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HRPP Policy - Reliance
About This Policy
- Effective date:
- Last updated:
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IU Human Subjects Office
This policy applies to the conduct of human subjects research under the jurisdiction of the IU Human Research Protection Program (HRPP). This includes research under the oversight of the IU IRBs and research for which IU or its affiliates are relying on an external IRB for oversight.Back to top
Where appropriate, IU may enter into reliance arrangements, under which IU-affiliated research personnel utilize the services of and rely on an external, reviewing IRB for IRB review and oversight. Alternatively, the IU IRBs may provide IRB review and oversight for non-affiliated research personnel. Reliance may be appropriate for any of the following reasons, among others:
- Sponsor or funding agency request or requirement
- Study is part of an existing network, consortium, or agency which encourages or mandates single IRB review
- Proposed external IRB has already reviewed the study or a similar study
- IRB expertise concerns (e.g., special subject population, untypical research design, sensitive topics)
- Efficiency considerations, especially for collaborating research
- Feedback or request from Institutional Official, HRPP staff, IRB, etc.
- Conflict of interest concerns (e.g., institutional conflict of interest)
Reliance is generally not considered appropriate for the following types of research, unless a compelling reason for reliance exists:
- Research previously approved by the IU IRBs When research has already been approved by the IU IRBs, arguments for potential efficiencies to be gained by use of a single IRB are difficult to make. Transfer of oversight between IRBs places additional burden on both IRB and study staff for little benefit and may give the perception of forum-shopping. In addition, institutional knowledge about a protocol created through multiple IRB reviews is likely to be lost during the transfer process.
- Research for which an IU investigator holds the IND or IDE As the IND or IDE holder, the investigator assumes the responsibilities of the sponsor, resulting in additional responsibility and oversight which make reliance on an external IRB inappropriate.
- Compassionate use protocols when approval of each patient is required by the FDA, IRB, or sponsor in order to provide treatment at the participating institution Since treatment is specific to the local institution, local IRB review is required.
- Comparative effectiveness research, as identified by the HRPP, unless an IRB Chair or member with expertise in the relevant specialty agrees to the reliance. This type of research often compares standard-of-care methodologies which can vary by location and require specific knowledge of local context.
- Planned emergency research Planned emergency research requires a community consent plan which would require specific knowledge of local context; as such, reliance on an external IRB would not be sufficient to protect subjects.
- VA research, unless the reviewing IRB is the VHA Central Office IRB, an IRB of another VA facility, an IRB of another federal agency, or a non-affiliated IRB that has been specifically designated by ORD, pursuant to VHA Handbook 1200.05(f)(8)(a)
When reliance is accepted, the relying institution may not approve the research if not approved by the reviewing IRB and vice versa.
When reliance on an external IRB is requested for research which is greater than minimal risk, the reviewing IRB must be deemed qualified by HRPP and Office of Research Compliance (ORC) leadership in accordance with 3.3 below. Qualification of the reviewing IRB is not required when the reviewing IRB will review only (1) minimal risk research or (2) greater than minimal risk research when IU-affiliated research personnel are only engaged in minimal risk research activities.Back to top
Study teams may request reliance on an external IRB for any of the above reasons by submitting a Reliance Request to the HRPP. HRPP staff evaluate the request, ensure all institutional responsibilities are met, and determine on a case-by-case basis whether reliance on the external IRB is acceptable. If the HRPP determines that reliance is not appropriate, the study must be submitted to the IU IRB for review.
Research personnel conducting VA research utilizing the VA CIRB are not required to submit a Reliance Request.
After the HRPP has accepted reliance on an external IRB for review and oversight of research, the following information must be reported to the HRPP:
- PI and personnel changes
- Changes that require revisions to the HIPAA authorization
- Potential conflicts of interest, including institutional and potential financial interests, that could affect or be affected by the research
- Study closure
Reviewing, external IRBs are evaluated and deemed qualified based on a balance of the following factors:
- IRB has been granted AAHRPP-accreditation
- IRB's membership satisfies the requirements of 45 CFR 46.107 and 21 CFR 56.10 and documentation has been provided
- Policies and procedures for the IRB are publicly available for review, or the IRB has an appropriate process in place for making policies and procedures available to research personnel
- IRB has a process for notifying ORC of determinations of unanticipated problem involving risks to subjects (UPIRTSO), serious and/or continuing noncompliance, suspensions, and terminations
- IRB has a process for ensuring ORC has access to IRB approvals, determinations, and documentation, either in real-time or upon request.
Insufficiency in one of the above factors may be outweighed by consideration of the other factors and does not automatically deem the external IRB unqualified. Qualification requests are approved by the University Director, HRPP, and Associate Vice President for Research Compliance and documented via the IRB Qualification Request.
Study teams may request that the IU IRB provide IRB approval for non-affiliated research personnel. The study team must provide a plan for management and communication of IRB-related information, including ensuring non-affiliated research personnel are familiar with and will follow IU HRPP policies and procedures. The study team must also ensure all required reporting and requests for amendments by non-affiliated research personnel are submitted to the IU IRB, and IRB decisions and approved documents are communicated to sites and/or non-affiliated research personnel. HRPP staff evaluate the request, ensure all institutional responsibilities are met, and determine on a case-by-case basis whether reliance is acceptable. If the HRPP determines that reliance is not appropriate, the non-affiliated research personnel must obtain IRB approval from an appropriate, external IRB for their participation in the research.
When non-affiliated research personnel are conducting the research on behalf of an external institution, the external institution must agree to rely upon the IU IRB for IRB review and approval of the research personnel's participation.
When the IU HRPP agrees to rely on an external IRB, or when an external institution agrees to rely on the IU IRB, the responsibilities of the reviewing IRB and the relying institution are documented through a written agreement between the reviewing IRB and the relying institution (e.g. reliance agreement). When the IU IRB provides approval for non-affiliated research personnel in research not federally-funded who are not conducting research on behalf on an institution, the research personnel must provide written attestation of knowledge of and agreement to follow the IU HRPP Policies. Alternatively, the HRPP may determine that an agreement or attestation is unnecessary and that responsibilities may be documented in institutional policy or the specific research protocol.
When IU extends its Federalwide Assurance to cover non-affiliated research personnel, the extension will be documented by a written agreement signed by IU, the IU PI, and the non-affiliated research personnel.
Responsibilities are governed by the relevant reliance agreement, where applicable, and the reviewing IRB and relying institution shall comply with all terms and conditions of the reliance agreement. At a minimum, responsibilities should include those listed below.
Reviewing IRB Responsibilities
Unless otherwise dictated by the written reliance agreement, the reviewing IRB shall:
- Perform initial and continuing review and review amendments and reportable events for all sites
- Ensure criteria for approval are met for all research and all sites, taking into account local context information provided by relying institution
- Review consent forms, when applicable
- Make Privacy Board determinations per HIPAA, when applicable
- Consider conflict of interest determinations, including any management plans, relating to the research and ensure plans are incorporated into IRB review as applicable
- Notify PI of IRB decisions, etc., and ensure appropriate communication plan for dissemination between sites
- Maintain appropriate IRB records and documents relating to the IRB review, and make records available to relying institution upon request
- Notify the relying institution of any of the following which relate to the conduct of research at the relying institution
- Serious and/or continuing noncompliance, suspensions, and/or terminations
- Audits, including findings and corrective actions
- Reporting to a federal agency
- Communication with regulatory agencies
Relying Institution Responsibilities
Unless otherwise dictated by the written reliance agreement, the relying institution shall:
- Ensure research personnel are appropriately qualified and meet relying institution standards for eligibility to conduct research, including but not limited to human subjects protection training and collection and maintenance of conflict of interest disclosure forms
- Provide local context information to the reviewing IRB and ensure required information is incorporated into IRB-approved documents
- Ensure research personnel are notified of their responsibilities when conducting research pursuant to a reliance agreement
- Ensure compliance with the reviewing IRB determinations and requirements, applicable federal regulations, and all applicable state and local laws and institutional requirements
- Ensure appropriate monitoring of research and perform reviewing IRB-directed audits upon request
- Establish a process for reviewing conflicts of interest and creating management plans when appropriate
- Notify the reviewing IRB of any of the following which relates to research under the oversight of the reviewing IRB:
- Serious and/or continuing noncompliance
- Restriction/suspension of research activities
- Audits, including findings and corrective actions
- Communication with regulatory agencies
- Legal claims
- Research misconduct
- Receive notifications of issues from the reviewing IRB and take additional local action, if applicable
IU IRB Responsibilities
Unless otherwise dictated by written agreement, the IU IRB retains the following responsibilities even when IU has relied upon an external IRB for review:
- Provide IRB review upon request by the HRPP or the institution. This may include local review of reviewing IRB determinations of unanticipated problem involving risks to subjects or others (UPIRTSO), serious/continuing noncompliance, suspensions and terminations.
- Review reports of audits conducted by the ORC Human Subjects Auditors.
Research Personnel Responsibilities
IU-affiliated research personnel conducting research for which an external, reviewing IRB has provided approval must fulfill all responsibilities outlined by the IU HRPP Policy on Research Personnel Responsibilities, plus the following:
- Submit Reliance Request via KC IRB
- Obtain IRB approval for conduct of the research by IU-affiliated research personnel from the reviewing IRB, including ensuring all IU-affiliated research personnel are listed on the IRB documentation as required by the reviewing IRB
- Ensure the IRB-approved documents are accurate and consistent with conduct of the research by IU-affiliated research personnel
- Conduct research in accordance with the reviewing IRB's policies and procedures, the IRB-approved documents and conditions of approval, and any applicable laws and regulations
- Ensure all IU-affiliated research personnel are appropriately qualified and have met IU or IU-affiliate standards for eligibility to conduct research, including but not limited to human subjects protection training and disclosure of conflict of interest disclosure forms
Individuals found to be in violation of this policy may be subject to sanctions relating to their participation in research with human subjects, up to and including permanent suspension or debarment from engaging in research with human subjects at Indiana University.Back to top
IU HRPP Policies
Related Policy Documents
IU HRPP Guidance
Related Guidance Documents
IU HRPP Documents
Related IRB Questionnaires
- Reliance Request
- Questionnaire C – Sites & Collaborations
Related Forms and Templates
- IU HRPP Reliance Forms
- IRB Qualification Request
- Research Personnel Responsibilities
- Relying Site Local Context Checklist
- Relying Site Personnel List
- IU-PU-ND Request for Deferral Form
- Non-Affiliated Investigator Agreement
- AAHRPP Standards
- Standard I-9
- NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research
- SMART IRB master reliance agreement and online reliance system
- VHA Directive 1200.05 - Requirements for the Protection of Human Subjects in Research, especially 1200.05(5)(f)(8)(a)
audit (see also for-cause (directed) audit, internal audit, and not-for-cause (scheduled) audit) A systematic and independent examination of study-related activities and documents to determine whether the evaluated study-related activities were conducted, and the data were recorded, analyzed, and accurately reported, according to applicable federal regulations, state laws, and institutional policies. Includes audits, monitoring visits, and compliance inspections.
continuing noncompliance (see also noncompliance, minor noncompliance, observed or apparent noncompliance, serious noncompliance) A pattern of the same or similar instances of noncompliance, occurring in reasonably close proximity, which continues to occur after discovery of noncompliance and implementation of a preventive action plan, or results from failure to implement a preventive action plan approved by the IRB.
corrective action Action taken to correct a noncompliant situation that has occurred.
federalwide assurance (FWA) Written assurance of compliance with the Common Rule to OHRP from institutions engaged in non-exempt human subjects research conducted or supported by HHS.
HIPAA The Health Insurance Portability and Accountability Act of 1996. See also Privacy Rule.
investigator (FDA, see also research personnel, IU-affiliated research personnel, key personnel, non-key personnel, non-affiliated research personnel, principal investigator (PI), student, fellow, resident PI, site-specific PI) In research subject to FDA regulations, an individual who actually conducts a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to, or used involving a subject, or, in the event of an investigation conducted by a team of individuals, is the responsible leader of that team.
IU-affiliated research personnel (see also research personnel, Investigator, key personnel, non-key personnel, non-affiliated research personnel, principal investigator (PI), student, fellow, resident PI, site-specific PI) research personnel who are Indiana University faculty, staff, and students or employees and staff of IU affiliate institutions that have contracted with the IU IRBs for review and oversight of human subjects research. IU affiliate institutions include Goodman Campbell Brain & Spine, Eskenazi Health, Indiana State Department of Health, IU Health, Purdue Pharmacy Practice, Regenstrief Institute, Rehabilitation Hospital of Indiana, Roudebush VAMC, and Sigma Theta Tau International.
minimal risk The probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.
non-affiliated research personnel (see also research personnel, Investigator, IU-affiliated research personnel, key personnel, non-key personnel, principal investigator (PI), student, fellow, resident PI, site-specific PI) Research personnel who are not faculty, staff, or students of IU, or employees or staff IU affiliate institutions.
noncompliance (see also continuing noncompliance, minor noncompliance, observed or apparent noncompliance, serious noncompliance) Any action or activity associated with the conduct or oversight of research involving human subjects that fails to comply with federal or state regulations, requirements of VHA Handbook 1200.05, or institutional policies governing human subjects research or the requirements or determinations of the IRB.
principal investigator (see also research personnel, Investigator, IU-affiliated research personnel, key personnel, non-key personnel, non-affiliated research personnel, student, fellow, resident PI, site-specific PI) Responsible leader of a team of research personnel who has the ultimate responsibility for the conduct of the research.
privacy board Under the Privacy Rule, the group of individuals charged with the review and approval of waivers of authorization.
regulatory agencies Government organizations, anywhere in the world, that set standards, establish policies, advocate laws, and provide oversight of specified activities within a country, such as the United States Food and Drug Administration (FDA).
reliance An instance of IRB review when one or more relying institutions choose to accept IRB review and oversight for a research project from another institution's reviewing IRB. In these situations, the reviewing IRB provides IRB review and oversight for conduct of the research at the relying institution(s).
relying institution An institution that agrees to accept IRB review and oversight from a reviewing IRB.
reportable event An event which may represent noncompliance or an unanticipated problem involving risks to subjects or others. Reportable events are reported to the IRB in accordance with the IU HRPP Policy on Reportable Events.
research A systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge (Synonymous with clinical investigation For research subject to FDA regulations, any experiment that involves a test article and one or more human subjects, and that either must meet the requirements for prior submission to the FDA under §505(i), §507(d), or §520(g) of the Food, Drug & Cosmetic Act, or need not meet the requirements for prior submission to the FDA under these sections of the act, but the results of which are intended to be later submitted to, or held for inspection by, the FDA as part of an application for a research or marketing permit. The term does not include experiments that must meet the provisions of part 58 regarding nonclinical laboratory studies (21 CFR 50.3(c)).) The following activities are deemed not to be research under this definition: Scholarly and journalistic activities (e.g., oral history, journalism, biography, literary criticism, legal research, and historical scholarship), including the collection and use of information that focus directly on the individuals about whom the information is collected; Public health surveillance activities, including the collection and testing of information or biospecimens, conducted, supported, requested, ordered, required, or authorized by a public health authority. Such activities are limited to those necessary to allow a public health authority to identify, monitor, assess, or investigate potential public health signals, onsets of disease outbreaks, or conditions of public health importance (including trends, signals, risk factors, patterns in diseases, or increases in injuries from using consumer products). Such activities include those associated with providing timely situational awareness and priority setting during the course of an event or crisis that threatens public health (including natural or man-made disasters); Collection and analysis of information, biospecimens, or records by or for a criminal justice agency for the activities authorized by law or court order solely for criminal justice or criminal investigative purposes; Authorized operational activities (as determined by each agency) in support of intelligence, homeland security, defense, or other national security missions.
research personnel (See also investigator, IU-affiliated research personnel, non-key personnel, non-affiliated research personnel, principal investigator (PI), Student, Fellow, Resident PI, site-specific PI) Individuals engaged in human subjects research; specifically, individuals who interact or intervene with human subjects or access identifiable information for research purposes. May also be called investigators.
reviewing IRB The IRB responsible for review and oversight of a research project. Also known as the IRB of record or the single IRB (sIRB).
serious adverse event (SAE) Any adverse event that results in death, a life-threatening experience, inpatient hospitalization, prolongation of hospitalization, persistent or significant disability/incapacity, congenital anomaly, or birth defect, or that requires medical or surgical intervention to prevent such an outcome.
sponsor An individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of research.
suspension Temporary cessation of some or all activities in a currently approved research study.
termination Determination made by the IRB to permanently withdraw approval for some or all activities of a currently approved research study.
unanticipated problem involving risks to subjects or others (UPIRTSO) In general, this includes any incident, experience, or outcome that meets all of the following criteria: 1) is unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied; 2) is related or possibly related to participation in the research ("possibly related" means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); and 3) suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.Back to top