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/ATLANTA/services/research/about.asp Clinical Studies Center forms and policies are located at: http://www.atlanta.va.gov/services/research/investigators.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/research/investigators.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 the 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 and 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 • 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. Procedures for Industry-Sponsored Clinical Trials

14. Preparing for a Research Study 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/research/investigators.asp For Industry- Sponsored Clinical Trials

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/research/investigators.asp General Guidelines on Writing a Consent: http://www.irb.emory.edu/forms/index.html

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, risk, or data repository. 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. Approval Process • 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) • Upload CITI training certificate, Key Concepts for PI and CO-I, and Intro to Clinical Research (if applicable) • Upload Lay Summary • Upload Full Protocol • Upload Investigator’s Brochure, if applicable • Upload the VA Informed Consent Form (ICF) 10-1086 into eIRB. Use the “VA Informed Consent Form Template” located on the Atlanta VA research website. • Upload the VA HIPAA Authorization Form into eIRB. Use the “VA HIPAA Authorization template” located on the Atlanta VA research website. • Upload the VA Revocation Form into eIRB. Use the “VA HIPAA Revocation Letter template” located on the Atlanta VA research website. • Oncology protocols must include approval documentation of Winship Cancer Center Review Committee. • Upload recruitment and/or advertisement materials, if applicable, 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): • Website: https://vaww.gateway.research.va.gov/errrp/ • 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. **eRRRP is INTRANET ONLY**

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 • 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 • the creation or amendment to a data repository Protocol Modifications

25. Approval Process Protocol Modifications • Amendments/modifications involving Privacy, Information Security, BioSafety and/or Radiation will be routed by the SIO to the appropriate individual or subcommittee for review and approval PRIOR to review and approval from the R&D Committee. • Some examples include but are not limited to changes in 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 • 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 by not letting the study lapse. Lapses = required reporting to the Office of Research Oversight (ORO). IRBContinuing Review

27. Recruitment of Research Subjects • Indirect – The potential subject contacts the study team. • Examples include flyers, advertisements, radio, television, etc. Requires IRB and Office of Public Affairs approvals prior to use. • Direct – The study team contacts the potential subject . • Examples included person-to-person, letter, or telephone. Letters require IRB approval prior to use. • “Cold Calling” is making contact either by person-to-person, letter, or by telephone when the potential subject is not expecting such an interaction. • “Cold Calling” is not allowed at the Atlanta VAMC.

28. Recruitment of Research Subjects Recruitment Methods: Recruitment from subjects provider • Provider gives written permission for his patients to be contacted by the study team (permission from the provider is by email or letter). • Provider gives out research flyers, etc. to potential subjects • Provider makes an introduction to a research team Recruitment from the Investigator’s own patients • The Clinician / PI can provide written materials in advance & allow the patient to contact a study team member later if interested or not interested • Another Co-I or member of the study team who is not the treating physician can talk to the subject about the research

29. Recruitment of Research Subjects Recruitment Letters • Must be on official VA letterhead • Introduction-name study/group • Purpose of study • Participation is voluntary • Participation will have no effect on benefits • Minimize focus on compensation • Provide a contact name, telephone number and schedule-voice mail • Inform subject of any follow-up (date/type) • Letter must originate from PI (Provider may co-sign)

30. Recruitment of Research Subjects • Protect the Confidentiality of Subjects • Provide Equal Opportunity to Participate or Not to Participate • Do not use any diagnosis, prognosis, or treatment language relating to substance abuse, HIV, sickle cell anemia or mental health. • Do not use references to military sexual trauma, PTSD, or STDs, etc.

31. 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

32. 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.

33. 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).

34. 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 or acknowledgement.

35. 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 be 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.

36. 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.

37. The Informed Consent Process • You Tube Informed Consent Video • https://www.youtube.com/watch?v=Vb7e_0Mw4ps

38. 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.

39. 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.

40. 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:

41. 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:

42. 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.

43. 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

44. HIPAA & Research HIPAA = Health Insurance Portability and Accountability Act • Purpose is to ensure that Patient Health Information (PHI) is safe and secured from individuals and entities that are not authorized to use or transfer PHI. • HIPAA regulates how researchers are able to use and access PHI • Research activities are not considered to be part of normal healthcare operations and therefore a HIPAA waiver or signed HIPAA authorization is required

45. HIPAA & Research The Privacy Rule permits a covered entity (i.e. medical center) to use and disclose PHI for research purposes, without an individual’s authorization, provided the medical center obtains either: • Documentation that an alteration or waiver has been approved by the IRB • The researcher states the use and disclosure of PHI is solely to prepare a research protocol • The researcher describes how PHI is necessary to conduct the research

46. HIPAA& Research HIPAA & Research HIPAA (Alteration) Waiver Worksheet Is a required document and must be completed at time of initial submission Is found on the AVAMC research website Describes: • The use or disclosure of PHI involves no more than a minimal risk to the privacy of individuals • That the research could not practicably be conducted without the waiver or alteration • That the research could not practicably be conducted without access to and use of the protected health information.

47. HIPAA& Research HIPAA & Research Types pf HIPAA waivers • Full/Complete: A complete HIPAA waiver allows an investigator to use and disclose PHI for a particular research trial or activity without obtaining either a verbal or written authorization from the participants. It is granted by the IRB. • Partial: A partial HIPAA waiver permits the use of PHI for recruitment purposes only, to allow identification and, as appropriate, contact of potential participants to determine their interest in study participation. It is granted by the IRB.

48. HIPAA & Research • Must have HIPAA authorization signed by subject or have full waiver granted by the IRB if using or disclosing PHI for “research purposes” • The protocol, ICF, eIRB, and eRRRP must be consistent with the HIPAA authorization. • Use the AVAMC template located on the AVAMC research website • VA HIPAA is a stand-alone document • AVAMC Privacy Officer reviews and approves VA HIPAA

49. HIPAA & Research Core Elements of the HIPAA Authorization: • Clear description of the PHI to be used and disclosed (lab results, medical history, HIV diagnosis, demographics ,etc.) • Specific information about the persons or groups authorized to use or disclose PHI (PI, research team, etc.) • To whom the PHI is used or disclosed to (FDA, Sponsor, Emory, etc.) • Description of purpose for use or disclosure • Expiration date • End of research study • None (data repository or registry) • Location where PHI will be stored • Patient rights: to revoke authorization at any time • Signature of subject or LAR

50. 18 HIPAA Identifiers • Names • All geographical subdivisions smaller than a state, except the initial three digits of a zip code for all such geographic units containing 20,000 or fewer people is changed to 000 • All elements of dates except year and all ages over 89 • Phone numbers • Fax numbers • Electronic mail addresses • Social Security numbers • Medical record numbers • Health plan beneficiary numbers • Account numbers • Certificate/license numbers • Vehicle identifiers and serial numbers, including license plate numbers • Device identifiers and serial numbers • Web Universal Resource Locators (URLs); • Internet Protocol (IP) address numbers • Biometric identifiers, including finger and voice prints • Full face photographic images and any comparable images • Any other unique identifying number, characteristic, or code (note this does not mean the unique code assigned by the investigator to code the data)