What Happens After IRB Approval?

1. What Happens After IRB Approval? Aliese Seawright, MS, CIP Human Research Protection Program 4.20.2012 1

2. Changes to Previously Approved Research Federal Regulations and IRB policy require that all changes in research, no matter how minor, be reviewed and approved by the IRB before being implemented except when necessary to eliminate apparent immediate hazards to the human subjects. OHRP 45 CFR 46.104(b)(4)(iii) and FDA 21 CFR 56.108(a)(4) 2

3. Changes to Previously Approved Research All these terms are used interchangeably. 3

4. Changes to Previously Approved Research Full Committee Review: Amendments that do not meet the criteria for expedited review must be reviewed by the Full Committee at a convened meeting. Expedited Review: Amendments that meet the criteria for expedited review will be reviewed by a Chair or Chair designee according to the Expedited Review procedures. Expedited Review or Full Board Review? 4

5. Changes to Previously Approved Research Modifications that do not fulfill the above criteria may require Full Board review. 5

6. Changes to Previously Approved Research

7. Changes to Previously Approved Research IMPORTANT NOTE: These above tables may be used as guidance for the investigators but the IRB will make the final determination of appropriate review level. 7

8. Changes to Previously Approved Research The principal investigator should evaluate whether an amendment is major or minor using the tables above as a guide. The determination depends on whether risks to participants are increased and the complexity of the changes. Major modifications require more intensive review than minor or administrative changes. Contact the IRB if you have questions about how to submit a modification. Review and Approval Criteria: The criteria for reviewing and approving an amendment are the same as those for initial review. When reviewing the recruitment, screening and/or consent documents, the IRB will ensure the following: • The currently approved or proposed documents are complete, accurately reflect the information in the study application, and meet all the regulatory and institutional criteria for approval. • Any new findings that may relate to the subject’s willingness to continue participation are provided to the subject in an updated informed consent form or other approved form of communication. The approval period does not normally change following IRB approval of an amendment to a protocol. 8

9. Continuing Review of Previously Approved Research How often is Continuing Review Required? • Continuing review of all research involving human subjects is required at least annually (CFR 46.109(d) and 21 CFR 56.109(d)) o Even if no changes are made, o Even if the only study activity is participant follow-up, and o Even if the only study activity is data analysis. • The IRB may require more frequent review depending on the level of risk. • At LSUHSC-S studies that have been determined as exempt will automatically be closed after three years unless a request to renew the study is submitted. 9

10. Continuing Review of Previously Approved Research Reminders and Notices • As a courtesy the IRB sends out continuing review reminders approximately 60 and 30 days before studies expire. Additionally, the IRB staff may also follow up with investigators. • Investigators are advised to complete the Continuing Review Application and submit the required accompanying documentation at least thirty days prior to the study’s approval period end date. • However, it is ultimately the investigator’s responsibility to initiate a continuing review application and to allow sufficient time for the review and re-approval process to be completed before the current approval period expires. 10

11. Continuing Review of Previously Approved Research Importance of Avoiding Lapses in IRB Approval • If an IRB approval expires, ALL RESEARCH ACTIVITIES INVOLVING HUMAN SUBJECTS MUST STOP! These activities include subject contact, data collection and data analysis. The only exception to this requirement is for activities that are needed for participant safety. Contact the IRB immediately if this occurs. No new subjects may be enrolled. • The IRB determines on a case-by-case basis whether treatment may continue for currently enrolled subjects after a study has lapsed in approval. The IRB will notify the investigator if it is permissible under federal guidelines to continue limited research activities. If any data is collected during an approval lapse, it cannot be used for research unless approved by the IRB. 11

12. Continuing Review of Previously Approved Research Importance of Avoiding Lapses in IRB Approval • If study activities occur or continue after the expiration date, the investigator is out of compliance with both federal regulations and institutional policy. Retrospective approval for work done after the expiration date cannot be granted. Even if the continuing review application has been submitted to the IRB, all activities must stop until approval is granted. • The application for continuing review will ask for details about any lapses and will also ask for a corrective action plan to ensure such lapses do not occur in the future. 12

13. Approval Period The IRB will indicate a protocol approval period with an Approval Start Date and an Approval End Date. These two dates will be specified for each initial protocol that is approved and for each protocol that is approved at the time of continuing review. IRB approval will lapse at midnight on the end date of the approval period. The study’s IRB approval start date and approval end date are clearly printed on all IRB Notices of Approval sent to the principal investigator. The IRB staff will also stamp the upper right hand corner of the consent document with the approval period. Approval Start Date: Approval End Date: mm-dd-yyyy mm-dd-yyyy

14. Continuing Review of Previously Approved Research Appropriate Levels of Review Full Committee Review: Human research which does not meet the criteria for expedited review must be reviewed by the Full Committee at a convened meeting. A protocol which initially required Full Committee review and approval will be reviewed by the Full Committee unless the study meets the requirements for expedited review under federally defined expedited review categories at 45 CFR 46.109 or 21 CFR 56.110. 14

15. Continuing Review of Previously Approved Research Appropriate Levels of Review Expedited Review: A protocol which initially was reviewed using the expedited review procedures may be reviewed for continuing review under the expedited review procedures. However, research protocols that previously met the criteria for expedited review will require Full Committee review if changes to the protocol are submitted which: (1) present more than minimal risk to human subjects or (2) involve procedures which do not meet the criteria for expedited review. 15

16. Continuing Review of Previously Approved Research Review Criteria Continuing review of research must be substantive and meaningful. The criteria for continuing review are the same as those for initial review. Therefore, the IRB must determine that all of the federal and institutional requirements are satisfied. Determining Appropriate Interval for Continuing Review The IRB will determine when research requires review more often than annually in order to ensure the continued protection of the rights and welfare of the research subjects. The IRB considers the following factors, along with any other relevant factors, in determining the frequency of review: the nature of the study, the degree of risk involved and the vulnerability of the study subject population. 16

17. Study Closure • All studies require a study close out report. • Use the Study Closure Form found on the HRPP website. • Study Closure Forms should not be submitted until after any close-out monitoring visit scheduled by the sponsor or sponsor's agent. • A copy of the report generated by the close-out visit must be submitted to the IRB. • The Principal Investigator must report closure of a research study to the IRB immediately or within thirty (30) days of closure. 17

18. Study Closure • Study activities that occurred within the current review period must be reported. • This report updates the IRB on the conduct and outcomes of the study, including any risks or problems that may have arisen since the last study renewal and which may need to be disclosed to the study participants or others. 18