sae reconciliation how to handle ‘a waterfall’ of saes? albert hage astellas pharma europe bv...
TRANSCRIPT
SAE ReconciliationHow to handle ‘a waterfall’ of SAEs?
Albert Hage Astellas Pharma Europe BV
The Netherlands
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How to reconcile this?
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Topics
Astellas Pharma Europe
Overview of the process
Initial process
Intermediate solution
Future process
Conclusion
Questions
Discussion topic
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Astellas Pharma Europe
European R&D centre in Leiderdorp, The Netherlands
Organization of 350 employees
Broad spectrum of departments covering R&D
Our therapeutic focusUrologyTransplantationDermatologyAnti-infectivesCardiovascularOncologyDiabetesCNS
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Astellas Pharma Europe
Clinical Data Science DepartmentEDC and CDS SupportData ManagementClinical ProgrammingBiostatistics
Currently we have a staff of more than 50 people of 14 nationalities
We are responsible for all Ph. I – IV studies in EuropeProviding scientific input into clinical drug development plans, synopses and
protocolsCollection, cleaning, analysis and reporting of clinical data from clinical studiesData pooling and integrated analyses to support regulatory submissions
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Definition
A serious AE is any untoward medical occurrence that at any dose
Results in deathIs life threateningResults in persistent or significant disability/incapacityResults in congenital anomaly, or birth defectRequires in-subject hospitalization or leads to prolongation of
hospitalization Other medically important events
An SAE will be followed until
Safety: Resolved or judged to be no longer clinically significantClinical: Patient’s last visit according the study protocol
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Overview of the process
Two departments are involved
Drug Safety and PharmacovigilanceClinical Data Science – Data Management section
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Overview of the process - DSP
SAE data is collected in Safety DatabaseVia SAE Report Form and data entry
Data validation100% check of entered items
Medical reviewMedical evaluationMedDRA coding of event
FinalizationAsk for follow-up informationLock case and report to authorities within 7 days (fatal and life-threatening)
or 15 days (for related non-fatal SUSARs - Serious unexpected suspected adverse drug reactions)
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Overview of the process - DM
SAE data is collected in Clinical Database
SAE data is part of AE data moduleVia CRF and double data entryOr Directly via EDC
Data cleaning will be performed
According to Data Validation SpecificationsQuery handling processMedDRA coding of eventMedical review
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SOP/Working Practice Document
SAE Reconciliation is performed by Data Management (with support of DSP)
For this we need a SAE Reconciliation Plan
Process is embedded in DM SOPCreate Data Management Plan
Working Practice DocumentDMP Module 2: Enter and validate study data
SAE Reconciliation process is described Appendix 4List of items to be reconciled
For each study a DMP Module 2 will be created and signed off by Data Manager, Study Manager and Pharmacovigilance Physician
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SAE Reconciliation process
The SAE Reconciliation process can start
The data in the Clinical and Safety databases are availableWe have an approved SAE Reconciliation Plan
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SAE Reconciliation Plan
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Initial process
Timing is near the end of a studyData in both databases have been cleaned CIOMS forms from DSP will be retrievedManual comparison of CIOMS forms with Clinical DatabaseDiscrepancies will be queried by DMThe Site will answer the QueryDM will check the resolved Query and make a judgment
No update needed (clarification)/No update possible (re-query)Clinical Database have to be updated by DM (for paper Queries)Forward Query/Screenshot EDC to DSP to update the Safety DatabaseBoth the Clinical and the Safety Database have to be updated
Perform a final check shortly prior to Database Soft Lock
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CIOMS Form
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Initial process
The life of a Data Manager was easy and simple in Leiderdorp
We perform a lot of Phase I studies with hardly any SAEsWe have relative light indications as Urology with a low number of SAEs
(10-20/1000 patients)
Due to the low number of SAEs it was manageable to perform SAE reconciliation with this process and not jeopardizing the Database Hard Lock timelines
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New indications
Nowadays life is not so easy any more
As we got involved in more difficult indications such asTransplantationOncologyCV in patients undergoing surgery
And these indications have loads of SAEs
Transplantation: 1000-1500/1000 patientsOncology: 20/40 patientsCV: 100/1000 patients
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Intermediate solution
How to handle this?
We have looked how it was done at our Transplantation Unit siteBroaden the range of acceptanceLimited the number of items to be reconciledReceive weekly line listings (excel) from Safety database instead of CIOMS
formsPerform an ongoing reconciliation, which starts directly after DM cleaning
processOngoing final check and mark patients when reconciledAll other processes remains the same
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SAE Reconciliation Plan
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Line listings
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Intermediate solution
Feedback
With this process we where able to meet tight timelinesTiming is delicate
An early start has the disadvantage of less clean data and a consistent flow of data changes due to other cleaning processes
With a late start the workload will shift to the end with a possibility that the process is not finalized on time or the quality is reduced
It is still a manual processDifficult to control changesVery time consuming
The process should be made more efficient to handle a high number of SAEs as we are also constantly aiming to reduce the timelines
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Future process
Which improvements can we make?
System interface between EDC system and Safety DatabaseLink the SAE data of the EDC Clinical Database with the Safety Database
To support computerized reconciliation checksNew changes in both databases can be spotted immediatelyPreferably with a tracking tool of outstanding discrepancies and
accepted inconsistencies Agree upon a standard set of variables to reconcile for all studies
Currently this list is discussed within a Study TeamMake clear agreements between DM and DSP
Responsibility for follow-up actions (like missing data)Timelines (focus for DSP is reporting; for DM database lock)
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Future process
What are the minimal requirements?
Is there any regulation or should this be defined per company?Is the following item list for reconciliation acceptable?
Study No.Patient No.EventStart DateStop DateRelationship/Causality
Should the focus be on related SUSARs only?Manufacturer’s and/or Investigator’s causality to Study Drug is Possible
or Probable
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Future process
Which contemplations do we have?
Organizational
Information from the ‘source’ will vary gradually in both databasesCombined DSP/DM training for Investigators, Monitors and DSOsCoordination needed to limited the number of Queries to the sitesUse the information of the other database for updates
Possible faster reporting of SAEs in EDC system than in Safety databaseReconciliation process should wait until DSP has finalized their processPossibility that in Clinical Database symptoms are reported and only a
diagnosis in the Safety Database
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Future process
Which contemplations do we have?
Technical
Probably manual linking needed of the SAEs in the two database systemsWill be a critical success factor
Process
Global process is neededTendency is to work more on Global or Trans-Atlantic studies
Process should be feasible to outsource to DM CRO
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Conclusion
This presentation gave an overview of Astellas’ current process and the way forward we would like to make
We need an efficient SAE reconciliation process which fulfills the need of Clinical, Safety and regulations
We like to use today for discussions on industry best practice
We are looking forward to the outcome of the discussion groups, we have some questions and we would be very happy if we could leave the meeting with the answers
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Questions
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Discussion topic
Only to be reconciled is :
Study No.Patient No.EventStart DateStop DateRelationship/Causality
And:
For related SUSARs only