RTOG Audit Program

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RTOGAuditProgram
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Director of Protocol Development Regulatory
ComplianceWilma Hoffman
Quality Control Auditors Eileen Keevill, B.S.,
CCRP Elaine M. Boyle, RN Valerie Geissenhainer,
BS, RN

Administrative Assistant Randomization
SecretariesRosemarie Ball Sharon Allen
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Why Do We Audit?

• Mandated by National Cancer Institute
• Usually done every 3 years
• To Verify
• Accuracy of data submitted
• Protocol compliance
• Adherence to Institutional Review Board and
  Investigational New Drug regulations for
  protection of human subjects and handling of
  investigational agents.
• To discourage fraud

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How Do We Prepare?

• Regular meetings of Director and Auditors
• -- Update latest guidelines
• Annual meeting of auditors
• Identify institutions due for audit
• Auditor assignments
• Obtain from the database a list of all cases
  entered at the institution since last audit (or
  since activation)
• Random selection of cases for audit

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Then what?

• Letter is sent to Principal Investigator
• Auditor schedules date of audit with
  institutional RA
• Date of audit is entered into NCI and RTOG data
  bases
• Confirmation letter is sent with selected cases,
  IRB and IND (Investigational Drug) lists and
  audit handbook four weeks prior to the audit (as
  per CTMB audit procedures).

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and then?

• Auditor prepares audit packet
• Audit packets consist of print-outs of submitted
  data and individual protocol requirements

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What Do We Audit?

• Three major components
• Institutional Review Board (IRB) and Informed
  Consent Content (ICC)
• Drug Accountability
• Patient Case Assessments
• Based on Code of Federal Regulations
• (CFR) for Protection of Human Subjects

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What Do We Look For

• IRB
• Initial Full Board approval for each study for
  which patients were accrued during the audit
  period
• Annual re-approvals (within 365 days of last
  approval or the proper use of the Anniversary
  Date)
• Protocol Amendments reviewed and approved within
  90 days.
• Serious Adverse Events (SAE) reported
  appropriately per protocol.
• ICC
• Review consents
• Most current consent must contain all required
  components
• Correct version must be used for each patient
  case

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What Do We Look For?

• Investigational New Drug (IND)
• Storage and security
• NCI Drug Accountability Report Forms (DARF)
• Compare pharmacy shelf and DARF log counts
• Confirm doses of dispensed drug for individual
  patients match the DARF
• Verify drug was not used for any other purpose
• Verify commercial drug was not substituted when
  NCI drug is supplied for the protocol
• Verify shipping forms from the NCI to the
  institution and return of drug to the NCI (if
  applicable).

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What Do We Look For?

• Patient Case Assessment
• Documentation for
• Informed Consent
• Eligibility
• Protocol Treatment
• Disease Outcome
• Toxicity
• General Data Quality
• Please note Printed Versions of Electronic
• Data Must be Available at the Audit

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Informed Consent

• Consent form Missing
• Consent form not signed and dated by patient
• Consent form signed after patient started on
  treatment
• Consent form does not contain all required
  signatures
• Consent form used was not current IRB-approved
  version at time of patient registration
• Consent form not protocol specific
• Consent form does not include updates or
  information required by IRB

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Eligibility

• Review of documentation confirms patient did not
  meet all eligibility criteria as specified by the
  protocol
• Documentation missing unable to confirm
  eligibility

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Treatment

• Incorrect agent/treatment used
• Additional agent/treatment used not permitted by
  protocol
• Dose deviation incorrect (error gt /-10)
• Treatment doses incorrectly administered,
  calculated or documented.
• Unjustified delays in treatment

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Disease Outcome/Response

• Inaccurate documentation of initial sites of
  involvement
• Tumor measurements/evaluation of status or
  disease not performed according to protocol
• Protocol-directed response criteria not followed
• Claimed response (PR,CR) cannot be verified
• Failure to detect cancer (as in a prevention
  study) or failure to identify cancer progression

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Toxicity

• Grades, types, or dates/duration of serious
  toxicities inaccurately recorded
• Toxicities cannot be substantiated
• Follow-up studies necessary to assess toxicities
  not performed
• Failure to report a toxicity that would require
  filing an Adverse Event Reaction (AER)
• Recurrent under-or over-reporting of toxicities

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General Data Quality

• Recurrent missing documentation
• Protocol-specified laboratory tests not
  documented
• Protocol-specified diagnostic studies not
  documented
• Frequent data inaccuracies
• Errors in submitted data
• Delinquent data submission

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Scoring the Audit

• Acceptable
• No or few minor deficiencies
• Acceptable, needs follow-up
• A major or multiple minor deficiencies
• Unacceptable
• Multiple major deficiencies recurring
  deficiencies a single, flagrant major deficiency
• Unacceptable, Requires NCI Follow-up
• Suspected scientific misconduct, fraud, or
  intentional misrepresentation of data or
  disregard for regulatory safeguards

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Scoring the Audit

• Any institution having two unacceptable audits
  which are not corrected to the satisfaction of
  the RTOG Quality Assurance Committee, would only
  be permitted one more unacceptable site visit
  before being asked to withdraw from participating
  in RTOG studies.

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Completing the Audit at the Institution

• Auditor conducts the exit interview with PI and
  Research Staff to discuss findings, requirements
  for response to deficiencies (the corrective
  action plan) and answer questions
• Preliminary report is faxed to NCI RTOG-HQ
• Audit Report is entered into the NCI Database and
  finalized.
• Copy of Audit Report along with letter sent to
  PI.

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Completing the Audit at HQ

• Institutions response due at HQ within two
  weeks of receiving the audit report.

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Institutions Response

• Corrective action letter must address all Major
  Deficiencies or Multiple Lesser Deficiencies by
  providing a prospective plan.
• This response must be dated, on institution
  letterhead and signed by the PI.
• Include with the letter any required revised
  forms or source documentation.

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What Happens Then?

• Institutional response is submitted to NCI for
  review
• NCI may request more information or a more
  detailed action plan
• Reports are provided to the RTOG Quality Control
  Committee semi-annually.