Definition of SAEs Reconciliation

Serious adverse events data Reconciliation is the comparison of key

safety data between two database (a clinical database defined as a
closed system and a safety database defined as an open system)

A clinical database is defined as closed since it can receive

data only for a very short period of time that is the lasting of
the trial.
A safety database is defined as an open system since
it continues to receive new SAEs or updates of pre-
exiting SAEs concerning any clinical trials even when
they are locked.
 SAEs Reconciliation management

SAEs Reconciliation is ruled by an appropriate SOP that

describes the general workflow and that

1. Lists all the 2. All the tasks to be

responsibilities performed
 SAEs Reconciliation

The cut-off*
The time
differences
Key safety that may be
data to be acceptable
reconciled in the key
safety data
 Key safety data
Key safety data to be reconciled could be but not
limited to:
Subject ID and
randomization 2. SAE verbatim 3. LLT term 4. PT term
number

5. SOC 6.Onset date 7. Stop date 8. Outcome

11. Causal
10. Seriousness relationship 12. Action taken
9. Severity
criteria with study with study drug
drug
Key Safety Data
key safety data fields are in the same (both in
manual and electronic comparison)
They are in the same format (electronic comparison)
They share the same values code list for the same
field when applicable
Demographic panel data
Physical examination
Concomitant medication
Administration panel data
Acceptable Differences Between Key Safety
Data
List of all differences that both DM Dept and Pharmacovigilance
Dept judge not to decrease consistency between data such as

A slight difference in the verbatim not affecting the medical coding

• clinical database verbatim reported ‘EAR PAIN’, safety database

verbatim reported ‘EARACHE’ if the two are the same also when
considering the medical coding of the terms (LLT, PT,SOC) the two
stay different.1

structural difference between the two databases that obliges to record

data in a different manner
• clinical database field ‘Worsening of pre-study condition?’, safety
database has no such a field so this information is captured by
adding a new record such as ‘CONDITION AGGRAVETED’
 Cut-off point

cut-off point after which no new SAEs or updates will be

added to the clinical database so that the process will be
considered as closed for the clinical database even if the
safety database continue to receive new SAEs or updates
concerning that specific clinical trial.
Cut-off point Procedure
The procedure is organized as it follows:

Retrieving
Check
data from
between
the two
information
database

Actions to Process
be taken Tracking
 Data From The Two Database

First step is to retrieve data from the database and to create two
hard- copy listings/two electronic listings and the two source will
be reconciled through direct comparison by adding each
difference or with a pen or electronically. This step can be done by
DM Dept when receiving data from Pharmacovigilance Dept or
vice versa.
 Checking information

Verify that number of patients that experienced SAEs in both

databases is the same at the time of reconciliation

Verify that all SAEs recorded in the safety database are

recorded in the clinical database as well and vice versa at the
time of reconciliation

Verify all the key safety data defined as mandatory in the DMP
 Actions to be taken

SAEs that are in the clinical database but not in the Safety.
Those can be potentially unreported events so copies of the
appropriate pages of CRF must be forwarded to
Pharmacovigilance
SAEs that are in the safety database but not in the clinical
database. If the visit has been monitored, collected and
processed the site can be queried and a data clarification form is
issued
No SAEs can be added to the clinical database without the data
for that visit having been monitored against source documents.
Action taken on Key Safety data
discrepancies acceptable
Nature of discrepancies the DM can decide to issue a
data clarification form to the site

The review of all the unacceptable discrepancies is

made by comparing the information reported in the
clinical database and SAE Form that is attached to the
CRF.

The data clarification form are signed by the

investigator will be used to update either or both
databases by their respective staff
 Process Tracking

The process has been done accurately and

consistently.

Reconciliation has been done for all SAEs.

All expected SAE information has been received.

At the end a written communication should be made

when the entire process has been successfully
completed to point out that the Safety database must
be held open for updates after study closure
 Electronic SAE Reconciliation
Based on a manual activity of reconciliation
but SAEs reconciliation can also be done
automatically.

If the share the

key safety data same values code
If they are in the
fields are in the list for the same
same format
same field when
applicable.
Electronic SAE Reconciliation

A program that creates a output table of all

discrepancies between the two databases is an
effective mean to perform this activity that
frequently is time consuming so when an application
is designed for the purpose it is necessary to validate
and to verify that the new software fulfill all the user
and regulatory requirements.