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QMS at the Site
- 1. Quality Management System atthe clinical research site – a paradigm shift Shari Sharif, CCRP Director of Regulatory Affairs & Quality Management
- 2. ICH-GCP Q9 Quality RiskManagement principles which are process-based Risk = combination of probability of the occurrence of harm and the severity of that harm A systematic approach to ensuring that all possible and probable causes of harm around a compound is mitigated Harm against subjects Harm against the viability of new therapies (valid data) A solid assurance system within research and development (Q8 & Q10)
- 3. History Pharmaceutical development (ICHQ8) has been under the scope for years and therefore, very much interested in reducing harm at the Site level, where subjects are seen and data is first captured Some trial sponsors and CROs have incorporated risk-based principles into their Quality Assurance Systems (Q10): Risk-Based Monitoring Adaptive Monitoring Quality Risk Management Focused Monitoring
- 4. Focused Monitoring Monitoringhigh-risk sites more frequently than others Monitoring regulatory compliance Monitoring focused on safety data and primary outcomes SDV of 100% of some items (ie, ICFs, I/E, AEs/SAEs) SDV of <100% of all other data Remote monitoring Utilization of technology to capture raw data (ie, eConsent, diaries, etc.) Utilization of an in-house CRA to ensure ISF and TMF match
- 5. Today About half ofthe industry has begun the implementation of RBM (M. Massim, CEO, Florence Healthcare, Atlanta, GA) RBM only works with cooperation from the Sites (Todd Davies, Dir, Marshall Clinical Research Center)
- 6. The Site facesan increased challenge Agency Warning Letters are still issued We have to adapt to industry standards and current trends Monitoring in general has changed Studies are more complex We can no longer completely depend on the monitor to catch every mistake In order to be sustainable, we have to focus on quality and not just quantity
- 7. The Successful Site Expects audits Expects various monitoring approaches (ICH-GCP Q9) Standard operating procedures and/or Work Instructions Adaptable to changes in the industry and at the Site Effective qualified staff recruitment, allocation and retention Clear job descriptions
- 8. The Successful Site Solid ongoing staff training & development with consistent evaluation and feedback Site-specific Study-specific Balance quantity and quality Quantity of studies , staff and subjects Quality of selected subjects and data Quality Management System (process)
- 9. Quality Management Systemat the Site Build solid source documents: A preventive approach Designate competent source document creator(s) Streamlined according to the site’s operational flow Tailored for the protocol, CRF and other written guidelines Template should promote internal and external consistency of data Reviewed/revised with each approved protocol amendment Audited prior to use Completed source template should be auditable by site reviewer(s)
- 10. Quality Management Systemat the Site System to identify the critical study parameters in every study Phase of study and the Site’s enrollment goal Drug safety profile Study Coordinator preparedness and study workload Complexity of the trial (number of study arms, randomization steps, length of treatment)
- 11. Quality Management Systemat the Site Informed consent process Subject eligibility Protocol adherence (following the investigational plan) Primary objectives/endpoints Safety reporting IP administration
- 12. Quality Management Systemat the Site IP control/accountability/maintenance of study blind Record keeping (regulatory and subject records) Elimination of misconduct: look for and recognize signs of fraud Computerized system validation Source data verification/query response
- 13. Risk assessment viaAudit system at the Site Quality Management Every day operational techniques: Practicing GCP, ALCOA and following protocol Audit Review source data (and CRF) and identify discrepancies within the chart and question non-compliance with study protocols and/or the site’s standard practice
- 14. Auditing at theSite A review system based on each study’s risk profile Full, partial, and/or for cause eg, investigator, coordinator or subject complaints eg, high number of SAEs eg, high enrollment / eligibility violations eg, consent errors
- 15. Auditing at theSite Notice and evaluate trends Conduct root cause analysis Review of the facility, its certificates Review recruitment system and pre-screening procedures/documents Streamlined reporting system to the Investigator
- 16. Internal auditing contributesto a successful Quality Management System Communicate with the Study Team Incorporate corrective action as a standard quality management procedure. This shows that you are able to identify risks and mitigate risks ahead of time Identify a local IRB and use them as a resource
- 17. Quality Management System ReviewSite processes for trends/gaps/deficiencies Revise/refind systems that make the Subjects, studies and the Site’s sustainability/reputation vulnerable eg, system by which revised and approved ICFs are retrieved and used eg, system by which protocol amendment training and source revisions occur prior to implementing the new amendment eg, system by which monitoring follow-up letters are reviewed and action items addressed
- 18. Always ask What couldgo wrong? What is the probability of it going wrong? What are the consequences?
- 19. How do weensure validity of data ? Create accurate source data templates Conduct our studies the sponsors intend Report and resolve issues/errors in a timely manner Audit of subject charts for discrepancies and non-compliance after data collection, and feedback prior to data entry
- 20. Resources ICH-GCP E6:Overseeing the progress of a clinical trial and ensuring data is recorded and reported in accord with SOPs, GCPs and other regulatory requirements ICH Q9: Step-by-step instructions for quality risk management BIMO in FDA’s Compliance Program Guidance Manual