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SAE Reconciliation How to handle a waterfall of SAEs

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... covering R&D. Our therapeutic focus. Urology. Transplantation ... We have relative light indications as Urology with a low number of SAEs (10-20/1000 patients) ... – PowerPoint PPT presentation

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Title: SAE Reconciliation How to handle a waterfall of SAEs


1
SAE ReconciliationHow to handle a waterfall of
SAEs?
  • Albert Hage
  • Astellas Pharma Europe BV
  • The Netherlands

2
How to reconcile this?
3
Topics
  • Astellas Pharma Europe
  • Overview of the process
  • Initial process
  • Intermediate solution
  • Future process
  • Conclusion
  • Questions
  • Discussion topic

4
Astellas Pharma Europe
  • European RD centre in Leiderdorp, The
    Netherlands
  • Organization of 350 employees
  • Broad spectrum of departments covering RD
  • Our therapeutic focus
  • Urology
  • Transplantation
  • Dermatology
  • Anti-infectives
  • Cardiovascular
  • Oncology
  • Diabetes
  • CNS

5
Astellas Pharma Europe
  • Clinical Data Science Department
  • EDC and CDS Support
  • Data Management
  • Clinical Programming
  • Biostatistics
  • Currently we have a staff of more than 50 people
    of 14 nationalities
  • We are responsible for all Ph. I IV studies in
    Europe
  • Providing scientific input into clinical drug
    development plans, synopses and protocols
  • Collection, cleaning, analysis and reporting of
    clinical data from clinical studies
  • Data pooling and integrated analyses to support
    regulatory submissions

6
Definition
  • A serious AE is any untoward medical occurrence
    that at any dose
  • Results in death
  • Is life threatening
  • Results in persistent or significant
    disability/incapacity
  • Results in congenital anomaly, or birth defect
  • Requires 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 significant
  • Clinical Patients last visit according the
    study protocol

7
Overview of the process
  • Two departments are involved
  • Drug Safety and Pharmacovigilance
  • Clinical Data Science Data Management section

8
Overview of the process - DSP
  • SAE data is collected in Safety Database
  • Via SAE Report Form and data entry
  • Data validation
  • 100 check of entered items
  • Medical review
  • Medical evaluation
  • MedDRA coding of event
  • Finalization
  • Ask for follow-up information
  • Lock 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)

9
Overview of the process - DM
  • SAE data is collected in Clinical Database
  • SAE data is part of AE data module
  • Via CRF and double data entry
  • Or Directly via EDC
  • Data cleaning will be performed
  • According to Data Validation Specifications
  • Query handling process
  • MedDRA coding of event
  • Medical review

10
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 SOP
  • Create Data Management Plan
  • Working Practice Document
  • DMP Module 2 Enter and validate study data
  • SAE Reconciliation process is described
  • Appendix 4
  • List 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

11
SAE Reconciliation process
  • The SAE Reconciliation process can start
  • The data in the Clinical and Safety databases are
    available
  • We have an approved SAE Reconciliation Plan

12
SAE Reconciliation Plan
13
Initial process
  • Timing is near the end of a study
  • Data in both databases have been cleaned
  • CIOMS forms from DSP will be retrieved
  • Manual comparison of CIOMS forms with Clinical
    Database
  • Discrepancies will be queried by DM
  • The Site will answer the Query
  • DM 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 Database
  • Both the Clinical and the Safety Database have to
    be updated
  • Perform a final check shortly prior to Database
    Soft Lock

14
CIOMS Form
15
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 SAEs
  • We 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

16
New indications
  • Nowadays life is not so easy any more
  • As we got involved in more difficult indications
    such as
  • Transplantation
  • Oncology
  • CV in patients undergoing surgery
  • And these indications have loads of SAEs
  • Transplantation 1000-1500/1000 patients
  • Oncology 20/40 patients
  • CV 100/1000 patients

17
Intermediate solution
  • How to handle this?
  • We have looked how it was done at our
    Transplantation Unit site
  • Broaden the range of acceptance
  • Limited the number of items to be reconciled
  • Receive weekly line listings (excel) from Safety
    database instead of CIOMS forms
  • Perform an ongoing reconciliation, which starts
    directly after DM cleaning process
  • Ongoing final check and mark patients when
    reconciled
  • All other processes remains the same

18
SAE Reconciliation Plan
19
Line listings
20
Intermediate solution
  • Feedback
  • With this process we where able to meet tight
    timelines
  • Timing 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 process
  • Difficult to control changes
  • Very 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

21
Future process
  • Which improvements can we make?
  • System interface between EDC system and Safety
    Database
  • Link the SAE data of the EDC Clinical Database
    with the Safety Database
  • To support computerized reconciliation checks
  • New changes in both databases can be spotted
    immediately
  • Preferably 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
    Team
  • Make clear agreements between DM and DSP
  • Responsibility for follow-up actions (like
    missing data)
  • Timelines (focus for DSP is reporting for DM
    database lock)

22
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.
  • Event
  • Start Date
  • Stop Date
  • Relationship/Causality
  • Should the focus be on related SUSARs only?
  • Manufacturers and/or Investigators causality to
    Study Drug is Possible or Probable

23
Future process
  • Which contemplations do we have?
  • Organizational
  • Information from the source will vary gradually
    in both databases
  • Combined DSP/DM training for Investigators,
    Monitors and DSOs
  • Coordination needed to limited the number of
    Queries to the sites
  • Use the information of the other database for
    updates
  • Possible faster reporting of SAEs in EDC system
    than in Safety database
  • Reconciliation process should wait until DSP has
    finalized their process
  • Possibility that in Clinical Database symptoms
    are reported and only a diagnosis in the Safety
    Database

24
Future process
  • Which contemplations do we have?
  • Technical
  • Probably manual linking needed of the SAEs in the
    two database systems
  • Will be a critical success factor
  • Process
  • Global process is needed
  • Tendency is to work more on Global or
    Trans-Atlantic studies
  • Process should be feasible to outsource to DM CRO

25
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

26
Questions
27
Discussion topic
  • Only to be reconciled is
  • Study No.
  • Patient No.
  • Event
  • Start Date
  • Stop Date
  • Relationship/Causality
  • And
  • For related SUSARs only
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