Standard Operating Policy and Procedures (SOPP) 3:

Transcription

1 Standard Operating Policy and Procedures (SOPP) 3: INITIAL AND CONTINUING REVIEW BY THE IRB: REQUIREMENTS FOR SUBMISSION OF APPLICATIONS, APPROVAL CRITERIA, EXPEDITED AND CONVENED COMMITTEE REVIEW AND POST APPROVAL PROCEDURES Introduction Research activities that meet SJU s definition of Human Subjects Research (SOPP1, 2.1.1), but do not meet criteria for exemption (SOPP2, 3) must be reviewed and approved by the IRB. Once approved by the IRB, research protocols are subject to continuing review. This policy describes the criteria under which approval may be granted, and the procedures for applying for IRB approval and continuing review of previously approved research. 1. Policy Statements 1.1. If a research activity (a) constitutes human subject research, and (b) the IRB Administrator determines that the research activity is not eligible for exemption (See SOP2), the protocol must be reviewed under the IRB s Expedited Review or Convened (full board) Review process All study protocols reviewed at the Expedited and Full Board levels are first considered for Exemption. See SOPP2, 1 for submission requirements Research activities may not commence until the PI receives written notice of IRB approval Changes to approved research activities and/or materials must be submitted for IRB review and may not be implemented until the PI receives written notice of IRB approval Researchers are responsible for ensuring full and continuing compliance with all

2 applicable Federal, State, University and IRB regulations/policies in the conduct of their research. 2. Procedures 2.1 EXPEDITED REVIEW. Protocols that do not meet the criteria for exemption (SOPP2, 3) will be forwarded by the IRB Administrator to the IRB for review. The initial IRB review process normally takes up to 10 business days. Within that initial review period, at least one (1) member of the IRB will review the submission and the PI will be notified in writing of the IRB determination: approval, modifications required, or referral to Full Board for review. Determinations are made based on the IRB s assessment of the level of risk to participants. If the reviewer(s) find that the protocol (1) involves no more than minimal risk and (2) meets Expedited criteria as set forth in 45 CFR 46, the following determinations will be reported in writing: APPROVED. Official IRB Approval consists of a letter outlining the scope of the approval. PIs will receive notification from IRBNet when the Approval Letter has been published. The letter is available for download via IRBNet. PI may initiate research activity upon receipt of notice of approval. Expedited approvals are subject to continuing IRB review and require official closure when research is complete (See section 2.3.3) MINOR MODIFICATIONS REQUIRED. The Expedited reviewer(s) may stipulate that approval of the research protocol will be granted only after the PI makes specific minor revisions to the protocol, informed consent documents and/or process, recruitment materials, etc. The PI will receive a notification of the required changes, make revisions as requested and submit them for review via the expedited review process. After all specific minor revisions have been approved, notice of approval will be published in IRBNet and the PI will receive confirmation via . Upon receipt of the notice, the PI may initiate the research activities. If, however, the PI suggests or makes revisions that the reviewer(s) determines affect the risk-benefit ratio of the project, such revisions may be designated as major and referred for review by the Convened IRB. With each modification submission, the IRB will reassess the risk level and determine if the protocol is eligible for expedited approval or requires referral for Full Board review. After all modifications have been reviewed, and notice of approval has been issued in IRBNet, the PI may initiate the research activities MAJOR MODIFICATIONS REQUIRED: The Expedited reviewer(s) may request additional information, substantive clarifications or modifications regarding the

3 protocol, informed consent documents, etc. that are relevant to the evaluation of the risk/benefit ratio required for approval. When major modifications are required, the IRB Chair shall draft and transmit to the PI a memorandum summarizing the required modifications. The PI will have an opportunity to respond to the concerns outlined in the memorandum and to make appropriate revisions to the documents in question. The PI will submit any revisions and responses to the concerns or questions outlined in the memorandum, through IRBNet. The IRB may make one of the following decisions with respect to a revised research protocol application: (1) approved, (2) specific minor revisions required for approval, (3) major modifications, or (4) referral to Full Board. This cycle will continue until the protocol is approved at the Expedited review level, or referred to the Full Board. 2.2 CONVENED (FULL BOARD) REVIEW If the reviewer(s) find that the protocol involves greater than minimal risk, the protocol will be added to an agenda for an upcoming Convened (full board) Meeting. The PI (and Faculty Advisor, when applicable) will be notified of the meeting date and invited to attend (or be available via telephone) to answer clarifying questions that may assist the Board in its review. The following determinations may be made at the Convened meeting and will be reported to the PI in writing within three (3) business days after the convened meeting: APPROVED. Official IRB Approval consists of a letter outlining the scope of the approval. PIs will receive notification from IRBNet when the Approval Letter has been published. The letter is available for download via IRBNet. PI may initiate research activities upon receipt of notice of approval. Full board approvals are subject to continuing IRB review and require official closure when research is complete (See section 2.3.3) MINOR MODIFICATIONS REQUIRED. The Convened IRB may stipulate that approval of the research protocol will be granted only after the PI makes specific minor revisions to the protocol and supporting documentation. The PI will receive a notification of the required changes. If the PI makes the revisions, s/he shall submit them for review via the Expedited Review process. After all specific minor revisions have been approved, notice of approval will be published in IRBNet and the PI will receive confirmation via . Upon receipt of the notice, the PI may initiate the research activity. If, however, the PI suggests or makes revisions that the reviewer(s)

4 determines affect the risk-benefit ratio of the project, such revisions may be designated as major and referred back to the Convened IRB. With each modification submission, the reviewer(s) will reassess the risk level and determine if the protocol is eligible for expedited approval or if the revisions require Full Board review. After all modifications have been reviewed, and notice of approval has been issued in IRBNet, the PI may initiate the research activities TABLED: A protocol is tabled when the Convened IRB requests additional information, substantive clarification and supporting documentation that is relevant to the evaluation of the risk-benefit ratio required for approval. When a protocol is tabled, the IRB Chair shall draft and transmit to the PI a memorandum setting forth the reasons for this action. The PI shall have up to 90 days to respond to any concerns outlined in the memorandum and to make appropriate revisions to the documents in question. The PI will submit any revisions and responses to the concerns or questions outlined in the memorandum, through IRBNet. The IRB may also table a protocol when it does not have a member with expertise adequate to the scope and complexity of the proposed research and thus seeks review by an expert in the appropriate field or when there is lack of time or loss of quorum. In these cases, the IRB will make an effort to accommodate a review of tabled protocols at the earliest possible opportunity. The IRB may make one of the following decisions with respect to a revised research protocol application: (1) approved, (2) specific minor revisions required for approval, (3) tabled, or (4) disapproved. This cycle will continue until the IRB issues a final decision either approved or disapproved. If the PI fails to respond to the concerns in writing within 90 days, the submission will be closed administratively DISAPPROVED: The IRB at a Convened meeting may elect to disapprove a research protocol when it identifies significant concerns about potential risk to participants. The IRB Chair will provide the PI with a written statement of the reasons for the IRB s decision. The PI will have the opportunity to respond in writing and may request an opportunity to present their appeal at a convened board meeting. The IRB, at a Convened meeting will review any written responses and make a decision about the appeal of the initial decision to disapprove the research protocol. As with all protocols, the PI may not initiate the corresponding research activity until the protocol has been

5 approved by the IRB. The PI always has the right to submit a new protocol that addresses the concerns outlined during the initial review. 2.3 POST-APPROVAL Investigator responsibilities do not end upon approval. A PI may not implement an amendment to previously approved research, even if requested by a sponsor, unless and until the PI receives written notice of approval of their application for Amendment (See Section 2.3.1). The IRB will also conduct Continuing Review of all ongoing research protocols no less than once per year. The PI is expected to submit an Application for Continuing Review/Renewal in a timely manner to facilitate meaningful continuing review (See Section 2.4.1). At such a time that the research has concluded (all interactions/interventions with human subjects and/or analysis of identifiable data have ceased), the PI is expected to submit an application for Closure/Final Report (See Section 2.3.3). In addition, federal regulations require prompt reporting to the IRB, appropriate institutional officials, and the department or agency head, of any unanticipated problems involving risks to subjects or others. It is the responsibility of the PI to promptly report (within 1 week) such problems to the IRB through submission of the Unanticipated Problem form in IRBNet. (See SOPP 4) AMENDMENT: A PI may not implement an amendment to previously approved research, even if requested by a sponsor, unless and until the IRB reviews and approves it under the Expedited or Convened Committee Review process, except where necessary to eliminate apparent immediate hazards to human subjects. An amendment is necessary for all modifications or changes to the research protocol. The IRB will review the amendment in the context of the entire research protocol and will approve the amendment before may be incorporated into the approved research protocol. There are two types of modifications: minor modifications and major modifications. Minor modifications to previously approved research protocols are those that meet all of the following criteria: (1) Involve the addition of no more than minimal risk or reduce a risk that was reviewed and approved previously by the Convened IRB; and (2) Involve the addition of procedures or activities that would be exempt from IRB review or eligible for initial review under the Expedited Review process if they were considered independently of the previously approved research protocol. Examples of minor modifications include, but are not limited to: (1) minor increases or

6 decreases in the number of participants; (2) changes in remuneration; (3) changes to improve the clarity of statements or to correct typographical errors in informed consent documents or debriefing texts, provided that the changes do not alter the content or intent of the statements; and (4) additions or deletions of co-investigators or key personnel. Minor modifications may be eligible for Expedited Review. Modifications that do not meet the above criteria are major modifications. Major modifications may require review and approval under the Convened (full board) Review process for protocols previously approved following expedited review, and must be reviewed by a Convened Board in cases of protocols previously approved by a Convened Board Documents to Submit: The PI must submit an Amendment through IRBNet. The PI must attach the Amendment form as well as all new and/or revised supporting documentation and should highlight proposed modifications. These documents will comprise the amendment application Expedited or Convened Committee Review: Upon receipt of the Amendment submission, the IRB Administrator will evaluate the amendment and its risk level to determine whether it is appropriate for review under the Expedited or Convened (full board) Review process. If there is doubt as to whether an amendment qualifies for Expedited Review, it will be reviewed by the Convened IRB. If the amendment is suitable for Expedited Review, that review will take place under the same Expedited procedures outlined above in Section 2.1. If the amendment requires Convened (full board) Review, or is referred for such review by the Expedited Reviewer(s), that review will take place under the same Convened (full board) Review procedures outlined above in Section 2.2, except that all members of the IRB will receive the amendment application for review. Full documentation for the previously approved protocol will also be available to the IRB members CONTINUING REVIEW: The IRB will conduct Continuing Review of all ongoing research protocols in order to ensure that the protection of human subjects is consistent throughout the execution of the research project and that the research protocol is revised, when appropriate. Continuing Review shall not occur less frequently than once per year, but may occur more frequently depending upon the perceived risk of the

7 research activity and the uniqueness of the specific research protocol. Neither the collection of prospective research data nor the performance of researchrelated procedures can occur after the approval expiration date until an Application for Continuing Review for Renewal has been reviewed and approved under the Expedited or Convened (full board) Review process, as appropriate. Data collected after the expiration of a previous approval period, and before the approval of a continuation shall not be eligible for use in the research protocol. Continuing Review is required as long as the research project remains active for longterm follow- up of participants, even when the research is permanently closed to the enrollment of new participants and all participants have completed all research-related interventions. Continuing Review is also required when the remaining research activities are limited to analysis of private identifiable information INTERVALS FOR CONTINUING REVIEW: Research activities are approved for a specific time period and use of any data after expiration of the approval period is considered unapproved research. The IRB will conduct Continuing Review of all ongoing research protocols at intervals relevant to the degree of risk involved, but not less than once per year. The purpose of the Continuing Review is to ensure the continuing protection of human participants in the research and modification of the research, as appropriate, to reduce risk. Research must be reviewed and approved on or before the date of expiration of the current approval period, even though the research activity may not have been initiated until some time after the IRB granted approval. The approval period will be specified in a written approval notice, published in IRBNet. No research may be conducted outside of the time period identified in the approval notice. In accordance with the guidance provided by the OHRP on this topic, SJU IRB recognizes the logistical advantages of keeping the IRB approval period constant from year to year throughout the life of each project. When continuing review occurs annually and the IRB performs continuing review within 30 days before the IRB approval period expires, the IRB may choose to retain the anniversary date as the date by which the continuing review must o PROCEDURES FOR CONTINUING REVIEW: Investigators are responsible for maintaining their IRB approval and for submitting a continuation

8 application to the IRB, as appropriate. As a courtesy and service to the PI, IRBNet is set up to send automatic reminders to PIs, 60 days and 30 days prior to the protocol approval expiration date, requesting that they complete and submit an Application for Continuing Review for Renewal or an Application for Closure if no research with human subjects is expected to continue past the expiration date (See Section 2.3.3) Documents Constituting Protocol Continuation Application: The submission of an Application for Continuing Review for Renewal must include the signatures of all investigators and the faculty advisor (if applicable). Pis must submit the application form through IRBNet in sufficient time to allow review and approval of the application before the expiration date. The PI is also required to submit supporting documentation to include any revisions to the previously approved protocol Continuing Review Process: Upon receipt of the continuation application, the IRB Administrator will verify the completeness of the materials or coordinate with the PI to achieve completion; review the application to determine whether the Expedited or Convened Committee Review process is appropriate; and initiate the review process for the application. The following types of protocols will receive Continuing Review under the Expedited process: (1) a protocol that falls within one of the seven categories of research activities eligible for Expedited Review; OR (2) a protocol that was reviewed and approved previously under the Expedited process and to which no changes have been made that render it appropriate for Convened Committee Review; OR (3) a protocol that was reviewed and approved previously under the Convened Committee process, but meets the following conditions: (i) the research is permanently closed to the enrollment of new subjects; (ii) all participants have completed all research-related interventions; and (iii) the research remains active only for long-term follow up of subjects; OR (a) no subjects have been enrolled and no additional risks have been identified; OR (b) the remaining research activities are limited to data analysis; OR (4) research, where item (3) above does not apply, but the IRB has determined and documented at a Convened meeting that the research involves no greater than

9 minimal risk and no additional risks have been identified. Any protocol which poses or has been revised to pose more than minimal risk will be reviewed under the Convened Committee process. Protocols that initially required Convened Committee Review will generally receive Continuing Review under the same process. The IRB Administrator will attempt to assign continuation applications to the protocol s original reviewer(s). The continuing reviews for the Convened IRB will be added to a future meeting agenda, and every member of the IRB will have access to the complete continuation application in IRBNet Consequences of Failure to Submit for Continuing Review: There is no grace period extending the conduct of the research beyond the expiration date of the approval period. Extensions beyond the expiration date are not granted. If the continuation application is not received as required, and continuation of the research has not been approved, the PI must terminate the research on the date of expiration unless the safety of the research participants would be compromised. Principal Investigators should consult with the IRB on the process for withdrawing human participants from the research protocol when there is concern about their safety Expedited or Convened Committee Review: Upon receipt of the Application for Continuing Review for Renewal, the IRB Administrator will evaluate the amendment and its risk level to determine whether it is appropriate for review under the Expedited or Convened (full board) Review process. If there is doubt as to whether an application for continuing review qualifies for Expedited Review, it will be reviewed by the Convened IRB. If the amendment is suitable for Expedited Review, that review will take place under the same Expedited procedures outlined above in Section 2.1. If the amendment requires Convened (full board) Review, or is referred for such review by the Expedited Reviewer(s), that review will take place under the same Convened (full board) Review procedures outlined above in Section 2.2, except that all members of the IRB will receive the continuation application for review. Full documentation for the previously approved protocol will also be available to the IRB members.

10 CLOSURE At such a time that research activities have concluded (all interactions/interventions with human subjects and/or analysis of identifiable data have ceased), the PI is expected to submit an Application for Closure/Final Report for IRB review and approval. 3. Regulations and Guidance Applicable to Submission of Protocols & IRB Review Procedures 3.1. Federal Regulations CFR 46 (Protection of Human Subjects): Requirement for IRB review and approval of human subject research before its initiation CFR & 21 CFR : IRB Review of Research CFR & 21 CFR : Criteria for IRB Approval of Research CFR : IRB Functions and Operations, including for Expedited Review CFR : Eligibility and Procedures for Expedited Review CFR (b): Requirement for Convened Committee Review when Expedited Review is not used CFR (e): Continuing Review of research by IRB OHRP Guidance on Continuing Reviews, July 11, Ethical Codes The Nuremberg Code (1948) The Belmont Report (1974) Declaration of Helsinki (last revised in 2000)