Download InterMune, Inc.

PSDM 22 May 2008
Focused on Pulmonology and Hepatology
SAE RECONCILIATION: Determining how
much to reconcile
Jennifer Juntado, Sr. Manager, Data Management
Confidential. Property of InterMune, Inc. Any unauthorized review, use,
disclosure or distribution is prohibited.
Typical Data Flow
Data exchange
between ITMN
and coding
vendor
CRF Data
“paper”
Paper is imaged
and data is double
data entered off
the image
The system runs
checks on the data
Monthly
data
transfers
from CRO
InterMune
ITMN
ITMN DSRM
provides
ITMN DM SAE
database extract
ITMN DM SAE
Recon
SAE Collection and Reconciliation
3
Typical SAE Collection Period
Patient withdraws from study
early:
SAE collection period ends at
earlier of below two time points
1) Time of study withdrawal
2) 28 days after last dose of
study treatment:
ICF Signed:
SAEs only
reported if
related to
protocol
procedure
Study drug
initiated:
Final Followup Visit:
All AE/SAEs
reported per
protocol
End of SAE
collection
period
SAE/AE Collection Period Examples
» Patient discontinues drug and the next day withdraws from study, but
agrees to vital status:
– Any SAEs occurring after the withdrawal date will not be collected
» Patient discontinues drug and 35 days later withdraws from study:
– Any SAE occurring after the 28th day following study drug discontinuation
will not be collected
» Patient permanently discontinues drug on 01 August 2007 and
experiences an SAE on 12 Sept 2007:
– SAEs are to be collected until the end of study (Final Follow-up Visit)
» Patient experiences an SAE of Pneumonia on 01 June 2007 and
discontinues study drug the same day. Patient then withdraws from
study on 15 June 2007 with the pneumonia still ongoing:
– Pneumonia will be followed to resolution by DSRM
Documentation
» CRFs – Data Management
» CRF Completion Guidelines – Clinical Operations
» SAE Report Form – Drug Safety
» SAE Reconciliation Plan – Drug Safety
» Coding Guidelines – Data Management
» Data Handling Report – Data Management
– To document the evaluation and resulting action of data discrepancies
between the Drug Safety serious adverse event (SAE) database and the
Clinical adverse event (AE) database between database soft lock and hard
lock
– To document how “Handling Discrepancies between SAE and AE
Databases” deviates from the study’s Serious Adverse Event
Reconciliation Plan in the Data Management Plan.
SAE Reconciliation Flow Chart
ITMN Drug Safety
(ITMN DSRM)
provides:
1) SAE extract
2) Query report
The Site is
responsible
for completing
the SAE Form
and AE CRF
in a timely
manner.
ITMN DM updates the
TRACKING
spreadsheet
(all discrepancies)
on the shared drive
(within 10 days)
ITMN DM identifies
discrepancies
“IDENTIFICATION”
CRO Data
Management (CRO
DM) provides:
1) raw datasets
2) unresolved DCF
text report
ITMN DSRM
does a full review of all discrepancies
and updates the TRACKING
spreadsheet on the shared drive
with a recommendation
“VERIFICATION”
(within 10 days)
Create a DCF?
NO
Done for now
(DFN)
YES
ITMN DM updates the TRACKING
spreadsheet with suggested DCF Text and
sends the proposed DCF Text to Clinical,
c.c. DSRM (within one business day)
CRO and ITMN Clinical Ops
are responsible for DCF
resolution from Site
CRO DM sends ITMN
DM Outstanding DCF
Text report within two
business days
CRO DM creates and
sends DCF to the sites
within two days. The
DCF Text starts with
***SAE RECON***
ITMN DM sends
the DCF Text to
CRO DM
(within two
business days)
ITMN Clinical (and DSRM)
review of DCF Text (within
one business day)
DFN
NO
CRO DM:
OC DB
update?
CRO DM
evaluates if DCF
resolution if an
OC DB is
necessary
CRO DM communicates
daily if resolved SAE DCFs
have been received.
CRO DM sends copy of all resolved DCFs
to ITMN DM and ITMN DSRM OR an email
stating no resolved SAE DCFs were
received
by 2 PM local time of day received
ITMN DM
evaluates
DCF
resolution
YES
CRO DM
Updates OC
database
DFN
CRO DM sends
ITMN DM
Outstanding DCF
Text report (within
two business
days)
CRO DM creates and
sends DCF to the sites.
The Re-DCF Text
starts with
***RE-QUERY SAE
RECON***
ITMN DM
sends the DCF
Text to CRO
DM (within two
business days)
SAE
database
update?
Re-DCF?
ITMN Clinical (and
DSRM) review of
DCF Text (within one
business day)
ITMN DM
suggests Re-DCF
Text
YES
NO
NO
YES
DFN
ITMN DM updates
TRACKING
Spreadsheet. REDCF goes through
resolution loop
ITMN DM updates
TRACKING
spreadsheet
ITMN DSRM updates Drug
Safety database with DCF
resolution or processes the
updated SAE Report Form, if
applicable.
SAE Reconciliation Cheat Sheet
SAE Reconciliation
Data Management goes beyond typical SAE
Reconciliation
10
Beyond SAEs: Other Data
» Patient Disposition:
– Termination of Study Treatment
• Date of last study drug
• Termination due to AEs (or Serious AE) or Reasons where it might be an AE
• If an AE or SAE states that treatment was discontinued, then this data must
correlate.
• If early termination of study treatment is due to an AE (or Serious AE, if
applicable), then the AE must be captured with consistent information.
– Study Completion/Early Discontinuation from Study
• Date of study discontinuation
• Discontinuations due to AE (or Serious AE) or Reasons where it might be and
AE
– Mortality
• Date of death
• Primary cause of death
Snapshot of the listing – level 1
Snapshot of the listing – level 2
Snapshot of the listing – level 3
Approaching database lock… now what?
15
Prior to database lock
What other data points can remain discrepant,
yet assuring our regulatory obligations and
maximizing subject safety?
17
Questions?
18