Review 1st Priority for Monitoring Visit
- ICF Review of all newly enrolled patients. If new ICF version, verify all applicable pts have been newly consented
- Review newly reported SAEs and SAE follow-up information. SDV SAE forms.
- Review IMP receipt, handling and storage
- Immediate Escalation of crucial issues
Monitoring Definition
Act of overseeing the progress of a clinical trial, ensuring it is conducted, recorded and reported in accordance with protocol, SOPs, GCP and reg requirements
Purpose of Monitoring (6)
○ Check if rights and safety of patients are protected at every stage
○ Confirm information from investigators
○ Confirm IMP acct
○ Confirm timeliness and accuracy of site records and reports
○ Maintain a record of findings, conclusions and actions taken to correct deficiencies
○ Follow up with all identified issues until resolution
- Monitor begins with the first contact with the investigator and ends with last contact (may be before the study and/or after the study)
Sponsor must ensure trials are adequatley monitored, before during and after the trial.
Monitoring Fundamental Responsibilities: Control
- Verifies: Verification of source documentation
- Monitors: Review of study logs
- Checks: Monitoring of drug accountability
Monitoring Fundamental Responsibilities: Active Proceeding
- Ensures
- Acts
= Constantly work with site to prepare them for proper study conduct, proactively help the site to avoid issues and mistakes, and act if issues are occurring to correct and prevent.
Monitoring Fundamental Responsibilities: Main communication btwn sponsor and site
- Reports
- Communicates
With site staff - reporting any discrepancies, noncompliance and providing support in the resolution
With sponsor - reporting site’s performance and actions taken to improve it
Between site staff and sponsor: exchange all relevant study related information
MV Preparation
Plan site visit by: reviewing MVRs, system listings, open issues, data metrics
TO be done before visit: prepare documents, review open issues, review site performance/metrics, study status (#pts, completed visits, completed CRF pages, IVRS/IWRS data, open queries, site inventory of IMP/Kits)
Review Secondary Priority for MV
Meeting with PI/Site staff
SD review and verification
CAPAs for identified issues
f/u on identified problems
ISF review
After MV:
- Immediate Reporting of urgent/major issues
- MVR: contains a summary of everything reviewed, all findings, actions closed and/or to be taken
- FUL: contains activities completed during MV, identified issues, actions required to be taken or already taken
Study Monitoring Levels
- Study (protocol amendment)
- Country (country recruitment goal)
- Site (new investigator)
- Patient (pt diary not completed)
- Patient visit (pt did not come to visit)
- Visit procedure (blood not drawn from pt)
–> monitor responsible for all levels/study success overall and to work with PM regarding any issues
Monitor Responsibilities
- Recognition of the issue (understanding, identifying reasons /context)
- Proposing or executing corrective action (set of activities meant to undo the result of the issue)
- Proposing or executing preventive action (should prevent reoccurrence of event)
Site MGMT: Issue
action item, a general term for a situation that requires follow up
Site MGMT: Resolved
issue resolved and can be closed
Site MGMT: Closed
some issues cannot be solved. In these exceptional circumstances, the action can be marked as closed and not resolved. CRA must have shown due diligence to attempt to close the item
Protocol Deviation
documented separately from an issue and do NOT need to be repeated as a site issue
HOWEVER, some PDs need follow up actions and this should be documented as an issue. Ex: retraining staff, recruitment hold etc.
CRA Responsibilities in Issue Management
- Overall site performance and related issue resolution = inspection readiness
- Proper issue description
- Owner of the action and timeline by when the action is to be taken
- Accountable for follow up with the relevant party within timeline
- First time drafts of MVRs should be best possible quality.
- Issue management: 90 calendar days from issue identification
7 W’s in reporting an Issue
What
where did it happen
why did it happen
who was involved
when did it happen
were subjects/IMP/other study items affected
what method should be used to correct it and prevent recurrence
RISK
potential issue that may or may not happen
Issue
something that already happened and needs proper management
Steps in a CAPA
○ Identification: identify potential area of impact and impact level
○ Root cause analysis: identify initiating cause and work to address the cause not the symptom. Often, there are more than one cause to the issue.
○ Corrective action: fixing the current problem/symptom
○ Preventive action : correcting processes to avoid future recurrence
Follow up to ensure the CAPA plan has worked
Risk Management Elements
Elimination, mitigation, control and avoidance, delay
Issues Requiring immediate reporting
- Issues related to patient rights and safety
- Issues related to data quality or integrity
- Issues related to subjects recruitment
* all would be escalated to PM or MM within 24h*
