1	RTOG Audit Program
2	Director of Protocol Development & Regulatory Compliance Wilma Hoffman
3	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
4	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
5	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).
6	and then? Auditor prepares audit packet Audit packets consist of print-outs of submitted data and individual protocol requirements
7	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
8	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
9	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).
10	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
11	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
12	Eligibility Review of documentation confirms patient did not meet all eligibility criteria as specified by the protocol Documentation missing; unable to confirm eligibility
13	Treatment Incorrect agent/treatment used Additional agent/treatment used not permitted by protocol Dose deviation incorrect (error > +/-10%) Treatment doses incorrectly administered, calculated or documented. Unjustified delays in treatment
14	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
15	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
16	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
17	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
18	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.
19	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.
20	Completing the Audit at HQ Institution’s response due at HQ within “two weeks” of receiving the audit report.
21	Institution’s 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.
22	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.