Atlanta VAMC Clinical Studies Center

WELCOME TO THE ATLANTA VA MEDICAL CENTER

This presentation will provide you with the Atlanta VA Medical Centers 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.

112/07/20151Use this template to create Intranet web pages for your workgroup or project. You can modify the sample content to add your own information, and you can even change the structure of the web site by adding and removing slides. The navigation controls are on the slide master. To change them, on the View menu, point to Master, then choose Slide Master. To add or remove hyperlinks on text or objects, or to change existing hyperlinks, select the text or object, then choose Hyperlink from the Insert menu.

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For more information, ask the Answer Wizard about:The Slide MasterHyperlinks Atlanta VA Medical Center Research webpage location:

http://www.atlanta.va.gov/ATLANTA/services/research/about.asp

Information for Research - Investigators:http://www.atlanta.va.gov/services/research/investigators.asp

Clinical Studies Center forms and policies are located at the Conducting Human Research website:

http://www.atlanta.va.gov/services/research/Conducting_Human_Research.asp

212/07/20153 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 required VA trainingInvestigators Responsibilities12/07/201534Ensure 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.

Investigators Responsibilities12/07/20155 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 (SRS) , VA Radiation Safety Sub-Committee (if applicable), ISO/PO (Information Security Officer/Privacy Officer) and R&D Committee approval prior to initiating any study activities. These will be represented in a FINAL letter of approval from the Associate Chief of Staff for Research (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.

Investigators Responsibilities12/07/20156 Document research encounters in the subject's medical record. Studies with Certificates of Confidentiality (CoC) will need to consult CoC procedures.

Comply with protocol reporting obligations to the IRB and R&D Committee regarding study changes, annual progress, unanticipated problems, 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.

Investigators Responsibilities12/07/2015Complete 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 mailbox at the Clinical Studies Center (Room 11c119). These may include: ICF, HIPAA, Accounting of Disclosure Form, Notice of Privacy Practices Acknowledgement - VA form 10-0483 , and VA form10-9012 .

Documents are picked-up at the CSC daily.

Medical Records scanning staff will shred the ICF paper copy unless otherwise specified .THEREFORE DO NOT SUBMIT THE ORIGINAL FOR SCANNING!

The original documents should be kept by the PI and/or designee.55Scanning Forms into CPRSProcedures:12/07/2015Complete 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.

8Research Staff Responsibilities12/07/2015Recruit 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 PI, 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 observations during the study.

9Research Staff Responsibilities12/07/2015Attend the sponsor investigator meetings as required.

In the event that conflicting research studies are being conducted, the PI should negotiate access to study population with the Investigator involved.

Contact CSC (Clinical Studies Center) Medical Director for guidance with protocol design and review.

Contact the Human Studies Analyst (HSA) for assistance with VA forms and overall aspects of the protocol submission process.

Prepare recruitment materials for IRB review and approval.

11Preparing for a Research Study12/07/2015Prepare 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 .

12Preparing for a Research Study12/07/2015If the research study involves drugs:

Provide a copy of the Protocol and Investigational Brochure to the Research Pharmacist for review and approval.

Complete an FDA 1572 form (Investigators Agreement), if applicable.

Complete VA Form 10-9012 and pharmacy impact form available at:

http://www.atlanta.va.gov/services/research/Conducting_Human_Research.asp

14For Industry-

Sponsored

Clinical TrialsPreparing for a Research Study12/07/2015VA Consent Template, VA HIPAA Authorization Form, and the VA Revocation Letter are located at:

http://www.atlanta.va.gov/services/research/Conducting_Human_Research.asp

General Guidelines on Writing a Consent:

http://www.irb.emory.edu/forms/index.html

15Informed Consent Form Writing Guidelines12/07/201516Objectives

Policy

Principal InvestigatorsResponsibilitiesTo outline approval processes for the Institutional Review Board (IRB) and the AVAMCs Officers and Committees.

A final letter of approval must be obtained from the AVAMCs 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 needed and submit for filing to VA)Amendments to the original protocol (IRB approval needed, *unless there is a change in PI, risk, or data repository - then need *R&D approval* also in those cases).Approval Process12/07/201516SUBCOMMITTEES 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 is 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.

17Approval Process12/07/2015All 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).

18Approval Process12/07/2015Log 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 approval is obtained, the project can be submitted for R&D review through eRRRP https://vaww.gateway.research.va.gov/errrp

Approvals will not be granted if CITI training is not current.

19Approval Process12/07/2015eIRB Initial Submission (requires the Department Chairs Approval)Upload CITI training certificate, Key Concepts for PI and CO-I, and Intro to Clinical Research (if applicable)Upload Lay Summary Upload Full ProtocolUpload Investigators 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

20Emory eIRB Submission Checklist12/07/2015R&D COMMITTEE REVIEW & APPROVAL

Submit protocols for R&D Committee review and approval through eRRRP (electronic request to review research projects) using your AREF username and password at:

Website: https://vaww.gateway.research.va.gov/errrp/ The R&D Committee meets on the first Wednesday of each month

Address all COMMENTS in eRRRP at this time and then submit complete and final project through eRRRP no later than the Wednesday prior to the convened meeting.

**eRRRP is INTRANET ONLY**

21Approval Process12/07/2015The 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/amendment to the IRB.

Study activities (including screening) may not start until the ACOS/R notification of approval letter has been obtained.

22Approval Process12/07/2015The IRB must approve any changes made to the originally approved investigational plan. These changes are called modifications or amendments.

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, the study team is responsible for ensuring that the approval is forwarded to the Science Information Office (SIO) at the AVAMC.

23Protocol

Modifications

Approval Process12/07/2015Then, 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

24Protocol

Modifications

Approval Process12/07/2015Amendments/modifications involving Privacy, Information Security, BioSafety and/or Radiation will be routed by the Science Information Officer (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

25Protocol

Modifications

Approval Process12/07/2015Continuing reviews (sometimes called renewals) 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.

Ensure that the IRB liaison has forwarded a copy of the continuing review approval and any updated corresponding forms (if applicable) to the SIO.

It is the PI/Study Staffs ultimate responsibility to keep up with Continuing Review by not letting the study lapse. Lapses = required reporting to the Office of Research Oversight (ORO).26IRB Continuing

Review

Approval Process12/07/2015Indirect The potential subject contacts the study team. Examples include flyers, advertisements, radio, television, etc. Requires IRB and Atlanta VAMC Office of Public Affairs approvals prior to use.

Direct The study team contacts the potential subject. Examples include 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.

27Recruitment of Research Subjects12/07/2015Recruitment Methods:

Recruitment from potential subjects provider-Provider gives written permission for his patients to be contacted by the study teamProvider gives out research flyers, etc. to potential subjects Provider makes an introduction to a research team

Recruitment from the Investigators 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 interestedAnother Co-I or member of the study team who is not the treating physician can talk to the potential subject about the research

28Recruitment of Research Subjects12/07/2015Recruitment 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 may originate from PI (Provider co-signs if applicable) 29Recruitment of Research Subjects12/07/2015Recruitment Letters (continued)

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.

30Recruitment of Research Subjects12/07/201531Objectives

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 to ensure that research volunteers are consented properly.

Comply with federal guidelines and the Atlanta VAMC policies and procedures regarding the consenting process.

The Informed Consent Process12/07/2015The 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.

32Informed Consent Process Definition:

The Informed Consent Process12/07/2015Obtain informed consent from all subjects prior to initiating any study activity.

Use the most current IRB approved VA Form 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 subjects electronic medical record (unless waived by the IRB or the project has a CoC that does not allow documentation).

33The Informed Consent Process12/07/2015Discuss 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 subjects ability to read and comprehend the consent document and their understanding about the research and its risks by asking a few simple questions.

If the subjects 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.

36Procedures:

The Informed Consent Process12/07/2015You Tube Informed Consent Video

https://www.youtube.com/watch?v=Vb7e_0Mw4ps

37

The Informed Consent Process12/07/2015The original signed and dated ICF must be kept with the investigators study files.

Provide a copy of the signed and dated consent form to:The study subjectThe Research Pharmacist (if the study involves drugs)

Document the consent process in CPRS. If this is a re-consent, this must be documented also. Studies with CoCs will need to refer to CoC guidance re: documentation requirements.

Reinforce the study information throughout the course of the study.

The Informed Consent Process policy is located on the Atlanta VA research website.

38Procedures: The Informed Consent Process12/07/2015Under appropriate conditions, informed consent may be obtained from the subjects 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.39Legally Authorized Representative (LAR) Consent:

The Informed Consent Process12/07/2015The 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.40LAR Consent:The Informed Consent Process12/07/2015A Legally Authorized Representative (LAR) can be (in this order):

Individuals with durable power of attorney for healthcareLegal guardiansSpouseAdult childrenParents of adult childrenSiblingsGrandparentsGrandchildrenClose Friend

41LAR Consent:The Informed Consent Process12/07/2015If 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 subjects LAR.

Staff should contact the Regional Council regarding any legal questions about a LAR or other legal matters.42LAR Consent:The Informed Consent Process12/07/2015Purpose 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.

44HIPAA = Health Insurance Portability and Accountability Act

HIPAA & Research12/07/2015The Privacy Rule permits a covered entity (i.e. medical center) to use and disclose PHI for research purposes, without an individuals 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

45HIPAA & Research12/07/2015HIPAA (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 individualsThat the research could not practicably be conducted without the waiver or alterationThat the research could not practicably be conducted without access to and use of the protected health information.

46HIPAA & ResearchHIPAA & Research12/07/2015Types of 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 a 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.

47HIPAA & ResearchHIPAA & Research12/07/2015Must 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

48HIPAA & Research12/07/2015Core Elements of the HIPAA Authorization:

Description of the PHI to be used and disclosed (VA health records, demographics photographs, audio recordings, 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 studyNone (data repository or registry)Patient rights: to revoke authorization at any timeSignature of subject or legal representativeOptional authorization supplement for placing data or specimens in a repository or future use projects.

49HIPAA & Research12/07/2015NamesAll 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 000All elements of dates except year and all ages over 89Phone numbersFax numbersElectronic mail addressesSocial Security numbersMedical record numbersHealth plan beneficiary numbersAccount numbersCertificate/license numbersVehicle identifiers and serial numbers, including license plate numbersDevice identifiers and serial numbersWeb Universal Resource Locators (URLs);Internet Protocol (IP) address numbersBiometric identifiers, including finger and voice printsFull face photographic images and any comparable imagesAny other unique identifying number, characteristic, or code (note this does not mean the unique code assigned by the investigator to code the data)

5018 HIPAA Identifiers12/07/2015Preparatory to Research

Data repositories (including VA medical records) may be used (i.e., accessed) by VA investigators for activities that are preparatory to VA research without the requirement to obtain either a HIPAA authorization from the subject or a waiver of HIPAA authorization by an IRB or Privacy Board. This includes use of PHI for the preparation of a research protocol prior to submission to the IRB(s).

Preparatory to Research activity is the only instance of access for research purposes allowed in VHA without a written HIPAA authorization signed by the individual, a waiver of HIPAA authorization by an IRB or Privacy Board, or approval by the IRB(s). This access is granted only to VHA researchers.

51HIPAA & Research12/07/2015Preparatory to Research

The PI must document in his research files:1. The access to PHI is only to prepare a protocol; 2. No PHI will be removed from the covered entity (i.e., VHA); and 3. The PHI accessed is necessary for preparation of the research proposed.

Only aggregate data may be recorded and may be used only for background information, to justify the research, or to show that there are adequate numbers of potential subjects No recording of Individually Identifiable Health InformationNo recruiting from the dataPilot studies are not considered to be activities preparatory to researchThe preparatory to research activities end once the protocol has been submitted to the IRB and R&D Committee.Must comply with all VA Data Repository Requirements

52HIPAA & Research12/07/2015Data Repository - is a database or a collection of databases that have been created or organized to facilitate the conduct of multiple research protocols, including future protocols not yet envisioned.

Research Data Repository is a data repository created from data obtained either to conduct a research protocol(s) or gathered in the course of conducting a research protocol and is maintained after the completion of the research protocol.

Establishment of Data Repositories need IRB and R&D approvalRequire Standard Operating Procedures (SOPs)Require annual review by IRB and R&DReleasing data from the repository requires IRB & R&D approvalData Repository policies and tools are located on the AVAMC research website.

53Data Repository12/07/2015Objectives

ProceduresOutline scanning procedures for VA form 10-9012 and VA form 10-0483. Scanning signed ICF, HIPAA, and Revocation Letter is optional.

Provide a good quality copy of documents with the subjects full name and social security number on the bottom of the first page of the document.

54Scanning Forms into CPRS12/07/2015Objectives:

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 form 10-9012 is scanned in CPRS when investigation drug is despensed to the study subject.56Scanning the Investigational Drug Information Record12/07/2015Provide a good quality copy of VA Form 10-9012 with the subjects full name and social security number on the first page of the document.

Complete a Research Documents Scanning Request Form 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.

57Procedures:

Scanning the Investigational Drug Information Record12/07/2015Non-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 in 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.).

Refer to Notice of Privacy Practices for Non-Veterans (NOPP) policy located on the AVAMC research website.

Contact the CSC for further details and instructions on enrolling a non-Veteran in research.59Documentation Requirements12/07/2015

60A 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 is on the Atlanta VA website.

Research Clinics12/07/201561The Principal Investigator and/or designee is responsible for keeping complete and accurate regulatory documents for the study. Collect, organize, and maintain all documents in a regulatory binder. If it isnt 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 on the Atlanta VA research website.Please refer to Regulatory Documents Policy located on the Atlanta VA research website. This includes the Regulatory Document Checklist.

Regulatory Documents12/07/201561Protocol and any amended protocolsIRB & R&D approval documentation Copies of the eIRB initial submissionCopies of the eRRRP submissionApproval letter from ACOS for ResearchApproved Informed Consent Form and HIPAA Documents

Modifications forms with supporting documentsContinuing review approval documentationReportable Events (SAEs, UPs, SPs, RIIs)Recruitment materialsIRB, R&D, and Sponsors CorrespondenceProtocol Termination form

62Regulatory Documents Checklist12/07/2015Investigators BrochureFinal signed 1572 and amended FDA 1572sPrincipal Investigators CVCopy of randomization codesInvestigational article log and copies of drug/device shipment/retrieval Lab CertificationAccounting of Disclosure Form

Enrollment logMonitoring visits reportsResearch Training CertificationSignature and Delegated Responsibilities LogAbstracts or manuscripts with study results

63Regulatory Documents Checklist12/07/2015Source Documents are any forms, records or documents where study data is first recorded. Information captured in source documents includes clinical findings, observations, and other study activities and is used to complete the Case Report Forms (CRFs). Source documents must be attributable, legible, contemporaneous, accurate, complete, & verifiable.

Principal Investigators and/ or designee are responsible for maintaining complete and accurate Source Documents.

Source Documents are important because they:Promote data consistency and ensures that information required for transcription to CRFs is captured. Verify the subjects participation in the study as well as data integrity.Are Good Clinical Practice and are FDA required.

Corrections should be initialed/dated by the person making the correction.

No whiteout or other means of concealing errors should be used on any research document.

Please refer to the Source Documents policy on the Atlanta VA website.

64Source Documents12/07/2015Study information that is identifiable, sensitive, and/or has PHI must be saved in the secured server specifically designate dfor research. Contact the Director of Research Operationsfor access.

Secure study files in a locked cabinet and in a locked office at the VA. Never leave PHI unattended.

All VA sensitive research information needs to be used and stored within the VA.

A data transfer agreement (DTA) is required if VA sensitive data is transmitted or removed outside the VA .

PHI and/or identifying information should not be included in the CRFs unless special authorization for a limited data set has been granted.

Social security numbers should not be recorded in the CRFs. Only use a study ID to identify study participants.

65Data Management and Security12/07/2015Contact the Information Security Officer (ISO) at VA extension 5081 for information about data transfer agreements and other security issues.

You must have permission from the ISO if any data is going off-site (i.e. Emory).

Laptops and flash drives must be encrypted by the VA if used for transporting data outside the VA.

Know where your data are located and where are going. This must be stated in the Protocol, ICF and HIPAA forms. Study subjects need to be informed how their PHI is used, accessed, or disclosed. Report any Research Information Incidents within one hour to the ACOS, PO, ISO, and RCO.

Review VHA Privacy and Information Security Awareness and Rules of Behavior and VHA Privacy and HIPAA Training in TMS for more information or contact any research staff member with questions. The Data Management policy is located on the Atlanta VA website.

66Data Management and Security12/07/201567An investigational drug is a medication for which an Investigational New Drug (IND) application has been filed with the Food and Drug Administration (FDA) .

At the VA, an investigational drug is also defined as an approved drug that is being studied for an unapproved or approved use in a controlled, randomized, or blinded clinical trial.

The Principal Investigator (PI) is responsible for complying with VA policy regarding storage and dispensing of investigational drugs.

The Clinical Research Pharmacist , Dr. Mehran Salles, is responsible for assessing the investigational drug feasibility prior to protocol approval. E-mail: khadijeh.salles-shahid@va.gov

Provide a completed Investigational Drug Information Record VA Form 10-9012 for each drug used in the clinical trial.

Staff working with studies involving drugs are required to take additional training regarding the pharmacy procedures. Training is provided by the Research Pharmacist.

Management of Investigational Drugs12/07/2015Investigational Drug Policies and Forms are located on the Atlanta VA website:

Investigators Instructions for Placing Orders in CPRS for Investigational Drugs

Research Coordinators Instructions for Placing Orders in CPRS for Investigational Drugs

Management of Investigational Drugs Procedures

Procedures for Scanning the Investigational Drug Information Record VA Form 10-9012

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Management of Investigational Drugs12/07/201569An Investigational device is a device, including a transitional device, that is the object of an investigation. Generally, these devices are not approved by the FDA, or are being tested or studied for indications not previously approved by the FDA.

The Principal Investigator (PI) is responsible for controlling, securing, accounting for, and using Investigational Devices properly.

The Research Compliance officer is responsible for assessing the investigators control of investigational devices.

Refer to the Management of Investigational Devices Procedures policy on the Atlanta VA website.

Contact the CSC Manager for further guidance.Management of Investigational Devices12/07/2015The R&DC determines if posting a Patient Record Flags: Category II warning in CPRS is required for VA patients participating in a research study.Study teams may decide to post a Research Flag because it lends additional protection to patients that are participating in research studies by informing the subjects healthcare providers of their research participation.

Procedures to Post, Remove & Edit Research Flags in CPRS can be found on the Atlanta VA website.

70Flagging Medical Records12/07/2015The terms and conditions of reimbursement for research participants should be disclosed in the research proposal.

In the Informed Consent Form, specify the reimbursement amount, payment form (cash, check, etc.), when, and how it will be done.

The investigator must ensure that reimbursements are appropriate, prorated, and do not constitute or appear as undue pressure and/or coercion to the subject.

The investigator may delegate to a research team member the responsibility of handling reimbursements for study participants.

Reimbursement procedures depend on where the funds are managed (VA, Emory, AREF).

Maintain clear documentation of any subject reimbursement.

Refer to Research Participants Reimbursement Procedures located on the Atlanta VA website.

71Research Subject Reimbursement12/07/2015VA Investigators must report unanticipated and related: Local research deathsLocal Serious Adverse Events (SAE)Serious Problems (SP)

Unanticipated/unexpected refer to an event/problem in human research that is new or greater than previously known in terms of nature, severity, or frequency, given the procedures described in protocol documents and the characteristics of the study population.

A related adverse event, death, or problem is one that may reasonably be regarded as caused by, or probably caused by, the research.

72Reportable Events12/07/2015A Serious Adverse Event (SAE) is an untoward occurrence in human research that results in death, a life-threatening experience, inpatient hospitalization, prolongation of hospitalization, persistent or significant disability or incapacity, congenital anomaly, or birth defect, or that requires medical, surgical, behavioral, social, or other intervention to prevent such an outcome.

Serious Problem (SP) is a problem in human research or research information security that may reasonably be regarded as: (1) Presenting a genuine risk of substantive harm, to the safety, rights, or welfare of human research subjects, research personnel, or others, including their rights to privacy and confidentiality of identifiable private information; or (2) Substantively compromising a facilitys HRPP or research information security program. (VHA Handbook 1058.014t)

73Reportable Events12/07/2015Deaths that are unanticipated and related to the research conducted in local VA studies must be orally and immediately reported to the IRB and reported in eIRB within 5 business days.

Other Reportable Events should be reported in eIRB within 5 business days of learning of the event.

Follow instructions Steps for Filling Out eIRB for an Internal or External Event.

Start by selecting New Reportable Event on the left side of the eIRB page.

For question 1.0 - indicate that Atlanta VAMC is part of the event title.

74Reportable Events12/07/2015Once eIRB is filled out, send an email to :

VAReportableEvents@atlaref.org Include the PIs name and eIRB number to alert the research office that a reportable has been submitted to the IRB.

The Reportable Event Policy, the Reportable Event Flowchart, as well forms and instructions are located on the Atlanta VA Research website.

75Reportable Events12/07/2015Continuing Review:

The PI is responsible for submitting a summary of all local reportable events at Continuing Review to the Emory IRB using the Atlanta VA Periodic Reportable Event Summary posted on the Atlanta VA research website. The PI is also responsible for tracking any events that did not meet the 5 business day reporting threshold and documenting why this event did not need to be reported within that time frame.

76Reportable Events12/07/2015Protocol Deviations (PD)Definition A departure from the IRB-approved protocol.

Report PDs to the IRB if there has been a substantive deviation from the protocol that could or did adversely affect at least one of the following:

The rights, welfare, or safety of subjects;The subjects willingness to continue participation; orThe scientific integrity of research data

77Reportable Events12/07/2015Non-compliance definition:Failure to comply with any of the regulations and policies in the IRB and VA Policies and Procedures and failure to follow the determinations of the IRB.

Consult the IRB or the VA Research Compliance Officer (RCO) for questions about what to report and how.

Reportable Research Incidents: Incidents, events or problems that involve the unauthorized use, disclosure, transmission, removal, theft, loss, or destruction of VA research-related protected health information (PHI), individually identifiable private information, or confidential information as defined by the HIPAA Privacy Rule, the Common Rule, the Privacy Act or 38 U.S.C. must be reported within 1 hour as described in the AVAMC policy entitled: Research Information Incidents. This policy can be found on the AREF website.78Reportable Events12/07/201579The AVAMC QA/QI Program:Identifies and corrects deficiencies on an ongoing basis.Provides ongoing training and education to VA research staff regarding ethical principles and proper research conduct.Ensures the quality and integrity of data when conducting human research studies. Ensures regulatory compliance with VA policies and procedures.Ensures that all study staff adhere to the study protocol for quality and consistency.Schedules visits annually or on an as needed basis to assess study performance.

After initial review, the RCO will meet with the study coordinator (and PI if necessary) to discuss discrepancies, findings, and to make study performance improvement recommendations.

If corrective actions are needed, the assessment form is submitted to the Emory IRB for review.

The Principal Investigator is responsible for ensuring that research studies are conducted in compliance with federal regulations and institutional policies.

QA policy and forms are available at the Atlanta VA research website:Quality Assurance / Improvement Program Policy QA form for general research studies QA form for drug/device research studies

Research Quality Assurance & Improvement Program12/07/2015All study monitors and/or external auditors need to check-in at the Clinical Studies Center (CSC) and provide a copy of the Entrance Briefing Form to the CSC Administrative Assistant.

Note: No entity other than those listed on the consent and HIPAA form may have access to any documents with Protected Health Information.

All forms and instructions are found on the AREF website:

Procedure for External Monitoring VisitsVHA Privacy Policy Training Instructions for Monitors (if applicable)Monitoring Visit Report Entrance Briefing FormMonitoring Visit Report Exit Briefing Form

80Monitoring & Audit Visits12/07/2015Monitors Access to CPRS:

The Atlanta VA Employee Driver Method:The Atlanta VA Medical Center (AVAMC) study team member is present while monitor reviews CPRS and/or paper records. The monitor only has access to research subjects information associated with the research project, and is supervised by the study team throughout the visit. If accessing CPRS, the AVAMC study team member logs in, opens the appropriate screens in CPRS, and is present during the review of CPRS. Monitors are not allowed unsupervised access to CPRS.

The Atlanta VA Employee Driver Method is the preferred method for Monitors to view CPRS.

81Monitoring & Audit Visits12/07/2015The monitor is responsible for conveying any potential or actual serious findings to the PI and theResearch Compliance Officer (RCO).

Findings that require an exit interview include, but are not limited to:

Any suspicions or concerns that non-compliance may exist.

Serious non-compliance with the study protocol, Emory Institutional Review Board (IRB) requirements, or applicable regulations and policies such as:

Failure to consent subjects prior to initiating study activitiesEnrolling subjects who do not meet study inclusion criteriaFailure to report serious or unexpected adverse events

The research office is required to report to the VA Office of Research Oversight (ORO) all findings of serious non-compliance through the Medical Center Director.

Contact Information: Research Compliance Officer Rodney Thompson Phone: (404)321-6111 ext. 6964 Fax: at: (404) 417-2927

82Monitoring & Audit Visits12/07/201583A study is "closed" when:All subjects have completed study participationData collection is completedThe sponsor decides to terminate the study and/or completes a study close out visitData analysis is complete

The Principal Investigator (PI) and/or designee is responsible for following the Procedures for Closing Research Studies. The policy is located on the Atlanta VA website.

Close out the study with the R&D Office by turning in the following via email to the SIO: A copy of the IRB Close Out approval letter An end of study summary abstract

RCO needs to review study prior to preparation of study files for short term or long term storage.

Ensure that all electronic study identifying information has been saved in the secured research server.

Never destroy any research data and store ALL data at a VA storage facility indefinitely.

Study Close Out Procedures12/07/201584The VA Central Office (VACO) requires that research records be stored indefinitely.

Research records are the responsibility and property of the VA Medical Center.

The Atlanta VAMC is responsible for storage and retention of research records of studies that have been closed.

The PI is responsible for preparing and submitting research records for storage when the study is closed.

Contact the CSC Administrative Assistant (AA) and/or Manager to get boxes and receive instructions to prepare records for storage.

Submit a completed Research Records Storage Request by email to the CSC AA, prior to submitting records for storage. The request form is available on the Atlanta VA research website. Also refer to the Research Record Retention & Storage Policy.

Research Records Retention & Storage12/07/2015In order to be engaged in research at the Atlanta VA, Investigators must have a VA appointment or a collaborator (Co-PI) who is a VA staff physician or a practitioner with VA privileges.

Physicians may get a WOC (without compensation) appointment; however, they must be sponsored by a clinical division and privileged through the VA Medical Center Chief of Staff Office.

All RNs, LPNs, MDs, and other licensed personnel must complete VetPro credentialing prior to engaging with research subjects. Specific duties and role as a research coordinator vs. research nurse should be discussed with Antonio Laracuente prior to engagement in research.

CITI certification must be updated every three years on your anniversary date. There is no grace period. Please view Credentialing to Engage in Human Subjects Research presentation located on the research website.

85Staff Credentialing & Training Requirements12/07/2015All study staff members involved directly or indirectly in the study must be listed in eIRB under study staff.

Additional training is required if:Performing phlebotomy, inserting IVs, or processing specimens. Contact the CSC Manager to arrange training.Transporting hazardous materials. The packaging and shipping training in CITI named Packaging and Shipping of Class 6.2 Agents must be completed every two years.

VA appointments are handled by the VA Medical Staff Coordinator.

For credentialing and training specifics, contact Nakela Jackson, the Research Training Coordinator at (404) 321-6111 ext. 6177 or check on the Atlanta VA or AREF website.86Staff Credentialing & Training Requirements12/07/2015Atlanta VA Website: http://www.atlanta.va.gov/ATLANTA/services/research/about.aspAtlanta VA Website for Investigators: forms and policies: http://www.atlanta.va.gov/services/research/investigators.aspAtlanta VA Website for Conducting Human Research: http://www.atlanta.va.gov/services/research/Conducting_Human_Research.asp

Atlanta Research & Education Foundation Website: www.atlaref.org Emory IRB Web Page: www.irb.emory.edu Collaborative IRB Training Initiative (CITI): www.citiprogram.org Office of Human Research Protection (OHRP): www.hhs.gov/ohrp/ Office of Research Oversight (ORO) vaww1.va.gov/oro/ Public Responsibility in Medical Research: www.primr.org National Institute of Health (NIH): www.nih.gov Food and Drug Administration (FDA): www.fda.gov FDA Information Sheets: www.fda.gov/cber/infosheets.htm 45 CFR 50 Protection of Human Subjects: www.gpoaccess.gov/cfr/index.htm

Research Professional Organizations:Society of Clinical Research Associates (SOCRA): www.socra.org Association of Clinical Research Professionals (ACRP): www.acrpnet.org Public Responsibilities in Medicine and Research (PRIM&R):www.primr.org 87Research Related Web Sites12/07/2015The Principal Investigator (PI) or designee is responsible for contacting the AREF Contracts/Grants Administrator and informing him/her of his/her interest in participating in an industry-sponsored clinical trial.

The PI is required to provide AREF with a completed Assessment of Clinical Impact Form located on the Atlanta VA website, outlining the obligations of the study for the Atlanta VA Medical Center and a copy of the study protocol. Instructions can be found on the Atlanta VA website.

The AREF Contracts/Grants Administrator is responsible for the legal review and final negotiation of agreements, including the budget.

All research projects administered by AREF must have a signed agreement between the Collaborator and AREF. VA Research & Development (R&D) Committee approval may be sought simultaneously while establishing the AREF contract.

As a general rule, no research funds should be expended until IRB and R&D (ACOS/R) approval have been obtained. However, reasonable and usual preliminary costs for project planning prior to approval are allowable according to VA policy. For AREF administered studies, PIs must have a signed agreement before studies are initiated (= enrollment of first study subject).

88Research Agreements with Collaborators12/07/2015The Clinical Studies Center (CSC) is a controlled and professional research center designed to promote and facilitate clinical research for human subjects at the Atlanta VA Medical Center.

The CSC is designed to conduct outpatient research studies and is located on the 11th floor at the Atlanta VAMC.

The Clinical Studies Center consists of the following:

Administrative offices: Medical Director, CSC Manager, and Administrative Assistant

Two Workstations: for research coordinators and study monitors

Five exam rooms: equipped with exam tables, vital signs monitoring machine, X-ray view box, phlebotomy chairs, ophthalmoscope/otoscope, and computer access

89Clinical Studies Center12/07/2015On site record storage for studies which have been closed

A laboratory to prepare research specimens for shipping or storage. This includes:Bio-Safety cabinet -80C freezerRefrigerator CentrifugeRefrigerated centrifugeDry ice90Clinical Studies Center

12/07/2015To reserve an exam or interview room at the CSC, email the CSC Room Request Form to the CSC Administrative Assistant or CSC Manager with the following information :

Room type (exam/interview/monitor station)

Requestors name

Study Name

Date, time, and length of time needed

Please do NOT enter subject name, initials, or any identifiers (study ID only)

People using the CSC rooms are responsible for greeting participants in a timely manner and notifying the CSC of appointment cancellations.

The Clinical Studies Center Operating Guidelines are located on the Atlanta VA website.

91Clinical Studies Center 12/07/2015Lawrence Phillips, MD is the Clinical Studies Center Medical Director.

He is a Professor of Medicine and Associate Professor of Physiology, appointed to the Division of Endocrinology. In the past, he served as the Director of Endocrinology and Program Director of the Emory University GCRC. He served on the Editorial Boards for the journalsDiabetes and Endocrinology, and as a member of the NIDDK- B NIHStudy Section that reviews grants. He is experienced in trainingJunior Faculty members and Fellows who have gone on to pursue anacademic career in clinical investigations.

Dr. Phillips is experienced in peer-review standards for research quality as exemplified by the awarding of extramural research support, and is personally involved in clinical investigations on a daily basis.

Dr. Phillips currently directs the Atlanta VA Clinical Studies Center Investigator Mentoring Program. He interacts, mentors, and trains VAjunior investigators at multiple levels.92Clinical Studies Center Staff12/07/2015 Jane Guidot, RN, CCRC is the Clinical Studies Center Manager.

Jane has been a clinical research coordinator at the Atlanta VAMC since 1995. She has worked with the cardiology, infectious disease, neurology, pulmonary, and vascular surgery departments on a large variety of projects. She has also worked as a research coordinator at Emory University. She has served on a variety of committees concerned with the conduct of human research.

She is responsible for the day-to-day operations of the CSC and for providing training and education to Investigators and Research Coordinators involved in human subjects research.

93Clinical Studies Center Staff12/07/201594Laurie Hunt, MPH, CIP, is the Human Studies Analyst (HSA). She provides guidance and support to research staff with initial and ongoing human research projects conducted at the Atlanta VAMC. The HSA services include assistance with:

Protocol Submissions to the Emory IRB, VA R&D and CIRB CommitteesInformed Consent Form writing/formatting & HIPAA requirements and documentsOnsite and Offsite Tissue Banking Project queries Continuing Reviews Modifications and/or Amendments Information on changes in Policies and Procedures within the HRPP

Clinical Studies Center Staff12/07/2015David Worley is the CSC Administrative Assistant. He has extensive knowledge of the Atlanta VAMC, VA policies and VA procedures. His office is located at the CSC in room 11C119. He is a veteran with 22 years of active service in the US Air Force.

He supports research teams and the CSC on a daily basis. His responsibilities include: staffing the CSC office, greeting study subjects, scheduling CSC exam rooms, control and storage of long and short term study records, IT requests for CSC personnel, submitting CSC clinic setups in CPRS, problem solving, and many other day-to-day tasks associated with operating the CSC.

95Clinical Studies Center Staff12/07/2015Associate Chief of Staff, Research ServicesMichael Hart, MD(404) 728-7772michael.hart3@va.gov

Director, Research OperationsAntonio Laracuente, MBA(404) 728-7643antonio.laracuente03@va.gov

Science Information OfficerDavid Knightdavid.knight2@va.gov Ext. 4827Research Compliance Officer (RCO)Rodney ThompsonExt. 6964Fax (404) 417-2927rodney.thompson2@va.gov

Research Compliance AuditorMarquisette Glass-LewisExt. 1790Marquisette.Glass-lewis@va.gov

Research Pharmacist Mehran Salles, Pharm DExt. 4214, Pager (404) 596-8692Fax (404) 417-1809khadijeh.salles-shahid@va.gov 96VA Contact Information96Medical Director, Clinical Studies CenterLawrence Phillips, MDExt. 7608medlsp@emory.edu

Manager, Clinical Studies CenterJane Guidot, RN, CCRCExt. 6933 Fax (404) 417-2902jane.guidot@va.gov

HRPP Quality ManagerJennifer Whelan jennifer.whelan@va.gov Ext. 3452Human Studies AnalystLaurie Hunt, MPH, CIPExt. 4750laurie.hunt@va.gov

CSC Administrative Assistant, Clinical Studies CenterDavid WorleyExt. 4934Fax (404) 417-2991 david.worley@va.gov

97CSC Contact InformationEmory IRB Office Location: 1599 Clifton Road5th floor, Room 213 Atlanta, GA 30322

IRB Office Numbers: Phone: (404) 712-0720Toll free: 1-877-503-9797Fax: (404) 727-1358

IRB Department Email:IRB@emory.edu

98IRB Director: Rebecca Roussellerebecca.rousselle@emory.edu(404) 712-9750

VA/IRB LiaisonDaniel Roysden, PhD, ThMdroysde@emory.edu(404) 712-9749

IRB Contact Information12/07/2015Main OfficePhone Number:(404) 728-7643Fax (404) 728-4847

AREF ControllerJenna Zargon Ext. 4856 Fax (404) 235-3061jenna.zargon@va.gov

Chief Operating OfficerAREFLeslie Henry Ext. 2535Leslie.Kitchen-Henry@va.gov

Human Resources ManagerEllen Schneider Ext. 7271ellen.schneider@va.gov

WOC CoordinatorNakela JacksonExt. 6177nakela.jackson@va.gov

99AREF Contact Information

12/07/2015