Study Close-Out Procedures

2. Study Close-Out Procedures Training for Investigators and Research Personnel

3. Pop Quiz D Name a department that the Principal Investigator and/or designee should notify to proceed with closeout procedures? • The Contracts and Grants Accounting Office (CGA) • The Office of Sponsored Programs (OSP) • Selection A • Selections A and B

4. Pop Quiz False True or false: The Principal Investigator or designee may wait to close a study upon their next IRB continuing review as long as the sponsor has requested that the study close.

5. Pop Quiz D You must ensure that all of the following departments are aware that a study is closing except for: • The Institutional Review Board • Contract and Grants Accounting • Office of Sponsored Programs • Office or Research Resources

6. Definition of Study-Closure This relates to the closure of a study at a participating site once all subjects have completed the study and all data queries have been resolved. Global Health Training Center

7. Three Areas of Focus • Site – This refers to closing the study with sponsor approval and all the site procedures that are involved in closing the study at the site level • IRB – This refers to closing a study with the IRB and what that entails • Office of Sponsored Programs (OSP) and Contracts and Grants Accounting (CGA) – This refers to closing out the fund and determining the amount of residual funds left in the study-specific account

8. Site

9. Site • Study Forms • Ensure that all outstanding Case Report Forms (CRFs) have been corrected, completed, collected, organized and filed. • Make sure that all data queries are corrected and resolved • Ensure that all serious adverse events (SAEs) have been reported to the DSMB (or Safety Monitor), sponsor, IRB, and other organizations as specified in the protocol. • All adverse events and serious adverse events should be recorded and followed up to resolution in accordance with the protocol. http://www.ppru.org/Doc/StudyManagement/studycloseout.doc.

10. Site • Study Files • The investigator’s study files should be complete and up-to-date with originals of the following maintained in the Study Binder, as relevant: • Investigators’ Curriculum Vitae(s) (CVs), Investigator’s Brochure(s) • Protocol, all amendments, Informed Consents, annual reviews and advertisements (including updated approvals) • IRB membership list • All IRB correspondence (i.e. IRB approval letters) • All sponsor correspondence • Site signature log • Drug accountability records documenting the investigational product received, dispensed and returned or destroyed • Note that • All informed consents are signed and on file. • Record retention procedures are in place and conform to protocol and/or institutional requirements, whichever is longer (type and length of retention, consequences of improper record retention. • Indication of any study materials which will be shredded. (If Applicable) • Individual to contact for study files. (If Applicable) http://www.ppru.org/Doc/StudyManagement/studycloseout.doc.

11. Site • Clinical Supplies • Clinical supplies, such as lab kits, have been shipped or disposed of according to protocol directions. • Drug accountability records (shipping, receipt, dispensing, return or destruction) are up to date. (IP or devices) • Laboratory Records and Specimen Retention • Laboratory records are complete and up to date (reference ranges, laboratory certifications, specimen tracking records, specimen storage records). • A plan for storage/retention of samples and maintenance of patient confidentiality is in place. • Study specimens have been shipped to the analysis center. http://www.ppru.org/Doc/StudyManagement/studycloseout.doc.

12. Site Level • Notifications and Equipment Removal • A final report has been prepared (or will be prepared) for the Institutional Review Board (IRB). The report is likely to include, but is not limited to, study conduct and outcome, pertinent safety and efficacy observations, complete disclosure of any SAEs experienced during the course of the study, and the study close-out date. • An announcement on the study outcomes, including a report on study progress may be submitted to site by sponsor. • Arrangements for the removal and shipment of any study specific equipment received by the site (e.g., computers, diagnostic equipment, and participant monitoring devices) have been made. • Participant Rights and Notifications • A letter to thank each study participant has been prepared that includes the following information, as relevant: • Study findings • Treatment assignment • Explanation of reason for close-out • Treatment options: whether continued treatment with the assigned medication is indicated, and how and where treatment may be obtained • Transfer of care responsibilities • Rights to confidentiality, privacy, and to no further contact from study staff, it that is participant’s preference • Subsequent updates or recalls if new and important information emerges following separation • As relevant and depending on publication status, a copy of the first study article, or a copy of the letter should be included in the participant’s file. http://www.ppru.org/Doc/StudyManagement/studycloseout.doc.

13. Site Level NIH provides a very helpful checklist for closing out a study https://www.nidcr.nih.gov/research/toolkit/Documents/Study_Close_Out_Checklist_approved_v20.docx.

14. IRB • Sponsored Studies • The sponsor should submit a letter to your department stating that the study has closed and why it has closed • This letter gets added to “Other Study Documents” on iRIS and is submitted along with the “Study Closure Form” • The “Study Closure Form” lets you select why the study is closing • For Example: • Completed • Cancelled • Investigator-Initiated Studies • Once the PI has determined that the study is completed due to enrollment or that the study should be cancelled due to funding a “Study Closure Form” should be submitted

15. IRB

16. Please Note • Once a study is closed the IRB is no longer able to accept any submissions. • Prior to submitting the study closure form, all data must be de-identified and stored separately from any information that may identify the participants. • Additionally, any and all other identifiable information (i.e. videos, tapes, etc…) that the protocol or IRB application targeted for destruction at study completion must be destroyed. • A note-to-file must be created indicating what items are being destroyed for they study record.

17. Remember • The IRB shall retain IRB paper files for three (3) years after the final expiration date of the research study. • Electronic files are maintained in iRIS for a minimum of three (3) years after final expiration date of the research study. • All research records (including consent documents) must be kept for a minimum of three years after the close of the study at the local research site. Studies that involve drugs or devices seeking FDA approval must be kept for two years after the FDA has taken final action on the marketing application, or as directed by the Clinical Trial Agreement.

18. Contracts and Grants Accounting • Definitions • Residual AmountsResidual amounts are amounts remaining in a restricted FOP at the conclusion of a drug study, clinical trial, or other research project. A restricted FOP is established to account for the fiscal activity of research sponsored by a source external to TTUHSCEP. All amounts received from the sponsor must be deposited into this FOP and all expenditures allowed by the sponsor in support of the research project must be paid from this FOP. Residual amounts may not be retained if TTUHSCEP is contractually obligated to return any unspent amounts to the sponsor. • Fixed-Price Contract Fixed-Price Contracts are contracts which are awarded for a specific dollar amount, do not require invoices for reimbursable expenses, and do not require the return of unspent amounts. Contracts may be for and payment may be determined by the completion of a "deliverable" item, based on a set payment per activity, based on a set payment per patient, or based on payments made at established intervals (such as monthly, quarterly, or annually) during the contract period. • Investigator-Initiated ResearchInvestigator-Initiated Research is that research with protocol or research design that has been developed by the investigator and presented to a sponsor for funding. A project can be for basic research or clinical research. Industry-sponsored clinical trials with protocols and/or research designs that are developed by the sponsor are not included in this definition and are not classified as investigator-initiated. Investigator-Initiated Research projects for the purposes of this policy are those not solicited under any formal, peer-reviewed grants program. http://elpaso.ttuhsc.edu/opp/_documents/65/op6510.pdf

19. Contracts and Grants Accounting • Research personnel should review OP 65.03 Sponsored Program Fund Management, which specifies departmental fiscal management responsibilities during the conduct of a clinical trial. • The Principal Investigator and/or designee shall review the study’s financial status to assure that all invoices and payments due on the study have been paid. • The Principal Investigator and/or designee shall review transactions on the clinical trial fund to ensure that special augmentations are not paid from the restricted clinical trial fund. • The Principal Investigator and/or designee shall notify the Office of Sponsored Programs (OSP) and Contracts and Grants Accounting (CGA) to proceed with closeout procedures for the specific study. CGA shall commence closeout procedures to assess compliance with the internal budget and with the sponsor-approved budget, and will determine the appropriateness of all revenue and expense transactions posted to project fund. The Principal Investigator and/or designee shall complete and submit a signed copy of the Clinical Trial Closeout Checklist and Certification form. • CGA shall determine the final residual amount to be transferred to an unrestricted general designated account in the department of the Principal Investigator in accordance with OP 65.10. The department shall submit a budget revision in the budget revision system to transfer any final residual amount once notified by CGA.

20. Please Note • For most clinical trials the F&A rate is 25%. When a clinical trial fund is closed, CGA reviews all the payments received and determine which payments are subject to F&A. The most common payments that are not subject to F&A are: • Startup Fees • Pharmacy Fees • IRB Fees • Pass-thru payments • Payments not subject to F&A are stated in the clinical trial budget attached to the sponsor’s agreement. Once CGA calculates the total F&A, CGA adjusts the F&A already charged for the difference of the total F&A. Then CGA notifies the departments and lets them know the total residual amount they can transfer to their designated fund for research.

21. Contracts and Grants Accounting • Procedures for Sponsored Studies • Upon completion of a drug study, clinical trial, or fixed-price contract, the following steps must be performed: • A determination must be made that all amounts received from the external sponsor in support of the research project have been deposited into the restricted FOP. • A determination must be made that all expenses in support of the project, including salaries, have been paid from the restricted FOP. • A determination must be made that all indirect cost fees have been properly calculated and paid from the FOP. A final indirect cost fee will be assessed to capture the remaining indirect cost budget. • Any remaining encumbrances on the FOP must be released. Residual amounts remaining will then be transferred to a single general designated fund under the control of the department. If a FOP has not been established for the department, CGA will notify the department to establish a new fund. The designated FOP will hold the residual balances from all drug studies, clinical trials, and fixed-price contracts completed by investigators within the department. If individual departments wish to segregate the balances in the residual account by individual researcher, they may do so by using a multiple ORGNS spreadsheet or other accounting software. http://elpaso.ttuhsc.edu/opp/_documents/65/op6510.pdf

22. Contracts and Grants Accounting • Procedures for Investigator-Initiated Studies • When an Investigator-Initiated Research project is complete and residual funds remain in the restricted FOP, the residual amount can be transferred into a general designated account with the principal investigator named as the fund manager. A single fund will be established for each principal investigator to hold the residual amounts from all Investigator-Initiated Research. Upon agreement by the department chair and the principal investigator, residual amounts from Investigator-Initiated Research may be deposited into a general designated account under the control of the department. All of the requirements listed in the general section above must be completed before the transfer will be processed. http://elpaso.ttuhsc.edu/opp/_documents/65/op6510.pdf

23. Please Note • Amounts Used for Research • All residual amounts transferred to the designated FOP of the department or a principal investigator must be used for expenditures in support of research. Special Augmentation cannot be paid to faculty or staff from the residual amounts. http://elpaso.ttuhsc.edu/opp/_documents/65/op6510.pdf

24. Please Note • In order to notify the Office of Sponsored Programs and the Office of Contracts and Grants Accounting you will need to submit a “Clinical Trial Closeout Checklist and Certification to these departments.

25. Summary • There are 3 areas in which you need to ensure that study close-out occurs • Site • IRB • OSP and CGA • Ensure that all items are corrected and complete at site level per sponsor and institutional procedures • Ensure that the IRB is promptly notified when the sponsor designates that the study should be closed • Ensure that you notify both OSP and CGA so that you can receive and submit the required checklist

26. Resources • TTUHSC EP Research Compliance Page: http://elpaso.ttuhsc.edu/research/services/compliance/ • Office of Sponsored Programs Page: http://elpaso.ttuhsc.edu/research/osp/ • Contracts and Grants Accounting Page: http://elpaso.ttuhsc.edu/elpaso/fiscal/businessaffairs/grantaccounting/default.aspx • The Clinical Trials Guru: https://www.youtube.com/watch?v=ennu94KloJs • PPRU: http://www.ppru.org/Doc/StudyManagement/studycloseout.doc. • NIH: https://www.nidcr.nih.gov/research/toolkit/Documents/Study_Close_Out_Checklist_approved_v20.docx. • Global Health Trials: https://globalhealthtrainingcentre.tghn.org/site_media/media/articles/Study_Close_Out_-_GHT.ppt. • TTUHSC OP 65.03: http://elpaso.ttuhsc.edu/opp/_documents/65/op6503.pdf • TTUHSC OP 65.10: http://elpaso.ttuhsc.edu/opp/_documents/65/op6510.pdf

27. Questions?