Serious Adverse Events (SAE) information collected during interventional or non-interventional clinical trials are captured in two distinct databases; a clinical database reflecting adverse event information recorded in the Case Report Form (CRF) and a safety database containing information collected on the SAE Form and their respective follow ups. Making sure that the information pertaining to SAEs is matched in these two databases during the course of the study and particularly at the time of study database lock is a challenge impacting data quality, operations performance and compliance.
The parallel processing of SAEs in two different data sources may create discrepancies that need to be clarified and reconciled before the clinical database is locked. When reconciliation occurs, verbatim descriptions, coding terms, treatment and event onset/resolution dates, causality assessment, seriousness criteria, SAE outcome and other information can be found to be different. Based on each company's standards, some discrepancies must be resolved and others have a predefined margin of tolerance, but all must be compared, weighted, clarified and, if needed, queried and corrected in either dataset before the clinical database lock at the end of the trial. During the SAE Reconciliation process, a separate set of queries are therefore sent to the sites for clarification of identified discrepancies.
In practice, the routine steps of the reconciliation process consist of retrieving the SAE-related data from each of the two databases, usually exporting the data onto listings or Excel files and subsequently comparing the individual data points by navigating from one file to another. This task is further complicated by the ongoing database updates, forcing the same SAE to be reviewed repeatedly during the ongoing clinical trial and under considerable time pressure at the time of database lock. The risk of missing a change in the source data is substantial. Finally, whatever the method, evidence of SAE reconciliation and the resulting outcome must be documented and filed in the Trial Master File (TMF) for future inspection by health authorities.
Periodic SAE reconciliation must therefore be run in parallel to the trial while new events are reported, sometimes as follow-ups of earlier ones, and data are being continuously updated. In addition to this, it is common that people change roles and the continuity of the SAE reconciliation process may be disrupted. How can a sponsor be sure to have captured all important SAE discrepancies and performed the appropriate corrections prior to final database lock and at the same time track and document all actions performed during the process with the ability to report with confidence when inspection time comes?
Technology can greatly help manage the SAE reconciliation process and guarantee its quality. A properly designed and configurable electronic tool can help data managers and drug safety representatives to overcome the inherent challenges of the process and achieve high data quality, integrity and GxP compliance.
eReconciliation® was developed as a web-based tool to support the SAE data reconciliation process between clinical and safety databases. The software package was conceived as a support tool for data managers, clinical teams and safety teams and can be used for both interventional and noninterventional trials such as PASS (post-authorization safety studies) and registries. It is of particular interest in long-term trials or trials with a high expected number of SAEs with multiple follow up reports.
eReconciliation® can connect to any type of database and to as many databases as needed and import via an Application Programming Interface (API) the necessary SAE-relevant or other clinical study data points as defined by the users.
To support the SAE reconciliation process, the eReconciliation® interface typically displays SAE-related data points imported from clinical databases (such as RAVE or other EDC systems or even data from paper CRFs) and safety databases (such as ARISg or Argus) in side-by-side panels allowing easy comparison on a single screen. To further facilitate users' work, eReconciliation® allows filtering newly reported SAEs in either database and flagging changes in the source data, which the tool detects automatically, for the previously reconciled SAEs.
eReconciliation® enables grouping of fully matching, partially matching or non-matching items, and allows addition of comments (e.g. to highlight non-matching data points to be queried or to add a justification for an accepted discrepancy). The same feature can also be used to complete the allocation of follow-up actions (e.g. to provide instruction to the CRA for verification at a subsequent monitoring visit).
The specific advantage of eReconciliation® is that it facilitates cross-functional collaboration between the Data Management and Safety departments, allowing them to jointly review the discrepancies and decide on an appropriate action (e.g. a decision to issue a query to the investigating site). Finally, once the discrepancy is resolved, and either the pharmacovigilance or the clinical database was updated, the system detects this change automatically and brings this to data manager's attention.
In order to ensure full regulatory compliance, eReconciliation® captures all action assignments and corresponding comments in an automated, user-independent audit trail which can be easily exported in Excel or PDF for documentation or future audit purposes.
In summary, a properly designed and configurable electronic SAE reconciliation tool such as eReconciliation® will help Data Managers and Drug Safety to overcome the inherent challenges to any clinical trial SAE reconciliation process and support high data quality, integrity and GxP compliance. You can request a Free Demo of the eReconciliation® with no commitment needed from your side.
About Ethical GmbH
Ethical GmbH develops, implements and maintains personalized cloud-based software solutions helping biopharmaceutical companies and CROs to manage clinical trials in a simple, effective and GxP-compliant way.
For over twenty years, our software solutions such as eAdjudication® and eReconciliation® have supported some 300 international trials involving hundreds of thousands of patients in more than 10,000 investigators' sites.
Our agile team of experts is fully committed to data integrity, security and confidentiality. Our software and services comply with the ISO/IEC 27001 data security standard and with all appropriate regulations such as GxP, US 21 CFR Part 11, EU GMP Vol. 4 Annex 11, EU General Data Protection Regulation (GDPR).