1. New Research Service Standard Operating Procedures Kimberly Summers, PharmD Assistant Chief for Clinical Research South Texas Veterans Health Care System Research & Development Service

2. Standard Operating Procedures External Clinical Research Monitoring VisitsExternal Clinical Research Monitoring Visits Subject Recruitment and AdvertisingSubject Recruitment and Advertising Clinical Impact StatementsClinical Impact Statements

3. Monitoring By External Agencies Entities external to the facilityEntities external to the facility –Pharmaceutical companies –Study sponsors –Contract Research Organizations (CROs) –VA Cooperative Studies Program Monitors Site visitsSite visits –Routine –Conducted for specific cause

4. External Clinical Research Monitoring Visits VHA Memorandum From Chief Research and Development OfficerVHA Memorandum From Chief Research and Development Officer –Thru Deputy Under Secretary for Health –Subject: Reporting of All Study Site- Monitoring Visit Results –Charge: Each research office must develop procedures that will ensure all serious findings and concerns are appropriately addressed and the appropriate facility officials and committees are notified

5. Research Office Notification Findings and issues of concern must be forwarded to appropriate facility officials and committeesFindings and issues of concern must be forwarded to appropriate facility officials and committees –This is the responsibility of the Research office –Component of the STVHCS Human Subjects Protection Program (HRPP) If no serious findings or concerns are identified, the Research office must be notified in writing that there were no such findingsIf no serious findings or concerns are identified, the Research office must be notified in writing that there were no such findings

6. Why is Compliance with this Memorandum Important?

7. Office of Research Oversight (ORO) Primary VHA office in advising the Under Secretary for Health on all matters of compliance and assurance including:Primary VHA office in advising the Under Secretary for Health on all matters of compliance and assurance including: –Human subject protections –Animal welfare –Research safety and security –Research data security –Research misconduct Oversight is enforced by:Oversight is enforced by: –Performing periodic prospective and for-cause reviews –Conducting investigations –Assuring compliance with the laws, regulations, and policies applicable to VHA research.

8. Local Example Research office unaware of serious issues identified by external study monitors for a VA- approved research protocol Corrective actions were not put into place Serious consequences for the institution and investigator resulted

9. Upon Notice of Monitoring Visit Research staff scheduling or confirming the monitoring visit must notify the Research officeResearch staff scheduling or confirming the monitoring visit must notify the Research office –For scheduled monitoring visits notification should be by email to KimberlyK.Summers@va.gov KimberlyK.Summers@va.gov –For unscheduled monitoring visits notification may be by phone (210) 617-5123 directed to Kimberly Summers, Assistant Chief for Clinical Research Notification should be made as soon as study personnel are aware of the visitNotification should be made as soon as study personnel are aware of the visit

10. At The Time Of The Monitoring Visit Study monitor must sign in at the Research Office and receive a visitor badgeStudy monitor must sign in at the Research Office and receive a visitor badge –Check-in at Room Q202.1 –A Research Monitor Log will be maintained by the Research Office Study monitor will be providedStudy monitor will be provided –External Monitor Agreement Form Must be reviewed and signed at the time of check inMust be reviewed and signed at the time of check in –STVHCS Report of Clinical Research Monitoring Visit Must be returned to the Research officeMust be returned to the Research office

11. External Research Monitor Log

12. Visitor Badges Badges will be issued in exchange for a picture ID Badge must be worn at all times Badges must be returned to the Research office by 4:30pm – –If monitors will be conducting business past 4:30pm they should return to the Research office prior to 4:30 for their state issued ID and the responsible investigator or study staff must ensure the badge is returned the next business day Lost or stolen badges will be assessed a $25 fee to the responsible investigator Monitors assigned the visitor badge must be accompanied by a VA employee (paid or WOC)

15. Completion is required independent of the findings associated with the visit

16. Findings That Require an Exit Interview Suspicions or concerns that serious non- compliance may existSuspicions or concerns that serious non- compliance may exist All findings of serious non-compliance with study protocol, IRB requirements or applicable regulations and policiesAll findings of serious non-compliance with study protocol, IRB requirements or applicable regulations and policies Monitoring visits conducted by regulatory agencies (FDA, OHRP)Monitoring visits conducted by regulatory agencies (FDA, OHRP)

17. Compliance With External Clinical Research Monitoring Policies and SOPs STVHCS Compliance OfficeSTVHCS Compliance Office –Will verify results of external clinical research monitoring visits were reported to the R&D Office –Component of routine monitoring of investigator records Office of Research Oversight (ORO)Office of Research Oversight (ORO) –May perform periodic prospective and for-cause reviews to assure compliance with the laws, regulations, and policies applicable to VHA research STVHCS PoliceSTVHCS Police –Will audit appropriate security measures are in place for all visitors related to research –Will audit check-in and assignment of badges

18. Human Subjects Clinical Research Recruitment and Advertising

19. Recruitment “Researcher Contact with Veterans” – –VHA Memorandum 7/10/06 IRB-approved mechanisms – –Physician referral – –Posting of IRB-approved advertisements “Preparatory to Research” by HIPAA Privacy Rule – –VA guidelines are more restrictive

20. Researcher Contacts with Veterans All non-essential contact of veterans must stop – –Clinically essential contact that cannot be deferred is allowed – –Contact shall not solicit sensitive information Contact by researchers and study staff must be limited to procedures and data elements outlined in IRB and R&D approved protocols During recruitment – –Initial contact must be in person and/or by letter – –A telephone number must be provided for the veteran to verify the validity of the study – –http://www.clinicaltrials.gov/ website may be providedhttp://www.clinicaltrials.gov/ Following recruitment and during follow-up – –All telephone calls should begin by referring to previous contacts and information provided in the informed consent document 7/10/06 Principal Deputy Under Secretary for Health Memorandum

21. Physician Referral Veteran patients may be formally referred from VA staff for a VA-approved research protocol Veteran patients may NOT be formally referred from VA staff to off-site locations for non-VA approved research protocols – –Veteran patients have a right to seek care from and enroll in research studies outside the VA – –Informing veteran patients of the availability of an outside research study is not considered a referral, if the referring physician will not have ongoing participation in the care of the patient

22. Informing Veterans About Off-site Non-VA Research Studies Veterans must be informed that VA will not be responsible for any costs related to their care as part of the off-site research Enrollment should occur through the veterans’ own initiative in contacting the study personnel at the off-site institution Provision of information to a veteran regarding off-site research and their associated responsibility for cost should be documented by the VA physician in a progress note in CPRS VA records may not be accessed to obtain information for research purposes of a non-VA off-site study

23. Recruitment Advertisements Posted at the STVHCS Steps requiredSteps required –Approved and stamped by UTHSCSA IRB –Verification of active protocol and stamped by VA Research Office –Posting approval by VA Public Affairs Office Recruitment of VA patients into non-VA studies through posted advertisements in NOT allowedRecruitment of VA patients into non-VA studies through posted advertisements in NOT allowed

25. Expedited Posting Following IRB approval Investigator or study staff may hand deliver advertisementFollowing IRB approval Investigator or study staff may hand deliver advertisement –R&D office RM Q202RM Q202 Will verify study approval and stampWill verify study approval and stamp –Public Affairs office RM 118RM 118 Will approve and stamp for postingWill approve and stamp for posting –May be posted same day

26. “Preparatory to Research” Review of individually-identifiable information by a VA investigator to prepare a research protocol does not require IRB or R&D approval Examples: to generate a hypothesis, determine feasibility to conduct a study, determine the number of eligible patients In the VA, using individually-identifiable information to contact potential research subjects as part of recruitment into a research protocol is NOT considered “preparatory to research” – –VA regulations differ from those described in the HIPAA Privacy Rule – –IRB and R&D Committee review and approval required – –IRB approved waiver of authorization and waiver of informed consent required Pilot studies are NOT considered part of the activities “preparatory to research” – –IRB and R&D Committee review and approval required

27. Statement of Clinical Impact Forms

28. R&D Committee Review of Research The R&D Committee must evaluate the availability of adequate resources to conduct and complete the research – –Clinical hospital services must be notified if their services are required in order to conduct a research project – –Each affected service must verify resources within their respective service are adequate to conduct and complete the research project

29. Statement of Clinical Impact Radiology Service Nuclear Medicine Service Nursing Service Pharmacy Service Pathology and Laboratory Service Other Hospital Service

30. Electronic form available on Research website Items 1-7. All fields are required. Information entered on page 1 will be auto filled on pages 2 through 6. Item 8. Complete the applicable table for each VA Service that will be utilized as part of your project.

31. Routing Statement of Clinical Impact Forms Submit completed forms via email to stxresearch@va.govSubmit completed forms via email to stxresearch@va.gov stxresearch@va.gov If you have any questions completing the formIf you have any questions completing the form –Contact Angela Casas in the Research office at (210)617-5300 x 15523 The Research office will forward completed forms to the appropriate VA Services for signaturesThe Research office will forward completed forms to the appropriate VA Services for signatures An electronic signed copy will be provided for your recordsAn electronic signed copy will be provided for your records If project requirements change for any VA Service, a revised form must be submitted to the Research officeIf project requirements change for any VA Service, a revised form must be submitted to the Research office

32. Questions? Kimberly Summers, PharmD Office: (210) 617-5300 ext 15969 Email: kimberlyk.Summers@va.gov