WELCOME TO THE ATLANTA VA MEDICAL CENTER

1. WELCOME TO THE ATLANTA VA MEDICAL CENTER This reference manual will provide you with the Atlanta VA Medical Center’s policies and step by step procedures for conducting human subjects research. The Atlanta VA Human Research Protection Program has the infrastructure for conducting research that ensures consistency in quality and performance which is in accordance with federal regulations and institutional policies.

2. Atlanta VA Medical Center Research webpage location: http://www.atlanta.va.gov/services/Research.asp Clinical Studies Center forms and policies are located at: http://www.atlanta.va.gov/services/New_For_Investigators_and_Staff.asp

3. Investigator’s Responsibilities Principal Investigator Definition: An individual who conducts a research study and under whose immediate direction the investigation occurs. When a team of individuals conducts a study, the responsible leader of the team is the Principal Investigator (PI). • The Atlanta VA Research & Development (R&D) Committee is responsible for ensuring that: • Investigators are qualified to conduct the study. • The PI is trained and knowledgeable about the disease or condition described in the protocol. • The investigator has completed VA required training

4. Investigator’s Responsibilities • Ensure the safety and welfare of study participants. • Comply with VA policies and procedures and federal regulations for conducting human subjects research. • Is solely responsible for the conduct of the study. • Has sufficient, qualified, and trained study staff to conduct the study. • Ensure that all study team members complete research credentialing and training before engaging in research activities. • Document any delegated responsibilities to study staff in the research “Scope of Practice”. • Supervise and oversee all study activities.

5. Investigator’s Responsibilities • Communicate with study members on an ongoing basis about all aspects of the study. • Ensure that study members are knowledgeable about the protocol and follow study activities accurately. • Obtain Emory IRB, VA Sub-Committee on Research Safety, VA Radiation Sub-Committee (if applicable), ISO/PO and R&D Committee approval prior to initiating any study activities. These will be represented in a FINAL letter of approval from the ACOS/R. • Delegate in writing (in protocol or IRB submission) who will be obtaining consent. • Obtain informed consent & HIPAA Authorization from each participant prior to starting any study activities or delegates this responsibility to qualified research staff. • Adhere to the research protocol procedures. • Maintain adequate and accurate documentation for each participant.

6. Investigator’s Responsibilities • Document research encounters in the subject's medical record. • Comply with protocol reporting obligations to the IRB and R&D Committee regarding study changes, annual progress, research-related unanticipated problems involving risks to the subject or other individuals, Reportable Events and conflict of interest. • Keep study regulatory documents organized in a study binder and study records locked in a secured area (secured = behind TWO locks). • Keep all data collected for the research study at the VA (unless offsite authorization has been obtained). • Prepare for internal and external audits as required. • Follow study records retention guidelines. • Be available for Sponsor Site Visits prior to, during and at the end of the study.

7. Research Staff Responsibilities • Research Coordinator Definition: • The person who assists the Principal Investigator (PI) in the conduct of the study and usually handles most of the administrative responsibilities. In addition, acts as a liaison between the PI, sponsor, IRB, and R&D Committee. • The “Research Staff Responsibilities” policy is located at: • http://www.atlanta.va.gov/services/New_For_Investigators_and_Staff.asp

8. Research Staff Responsibilities • Complete required research training and credentialing prior to engaging in study activities. • Conduct study in accordance with federal regulations and institutional policies. • Follow the Privacy Rules regarding privacy and use of Protected Health Information (PHI). • Coordinate day-to-day study protocol activities as delegated by the PI. • Assist with IRB and R&D regulatory issues as required. • Ensure the safety and welfare of the study participants. • Perform protocol activities correctly and completely. • If appropriate, provide an in-service to hospital staff impacted by the research study.

9. Research Staff Responsibilities • Recruit and screen potential study participants according to the protocol criteria. • Document all research activities as required by VA policies. • When delegated, obtain informed consent and HIPAA Authorization from each subject prior to starting any study activities. • Promptly report any Reportable Events (REs) and Unanticipated Problems (UPs) to the Investigator, study sponsor, and the IRB. • Accurately collects study data in the Case Report Forms (CRFs) for each participant. • Maintain adequate and accurate source documents for each study participant and records all observations during the study.

10. Research Staff Responsibilities • Maintain an organized filing system for all regulatory documentation and other study records. • Keep accurate records of screened and enrolled subjects. • Maintain ongoing communication with the PI about study activities. • Obtain research education on an ongoing basis. Regularly attend research meetings. • Read all research policies and procedures located on the Atlanta VA research website. Stay informed of all policy and procedure changes by checking this website regularly. Regarding Industry-Sponsored Studies • Keep accurate records of the receipt, dispensing, return of all clinical supplies, and study drug or device accountability. • Communicate study activities to the sponsor as required. • Be available for the study sponsor monitoring visits to discuss and review study data.

11. Preparing for a Research Study • Attend the sponsor investigator meetings as required. • Identify study population and their availability. Based on this assessment, develop a recruitment plan. • In the event that conflicting research studies are being conducted, the PI should negotiate access to study population with the Investigator involved. • Contact CSC Medical Director for guidance with protocol design and review. • Contact the Human Studies Analyst for assistance with VA forms and overall aspects of the protocol submission process. • Prepare recruitment materials for IRB review and approval.

12. Preparing for a Research Study • Prepare Case Report Forms (CRF) for study data collection. • Start a Study Binder (available at CSC) to keep paper copies of all regulatory documents and prepare any study tools (source documents templates, tracking tools, etc). • Define study reimbursement procedures in advance. • Define and disclose the recruitment plan and how the study data will be secured, used, disclosed and/or transferred in the protocol. • Obtain access to the VA research secured server (authorized by the Director of Research Operations) to save all electronic study data. • In order to use the eIRB system, staff must obtain an account by following instructions at: www.irb.emory.edu .

13. Preparing for a Research Study Procedures for Industry-Sponsored Clinical Trials • Obtain the final research protocol from the study sponsor for review and feasibility. • After IRB and all relevant subcommittee approvals are obtained, proceed with R&D Committee submission for review and approval. • Schedule the sponsor’s site visit and include the Research Pharmacist and the CSC Manager for this visit. • For contracting issues, contact the AREF Contracts/Grants Administrator. • Receive the CRFs, Study Binder, and supplies from the study sponsor.

14. Preparing for a Research Study For Industry- Sponsored Clinical Trials • If the research study involves drugs: • Provide a copy of the Protocol and Investigational Brochure to the Research Pharmacist for review and approval. • Obtain the pharmacy chief’s approval. • Complete an FDA 1572 form (Investigator’s Agreement), if applicable. • Complete VA Form 10-9012 and pharmacy impact form available at: http://www.atlanta.va.gov/services/New_For_Investigators_and_Staff.asp

15. Informed Consent Form Writing Guidelines VA Consent Template, VA HIPAA Authorization Form, and the VA Revocation Letter are located at: http://www.atlanta.va.gov/services/New_For_Investigators_and_Staff.asp General Guidelines on Writing a Consent: http://www.irb.emory.edu/researchers/formstools/formstools.cfm

16. Approval Process Objectives Policy Principal Investigator’s Responsibilities • To outline approval processes for the Institutional Review Board (IRB) and the AVAMC’s Officers and Committees. • A final letter of approval must be obtained from the AVAMC’s ACOS/R prior to starting any research activities (this includes screening). • Obtain notification and/or approval for: • The original research protocol submission (IRB and VA approval) • “Continuing Review” (IRB approval only- submit for filing to VA) • Amendments to the original protocol (IRB approval only, *unless there is a change in PI or risk. Need *R&D approval* also in those cases).

17. Approval Process SUBCOMMITTEES REVIEW & APPROVAL • Research protocols to be conducted at the Atlanta VA must be submitted to the Emory IRB or VA Central IRB for review and approval. • IRB Submissions are completed online through the Emory eIRB system. • The “Study Application for PO/ISO Review” in eRRRP needs to be submitted prior to IRB review. • All VA protocols are reviewed by an Emory Biomedical IRB Committee. • VA Subcommittee on Research Safety (SRS or aka, “Biosafety”) and VA Radiation Subcommittees approval must be obtained prior to R&D Committee review. The SRS submission can be completed on-line as part of the eRRRP submission process. VA Radiation approval forms are available on-line and must be submitted before R&D committee review.

18. ApprovalProcess • All human research protocols must be reviewed and approved by the AVAMC Sub-Committee on Research Safety (aka- “Biosafety Committee”) regardless of whether there are any blood-borne pathogens, body fluids/specimens, etc. involved in the study. • Human research protocols performed at the VA involving radiation and radioactive materials must be reviewed and approved by the AVAMC Subcommittee on Radiation Safety Committee (RSC).

19. Approval Process • Log on to www.irb.emory.edu for submission guidelines and information. • The IRB will notify the PI in writing of their decision to approve, approval pending, defer, or disapprove the protocol. • Once IRB and all applicable subcommittee approvals are obtained, including PO/ISO review, the project can be submitted for R&D review using eRRRP https://vaww.gateway.research.va.gov/errrp

20. Emory eIRB Submission Checklist • eIRB Initial Submission (requires the Department Chair’s Approval) • CITI training certificate • Lay Summary (must be entered or up-loaded) • Full Protocol (must be up-loaded) • Investigator’s Brochure, if applicable (up-load a copy) • Upload the VA Informed Consent Form (ICF) 10-1086 into eIRB. Use the "Stamping Template” found on the Atlanta VA website. • Upload the VA HIPAA Authorization Form into eIRB. Use the "Stamping Template” found on the Atlanta VA website. • Upload the VA Revocation Form into eIRB. Use the "Stamping Template” found on the Atlanta VA website. • Oncology protocols must include approval documentation of Winship Cancer Center Review Committee. • Recruitment and/or advertisement materials, if applicable,(must be up-loaded) and any letters or other information given to the subject. • Any waiver forms required (Consent, HIPAA, flag waiver, etc.) • HIPAA Worksheet Application for Waiver of Authorization

21. Approval Process R&D COMMITTEE REVIEW & APPROVAL- ERRRP • Submit protocols for R&D Committee review and approval using eRRRP (electronic request to review research projects). https://vaww.gateway.research.va.gov/errrp/ **eRRRP is INTRANET ONLY** • The R&D Committee meets on the first Wednesday of each month • Submit complete project through eRRRP no later than the Wednesday prior to the convened meeting.

22. Approval Process • The Principal Investigator submits and the Service Line Chief must electronically sign off through eRRRP. • The Investigator should keep a paper copy of the FINAL, APPROVED submission packet for his/her files. • The R&D Committee may request additional changes after IRB approval has been obtained. • If so, the PI must submit a modification to the IRB. • Study activities (including screening) may not start until the ACOS/R notification of approval letter has been obtained.

23. Approval Process • The IRB must approve any changes made to the originally approved investigational plan. • A modification includes: protocol amendments, changes or additions of a procedure, consent form revisions, staff changes, request for recruitment, etc. • Submit the Modification through eIRB. Once approved, study team is responsible for forwarding to the SIO at the AVAMC. Protocol Modifications

24. Approval Process Protocol Modifications • Then, the amendment/modification will be communicated to the R&D Committee, and will be included in the minutes of the R&D Committee. • The amendment/modification must be reviewed and approved by the full R&D Committee if there is: • a change in the risk/benefit ratio • a change in the PI

25. Approval Process Protocol Modifications • Amendments/modifications involving BioSafety and/or Radiation will be routed by the SIO to the appropriate subcommittee for review and approval PRIOR to review and approval from the R&D Committee. • Some examples include but are not limited to additional x-ray or radiographic procedures, blood or other tissue collections that are: • not collected in the clinical setting and/or • have not previously been approved by the appropriate subcommittee

26. Approval Process IRBContinuing Review • Continuing reviews are conducted at intervals based on the degree of the risks, but not less frequently than once per year. • Continuing review requests should be submitted to the IRB 45 working days in advance. • For instructions about continuing review submissions, log on to www.irb.emory.edu . • Provide a copy of the continuing review approval and any updated corresponding forms (if applicable) to the Science Information Office (SIO). E-mail is preferred. • It is the PI/Study Staff’s ultimate responsibility to keep up with Continuing Review and not letting the study lapse. Lapses=required reporting to the Office of Research Oversight (ORO).

27. The Informed Consent Process • Outline policies and procedures regarding the Informed Consent Process. • Describe the policies and procedures for the review and documentation of the VA Research Consent Form (VA FORM 10-1086) to ensure that research volunteers are consented properly. • Comply with federal guidelines and the Atlanta VAMC policies and procedures regarding the consenting process. Objectives

28. The Informed Consent Process Informed Consent Process Definition: The Informed Consent Process is an exchange of information that takes place between a subject and investigator before, during, and sometimes after the study. Researchers should know that a written document alone will not ensure that individuals fully understand what participation in research means. Therefore, before, during, and after an individual participates in research, the study team discusses the purpose, procedures, risks and potential benefits, and rights of participants with that individual.

29. The Informed Consent Process • Obtain informed consent from all subjects prior to initiating any study activity. • Use the most current IRB approved VA Form 10-1086 Informed Consent Form (ICF). • Obtain written “HIPAA Authorization” from each subject prior to starting any study activity. • Provide the study subject with the “Revocation Letter”. • When the Principal Investigator (PI) delegates the responsibility of obtaining consent, he/she must ensure that the person is knowledgeable, trained & qualified. • PI must delegate in writing (in protocol or IRB submission) who will be obtaining consent. • Ensure that the consent process is documented in the subject’s electronic medical record (unless waived by the IRB).

30. The Informed Consent Process • The PI oversees compliance regarding the Informed Consent Process according to institutional policies and Federal Regulations. • The IRB and the VA Research Compliance Officer (RCO) have the authority to observe the consenting interview. • The R&D Committee (R&DC) may require additional changes in the consent form after IRB approval. If so, the consent must be re-submitted for IRB review and approval and then returned to the R&DC for final review and approval. • The consent must be written in a language that the subject and/or Legally Authorized Representative (LAR) can understand. • If the protocol is amended, the IRB may require that study participants are re-consented. • Any changes made to the consent, must be submitted to the IRB for review and approval, and then, forwarded to the R&DC for their approval.

31. The Informed Consent Process Procedures: • When obtaining written consent, the subject must read, sign and date the consent prior to starting any study activities. • In addition, the ICF must be signed & dated by: • The person obtaining consent. • A witness, IF requested by the IRB. • Allow subjects sufficient time to read the ICF, and consider whether or not they wish to take part in the study. • Provide a copy of the “Volunteering in Research” brochure to the subject. Provide a copy of the NOPP to any non-veteran who will receive clinical services as a result of taking part in a research study. • If necessary, provide or mail a copy of the ICF to the potential study participant prior to a scheduled discussion. • A rushed consent process increases the likelihood of an ill-informed, coerced decision.

32. The Informed Consent Process Procedures: • Discuss all elements of the consent and ensure that all questions are answered before the subject decides whether or not to participate in the study. • Assess the subject’s ability to read and comprehend the consent document and their understanding about the research and it’s risks by asking a few simple questions. • If the subject’s competency to provide consent is questionable, a clinical assessment is required. This must be done by a clinician that is not part of the study and this must be documented in CPRS in a signed/dated progress note. • Ensure that the subject gives consent without coercion or undue influence.

33. The Informed Consent Process Procedures: • The original signed and dated ICF must be kept with the investigator’s study files. • Provide a copy of the signed and dated consent form to: • The study subject • The Research Pharmacist (if the study involves drugs) • Scanning in the Computerized Patient Record System (CPRS) • Document the consent process in CPRS. If this is a re-consent, this must be documented also. • Reinforce the study information throughout the course of the study. • “The Informed Consent Process” policy is located on the Atlanta VA research website.

34. The Informed Consent Process Legally Authorized Representative (LAR) Consent: • Under appropriate conditions, informed consent may be obtained from the subject’s Legally Authorized Representative (LAR) if the prospective research participant is incompetent or has an impaired decision-making capacity. • LAR is an individual or body authorized under applicable law to provide permission, on behalf of a prospective subject, to a subject's participation in the procedure (s) involved in a research study.

35. The Informed Consent Process • The determination of competency must be documented and made according to the following requirements: • The practitioner, in consultation with the chief of service, may determine after a medical evaluation that the subject lacks decision-making capacity and is unlikely to regain it within a reasonable period of time. • Consultation with a psychiatrist or licensed psychologist must be obtained when the determination that the prospective research subject lacks decision-making capacity is based on a diagnosis of mental illness. LAR Consent:

36. The Informed Consent Process • A Legally Authorized Representative (LAR) can be (in this order): • Individuals with durable power of attorney for healthcare • Legal guardians • Spouse • Adult children • Parents of adult children • Siblings • Grandparents • Grandchildren • Close Friend LAR Consent:

37. The Informed Consent Process LAR Consent: • If possible, explain the proposed research to the prospective subject even when the LAR gives consent. • Under no circumstances may a subject be forced or coerced to participate in a research study. • The same consenting process and requirements followed for subjects, also apply to the subject’s LAR. • Staff should contact the Regional Council regarding any legal questions about a LAR or other legal matters.

38. The Informed Consent Process • The PI or the IRB will determine in which circumstances informed consent may be obtained in an alternative manner. • The IRB may waive the requirement for the consent process (or written documentation) if the research presents no more than minimal risk to study participants. • When this waiver is in effect, the IRB may require that the PI provides a written statement regarding the research to the study subjects. Procedures For Alternative Informed Consent

39. The Informed Consent Process Procedures for Alternative Informed Consent • If the standard written consent cannot be obtained, an IRB approved written summary that embodies the elements of the ICF can be read to the subject. • An unbiased person should witness the oral presentation. Whenever possible, the subject must sign the “short form” of the oral consent. • The witness (if required) and person obtaining consent must sign and date the short form and summary. • A copy of both the short form and summary is provided to the subject and the witness.

40. The Informed Consent Process • Obtaining consent shall be deemedfeasible unless both the Investigator and another physician who is not otherwise participating in the clinical investigation certifies in writing all of the following: • The subject is confronted by a life-threatening situation needing the use of the test article. • Consent cannot be obtained from the subject because of an inability to communicate with or obtain legally effective consent from the subject. • Time is not sufficient to obtain consent from the subject's legal representative. • There is no available alternative method of approved or generally recognized therapy that provides an equal or greater likelihood of saving the life of the subject. Exception from General Requirements

41. The Informed Consent Process • The approval for the above-mentioned situation is called emergency or compassionate use of an investigational article. • This usage must be reported to the IRB immediately and cannot be planned in lieu of standard consent methods. Exception from General Requirements

42. Scanning Forms into CPRS Objectives Responsibilities Procedures • Outline scanning procedures for the Informed Consent Form, the HIPAA Form, Revocation Letter (only if signed), VA form 10-9012, VA form 1032-03, and VA form 10-0483. • The Principal Investigator (PI) and/or designee ensures that the subject’s signed and dated ICF is scanned in CPRS. Submit scanning request within 72 hours of obtaining consent . • Enter the “Research Consent Progress Note” in CPRS prior to scanning the consent & HIPAA Authorization. • Provide a good quality copy of ICF and HIPAA Authorization form with the subject’s full name and social security number on the bottom of the first page of the document.

43. Scanning Forms into CPRS Procedures: • Complete the “Scanning Research Request” form for research documents. This form is located on the Atlanta VA website. • Place documents in privacy envelope and drop them at the designated drop mail box at the Clinical Studies Center (Room 11c119). These may include: ICF, HIPAA, Accounting of Disclosure Form, the Notice of Privacy Practices Acknowledgement form ,VA form10-9012 , VA form 1032-03, and VA form 10-0483. • Documents are picked-up at the CSC daily and available for viewing in CPRS within 24hrs. • Medical Records scanning staff will shred the ICF paper copy unless otherwise specified .THEREFORE DO NOT SUBMIT THE ORIGINAL FOR SCANNING! • The original ICF is kept by the PI and/or designee.

44. Scanning the Investigational Drug Information Record VA Form 10-9012 Objectives: Responsibilities: • Outline procedures for scanning the Investigational Drug Information Record VA Form 10-9012 in CPRS. • Provide additional protection for subjects who are participating in research studies involving drugs. • The PI or designee is responsible for ensuring that the VA Form10-9012 is scanned in CPRS right after a subject is enrolled in a study involving drugs.

45. Scanning the Investigational Drug Information Record VA Form 10-9012 Procedures: • Provide a good quality copy of VA Form 10-9012 with the subject’s full name and social security number on the first page of the document. • Complete a “Scanning Request for the Investigational Drug Information Record VA Form 10-9012” available at the Atlanta VA research website. • Deliver scanning requests to the Clinical Studies Center (CSC), Room 11C119. • Forms are picked-up at the CSC by 11:00 AM daily, Monday – Friday. • Scanned documents will be available in CPRS for viewing within 24hrs after being picked up. • The medical record scanning team will shred the consent copy after scanning, unless otherwise specified. • The PI and Pharmacy keep a copy of VA Form 10-9012 filed in the study binder.

46. CPRS Documentation Requirements • Document research encounters (face to face or phone) with research subjects in the Computerized Patient Electronic Record (CPRS) system. • CPRS access and training will be provided to staff. To schedule training, contact the Research Training Coordinator at ext.6177. • “Research Clinics” are non-billable clinics located in CPRS and are used to : • Document research encounters/visits • Place orders for investigational drug, tests or procedures required solely for the research study • Refer to “Procedure for Setting Up Research Clinics” located on the Atlanta VA website. • “ATL Research Study” is a general clinic location that can be used for studies that will not be impacting a hospital service. • Refer to “CPRS Documentation Requirements” and “Entering Research Progress Note in CPRS” policies located on the Atlanta VA website.

47. Documentation Requirements Non-Veterans Documentation Procedures: • Create a separate paper chart for non-veteran research participants. Document the consenting process and any other research encounters/visits (if applicable). Keep with study files. • Non-veteran research participants must be entered VISTA/CPRS system if using a hospital service for a test or procedure that is required as part of the research protocol (e.g. the VA laboratory, radiology, nuclear medicine, etc.). • Contact the CSC for further details and instructions on enrolling a non-Veteran in research.

48. Research Clinics • A “Research Clinic” is a virtual non-billable location created in CPRS to: • Document research encounters and distinguish research versus standard of care visits. • Order investigational drugs and tests/procedures that are above and beyond standard of care. • Avoid billing research participants for research procedures. • Comply with documentation requirements of the informed consent process and research encounters. • A protocol-specific “Research Clinic” location is needed when a research study impacts a hospital service by performing tests and/or procedures solely required for the study. For example: laboratory, radiology, Pulmonary Function Laboratory, Nuclear Medicine, etc. • The Clinical Studies Center handles and oversees the clinic setup process. • The “Procedure For Setting Up Research Clinics” policy may be found on the Atlanta VA website.

49. Regulatory Documents • The Principal Investigator and/or designee is responsible for keeping complete and accurate regulatory documentsfor the study. • Collect, organize, and maintain all documents in a regulatory binder. • Document everything: “If it isn’t written down, it never happened”. • At the end of the study, store the study binder with other research records. NEVER DESTROY ANY STUDY DOCUMENTS!!! • The “Procedure For Completing Accounting of Disclosure Form For Research” may be found atthe Atlanta VA research website. • Please refer to “Regulatory Documents Policy” located on the Atlanta VA research website. This includes the Regulatory Document Checklist.

50. Regulatory Documents Checklist • Protocol and any amended protocols • IRB & R&D approval documentation • Copies of the eIRB initial submission • Copies of the eRRRP submission • Approval letter from ACOS for Research • Approved Informed Consent Form and HIPAA Documents • Modifications forms with supporting documents • Continuing review approval documentation • Reportable Events (SAEs, UPs, SPs, RIIs) • Recruitment materials • IRB, R&D, and Sponsor’s Correspondence • Protocol Termination form