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Phase I Clinical Study Audits “A Deeper Scrutiny”

Phase I Clinical Study Audits “A Deeper Scrutiny”. Cheryl J. Priest, R.N. 24 February 2005. Phase 1 Clinical Study Audit. A Simple Audit ?. Phase 1 Clinical Study Audit. Not Necessarily!. What is a Phase 1 Clinical Study?. Initial introduction of a new drug in humans

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Phase I Clinical Study Audits “A Deeper Scrutiny”

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  1. Phase I Clinical Study Audits“A Deeper Scrutiny” Cheryl J. Priest, R.N. 24 February 2005 Falcon Consulting Group, LLC

  2. Phase 1 Clinical Study Audit A Simple Audit ? Falcon Consulting Group, LLC

  3. Phase 1 Clinical Study Audit Not Necessarily! Falcon Consulting Group, LLC

  4. What is a Phase 1 Clinical Study? • Initial introduction of a new drug in humans • Closely monitored and controlled • Healthy volunteers or patients (20-80) • Increasing doses and associated side effects • Drug metabolism, pharmacokinetics, mechanism of action • Assessment of Safety Falcon Consulting Group, LLC

  5. What Confronts the Auditor? • Phase III Pivotal Studies are CQA priorities: • 70% of companies audit all Phase III trials • 90% perform pre-inspection audits • Phase I Audits? • No GCP Quality Standards specific to Phase I • Customized Phase I Audit Plans • Different Phase I subject populations Falcon Consulting Group, LLC

  6. What Confronts the Auditor? • Broad subject screening and recruitment or very specific patient recruitment • Special Informed Consent processes • Diverse site personnel and roles • Focused assessment of Unit facilities • Controlled environment and workflow • Unique and varied study documentation Falcon Consulting Group, LLC

  7. What Confronts the Auditor? • Sometimes complex safety assessments • Potential expedited monitoring and data transmittal • Unique Investigational Products and dosing • Precise “systems” for biological samples Falcon Consulting Group, LLC

  8. Phase I Audit Plan • Customized GCP Audit Strategy • Audit details specifically related to: • Study design and complexity • Study population • Type of dosing and sampling • Type of Investigational Product • Facility/environmental controls • Who should audit? • When should you audit? • What should you audit? Falcon Consulting Group, LLC

  9. Phase I Subject Diversity • Healthy volunteers • Auditing of data more simple • Safety events easier to define and verify • Complex subjects – e.g. Cancer, HIV • Effectiveness of audit impacted by auditor therapeutic expertise • Safety events potentially “hidden” by disease and may be subtle to auditor review Falcon Consulting Group, LLC

  10. Phase I Subject Recruitment • Large scale “preliminary” screening and recruitment efforts needs auditor attention: • Systems • Documentation • Specifically selected diseased population with rigid entry criteria forces auditor to: • Verify entry criteria • Confirm protection of “vulnerable” population Falcon Consulting Group, LLC

  11. Phase I Informed Consent • Subject protection and ethics • Auditor verification: • Clearly stated study intent • No ambiguity or suggestion of individual benefit • Adequacy particularly for patient “vulnerable” subjects • Auditor specific and focused review: • Informed consent administration and “work flow” • Informed consent documentation Falcon Consulting Group, LLC

  12. Phase I Site Staff and Delegation • Auditor attention to: • Numerous and diverse roles • Qualifications and therapeutic expertise • Staff Training – specifically on Unit SOPs • Demonstrated knowledge of protocol and written standards • Appropriateness of responsibilities • Investigator oversight Falcon Consulting Group, LLC

  13. Phase I Site Facilities • Auditor observations for specific studies: • Academic or typical Phase I Unit? • Logistics and subject segregation • Security and environmental controls • Storage – Investigational Product and samples • Food preparation and diet management • Subject privacy and confidentiality • Emergency equipment and transport Falcon Consulting Group, LLC

  14. Phase I Documents and Data • Electronic source and/or study data (validated?) • Screening and recruitment forms or database • Worksheets and flow charts • Essential and regulatory Investigator documents • Outpatient or inpatient hospital records, other “source”? • Investigational Product accountability records Falcon Consulting Group, LLC

  15. Phase I Subject Safety • Auditor confirmation for specific studies: • Adequate medical oversight of dosing procedures • Adequate medical assessment of subject safety • Auditor intense review to ensure adequacy of safety reporting: • Complex source data for diseased subjects may be challenging Falcon Consulting Group, LLC

  16. Phase I Monitoring • Auditor evaluation of: • Monitor qualifications and relevant therapeutic experience • Monitor “real time” observation of dosing (as applicable) • Documentation of monitoring activities and findings • Frequency and adequacy of monitoring performance • Data integrity Falcon Consulting Group, LLC

  17. Phase I Investigational Products • Auditors must concentrate on: • Any special handling of Investigational Product (e.g. radio-labeled studies) • Special Investigational Product preparation • Sophisticated dosing schemes and regimens • Accountability procedures and documentation • Qualifications/appropriateness of “handlers” of investigational product Falcon Consulting Group, LLC

  18. Phase I Samples • Auditor close observations and critical review: • “Systems” for sample collection and processing • Study-specific workflow and precise timing • Verification of appropriate sample identification • Adequacy of sample storage and controls • Transmittal to analytical laboratory • Standards and procedures for sample handling Falcon Consulting Group, LLC

  19. Phase I Unit Quality System • Is there one? • Auditor needs to note: • Applicable written standards for the Unit? • SOPs for conduct of specific types of studies? • Emergency procedures and training • Systems integrity and testing .....to name a few...... Falcon Consulting Group, LLC

  20. Phase I Clinical Study Audits Simple? Falcon Consulting Group, LLC

  21. Phase I Clinical Study Audits Absolutely Not ! Falcon Consulting Group, LLC

  22. Phase I Clinical Study Audits Leaving thoughts....... Auditors: - Think more deeply - Look more deeply ....with GREATER scrutiny. Falcon Consulting Group, LLC

  23. References H. Gertzen, “ Clinical Quality Assurance Benchmarking”, Applied Clinical Trials, June, 2004. M. Agrawal, E. Emanuel, “ Ethics of Phase I Oncology Studies”, JAMA, June, 2003. www.fda.gov www.instituteof clinical research. org Falcon Consulting Group, LLC

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