversight of the HRPP, the following activities are mandatory:

(i.) Reports to the ACC. The ACC will receive regular reports from the CECO or his/her designee concerning audits conducted by Fred Hutch or any government or outside agency pertaining to the protection of human subjects and will receive immediate notification concerning matters that could materially and adversely impact patient safety or Fred Hutch operations.
(ii.) CECO Meeting with the IRBs. Not less than once each year, the CECO and the IO will meet with the IRBs to discuss (a) any problems or concerns that the IRBs may have including any problems or concerns with the operation of or compliance with the HRPP or its components or with the IRBs ability to function independently of other organizational units in their role of protecting research participants, (b) ways to address any problems or concerns and (c) possible improvements to the operation and functioning of the IRB within the HRPP. At least part of this meeting must be conducted in executive session without IRO staff. The IRO will be responsible for keeping minutes of these meetings (other than the executive session).
(iii.) Meeting on the Annual Report of IRO Director. At the end of each calendar year, the IRO Director will prepare an annual report concerning the IRBs and the IRO which may include a discussion of (a) key events from the preceding year, (b) problems with and (c) possible improvements to the operations of the IRBs and IRO, and (d) other matters the IRO Director deems relevant. The report will be distributed to the CECO, the IO, the General Counsel, and such other persons as the CECO may direct.
(iv.) Annual Budget. The IRO Director will provide the CECO an annual operations budget as part of Fred Hutch’s regular annual budgeting process. The CECO will determine if the resources are sufficient for the HRPP.
(v.) OGC Meetings with the IRB Chairs. Periodically, but not less than once each year, the General Counsel, the CECO and the IRO Director or their respective designees will meet with the IRB Chairs, and such other persons as the meeting participants may agree to include to discuss any problems or concerns with the effective operation of the HRPP or its components and to discuss ways in which that operation and compliance could be improved.
(vi.) Operations Meetings. Periodically, but not less than once each year, the General Counsel, the CECO, IRO Director, EH&S Director, Vice President for Research Administration or his/her designee, Vice President of CRS, and the Senior Director of OSR or their respective designees, and such other persons as the other participants may agree to include, will meet to discuss problems or concerns with the operation of and compliance with the HRPP and ways they could be improved. Representatives from the Cancer Consortium may be invited to participate in the Operations Meeting by the IRO Director.
(vii.) Internal Audit. From time to time Fred Hutch’s Director of Internal Audit may elect to conduct an audit of the IRBs, IRO or other components of the HRPP on his/her own initiative or at the request of the CECO, or IRBs. The audits will include reviewing the effectiveness of the HRPP; identifying possible areas of HRPP improvement; and, developing, implementing and then assessing the effectiveness of the improvements.
(viii.) External Review. From time to time, but not less than once every five years, the CECO will have an external review of the HRPP conducted. The CECO may, at his/her sole discretion, elect to treat audits and reviews of the IRBs and IRO, or the HRPP by government agencies, accrediting organizations, or external reviewers retained at the request of the ACC as satisfying this requirement. The review will focus primarily on the IRBs and the IRO but may include other components of the HRPP at the discretion of the CECO.
(ix.) Employee Questions, Suggestions and Concerns. Investigators and other employees are encouraged to report questions, concerns or suggestions about the HRPP to the CECO and IRO Director. The IRO Director will work with the CECO to ensure that questions, concerns and suggestions are appropriately addressed.
(x.) Research Participant Questions and Concerns. The IRO Director is responsible for developing appropriate means for research participants to report any questions or concerns about the research in which they are participating and for addressing those questions and concerns appropriately.

c. Reporting of Noncompliance and Sanctions. Non-compliance with this policy, the HRPP or the requirements and determinations of the IRB undermines Fred Hutch’s commitment to protect human subjects involved in research, and it is important that any such non-compliance be reported. It is the obligation of all Fred Hutch employees and others participating in research governed by the HRPP to report allegations, observations or evidence of non-compliance to either the IRO, the IO, the Office of the CECO or OGC, or through other normal organizational channels. The IRO Director is responsible for (i) developing policies and procedures for reporting non-compliance with the HRPP or the requirements and determinations of the IRB and unanticipated problems involving risks to research participants or others and (ii) ensuring that any serious or continuing non-compliance or problem is properly reported to the IO, the CECO, the IRBs and appropriate government agencies. Matters involving serious or continuing non-compliance or unanticipated problems involving risks to research participants or others relating to research reviewed by an IRB must be referred to that IRB for review and possible action including modification, suspension or termination of the relevant research. Serious or continuing violations of the HRPP will also be reported to the IO, the CECO and the Division Director(s) in appropriate cases for consideration of disciplinary action. Intentional or repeated violations of this policy or the HRPP by Fred Hutch scientific personnel or employees may result in immediate suspension or dismissal of employment in accordance with established personnel policies of Fred Hutch.

 

Definitions

The following definitions and abbreviations apply to the terms used in this policy:

“ACC” means the Audit and Compliance Committee of the Fred Hutch Board of Trustees.

“Belmont Report” means 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 Behavioral Research.

“Cancer Consortium” means the Fred Hutchinson/University of Washington Cancer Consortium.

“CFR” means the Code of Federal Regulations.

“CECO” means the Associate Vice President and Chief Ethics and Compliance Officer of Fred Hutch.

“COO” means the Executive Vice President & Chief Operating Officer of Fred Hutch.

“CROC” means the Clinical Research Oversight Committee for the Cancer Consortium.

“CRS” means the office of Clinical Research Support for the Cancer Consortium.

“DHHS” means the United States Department of Health and Human Services.

“Division Director” means a Fred Hutch Senior Vice President & Division Director.

“DSMB” means a local Data and Safety Monitoring Board.

“DSMC” means the Cancer Consortium’s Data and Safety Monitoring Committee.

“DSMP” means the Cancer Consortium’s Data and Safety Monitoring Plan.

“EH&S” means Fred Hutch’s Environmental Health & Safety Department.

“FDA” means the United States Food and Drug Administration.

“Fred Hutch” means the Fred Hutchinson Cancer Research Center including its subsidiary component organizations; Hutchinson Center Research Institute in South Africa and Hutchinson Center Research Institute in Uganda.

“FWA” means Fred Hutch’s Federal Wide Assurance.

“General Counsel” means the Vice President & General Counsel of Fred Hutch.

“HIPAA” means the Health Insurance Portability and Accountability Act Public Law 104-191 (1996).

“HRPP” means Fred Hutch’s Human Research Protection Program.

“IBC” means Fred Hutch’s Institutional Biosafety Committee.

"IO" means the Fred Hutch Institutional Official.

“IRB” means one of Fred Hutch’s Institutional Review Boards.

“IRO” means Fred Hutch’s Institutional Review Office.

“IRO Director” means the Director of the Institutional Review Office of Fred Hutch.

“OGC” means the Office of the General Counsel of Fred Hutch.

“OSR” means the Office of Sponsored Research of Fred Hutch.

“PRMS” means the Cancer Consortium’s Protocol Review and Monitoring System.

“RSC” means Fred Hutch’s Radiation Safety Committee.

“RCW” means the Revised Code of Washington.

“SRC” means the Cancer Consortium’s Scientific Review Committee.

“TPP” means Therapeutics Products Programs.

“VPRA” means Vice President of Research Administration.

Contacts

President and Director

Related Documents

Note

 

Approval