preparing for a va compliance audit kimberly summers, pharmd assistant chief for clinical research...

Preparing For A VA Preparing For A VA Compliance AuditCompliance Audit

Kimberly Summers, PharmDKimberly Summers, PharmD

Assistant Chief for Clinical Research Assistant Chief for Clinical Research

South Texas Veterans Health Care South Texas Veterans Health Care System,System,

San Antonio, TXSan Antonio, TX

An Active Monitoring and Auditing An Active Monitoring and Auditing Program is Important for…Program is Important for…

• Maintaining participant and staff safety

• Protecting the reputation of the PI, staff, sponsor, and institution

• Maintaining data quality• Protecting funding• Measuring compliance with

regulatory requirements

Components of a Monitoring Components of a Monitoring ProgramProgram

• Investigators and their staffInvestigators and their staff• Research Compliance OfficeResearch Compliance Office

– STVHCSSTVHCS– UTHSCSAUTHSCSA

• IRBIRB• Research PharmacyResearch Pharmacy• External Monitors External Monitors • R&D CommitteeR&D Committee

Layers of the Local Monitoring ProgramLayers of the Local Monitoring Program

Research

Subject

PI

Research staff

IRB

Compliance Office

Research Pharmacy

Specialized Monitoring

Pri

vacy

Offi

ceD

ata

Secu

rity

Sponsor Monitors

R&D Committee

QA/QI Subcommittee

Components of a Local Monitoring Components of a Local Monitoring ProgramProgram

• The PI has primary responsibility for the proper The PI has primary responsibility for the proper conduct of the study; this includes appropriate conduct of the study; this includes appropriate monitoring by the research teammonitoring by the research team

• Provides first and most important level of local Provides first and most important level of local research monitoringresearch monitoring

• Closest to the action; can respond to issues Closest to the action; can respond to issues earlier and more quicklyearlier and more quickly

• Can identify and correct problems before they Can identify and correct problems before they harm participants or reach institutional harm participants or reach institutional visibilityvisibility

Investigator ResponsibilitiesInvestigator Responsibilities

Role of External Monitors in local Role of External Monitors in local MonitoringMonitoring

• VHA Directive From Chief Research and VHA Directive From Chief Research and Development Officer:Development Officer:– Each research office must develop procedures that will Each research office must develop procedures that will

ensure all serious findings and concerns are ensure all serious findings and concerns are appropriately addressed and the appropriate facility appropriately addressed and the appropriate facility officials and committees are notifiedofficials and committees are notified

• Types of External monitoring visitorsTypes of External monitoring visitors– Pharmaceutical companiesPharmaceutical companies

– Study sponsorsStudy sponsors

– Contract Research Organizations (CROs)Contract Research Organizations (CROs)

– VA Cooperative Studies ProgramVA Cooperative Studies Program

– UTHSCSA Compliance OfficeUTHSCSA Compliance Office

Auditing vs MonitoringAuditing vs Monitoring

• Audits are in addition to the more detailed monitoring of studies by the research team and sponsor

• Audits are an independent evaluation by someone who is not directly associated with the research

‘‘Research is concerned with Research is concerned with discovering the right thing discovering the right thing to do; audit with ensuring it to do; audit with ensuring it

is done right’is done right’

Smith, 1992; editor of the BMJ

VHA Directive 2008-064VHA Directive 2008-064

• Research Compliance Officers And The Research Compliance Officers And The Auditing of VHA Human Subjects Research To Auditing of VHA Human Subjects Research To Determine Compliance With Applicable Laws, Determine Compliance With Applicable Laws, Regulations, and PoliciesRegulations, and Policies

• ““An active auditing program should provide An active auditing program should provide reasonable assurance of the reasonable assurance of the integrityintegrity of the of the research program and that adequate research program and that adequate protections for research subjects are in place.”protections for research subjects are in place.”

• The Director must “ensure that the local HRPP The Director must “ensure that the local HRPP conducts periodic audits of VA-approved conducts periodic audits of VA-approved research to assess compliance with all research to assess compliance with all applicable laws, statutes, regulations. . .”applicable laws, statutes, regulations. . .”

• Functions independently and objectively Functions independently and objectively in the monitoring of research activitiesin the monitoring of research activities

• Reviews research activities from both a Reviews research activities from both a regulatory and human subject regulatory and human subject protection perspectiveprotection perspective

• Reports to the Medical Center DirectorReports to the Medical Center Director

• Findings reported to IRB and R&D Findings reported to IRB and R&D Committee for appropriate actionCommittee for appropriate action

Research Compliance OfficeResearch Compliance Office

• Investigator Site AuditsInvestigator Site Audits– RoutineRoutine– For CauseFor Cause

• Monitoring the Informed Consent Monitoring the Informed Consent ProcessProcess

• Quality Assurance AuditsQuality Assurance Audits– IRB files and processesIRB files and processes– R&D files and processesR&D files and processes– Research Pharmacy files and processesResearch Pharmacy files and processes

How Does the Compliance Office How Does the Compliance Office Monitor ResearchMonitor Research

• Problem identified by a bad outcome Problem identified by a bad outcome • Potential problem identified by a component of Potential problem identified by a component of

the HRPPthe HRPP– Clinical, pharmacy, or other institutional staffClinical, pharmacy, or other institutional staff– IRBIRB– R&D OfficeR&D Office– SponsorSponsor– Research subjectResearch subject

• Increased potential for research non-complianceIncreased potential for research non-compliance– Evidence of a poorly educated investigatorEvidence of a poorly educated investigator– ““Flying under the radar” investigatorFlying under the radar” investigator

For-Cause or Targeted AuditsFor-Cause or Targeted Audits

Routine Investigator Routine Investigator AuditsAudits

• Check documents and procedures at the project level

• Each VA-approved human research protocol is completely audited at a minimum of once every 3 years

• Compliance with regulations for informed consent is audited at a minimum once a year

The audit process is The audit process is designed to be support designed to be support

rather than punitiverather than punitive

The process is meant to be useful in helping investigators

and staff to achieve best practice in their research

Approach to Research Approach to Research Compliance Monitoring and Compliance Monitoring and

AuditingAuditing

VS.VS.

Why Has My Study Been Why Has My Study Been Chosen?Chosen?

• Studies for routine auditing are chosen at random

• The STVHCS and UTHSCSA Compliance offices coordinate auditing visits to avoid duplication

What Will Happen at the What Will Happen at the Auditing Visit?Auditing Visit?

• The auditor will use an auditing tool consisting of a checklist for determining compliance with GCP and local policies and procedures

• STVHCS and UTHSCSA use the same auditing tool

• The auditors will visit the study staff work area to review study documents– A study staff member must be on hand to

facilitate the review

Elements of the Auditing ToolElements of the Auditing Tool• Regulatory documents• IRB submissions• Informed consent• Subject and/or data use• Banking of specimens• Inclusion / exclusion elements• Serious adverse events• Investigational drug• Study site• Confidentiality / data security

Additional Elements of the Additional Elements of the Auditing ToolAuditing Tool

• Participant review– Consent form– Inclusion / exclusion criteria– CRF / source documents– UPIRSO reporting– Exceptions / deviations– VA documentation

• Investigational devices• Principal investigator initiated / sponsored

trials

Participant and Regulatory Participant and Regulatory File Reviews – Your Record File Reviews – Your Record

KeepingKeeping• Purpose of record keeping

– To keep an orderly account of progress– To facilitate the detection of errors– To meet legal requirements– To supply information required for

taking certain actions• Deviations, exemptions, etc.• Notes to file

Participant Review Portion of AuditParticipant Review Portion of Audit

• Research records and source documentation• Adherence to IRB-approved research protocol

– Inclusion/exclusion criteria– Screening procedures– Study procedures– Follow-up procedures

• Documentation of informed consent– Consent enrollment note in CPRS– Informed consent document scanned in CPRS

Preparing For The Participant Preparing For The Participant Review Portion of the AuditReview Portion of the Audit

• Treat each patient as if he/she will be audited• Make the research interventions an obvious

portion of the patient’s chart• Use documentation templates for enrollment,

progress notes, and termination• Provide complete documentation of clinical

care and the rationale for protocol deviations or exemptions

• Document assessment of AEs and reporting of UPIRSOs

Components of the Components of the Regulatory FileRegulatory File

Audit of Regulatory FilesAudit of Regulatory Files• IRB correspondence

– Initial and continuing review approval letters– Waivers and authorizations

• R&D correspondence – Initial and continuing review approval letters– Clinical impact statements– Data security checklist– Research protocol safety survey

• Sponsor correspondence – Exemptions– Queries– Changes in conduct of the study

List in not intended to be all inclusiveList in not intended to be all inclusive

Audit of Regulatory Files Audit of Regulatory Files (cont)(cont)

• Protocol – Approved versions of the protocol– Protocol amendments– Investigator brochures

• Continuing review – Progress reports– DSMB minutes and reports

• Informed consent– All versions of IRB approved informed

consent documents



• Participant enrollment– Screening log

• Reason not enrolled if screen failure– Enrollment log

• Name• Last four• Assigned study number• Date informed consent was signed• Enrollment date• Termination date

– Must be able to account for each signed informed consent



• Patient safety and monitoring– Data Safety and Monitoring Plan

• Adverse event monitoring and summaries• Notes to file

– Reported UPIRSOs– IND safety reports– PBM alerts

• Note to file for the PIs assessment and actions



• Drug/device accountability – All versions of 1572 if applicable– Shipment receipts– Inventory logs– Dispensing log if not maintained by pharmacy– 10-9012 Investigational Drug Information forms– Contract if drugs are stored outside research

pharmacy (rare instances)

• Laboratory – Certifications– Normal values– Lab director CVs



• Investigators and study staff – CVs signed and updated within 2 years– Medical / professional licenses– Certificates of training– Scopes of practice– Responsibility and signature logs– COI disclosure forms

• Monitoring – Monitor sign in log– External monitor reports


Hierarchy of Audit Hierarchy of Audit ProblemsProblems

• I-words– Informed consent– Ineligibility– IRB– IND

• D-words– Drugs– Documentation– Diagnostic studies

• F-words– Follow-up– Forms

– pro Forma (practices that seek to satisfy the minimum requirements)

Standard Operating Standard Operating Procedures (SOPs)Procedures (SOPs)

• Informed consent process• Handling of body fluids / tissue samples• Protocol coverage when PI is

unavailable• Maintaining participant confidentiality• Handling participants’ comments,

complaints, or concerns• Unblinding procedures


Investigator Audit ReportInvestigator Audit Report

• Summary of visit– Recommendations for improving

practice– Action plan if necessary– Timelines for achieving compliance– Follow-up if required

• A process for Principal Investigators to A process for Principal Investigators to respond respond

• Communication with responsible Communication with responsible administratoradministrator

• Confidentiality Confidentiality

• Triggering of educational process as Triggering of educational process as neededneeded

• Appropriate committee reporting, review Appropriate committee reporting, review and action if neededand action if needed

AuditAudit Reports Should ProvideReports Should Provide

Following The AuditFollowing The Audit

• Re-examine strengths and weaknesses in your individual program

• Address any issues in a written response to the audit findings– Including findings that may have been

erroneous or require clarification

• Use this as a time to improve your research program

• VA Compliance Office– Kari Williams, Research Compliance Officer– Pam Cervantez, Research Compliance

Coordinator– Joanne Gonzales, Research Compliance Auditor

• UTHSCSA Compliance Office– Gayle Knight, Assistant Vice President for

Regulatory Affairs and Compliance– Anna Taranova, Manager of Clinical Study

Monitors

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Questions and Comments?Questions and Comments?

preparing for a va compliance audit kimberly summers, pharmd assistant chief for clinical research...

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