Transcript Heidelberg presentation

Handling and reconciliation of SAE
data: a CRO perspective
Gerald Ruiter, Senior Data Manager &
Drug Safety Officer
IATEC BV, Amsterdam, The Netherlands
Position of CRO:
• Different clients with different specific
requirements regarding handling and
reconciliation of SAE Data:
1. Third Party Service Provider or
2. Sponsor
IATEC clients
• “Big” Pharmaceutical companies
• Phase III-IV, observational studies
• “Small” Biotech companies
• Number is increasing
• Phase II studies
Pharmaceutical vs
Biotech companies
• IATEC usually acts as
third-party service
provider
• Sponsor responsibilities
are often delegated to
IATEC
• Client does not delegate
sponsor responsibilities
• Have their own Drug
Safety procedures
already at high level
Pharmaceutical
vs Biotech companies
• SAE handling often
limited to review and
forwarding of the SAE
report to client.
• IATEC responsible for
complete SAE handling
and SUSAR reporting
• DSO keeps track of
SAEs in Excel file
• SAE Management
System including
SUSAR reporting
functionality
• Periodically Excel files
are sent to client for
reconciliation purposes.
SAE Management System
The increasing number of clients that fully
delegate their sponsor requirements
with respect to SAE/SUSAR handling
increases the urge to use a proper SAE
Management System
SAE Management System
• eSafetyNet
• Integrated in IATECs Data Management
System (eDM)
• Allows electronic and continuously
reconciliation between Adverse Events
entered in eDM and SAEs entered in
eSafetyNet
SAE Management System
• E2B compliant: electr. SUSAR reporting
• Ready to be used within the next couple
of months
• Until then the reconciliation is performed
manually
SAE Data Collection
Immediate process
Patient
experiences
SAE
Investigator
completes
SAE report
Investigator
completes
CRF
Delayed process
Data Subject to Change
Investigator
faxes SAE
report
Monitor
collects CRF
Drug Safety
enters data
in SAE
database
Data
Management
enters data
in clinical
database
Manual Reconciliation
• Performed on different moments in analogy to
the SAE data collection: immediate vs
delayed to minimize the chance that the
clinical trial database is out of synchronization
with the SAE data
• Different people involved
• Highly dependent on proper communication
Immediate reconciliation
• The investigator is requested to fax SAE
report and following CRF pages
(not yet monitored)
•
•
•
•
- Medical and Medication History
- Adverse Events
- Concomitant medications
- End of study page (if outcome is fatal)
Immediate reconciliation
• The DSO performs an immediate
reconciliation between the faxed SAE
report and the
• - Medical and Medication History
• - Adverse Events
• - Concomitant medications
Immediate reconciliation
• Items checked by DSO:
• - Subject details: ID, DOB, Gender
• - Diagnosis in SAE report vs AE description on
CRF AE Form
• - Event on AE Form should be marked as “SAE””
• - Severity
• - Start Date / Date of Onset
• - Stop Date / Outcome Date
Immediate reconciliation
• Items checked by DSO (cont’ed):
• - Study Medication / Concomitant medication:
•
•
•
•
Description
Start Date / Stop Date
Indication
Likelihood that SAE was caused by this medication vs
relation to study medication on AE form
Immediate reconciliation
• The SAE report is forwarded to the
Study Medical Monitor (SMM, a
physician) after the immediate
reconciliation has been performed by
the DSO.
• The SMM performs a review on Medical
Plausibility on both the SAE report and
the faxed CRF pages.
• DSO completes section 1 of “DSO form 1”
• SMM completes section 2 of the “DSO form 1”
Immediate reconciliation
• CRA is main contact between DSO and investigator
• Questions resulting from reconciliation/review by DSO
and SMM are sent to investigator via the CRA.
• Answers to these questions are sent as follow-up
information (updated SAE report and updated CRF
pages)
• The DSO maintains a tracking of the SAEs and the
issues.
Delayed reconciliation
• During collection of CRF data by CRA
• - The CRA will monitor the completed SAE report and the
completed CRF pages
• - CRF pages are sent to the Data Manager
• - Updated SAE reports are sent as Follow-up information to
the DSO.
Delayed reconciliation
• During cleaning process by Data
Manager
• - The Data Manager is alerted by the query management
system in case of:
• AE flagged as “SAE”
• End of Study Reason: SAE
• Fatal Outcome
• - The Data Manager will check with the DSO whether the
SAE has been reported expedited.
Delayed reconciliation
• During cleaning process by Data
Manager
• - The DSO will perform a reconciliation between the SAE
database and the clinical database on the following items:
• Severity
• Start Date / Date of Onset
• Stop Date / Outcome Date
• - The DSO will notify the Data Manager in case of
discrepancies
Delayed reconciliation
• During cleaning process by Data
Manager
• - The Data Manager will sent out manual queries to the
CRA/investigator
• - Updates in clinical database will be performed by Data
Manager
• - Updates in SAE database will be performed by DSO
Delayed reconciliation
• Periodically by Medical Monitor
• - Safety Data from clinical database is printed on listings
• - Part of cleaning process
• - The listings are checked for medical plausibility and
suspected SAEs (not yet marked as SAEs).
• - Questions form the Medical Monitor discussed with Data
Manager (and DSO in case of SAE issues)
• - If necessary, manual queries will be created by the Data
Manager for the CRA/investigator
• - Immediate reconciliation will start upon receipt SAE report.
Delayed reconciliation
• Data Review Meeting
• - Safety Data from clinical database and SAE database is
printed on listings and discussed during Data Review
Meeting (last check by Study Team before DB Lock)
• - Action items will be described in the data review meeting
minutes
• - If necessary, manual queries will be created by the Data
Manager for the CRA/investigator
• - If necessary, the CRA will request the investigator to
complete a SAE report which will be sent to the DSO.
Summary
SAE report
and CRF
completed
by
investigator
Check by
DSO upon
receipt
Medical
Review by
SMM
CRA on site
CRA
collects CRF
Cleaning by
DM
Medical
Review by
SMM
Data Review
Meeting by
Study Team
DSO enters
data in SAE
database
Data
Management
enters data
in clinical
database
Investigator
completes a
SAE Form
Data
CRA
DM
SMM
DSO
Risk-Benefit
Patient
experiences
a SAE
Statement:
• Despite a good reconciliation process
the SAE Data only partly reflects the
reality
- SAE Form partly captures the patient’s condition
(limitation).
- Investigator’s opinion (interpretation)
- CRA can only rely on source on site (complete?)