1. STVHCS Research and Development Kimberly Summers, PharmD Assistant Chief for Clinical Research South Texas Veterans Health Care System Research & Development Service

2. What is Considered VA Research?

3. Definition of VA Research Research sponsored by the VA Research conducted using any property or facility of STVHCS Research conducted by or under the direction of any salaried or without compensation (WOC) employee of the STVHCS during and in connection with her/his STVHCS responsibilities Funds for the research activities are managed by the STVHCS or Biomedical Research Foundation of South Texas Research which recruits subjects at the STVHCS or uses the STVHCS's nonpublic information to identify or contact human research subjects for research purposes

4. R&D Approval – –Must have R&D approval letter prior to any of the following being conducted at the VA Recruitment Obtaining informed consent – –Having an IRB approved VA consent form does NOT constitute R&D approval Enrollment Providing patient follow up Accessing CPRS for research purposes – –An IRB approval letter does NOT constitute R&D approval

5. What Does It Mean To Have Research Privileges at the STVHCS?

6. Research Privileges Research credentialing and privileges are required prior to work on any VA protocol Requirements are different for the following groups – –VA Employees Investigators and study personnel – –Fellows, Residents, and Students – –Non-VA investigators or study personnel – –Exempt study staff

7. VA Research Privileges VA Appointment – –VA employee or WOC status with research privileges or Trainee – –All mandatory training courses – –Signed Intellectual Property Agreement (IPA)- WOCs, Trainees, Contract credentialed providers – –Signed Written Release of Information- WOCs only – –Copy of Appointment Memo- Trainees – –Medical Staff Member Appointment Request signed by appropriate Service Chief- Contract credentialed providers Documentation of Human Subjects Training Conflict of Interest Form – –Required for all investigators and study personnel Scope of practice – –Required for all investigators and study personnel EXCEPT credentialed medical staff providers – –Signed by principal investigator(s) and/or supervising physician

8. Exempt Personnel Study personnel who are not physically conducting research on VA property, only have access to de-identified data and/or not directly working with research subjects – –Examples: lab personnel, data or administrative personnel Requirements – –Information Security 201 for Research and Development Personnel LMS account created – –Memorandum from PI denoting what their role in the study will be – –Conflict of Interest Form

9. Conflict of Interest Form No longer protocol specific Required for all investigators and collaborators – –Collaborators = all research personnel New form will be collected as part of – –New personnel application – –New protocol submission if old version of form is on file Must be verified as accurate or updated annually – –Verified by the PI at continuing review – –New protocol submission if investigator or personnel have not been engaged in research for greater than one year

10. The R&D Submission Process

11. http://www.south-texas.med.va.gov/research

12. R&D Submission Date The first Monday of each month New Requirement – –One of the following must have occurred prior to application submission to the R&D office IRB final resubmission for full IRB Board 1 or IRB 3 research protocols IRB administrative review for IRB expedited or exempt research Final IRB approval

13. R&D Administrative Review Appointments New Requirement – –An appointment with the investigator and/or study coordinator is required to address any administrative stipulations – –The intent of the meeting is to address, correct, and finalize any administrative stipulations in real time to shorten the overall approval time – –This appointment may be made at the time of application submission or may be scheduled by calling the R&D office at VA ext 16335.

14. R&D Administrative Stipulations and Final Approval New Requirement – –All administrative stipulations must be addressed at least one week prior to the R&D Committee Meeting for the protocol to be placed on the agenda – –IRB approval may still be pending at the time of resubmission Final R&D approval can be granted when – –IRB approval is in place – –All R&D Committee stipulations have been addressed

15. R&D Submission Forms

16. Electronic form available on Research websiteElectronic 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.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.Item 8. Complete the applicable table for each VA Service that will be utilized as part of your project.

17. Statement of Clinical Impact Form Procedures must be consistent with protocol List ALL procedures beyond routine clinical care – –Additional, altered process or increased frequency – –Procedures should be specific Collaborating service will not sign off on statement of clinical impact if information provided is incomplete

18. 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 VA ext 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

19. VA Research Data Security Checklist Required for ALL submissions If the research does NOT involve human subjects OR their identifiable information – –Only PI signature on front page is required for completion

20. Data Security Checklist Documentation for – –Types of information collected – –Disclosures to third parties – –Location of storage – –Length of retention Should be consistent in the – –Protocol – –Data security checklist – –Informed consent document All sections should state the same information

21. VA-Sensitive Research Data Individually-identifiable research data collected on a veteran subject through a STVHCS approved protocolIndividually-identifiable research data collected on a veteran subject through a STVHCS approved protocol Individually-identifiable research data collected on a veteran or non-veteran within the STVHCSIndividually-identifiable research data collected on a veteran or non-veteran within the STVHCS Individually-identifiable research data collected as part of a VA-funded studyIndividually-identifiable research data collected as part of a VA-funded study

22. Individually-identifiable - Data HIPAA Identifiers 1. Names 2. ALL geographic subdivisions smaller than the state 3. All elements of dates smaller than a year and all ages over 89 4. Phone numbers 5. Fax numbers 6. E-mail addresses 7. Social Security numbers (SSN) 8. Medical record number 9. Health plan beneficiary numbers 10. Any other account numbers 11. Certificate/license numbers 12. Vehicle identifiers and license plate numbers 13. Device identifiers and serial numbers 14. WEB URL's 15. Internet IP address numbers 16. Biometric identifiers (fingerprint, voice prints, retina scan, etc) 17. Full face photographs or comparable images 18. Any other unique number, characteristic or code

23. HIPAA Identifiers Continued Any other unique number, characteristic or codeAny other unique number, characteristic or code –Scrambled SSN –Initials –Last four digits of SSN –Employee numbers –Etc. HIPPA also states that the entity does not have actual knowledge that the remaining information could be used alone or in combination with other information to identify an individual who is the subject of the informationHIPPA also states that the entity does not have actual knowledge that the remaining information could be used alone or in combination with other information to identify an individual who is the subject of the information

24. HIPAA and The Common Rule Two different regulationsTwo different regulations VA requires de-identification by bothVA requires de-identification by both Common Rule states the identity of the subject can not be readily ascertained by information remaining after removal of all 18 HIPAA identifiersCommon Rule states the identity of the subject can not be readily ascertained by information remaining after removal of all 18 HIPAA identifiers –After stripping all 18 identifiers the remaining information may still be identifiable (e.g. through statistical analysis)

25. Not VA-Sensitive Data Non-identifiable dataNon-identifiable data Data collected on non-veterans outside of the VA on a non-VA funded projectData collected on non-veterans outside of the VA on a non-VA funded project

26. Keys To Coding Systems Keys To Coding Systems If non-identifiable information is linked to identifiable information with the use of log (e.g. coding system)If non-identifiable information is linked to identifiable information with the use of log (e.g. coding system) –Logs are identifiable and VA-sensitive research data –Applies to both data and specimen logs

27. Disclosures to Non-STVHCS Entities Temporary access to research subject information, without removal of any data from the facility – –Examples: external study monitors, auditors, collaborators, etc Access to research subject information because the data will leave the STVHCS facility – –For identifiable information disclosed outside the STVHCS, you must state how the data will be securely transported – –Transfer or transmission other than to the sponsor or its designated contract monitor or data center, requires prior written approval by the ACOS/Research, STVHCS Privacy Officer and Information Security Officer The Data Security Checklist, HIPPA authorization, and protocol should all be consistent

28. Accounting of Disclosures An accounting of disclosures must be kept for all VA sensitive information transferred or transmitted outside the STVHCS – –Excluding non-identifiable data and limited data sets – –Limited data sets exclude certain direct identifiers but may contain some identifiable information Examples: city, state, zip code, scrambled SSN, or initials – –The web-based accounting for Disclosure of VA- sensitive Research Information can be found on the Research and Development Service Webpage: http://www.southtexas.va.gov/research. http://www.southtexas.va.gov/research

29. Storage of VA-Sensitive Paper Research Data Lower risk of loss or compromiseLower risk of loss or compromise Physical security controlsPhysical security controls –Within the VA system Locked room, locked cabinetLocked room, locked cabinet Access limited to research staffAccess limited to research staff –At the UTHSCSA Physical security arrangements must be inspected and approved by ACOS/Research and ISOPhysical security arrangements must be inspected and approved by ACOS/Research and ISO

30. Storage of VA-Sensitive Electronic Research Data Risk of loss or compromise is highRisk of loss or compromise is high Must be stored within the VA system (e.g. behind the VA firewall)Must be stored within the VA system (e.g. behind the VA firewall) –VA research server recommended Accessed directly through the VA network from a VA computer orAccessed directly through the VA network from a VA computer or Through VPN from a non-VA computerThrough VPN from a non-VA computer –Encrypted VA computer in VA office Rare instancesRare instances Explain requirement for storage outside the serverExplain requirement for storage outside the server

31. R&D Continuing Review Process

32. Continuing Review Process New form VA specific information in addition to IRB continuing review form – –Submission of the IRB continuing review form and/or approval letter to the R&D office is NOT required Exempt research – –VA continuing review form required at least annually – –Updated protocol abstract required anually

33. Continuing Review Process Protocol approval at the STVHCS will expire if – –Continuing review is not completed Must be approved by IRB AND R&D Committee prior to the expiration date – –Training requirements for the PI are not up-to-date at the time of continuing review Co-investigators and other study personnel will be removed from active protocols if training requirements are not up-to- date Expiration of approval will be corrected upon receipt and satisfactory review and approval of the required documentation

34. Documentation in the Medical Record

35. Research Record Must Contain Copy of the signed and dated consent and initial enrollment progress noteCopy of the signed and dated consent and initial enrollment progress note –Scanning of VA Form 10-1086 (Informed Consent Document) Information on possible drug interactions and adverse effects of investigational drugs being administeredInformation on possible drug interactions and adverse effects of investigational drugs being administered –Scanning of VA Form 10-9012 (Investigational Drug Information Record) Any research information which has the potential to impact medical careAny research information which has the potential to impact medical care –Research progress notes Disenrollment or termination from a studyDisenrollment or termination from a study

36. Enrollment Consent Template: Research Consent / Enrollment Note Must be entered into the subject’s health record (CPRS) after IC has been obtainedMust be entered into the subject’s health record (CPRS) after IC has been obtained Template in CPRS flags patients Medical Record in postingsTemplate in CPRS flags patients Medical Record in postings Template contains all the required information for documentation of consent processTemplate contains all the required information for documentation of consent process Template must be used in order to scan IC documentTemplate must be used in order to scan IC document Note must indicate if the study involves the use of investigational medicationsNote must indicate if the study involves the use of investigational medications

38. Investigational Drug Information Record (VA Form 10-9012) Required forRequired for –Investigational drug for which an IND has been filed –Approved drug being studied for unapproved use in a controlled, randomized, or blinded clinical trial –Approved drug being studied for approved use in a controlled, randomized, or blinded clinical trial PI must ensure a completed and signed copy is submitted to MR for scanningPI must ensure a completed and signed copy is submitted to MR for scanning Pharmacy will not dispense any study medication for a research subject until 10-9012 forms have been scannedPharmacy will not dispense any study medication for a research subject until 10-9012 forms have been scanned

39. Authorized Prescribers for Investigational Medications All prescribers for investigational medications must be listed on VA form 10-9012 – –Should be consistent with FDA 1572 Prescribers must be credentialed at the VA to write medication orders – –Should be consistent with Scope of Practice if applicable VA form 10-9012 must be amended if – –Prescribing investigators are added to a protocol – –Principal investigator changes Research Pharmacist verifies orders are received by an investigator listed on the 10-9012

40. Updated Consent Template: Research Consent / Update Note Any changes to the IC resulting in an addendum or updated IC documentAny changes to the IC resulting in an addendum or updated IC document –Must be entered into the subject’s health record (CPRS) after IC has been obtained –Template in CPRS flags patients Medical Record in postings All IC addendums and updated IC documents must be scanned in CPRSAll IC addendums and updated IC documents must be scanned in CPRS

41. Research Disenrollment Termination Note Must be entered into the subject’s health record (CPRS)Must be entered into the subject’s health record (CPRS) Template in CPRS flags patients Medical Record in postingsTemplate in CPRS flags patients Medical Record in postings Required information in template Required information in template –Title of Study –Date of disenrollment or termination –Contact name and number

44. External Monitoring Visits

45. 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 or on BRU –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

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

48. 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)

49. Research Referrals and Recruitment

50. 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

51. 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

52. CPRS can be accessed for information on any Veteran enrolled in a research protocol? YES – –For VA approved research – –Following signed informed consent by the veteran – –As per approved research protocol NO – –For Veterans enrolled in non-VA approved research Must obtain a signed release of information from the subject and receive copies thru Medical Records

53. 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

54. http://www.south-texas.med.va.gov/research

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