Auditing Clinical Documents

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Auditing Clinical Documents

• Sue Batdorf
• Alliance Research Consulting
• February 20, 2004

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Rules of the Game

• Informal Survey of various clinical document
  audit systems in use and the issues regarding
  them.
• The audience will participate.
• All situations will be considered hypothetical.

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What types of documents do we audit?

• Protocols
• Investigator Brochures (ROPI)
• Clinical Study Reports
• Informed Consents

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What types of documents do we audit?

• Data Listings
• Integrated Reports ISS/ISE
• Risk/Benefit
• Instructions for Use (IFU)
• Subject Diaries
• Dosing Instructions
• Recruitment Materials
• Subject ID Card

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Why do we audit clinical documents?

• Improve Compliance
• Improve Data Integrity
• Inform QA of study events and timing
• Inform QA of study participants
• CRO, central lab, specialty lab, and location
  of sites, whether there will be a DSMB
• Provide an independent review of documents

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What standard do we apply to clinical documents?

• Protocols ICH 6.1-6.16
• Investigator Brochure ICH 7.1-7.5
• Clinical Study Report ICH E3
• Informed Consent ICH 4.81-4.8.15
• Are templates provided for protocols and reports?
• Are separate templates utilized for Phase I vs
  Phase II III?

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Who writes your clinical documents?

• Internal clinical development
• Consultant collaboration
• External professional writing group
• Internal dedicated writing group

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Are all submissions made electronically?

• All or partial
• Drugs vs devices
• Do you audit the electronic record, the paper
  record, or both?

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Do you perform QC and QA for clinical documents?

• Is there a requirement for QC in Data Management?
• Is there a requirement for QC in Clinical
  Development?
• Are QA audits required? If so, on what
  documents?
• Are peer reviews required?

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Characterize the typical range of QC/QA findings

• Perfect documents, never any findings
• Average of 7 pages of observations

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Who receives results of the QC or QA review?

• Author only
• Author and their management
• Results are shared with all author groups
• What results?

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Is there any tracking and trending of document
audit results?

• If yes,
• What effect does this have and why?
• If the effect is negative, how could this be
  improved?
• If the effect is positive, could this be
  strengthened?

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Are authors required to take corrective action
based upon audit results?

• If yes, what requires them to do so and who
  verifies the corrective action is adequate?
• If no, should this be changed?

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What are the reasons document audit observations
occur?

• Unrealistic development timelines
• Prior documents used as templates
• Lack of experience and training of author
• Inadequate QC process prior to audit
• Inadequate peer review
• Validation issues for electronic data

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References

• ICH GCP Consolidated Guideline, Section 6,
  Published in the Federal Register CFR
  6225691-25709, released May 9, 1997
• ICH Guideline on the Structure and Content of
  Clinical Study Reports (ICHE3) Published in the
  Federal Register (CFR 6137319-37343) released
  July 17, 1996

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• THANK YOU FOR YOUR PARTICIPATION