Focused on Pulmonology and Hepatology

SAE RECONCILIATION: Determining how much to reconcile

PSDM 22 May 2008

Confidential. Property of InterMune, Inc. Any unauthorized review, use, disclosure or distribution is prohibited.

Jennifer Juntado, Sr. Manager, Data Management

Typical Data Flow

CRF Data“paper”

Data exchange between ITMN

and coding vendor

Paper is imaged and data is double

data entered off the image

The system runs checks on the data

ITMN DM SAE Recon

Monthly data

transfers from CRO

ITMN DSRM provides

ITMN DM SAE database extract

InterMuneITMN

3

SAE Collection and Reconciliation

Typical SAE Collection Period

ICF Signed:

SAEs only reported if related to protocol procedure

Study drug initiated:

All AE/SAEs reported per protocol

Final Follow-up Visit:

End of 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:

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

The Site is responsible

for completing the SAE Form and AE CRF in a timely manner.

ITMN Drug Safety (ITMN DSRM)

provides:1) SAE extract2) Query report

CRO Data Management (CRO

DM) provides:1) raw datasets

2) unresolved DCF text report

ITMN DM identifies discrepancies

“IDENTIFICATION”

CRO DM creates and sends DCF to the sites within two days. The DCF Text starts with***SAE RECON***

Create a DCF?Done for now

(DFN)NO

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)

YES

ITMN DSRM updates Drug Safety database with DCF resolution or processes the

updated SAE Report Form, if applicable.

DFN

ITMN Clinical (and DSRM) review of DCF Text (within

one business day)

CRO DM:OC DB update?

YES

CRO DMUpdates OC

database

DFN

NO

DFN

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

CRO DM communicates daily if resolved SAE DCFs

have been received.

ITMN DM updates theTRACKINGspreadsheet

(all discrepancies) on the shared drive

(within 10 days)

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)

ITMN DM sends the DCF Text to

CRO DM (within two

business days)

CRO DM sends ITMN DM Outstanding DCF Text report within two

business days

CRO DM evaluates if DCF resolution if an

OC DB is necessary

ITMN DM suggests Re-DCF

TextNO

ITMN Clinical (and DSRM) review of

DCF Text (within one business day)

ITMN DM sends the DCF Text to CRO

DM (within two business days)

CRO DM sends ITMN DM

Outstanding DCF Text report (within

two business days)

ITMN DM updatesTRACKINGspreadsheet

CRO DM creates and sends DCF to the sites.

The Re-DCF Text starts with

***RE-QUERY SAE RECON***

CRO and ITMN Clinical Ops are responsible for DCF

resolution from Site

ITMN DM updatesTRACKING

Spreadsheet. RE-DCF goes through

resolution loop

ITMN DM evaluates

DCF resolution

SAE database update?

Re-DCF?

YES

YES

NO

SAE Reconciliation Cheat Sheet

SAE Reconciliation

10

Data Management goes beyond typical SAE Reconciliation

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

15

Approaching database lock… now what?

Prior to database lock

17

What other data points can remain discrepant, yet assuring our regulatory obligations and maximizing subject safety?

18

Questions?