Site Visit Follow- Up: Notes to File, Visit Reports and ... · Notes to File, Visit Reports and...
Transcript of Site Visit Follow- Up: Notes to File, Visit Reports and ... · Notes to File, Visit Reports and...
MAGI's Clinical Research Conference
Site Visit Follow- Up: Notes to File, Visit Reports and
Corrective Action Plans Presented by:
Stacey Basham RN, RQAP-GCP President, Rialto Quality Group LLC
Brigid Flanagan, MS, RN, CCRC Senior Manager of Clinical Studies, Fresenius Medical Care
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Agenda
Discuss role of Investigator and Monitor in:
Site Visit Reports/Follow-up communications
Notes to File (NTF)
Corrective and Preventive Actions (CAPAs)
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Regulatory Review
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Regulatory Requirements - Sponsor
21 CFR § 11, § 50, § 54, § 56
21 CFR § 312, § 812
312.50, 812.40
Sponsor to ensure adequate information to conduct the study is provided to the investigator
Sponsor to ensure proper monitoring of study
312.56, 812.46 Sponsor shall monitor the progress of the study
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Regulatory Requirements – Sponsor (continued)
ICH-GCP 5.18 - Monitoring
5.18.6 ---Monitoring Report
A written report after each visit
5.18.4(q) deviations from the protocol, SOPs, GCP, and regulations are to be communicated to the investigator along with corrective action
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Regulatory Requirements – Sponsor (continued)
Guidance for Industry – Guideline for The Monitoring of Clinical Investigations (Jan1988) (Minor editorial and formatting changes Nov1998)
Record of On-Site Visits: The Sponsor should maintain a record of the findings, conclusions and actions taken to correct deficiencies…
Source: http://www.fda.gov/RegulatoryInformation/Guidances/ucm126400.htm
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Regulatory Requirements - Investigator
21 CFR § 312
21 CFR § 312.60 – ―…investigator is
responsible for ensuring that an investigation is conducted according … applicable regulations‖
21 CFR § 812
21 CFR § 812.100 – ―investigator is
responsible for ensuring that an investigation is conducted according to … applicable FDA regulations…‖
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Regulatory Requirements – Investigator (continued)
FDA Form 1572
21 CFR § 11, § 50, § 54, § 56, §
312, and § 812
Guidance for Industry Investigator Responsibilities — Protecting the Rights, Safety, and Welfare of Study Subjects (Oct2009)
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Visit Communications
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Site Visit Reports/Communications
Site Visit Reports
Monitor‘s communication of site visit findings
To the Sponsor (site visit report)
To the Investigator (site visit follow up letter)
Should be temporal to the site visit, e.g. within 10 business days from last date of visit
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Visit Reports – What We Are Hearing…
Comment Rationale
No follow-up letters • Not required per Sponsor SOPs
Late receipt of follow-up letter
• Tight timelines to complete numerous visits • SOP does not dictate timeline for submission of follow-up communications
Incomplete follow-up letters
• Was not generated after completed Sponsor report • Sponsor approved follow-up template set format.
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Visit reports – What We Are Hearing… continued
Comment Rationale
Inaccurate letters • Inadequate time for review of letter, e.g. letter went out before final sponsor report
Letter covered events for another site
• Lack of QC • Inadequate time for review
Format of follow-up letter ‗buries the lead‘
• Sponsor approved template does not allow for amending format of letters
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Suggested Follow-up Letter Formatting
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Examples of Outcomes of Inadequate Communications
PI cited for ―…failing to investigate for additional acts of falsification within the same clinical investigation or in other clinical investigations in which the study coordinator was involved…‘‖
―Regardless of your corrective actions, as the principal investigator you were ultimately responsible for the conduct of this study, including the fact that false information was submitted to the sponsor…‖
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It’s A Two-Way Street!
Investigator should have a plan for supervision and oversight of the trial…includes:
Routine Meetings with the sponsor‘s monitors
A procedure for dealing with data queries and discrepancies identified by the study monitor
CRA should document those meetings in follow up letter
PI should review and sign; respond in writing with any corrective actions taken.
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Expectations From Study Start – Clear Communication
At study start, make communication expectations clear.
For action items, respond in writing.
Remember, site visit communications are a permanent study record
Records measurement of compliance
Communications Should reflect collaborative effort
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Notes to File
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Notes to File
When used properly, they can be a positive practice.
A problem is identified
A corrective action is identified to prevent recurrence
Procedure is instituted
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Notes to File - continued
FDA will still cite you for the initial problem but the change in procedure mitigates the citation.
The NTF itself is not a corrective action. The corrective action taken and whether the action worked is what should be documented.
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Notes to File - continued
NTFs become part of the study record.
NTFs are a road map for any inspector.
FDA wrote ―Our investigation found (the sponsor) failed to take action except to generate numerous notes to file after all the subjects completed the study‖
Keep NTFs few and far between.
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Notes to File - example
NOTE TO FILE (example taken from actual NTF)
Date: 9 January 2010
RE: Protocol 012010
PI: Dr. XYZ
Our site was counseled and trained on the completion of study questionnaires. Dr. XYZ did the counsel 9Jan2010 @
site training meeting S. Coordinator 2/12/2010 B. CRA counseled via phone 22Jan2010 on all questionnaires. S. Coordinator
2/13/2010 A. XYZ, MD, 1/9/2010
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Notes to File - example
NOTE TO FILE (example taken from actual NTF)
Date: 9 January 2010
RE: Protocol 012010
PI: Dr. XYZ
The subject was seen on 10 November 2009 for Visit 7. The patient did not have labs drawn due to not fasting. Patient did not return for lab draw as scheduled. This has been reported as a protocol deviation.
Savvy Writer
Study Coordinator
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Corrective and Preventive
Action Plans
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Corrective and Preventive Action Plan (CAPA)
CAPA is the quality system used to identify, implement, track and evaluate effectiveness of actions taken as a result of deviations identified
CAPAs are another form of oversight to ensure compliance
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Corrective and Preventive Action Plan (CAPA) - continued
Identification of the deviation
Identification of the root cause
Corrective action/s to be taken to correct (when possible) the deviation
Preventive actions to be taken to prevent reoccurrence of the deviation
Measurement of preventive actions
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Corrective and Preventive Action Plan (CAPA) - continued
Site monitoring and follow-up communications—How do they compare to CAPAs?
Identify problems and deviations
Provide corrective action plans
Provide measurements of compliance with corrective action
Review of findings cited in a site visit follow-up communication
A CAPA may be initiated by site or by monitor
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Wrap-up
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Wrap-up
Communication, communication, communication
Role of Investigator and Monitor:
Site Visit Reports/Follow-up communications
Two-way street
Monitor to generate
Not receiving, ask why not!
Notes to File (NTF)
Over used
Corrective and Preventive Actions (CAPAs)
Need for may be identified from site visit communications
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Questions??
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References
FDA – www.fda.gov
CFR - http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm
GCP - http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/default.htm
Warning Letters - http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/default.htm
ICH E6 – Good Clinical Practice
http://www.ich.org/LOB/media/MEDIA482.pdf
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References - continued
FDA Guidance Documents
Devices - http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm
Drugs - http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
Biologics - http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
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References-continued
Anderson, C. ‗Note to Self: No More Notes to File‘. Applied Clinical Trials. March 1, 2008
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