SAE 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 lack of compatibility, determine whether it is acceptable or not and, if acceptable, document the differences. It is a repetitive 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 differences before final clinical database is ready in order to submit validated data to regulatory authorities.

Serious Adverse Events (SAE) reconciliation is a crucial step in the pharmacovigilance process not only because it improves the study data integrity and quality, but also because it is a requirement for ensuring patient safety. 

This is an important aspect that health officials have in mind during inspections and the main reason why auditors look closely at how the reconciliation has performed and tracked. Within companies that are not using an integrated platform for data capture and pharmacovigilance, many seem to resolve to manual processes, sometimes only performed close to the clinical database lock, for reconciling the critical SAE information.

SAE differences

A mismatch between the safety database and the clinical database identified during the reconciliation process. A difference 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

SAE reconciliation listing

File listing, generally in Excel format, used to review and document all differences, acceptable or not, found during SAE data reconciliation.

The SAE reconciliation process can be summarized in four - apparently easy - steps: 

• retrieve and compare data, 

• analyze the discrepancies, 

• resolve the discrepancies and make the necessary adjustments in the clinical or safety database. 

But the process is more complex than it seems as it requires a thorough management of the numerous tasks involved, especially as all decisions and actions must be fully documented for GxP-compliance.

Figure 1 Source https://www.google.com/url?sa=i&url=https%3A%2F%2Fwww.datareconciliation.com%2FData-Reconciliation-Blog%2Fsae-reconciliation-process-challenge&psig=AOvVaw1jc5CXPd38UpUns9165Yy8&ust=1672044405071000&source=images&cd=vfe&ved=2ahUKEwje8uL3sJT8AhUlKb

The SAE reconciliation process is driven by a Data Manager who, on a timely basis, reviews data in the clinical database and compares defined variables with the corresponding records in the safety database. Line to line descriptions, coding terms, dates and other information are frequently found to be different between the safety and clinical database Data Managers or CRO and Data Managers collaborate with Drug Safety for resolution.

Reconciliation of safety data collected in clinical trials is a important quality step that must be considered and planned early in the clinical process. Failing to do so may result in serious issues or delays in the final steps of the trial and can delay the submission and approval of a new drug. 

Here is a general overview of the “what”, “when”, “who” and “why” that clinical and safety personnel should know and remember.

Why should we reconcile?

During a clinical trial, safety data are collected in two parallel processes and stored in two separate flies - the clinical database and the safety database. 

These two sources must be reconciled before the database is ready to ensure completeness and consistency of the safety monitoring of the trial.

What should we reconcile?

Safety data reconciliation applies to all the data concerning to Serious Adverse Events (SAE). In the clinical database, all Adverse Events (AE) are reported in a similar way and set of information is recorded: AE, onset date, end date, severity, relation to the study drug or device, outcome and Seriousness. In parallel, all SAEs are reported through the safety process and are described in detail and followed up until resolved. 

When should we reconcile?

It is a common mistake to think that reconciliation should be done at the end of the trial. The right approach is to perform safety data reconciliation all along the conduct of the trial.

How can we manage it efficiently?

It is true that performing ongoing data reconciliation without the appropriate tools may prove very challenging and, at the end, counterproductive. However, with the right software the process can be made easy, transparent and efficient.

Risks:

Poor quality of the reconciliation process may result in incomplete safety information reported to health official.

 It can result in critical audit findings and may have serious issues to access to the market of the drug. 

A slow process may delay the submission and result in financial loss for the sponsor. 

Finally, a poorly organized process may create stress to employees.

Rutuja Gawate

Pharm D

Student ID: 197/1122