SAE RECONCILIATION in clinical data management

SAE data reconciliation
The process of comparing key safety data variables between the drug or device safety SAE database and the clinical database in order to identify any discrepancy, determine whether a discrepancy is acceptable or not and, if acceptable, document the discrepancy. It is an iterative process that occurs several times during the study. When to reconcile is determined by the frequency of data receipt, scheduling of safety updates and timing of interim and final reports. The objective is to reconcile all discrepancies before final clinical database lock in order to submit validated data to regulatory authorities.
SAE discrepancy
A mismatch between the safety database and the clinical database identified during the reconciliation process. A discrepancy can be for example:
An SAE present in one database but missing in the other one
Inconsistent SAE associated data between the databases
Missing SAE associated data in one of the databases
Mismatched SAE preferred term
All the identified discrepancies, actions taken to address the discrepancies, and the status relevant to the action taken are recorded in the SAE manual or electronic reconciliation tool.
Serious adverse event (SAE) report form
Form used to report an SAE. An SAE report form contains information such as the event onset date, date that it became serious and end date, seriousness criteria (resulted in death, was life-threatening, required hospitalization, etc.), the severity (e.g.: mild, moderate, severe), the outcome (fatal, not resolved, resolved, resolved with sequelae, resolving, unknown), suspected drug(s) information and a causality assessment. (see also SAE reporting regulations).
Suspected unexpected serious adverse drug reaction (SUSAR)
A serious adverse reaction (SAR) for which a reasonable causal relationship with the medicine used is suspected but not confirmed. Unexpected means not consistent with the applicable product information (e.g., Investigator's Brochure for an unapproved investigational medicinal product or package insert/summary for an approved product).
Trial Master File (TMF)
The collection of the essential documents of a trial which individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced. TMSs are established at the beginning of the trial, both at the investigator’s site and at the sponsor’s office and are updated with new relevant documents as new information becomes available.
Unexpected adverse drug reaction (UAR)
An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator's Brochure for an unapproved investigational medicinal product or package insert/summary for an approved product).
Serious adverse event or reaction (SAE or SAR)
Any untoward medical occurrence that at any dose:
results in death
is life-threatening
Safety database
The database used by safety groups to process and manage SAE data from clinical trials

1. SAE Reconciliation [email protected] | https://clinicalda.blogspot.com

2. Definition SAE data reconciliation is the process of reconciling the clinical database (i.e. Data collected on the CRF) with the Pharmacovigilance database (i.e. SAE forms) to ensure the data is consistent and not contradictory . Serious adverse event (SAE) reconciliation is one of the critical activities in clinical data management & also an important activity for clinical data manager.

3. Why sae reconciliation? Primary reason is to ensure the patient safety and integrity of clinical trial data, by comparing the SAE's reported between EDC and safety database for its completeness, accuracy & classification.

4. Steps in SAE Reconciliation 1. S AE Reconciliation plan? This can be documented as part of DMP or it can be standalone document & It covers imp items like a. Process & roles involved in SAE recon b. List of items to be reconciled c. Process to report discrepancies d. Action to take to correct the data in both databases

5. 2.Compare the SAE data b/w 2 sources : R eceive SAE dump or monthly SAE report from safety team & review the same for discrepancies in EDC data for the data points including From Adverse Event (AE) form: a. Protocol & Subject Number b. AE Term (Both reported terms & coded term) c. Severity Grade d. Start & End dates e. Death date (if any)

6. continues….. f . Outcome g. Seriousness criteria h. Relation to the drug i. Action taken with study drug From Demographics (DM): a. DOB b. Age c. Sex d. Race

7. From Concomitant Medication (CM) & Medical History (MH) a. Medication name / Medical condition / Surgery b. Start date c. Stop date or ongoing Indication From Study / Treatment Discontinuation (DS) a. Primary reason for discontinuation being an event b. Cause of hospitalization c. Cause of death listed on the death certificate d. Autopsy result

8. 3.Take appropriate action needed based on the discrepancies Lets see the major SAE reconciliation Errors found in SAE Reconciliation 1.Data entry errors : This can occur due to human error, transcription errors, or incorrect data entry fields. 2.Incomplete data : Incomplete SAE data can occur when events are not recorded in both the EDC and safety databases

9. continues…….. 3.Inconsistencies in coding : SAEs may be coded differently in the EDC and safety databases, leading to discrepancies 4. Inconsistencies in Reporting : this can happen when different investigators or study sites use different terminology or criteria for reporting SAE 5.Delaying Reporting : this may lead to a backlog of events to be reconciled.

10. Adverse event : Any effect/disease Study Drug Patient Any Effect occurs INTAKE Adverse event Might may be Not might drug involved drug Adverse event maybe : MILD,MODERATE,SEVERE

11. Sae reconciliation Flow chart SAE collected from clinical trial & marketed products Reporting containing SAE Case Goes to safety department Case of adverse effect

12. continues……. During clinical trial=SAE information also received through CRF or EDC stored in ADVERSE EVENT DMS Stored in clinical & safety database Important to match SAE with data management system SAE Reconciliation

13. During information following information are checked: Cases found in the SAE system but not in the CDM system—->(case of adverse effect)safety system. Cases found in the CDM system but not in the SAE system —>(adverse event)database system. Death —>any case—>found only one system–>.(cases of adverse effect) adverse event

14. Serious adverse event Patient Drug Adverse event Results in death • Is life threatening, or places the participant at immediate risk of death from the event as it occurred • Requires or prolongs hospitalization • Causes persistent or significant disability or incapacity • Results in congenital anomalies or birth defects • Is another condition which investigators judge to represent significant hazards

15. Need of SAE reconciliation=compare SAE with CDM TABLE SAE CDM Less organized more organized/defined data: eg: S ubject & investigate ID subject,investigate well defined in study data such as age, sex information Collected information but collect only events collected separately adverse event are collected event by event passociate each problem

16. Companies reports & manual comparison SAE reconclliation ON When the reporting system has access to the underlying database It might be possible to do initial match on some information such as study ID,Sub ID etc… Underlying database present in SAE system and CDM system. DEPENDS FOR