Section 2: Process of Review

2.1 Submission for Items for Review by the IRB

1.0 Purpose

The purpose of this policy is to describe Organization’s requirements for submission and pre-review of all applications and research related forms and reports.


2.0 Policy

It is the policy of the Organization that all submissions will be processed efficiently by the Office of Regulatory Affairs (ORA) for review in accordance with applicable HRPP policies.


3.0 Submission Requirements


4.0 Deadlines for Submission


5.0 IRB Review Limits


6.0 Determination of Required IRB Review


DOCUMENT HISTORY:

 Written: 4/4/2016 (Approved: 4/4/2016) - original author not recorded

 Revised: 2/5/2018 - revision not documented

 Revised: 7/19/2022 - Deleted list of types of forms for review; clarified which items allowable for submission in paper format; corrected deadlines for submission; clarified maximum number of protocols to be reviewed {Approved Chris Kratochvil (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

 Board Notified: 11/16/2022

2.2 Full IRB Review

1.0 Purpose

The purpose of this policy is to describe the Organization’s requirements for: 1) submission of items required for full IRB review; 2) organization, scheduling, and conduct of full IRB meetings; 3) IRB approval criteria; 4) IRB actions; and 5) IRB documentation of actions.


2.0 Policy

It is the policy of the Organization that:


3.0 Definitions


4.0 Procedures


5.0 Deadlines for PI Responses


6.0 Review of PI Responses


7.0 IRB Approval Periods


8.0 Final IRB Approval Letter


9.0 Review by Other Organizational Committees


DOCUMENT HISTORY:

 Written: 4/4/2016 (Approved: 4/4/2016) - original author not recorded

 Revised: 3/29/2018 - revision not documented

 Revised: 6/2/2021 - Added IRB-05; added definitions (section 3.0); simplified overall by referencing other policies where appropriate; revised procedures to reflect activities during teleconference meetings; clarified when meeting materials will be available (especially for RR-IRB and special review items); revised to delete references to paper copy distribution of materials (all materials available thru RSS); clarified assignment of reviewers; added that chair may vote to break a tie vote; clarified types of other IRB determinations (section 4.9); deleted list of types of items for which documentation of quorum required (section 4.12); revised deadlines for PI responses to be consistent with Policy 2.3. (Expedited Review); clarified that IRB administrator authorized to communicate with investigator to resolve inadequate or incomplete responses to request for minor modifications or clarifications; revised description of contents of condition approval and final approval letters; deleted references to pre-2018 Common Rule and corrected regulatory citations.

 Revised: 10/13/2022 - Modified definition of “controverted issues”; revised throughout to reflect meetings by video conference; clarified identification of members recused; deleted list of materials supplied to members and clarified that materials available in RSS; deleted 20 minute discussion time limit; clarified that IRB approval is distinct from ORA release; deleted IRB action “decline to review”; clarified criteria for disapproval; combined descriptions of contents of core minutes and addended letters; revised policy to require documentation of findings and determinations in the final ORA approval letter as opposed to the initial IRB review letter. {Approved Chris Kratochvil (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

 Revised: 10/13/2022 - amended section numbers due to removal of 4.10.5, amended 8.1.1 to align with heading 8.2, amended 8.2 sequentially to 8.3 (Robert Lewis - IRB Assoc)

 Board Notified: 11/22/2022

 Revised: 11/30/2022 - corrected language in 4.3.3 from: “IRB meetings may be conducted in person, or via video conferencing, as appropriate. In either case If meetings are conducted by video conference, Members will have access to all relevant materials prior to the meeting and will be able to participate actively and equally in all discussions.”, to: “IRB meetings may be conducted in person, or via video conferencing, as appropriate. Members will have access to all relevant materials prior to the meeting and will be able to participate actively and equally in all discussions.” (Robert Lewis - IRB Assoc)

 Revised: 7/31/2023 – revised sections 4.4.5 and 4.6.1.1 to more fully describe the assessment of the need for an expert consultant; added description of items to be reviewed (section 4.6.2); revised 4.10.3.2 to state explicitly that tabled protocols will be returned to the convened IRB for further review. {Approved Rusty McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

 Revised 3/29/2024 – revised criteria for disapproval (section 4.10.4). {Approved Rusty McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

2.3 Expedited Review

1.0 Purpose

The purpose of this policy is to describe the Organization’s requirements for using expedited review procedures for consideration of:

  1. new research proposals;
  2. continuing review of previously approved research;
  3. minor changes in protocol;
  4. minor complaints; and
  5. non-serious noncompliance.

2.0 Policy

It is the policy of the Organization that


3.0 Definitions


4.0 Expedited Review Categories


5.0 Procedures


6.0 Expedited Review Actions


7.0 Development of IRB Expedited Review and Final Approval Letters


8.0 Deadlines for PI Responses


9.0 Review of PI Responses


10.0 Final IRB Approval Letter


11.0 IRB Approval Periods


12.0 Documentation of Expedited Review


13.0 Review by Other Organizational Committees


DOCUMENT HISTORY:

 Written: 4/11/2016 (Approved: 4/11/2016) - original author not recorded

 Revised: 6/13/2018 - revision not documented

 Revised: 3/17/2021 - Clarified that IRB administrator may re-review “inadequate or incomplete responses” by investigators (or refer back to the expedited reviewer for re-review) and further communicate with the investigator to seek modifications or clarifications; deleted regulatory references to pre-2018 Common Rule; deleted list of “other determinations (section 5.4) and referenced policy 2.2 instead; deleted list of other organizational committees (section 13.1) and referenced policy 1.10 instead.

 Revised: 9/16/2021 - Revised time allowed for investigator to respond (section 8.1) to match policy 2.2

 Revised: 8/4/2023 – generally revised for clarity and for consistency with HRPP 2.2; deleted reference to limited IRB review (section 2.4) since the Organization does not utilize limited IRB review, as per policy HRPP 2.8; revised section 5.3 to better describe Expedited Review Procedures; revised section 5.4 to more fully describe Criteria for Expedited IRB Approval and Other Determinations and to clarify requirement for expedited reviewer to determine and document if research needs continuing review; added description of items to be reviewed (section 5.3.2); simplified section 8.0 (Deadlines for PI Responses; clarified that expedited reviewer may refer a protocol to the convened IRB if they believe it would be more appropriately reviewed by the convened IRB (section 6.4.1); corrected typographic and grammatical errors. {Approved Rusty McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

 Revised 1/24/2024 – added section 5.4.1 {Approved Rusty McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

2.4 IRB Review of Changes in Previously Approved Research

1.0 Purpose

The purpose of this policy and procedure is to describe the Organization’s requirements for IRB review of changes in previously approved research, including single subject protocol deviations.


2.0 Policy


3.0 Definitions


4.0 Procedures for Change Request in Protocol (other than Single Subject Protocol Deviation)


5.0 Procedure for Single Subject Protocol Deviation*


6.0 Changes in a research activity requiring immediate implementation


7.0 Provision of new information to subjects which requires immediate implementation


Appendix to HRPP Policy 2.4 (Changes in Previously Approved Research)

Examples of Major and Minor Changes in Protocol or Single Subject Protocol Deviations (per Sections 3.1 and 3.2)

Examples of Major Changes:

 Changes in inclusion or exclusion criteria that broaden eligibility (i.e., broadening the range of the inclusion criteria or narrowing the range of the exclusion criteria) when risks to new subjects will be different than to previously eligible subjects

 Addition of a vulnerable population (e.g., children, cognitively impaired, prisoners, socially or educationally disadvantaged, students)

 Increase in target accrual of subjects in studies where UNMC. CHMC and/or UNO are the only sites

 Increase in study wide accrual of subjects in a multi-institution study

 Increase in subject payment amount that exceeds criteria in HRPP Policy

 Change in study design, where such change might affect risk, potential benefit to subject or scientific value or validity

 Alterations in the dosage or route of administration of an administered drug

 Addition of research activities that carry greater than minimal risk

 Change in research activities where the change might negatively impact the potential benefit of the research (e.g., change from one questionnaire to another which is not substantively similar, or to a non-validated questionnaire; change from CT-based staging to clinically based staging of a tumor)

 Modification of research questionnaires or data collection instruments/processes to collect sensitive information (e.g., depression, sexuality, illegal activities)

 Addition of an element that may affect subject confidentiality (e.g., specimen banking or genetic testing; addition of focus groups or identifiable surveys)

 Extending substantially the duration of exposure to the test material or intervention

 Deletion of laboratory tests, monitoring procedures, or study visits directed at the collection of information for safety evaluations

 Addition of serious adverse events, serious UADEs or other significant risks to the Informed Consent process or form

 Addition of a new (additional) consent form

 Addition of a qualified investigator with a disclosable conflict of interest

 Changes, which, in the opinion of the IRB chairperson or his/her designee, do not meet the criteria or intent of a minor modification

Note: Multiple minor changes in the protocol, instruments, and/or consent may, together, be considered a major change subject to convened IRB review

Examples of Minor Changes:

 Changes in inclusion or exclusion criteria that narrow eligibility (i.e., narrowing the range of the inclusion criteria or broadening the range of the exclusion criteria).

Note: such changes should not appreciably reduce the likelihood that the research can be completed in a timely manner

 Changes in inclusion or exclusion criteria that broaden eligibility (i.e., broadening the range of the inclusion criteria or narrowing the range of the exclusion criteria) when the investigator provides evidence that risks to the new subjects will not be different than to previously eligible subjects

 Increase in local enrollment of subjects in a multi-institution study without a change in the overall study wide enrollment target

 Addition of research activities that constitute no more than minimal risk.

Note: addition of clinically indicated procedures where data will be used for research purposes (i.e., where the incremental risk is no more than minimal) are considered a minor change

 Addition of research activities that would be eligible for expedited IRB review (per §_.110(b)(ii)) under categories 1-7 (unless specifically defined as “major” above)

 Alterations in the dosage form (e.g., tablet to capsule or oral liquid) of an administered drug, provided the dose and route of administration are unchanged

 Decrease in the number or volume of biological samples collection, provided that such a change does not affect the collection of information related to safety evaluations;

 Decrease in the length of hospitalization or number of study visits, provided such a decrease does not affect the collection of information related to safety evaluations

 Alternations subject payment schedule, provided such payments remain fairly pro-rated

 Increase in subject payment amount provided such amounts are within criteria in HRPP Policy

 Changes to improve the clarity of statements or to correct typographical errors in the protocol, CF or any questionnaire, provided that such a change does not alter the content or intent of the statement

 Changes in recruitment materials and advertising, provided such items continue to satisfy criteria in HRPP Policy

 Revision of subject identification and recruitment strategy to include use of the Nebraska Medicine Conditions of Treatment Opt-In database.

 Addition or deletion of qualified investigators or personnel

 Addition of study sites (that have a valid FWA and Reliance agreement as appropriate); or that serve as performance sites where informed consent will not be obtained; or that serve as performance sites where informed consent will be obtained by a UNMC, CHMC or UNO investigator.


DOCUMENT HISTORY:

 Written: 1/5/2016 (Approved: 1/5/2016) - original author not recorded

 Revised: 1/24/2018 - revision not documented

 Revised: 10/4/2018 - revision not documented

2.5 Criteria for IRB Approval

1.0 Purpose

The purpose of this policy and procedure is to describe the Organization’s criteria for IRB approval for human subject research, reviewed both by the full convened IRB or thorough an expedited review process.


2.0 Policy

It is the policy of the Organization human subject research must satisfy certain basic ethical and regulatory requirements, including those described in 45 CFR 46.111 and 21 CFR 56.111.


3.0 Criteria for IRB Approval

Each of the following criteria for IRB approval must be satisfied in full accordance with applicable federal regulations and HRPP policies which contain greater detail about how the IRB interprets and applies these criteria. The criteria must be met before the IRB can grant approval of any submission by expedited review or full IRB review.


4.0 Additional Considerations

In addition to the specific criteria described in section 3.0, the IRB will consider other applicable federal, state and local law and regulations, Organization policies, and basic ethical principles (as described in the Belmont Report, or the World Medical Association Declaration of Helsinki) when deciding whether a research proposal is approvable.


DOCUMENT HISTORY:

 Written: 1/11/2016 (Approved: 1/11/2016) - original author not recorded

 Revised: 1/24/2018 - revision not documented

2.6 Exempt Research

1.0 Purpose

The purpose of this policy and procedure is to describe the Organization’s requirements for determining if a research proposal is eligible for exemption under 45 CFR 46.104(d) and 21 CFR 56.104, with appropriate protections in place for research subjects.


2.0 Policy

It is the policy of the Organization that:


3.0 Categories of Exemption


4.0 Limitations on Categories of Exemption


5.0 Procedures


6.0 Criteria for Approval of Exempt Research


7.0 Actions


8.0 Review by Other Organizational Committees


DOCUMENT HISTORY:

 Written: 1/5/2016 (Approved: 1/5/2016) - original author not recorded

 Revised: 2/5/2018 - revision not documented

 Revised: 8/11/2020 - Clarified eligibility of children for exemption category 2, clarified requirement for documentation of informed consent for exempt research

 Revised: 10/7/2020 - Deleted exempt categories from pre-2019 Rule (section 3.1); other minor clarifications and corrections

 Revised: 2/28/2022 - Corrected typographic errors; deleted references to pre-2019 Rule; other stylistic changes {Approved Russell McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

 Revised: 1/7/2024 – Addition of 3.1.4 (iv) to comply with revised Common Rule {Approved Russell McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

2.7 Continuing Review of Research

1.0 Purpose

The purpose of this policy is to describe the Organization’s requirements for continuing review of approved research


2.0 Policy

It is the policy of the Organization that:


3.0 Continuing Review Frequency


4.0 Criteria for Review


5.0 Investigator Responsibilities


6.0 ORA/IRB Responsibilities


DOCUMENT HISTORY:

 Written: 2/6/2018 (Approved: 2/6/2018) - original author not recorded

 Revised: 9/7/2018 - revision not documented

 Revised: 1/29/2021 - Clarified “procedures that subjects would undergo as part of clinical care” per (45 CFR 46.109(f)(iii)(B)) (section 3.2.3); clarified which IRBs can perform continuing review (sections 5.2 thru 5.5); various minor clarifications and corrections

 Revised: 1/30/2023 – Revised to stress distinction between FDA regulated and non-regulated research; clarified process for submission of demographic information for research that is exempt, or for which continuing review is no longer required (section 6.1.4); deleted requirement that convened IRB be notified of Request to Continue Treatment for Enrolled Subjects on Approval Expired Studies; changed “20 working days” to “30 calendar days”; reformatted; various minor clarifications and corrections. {Approved Chris Kratochvil (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

 Board notified: 1/31/2023

 Revised: 5/17/2023 - Corrected 6.14 to reflect accurate form name, corrected typo of 30 days to 20 days in 6.14.1 (Robert Lewis, IRB Assoc)

 Revised 1/12/2024 - Revised section 4.0 to clarify responsibilities of expedited reviewer; added section 6.1.3 to clarify research approved by expedited review prior to January 2019 may undergo expedited continuing review; revised section 6.7 to clarify materials available to, and expected to be reviewed by, the convened IRB or expedited reviewer; other minor stylistic changes. {Approved Russell McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

2.8 Limited IRB Review

1.0 Purpose

The purpose of this policy is to describe the Organization’s requirements and procedure for limited IRB review.


2.0 Policy

It is the policy of the Organization that the Organization does not utilize limited review as described in 45 CFR 46.104(d)(2, 3, 7 or 8).


DOCUMENT HISTORY:

 Written: 1/24/2018 - (Approved: 1/24/2018) - original author not recorded

 Revised: 6/5/2023 – deleted text; inserted statement that the Organization does not conduct limited review.{Approved Rusty McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

2.9 Closure of On-Going Research

1.0 Purpose

The purpose of this policy is to describe the criteria for, and process of, closing an on-going human research study, and to describe the Organization’s requirements of investigators when studies are closed.


2.0 Policy

It is the policy of the Organization that


3.0. Definitions


4.0. Closure for Inadequate Accrual


5.0. Closure of Studies in Standard Follow-Up


6.0 Closure Procedures


DOCUMENT HISTORY:

 Written: 1/12/2018 (Approved: 1/12/2018) - original author not recorded

 Revised: 1/29/2021 - Added inadequate accrual as reason for closure by IRB (section 3.1.4) and criteria and process for closure (section 4); added prolonged time in standard follow-up as reason for closure by ORA (section 3.1.5) and criteria and process for closure (section 5).

 Revised: 08/10/2023 – clarified that “closure” includes cessation of analysis of identifiable data; deleted definitions of suspension and termination as irrelevant to this policy; clarified possible options for improving accrual; clarified that closure for inadequate accrual, or of studies in prolonged follow-up may (not “must”) occur; clarified investigator responsibilities regarding study closure by the investigator; added that studies closed for failure to respond to “approval expired” notification may not be reactivated, but will require submission of a new application. {Approved Rusty McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}