Continuing Review VA Requirements Kevin L. Nellis, M.S., M.T. (A.S.C.P.) Program Analyst Program for Research Integrity Development and Education (PRIDE)

Topics IRB and Investigator requirements of continuing review IRB approval dates Requirements when IRB approval expires 2

Continuing Review Research Must be Substantive and Meaningful Includes, but not limited to: Review of the ongoing level of risks and benefits Assessment of the need for special safeguards to protect subjects Review of the adequacy of ongoing protection for potentially vulnerable individuals 3

Considerations for Continuing Review IRB must conduct continuing review of research at intervals appropriate to the degree of risk, but not less than once per year [38 CFR (e)] IRB must have written procedures for determining which projects require review more often than annually (38 CFR (b)(4)(ii)). Review may be by the convened IRB or by expedited review, if appropriate IRB approval criteria must be satisfied 4

Investigator Submits Protocol Summary & Written Status Report Brief summary of the research methodology Number of subjects entered and withdrawn (including reason) for the review period and since the inception Summary of complaints regarding the research since the last IRB review Gender and minority status of those entered into protocol, if appropriate Number of subjects considered to be members of specific vulnerable populations 5

Investigator Submits Protocol Summary & Written Status Report Copy of the current informed consent form(s) and any new proposed informed consent form(s) along with a description of changes in the new form Current HIPAA authorization List of all amendments since last IRB approval Information that may impact on the risk benefit ratio, such as SAEs and complaints regarding the research 6

Investigator Submits Protocol Summary & Written Status Report Summaries, recommendations, or minutes of the Data Monitoring Committee (DMC) meetings (if applicable) or findings based on information collected by the data and safety monitoring plan Assurance that all identified unanticipated internal or local SAEs, have been reported as required to the IRB of record Summary of all unanticipated problems involving risks to subjects or others, and all internal or local SAEs 7

Investigator Submits Protocol Summary & Written Status Report Research findings to date, if available Relevant multi-center trial reports New scientific findings in the literature, or other relevant findings, that may impact on the research PI statement certifying that all subjects on the master list signed an informed consent form prior to undergoing any study interactions or interventions (unless waived by IRB) 8

At Continuing Review All IRB members must receive and review a protocol summary and a status report on the progress of the research At least one voting member of the IRB (i.e., a primary reviewer) needs to receive a copy of the complete protocol, including any modifications previously approved by the IRB. All IRB members have access to the complete IRB protocol file and relevant IRB minutes 9

IRB Ensures Approval criteria are satisfied Informed consent is accurate and complete Informed consent form, HIPAA authorization, and protocol are consistent Significant new findings that may affect the subject’s willingness to continue participation are provided to the subjects 10

Expedited Continuing Review If expedited, IRB Chair or designee should receive and review all documentation and complete protocol Reminder: Determinations and protocol-specific findings justifying those IRB determinations must be documented in either the IRB protocol file or the minutes 11

Master List of Subjects IRB must ensure that the master list of subjects entered into the study contains only those subjects who have signed an informed consent form (unless waived) May rely on assurances from the PI and audits conducted by the RCO 12

13 IRB Approval Date – Convened IRB No Conditions = date of the convened IRB meeting at which approval was granted Minor Conditions = date the study was approved by the convened IRB contingent on minor conditions being addressed (NOT the date that the conditions are verified) Note: Substantive Conditions = defer approval

14 IRB Approval Date – Expedited IRB All conditions met = date the IRB Chair, or experienced IRB voting member(s) designated by the IRB Chair, signs IRB approval to the research study

If Approval Expires Local research office must promptly notifying the investigator Investigator must stop all research activities including, but not limited to Enrollment of new subjects Continuation of research interventions or interactions with currently participating subjects Data analysis. 15

If Approval Expires Investigator must immediately submit to the IRB Chair a list of research subjects who could be harmed by stopping study procedures. IRB Chair, with appropriate consultation with the Chief of Staff, determines if subjects on the list may continue participating in the research interventions or interactions 16

If Approval Expires Once the study approval has expired, IRB re-review and re-approval must occur before the study can resume The IRB cannot retrospectively grant approval to cover a period of lapsed IRB approval 17

“30 Day Rule” When continuing review occurs annually and the IRB performs continuing review within 30 days before the IRB approval period expires, the IRB may retain the anniversary date as the date by which the continuing review must occur. There is no provision for any grace period to extend the conduct of research beyond the expiration date of IRB approval. Therefore, continuing review and re-approval of research must occur on or before the date when IRB approval expires. 18

Timeline Example Convened IRB - No Conditions Convened IRB meets on March 15, 2009 and approves the protocol with no conditions Continuing review and re-approval of research must occur on or before the date when IRB approval expires, or March 15,

Timeline Example Convened IRB - Minor Conditions Convened IRB meets on March 15, 2009 and approves the protocol with minor conditions Investigator completes changes on March 20, 2009 IRB Chair verifies conditions are met on March 25, 2009 Continuing review and re-approval of research must occur on or before the date when IRB approval expires, or March 15,

Timeline Example - Expedited IRB IRB chair reviews protocol on March 15, 2009 and request more information from Principal Investigator Investigator makes additional changes and resubmits protocol on March 20, 2009 IRB Chair reviews final changes and approves protocol on March 25, 2009 Continuing review and re-approval of research must occur on or before the date when IRB approval expires, or March 25,

Timeline Example - “30 Day Rule” IRB approval of a protocol is set to expire on March 25, 2010 The IRB reviews and approves the protocol at a convened meeting on March 15, 2010 Continuing review and re-approval of research must occur on or before the date when IRB approval expires, or March 25,

Key Points Continuing review must be meaningful, substantive, and timely Investigators must submit required information Understand timeline for when continuing review and approval must occur Prevent expiration of IRB approval Understand what to do if IRB approval expires 23

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