1. Serious Adverse Event Reconciliation
- Aditi Bhat

2. Agenda Adverse Event Serious Adverse Event (SAE) Collection of SAE’s
SAE Reconciliation and Reasons for performing reconciliation
Different databases
Paper studies and Electronic studies
Points/Fields to be reconciled
Points to remember before performing SAE reconciliation
Reconciliation Process
Discrepancy with solutions
Query process
Roles and Responsibility
Data base lock activity
Documents

3. Adverse Event
An adverse event is any unfavourable and unintended sign (including abnormal laboratory findings), symptoms or disease temporarily associated with the use of a medical (investigational) product, whether or not related to the medical (investigational) product.

4. Serious Adverse Event
SAE (Serious Adverse Event) : Any untoward medical occurrence that at any dose results in:-
Death
Is life threatening
Requires inpatient hospitalization or prolongation of existing hospitalization
Persistent or significant disability/incapacity
Congenital anomaly or birth defect
Requires intervention to prevent impairment or damage

5. Collection of SAE’s
When SAE is reported on the site, it has to be reported to the Sponsor within 24 hours and to regulatory authorities within 7 days.
If the Site does not adhere to the mentioned timelines, it will be considered as protocol deviation.

6. SAE Reconciliation and reasons for performing reconciliation
It is necessary because SAE data is considered as CRITICAL DATA in both the safety and the project database. Clinical database is made up of dosing, demography, adverse event and final subject summary pages; all of which are data points that make up the case that are reported to the safety database.
It is essential to understand that these data is submitted to Regulatory Agencies at the end of the study and for subsequent aggregate reporting which occurs well after database lock.

7. Different databases used to perform reconciliation
Safety database: Sapphire BOR, Argus, etc. (Mainly built for Pharmacovigilance purpose)
Clinical database: AMOS, RAVE, COOL, INFORM, ORACLE

8. Paper studies Electronic studies
Data is entered on Paper case Report Form
Data entry associates will enter the data manually in Clinical database
Example: AMOS
Data is captured in electronic case report Form
Investigator enters data in to database
Examples: RAVE, INFORM

9. Fields to be reconciled
Site Number
Subject Number
Randomization Number
AE Term reported (verbatim Term)
Preferred term (Coded Term)
Start date of the event
Stop date of the event
Investigational drug
Causality
Outcome
Seriousness criteria
AE became SAE date

10. Points to remember before performing reconciliation
Reading of Data Handling Plan and Protocol are MUST before starting the reconciliation of the study which will give the below details,
When to start SAE reconciliation considering First Patient First Visit
Which fields to be reconciled
What would be the cutoff date for SAE
Which SAEs to be considered as expected SAEs, Unexpected SAEs, Which SAEs to be considered as End points.
End points are to be captured or not
Details of CRA, Investigator, CTH
Frequency of reconciliation to be performed

11. Process of reconciliation
Team Lead will assign the study
Apply for the required access
Read Protocol and DHP
Post getting the access send mail to study team to discuss the reconciliation date for the particular study
Pull the safety listings from Safety database / request for the Safety listings And pull the Clinical listings by SAS or the available tool
Perform the reconciliation
Record the discrepancies and action to be taken in one sheet [generally called as SAE reconciliation Spread Sheet (SRS)]
Raising queries - For missing SAEs query should be raised within 24 hours of the reconciliation
Before raising a query, kindly check if the query has been raised by TDM/DM for the particular SAE

12. Discrepancies with resolutions

13. Query Process
For missing SAEs from either of the database, query to be raised within 24 hours of the reconciliation process
If Query is not getting answered in 48 hours for missing SAE, send mail to CRA keeping CTH and study team in loop
For other discrepancies turn over time is 7 working days
Before raising any query, please check if the query has been raised
Every week Open query report to be run and if answers of raised queries are satisfactory in nature, query can be closed. If not a re-query can be raised
After raising 3 re-queries, answer is not satisfactory; send mail to CRA keeping study team in a loop

14. Roles and Responsibility
SAE Reconciler:
Extracting the data from Clinical database and Safety database
Reconciliation mandatory/agreed upon SAE data points
Communicating with coders to resolve the coding issue
Checking internally with data entry to resolve data entry issues if the study is paper based
Raising queries in the database
Preparing SRS log for discrepancies observed and action taken
Filling the monthly ongoing reconciliation form
Filling the Final SAE Reconciliation form.

15. Database lock activity
SAE Reconciler will receive a mail regarding database lock from study team. He/she needs to confirm about cutoff date regarding SAE
Frequency of reconciliation will be discussed with the study team.
Query report to be pulled on a regular basis
If queries are not getting resolved, mail can be sent to CRA keeping study team in a loop
Discrepancy report can be sent to the study team
Patient safety to be reported for the database lock.

16. Documents
SAE Reconciliation Spreadsheet
Monthly Ongoing SAE Reconciliation Form
Safety Database update Request Form
Coding Mismatch Tracker
Final SAE Reconciliation Form

17. Questions

18. Thanks