CMRSC Division of Hematology/Oncology

1. CMRSC Division of Hematology/Oncology Training Standard Operating Procedures for Good Clinical Practice at the Investigative Site Sections: DATA MANAGEMENT & QUALITY ASSURANCE

2. CMRSC 5.0 – Data Management Purpose: This SOP describes the processes followed for the collection of clinical research data, transcription of the data to case report forms (CRFs), and the management of the data, including procedures for: • Quality control • Data query resolution • Record retention and archiving

3. CMRSC 5.0 – Data Management Definition: Case Report Form (CRF): a printed, optical, or electronic document designed to record all of the protocol-required information to be reported to the sponsor on each trial subject.

4. CMRSC 5.0 – Data Management Collection of clinical research data: • Ensure that copies of the most recent IRB-approved consent form are available for subject enrollment. • Obtain source documentation from clinical documents.

5. CMRSC 5.0 – Data Management Transcription of the data to CRFs, including remote data entry: • Complete all fields in the CRFs according to sponsor specifications. • Correct errors by striking through the error once, dating and initialing it, and making the correction. Ensure the original entry is not obliterated. If necessary, note an explanation in the right margin. • Ensure that data for the CRFs are transcribed promptly from the source documentation. • If the sponsor requires remote data entry, ensure that data are entered by computer according to the sponsor’s specifications.

6. CMRSC 5.0 – Data Management Management of the data: • Ensure that the first sets of completed CRFs are reviewed for completeness and accuracy and signed off by the PI, Co-Investigator, or designee • Request a copy of the sponsor’s SOPs for making changes or corrections to the CRFs, if applicable • Ensure that copies of submitted data corrections are maintained in the patient study file. • At the close of the study, ensure data are retained according to regulatory and sponsor requirements. • Inform the sponsor of the study in writing and obtain approval prior to destroying any study-related data, if applicable.

7. CMRSC 5.1 – Management of Electronic Records and Signatures Purpose: This SOP provides additional guidance concomitantly required when all or portions of the data that are required by an FDA rule for submission or inspection, are collected, manages, and/or transmitted electronically, or include the use of electronic signatures in required records.

8. CMRSC 5.1 – Management of Electronic Records and Signatures Definitions: Audit Trail: a secure, computer-generated, time-stamped electronic record that allows reconstruction of the course of events relating to the creation, modification, and deletion of an electronic record. Certified Copy: a copy of original information that has been verified, as indicated by dated signature, as an exact copy having all of the same attributes and information as the original. Digital Signature: an electronic signature based upon cryptographic methods of originator authentication.

9. CMRSC 5.1 – Management of Electronic Records and Signatures Definitions: Direct entry: recording data where an electronic record is the original capture of the data. e-CRF: an auditable electronic record designed to record information to be reported to the sponsor. Electronic Patient Diary: an electronic record into which a subject enters observations

10. CMRSC 5.1 – Management of Electronic Records and Signatures System setup, training, security and maintenance: • Sponsor responsibilities: • Ensure computerized systems used at this facility are in compliance with regulations, regarding design and validation. • Train all clinical research team members on the proper use off all electronic systems used to capture study data (electronic patient diary, e-CRF), and on relevant regulatory requirements. • Train appropriate personnel to conduct reviews, if necessary, of electronic data and audit trails at designated time periods.

11. CMRSC 5.1 – Management of Electronic Records and Signatures System setup, training, security and maintenance: • CCHMC Information Systems (IS) Project Manager responsibilities: • Facilitate setup, implementation, maintenance of computerized systems. • Work with sponsor to ensure security systems are maintained.

12. CMRSC 5.1 – Management of Electronic Records and Signatures System setup, training, security and maintenance: • CMRSC member responsibilities: • Ensure computerized systems are securely stored when not in use. • Login using a unique User ID/Password. Do not share passwords with anyone • Log off when computer data entry/ management activities are complete.

13. CMRSC 5.1 – Management of Electronic Records and Signatures Transcription of the data to CRFs, including remote data entry: • Ensure that sponsor-provided computerized systems are used only for which they were intended and validated. • Ensure the audit trail documents all changes to electronic records • Check and correct all data before transmitting the e-CRF to the sponsor.

14. CMRSC 5.1 – Management of Electronic Records and Signatures Management of the data: • Ensure that an original or certified copy of all electronic source documents and audit trail records are retained on file. • With respect to an FDA audit, treat electronic records as you would paper records. • Ensure that changed CRFs and eCRFs also display all prior information. • Retain audit trail records according to regulatory and sponsor requirements.

15. CMRSC 6.0 – Audits Purpose: This SOP applies to the procedures to prepare for an audit of all clinical studies conducted within the Division of Hematology/Oncology. It describes the steps followed from the time the audit is scheduled until all follow-up activities associated with the audit have been completed.

16. CMRSC 6.0 – Audits Preparing for the audit: • If notified of an FDA audit, notify the sponsor as soon as possible. • Determine the scope of the audit, if possible. Inquire about: • The study or studies to be audited • Specific subjects being audited • How many auditors will perform the audit • The approximate length of the audit • Who from CCHMC the auditor(s) expect to be in attendance • Notify affected groups according to the checklist: Job aid!Preparing for an Audit Checklist

17. CMRSC 6.0 – Audits Preparing for the audit (cont.): • Ensure that all documentation, including informed consent forms, source documents, CRFs, and the regulatory binder for the study to be audited are accurate, complete, and available for review by the auditor. Use the Checklist!!!

18. CMRSC 6.0 – Audits During the audit: • Meet with the auditor or inspector. Request to see identification. • If an FDA audit, request Form FDA 482 (Notice of Inspection). • Provide orientation and access to the study records and files. • Provide copies of requested study-related documents. If originals are provided, keep a log of provided documents to ensure the documents are returned at the end of the audit. • Ensure all questions posed by the auditors are answered by appropriate personnel.

19. CMRSC 6.0 – Audits Following up after the audit: • Participate in the exit interview with the auditor. • If an FDA audit, request Form FDA 483 (Inspectional Observations), if available, from the auditor. • Respond to the audit report as soon as possible after its receipt.

20. You’re in the home-stretch: I’m sure you have a little bit of energy left to take the last Quiz! It’s a short one. • CMRSC SOPs - Data Mgmt & QA Sections Quiz