SAE Reconciliation Discrepancy
During SAE reconciliation for a Phase II study, the data manager compares the clinical database SAE log with the safety database. The clinical database has 23 SAEs; the safety database has 25. Two SAEs in the safety database are not in the clinical database: one is a hospitalization for pneumonia reported by the site directly to the safety department but not entered into the clinical database; the other is a death that was reported as an SAE in the safety database but is recorded as a fatal AE in the clinical database without the SAE flag. The data manager also notices that one SAE in the clinical database has a different onset date (2 days later) than in the safety database. The study is blinded, and the data manager is unblinded.
1. What steps should the data manager take to reconcile these discrepancies?
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The data manager should first document each discrepancy. For the pneumonia hospitalization: the data manager should query the site to enter the SAE into the clinical database, ensuring the SAE form is completed. The data manager should verify that the event meets SAE criteria and that the safety database entry is correct. For the death: the data manager should review the clinical database entry to confirm whether the event should be flagged as an SAE. If the event meets SAE criteria (e.g., death), the SAE flag should be added, and the SAE form completed. The data manager should also check if the death was reported to the safety database within the required timeframe. For the onset date discrepancy: the data manager should query the site to confirm the correct date, using source documents. The data manager should not assume one database is correct. After resolution, the data manager should update both databases accordingly and document the reconciliation. Because the data manager is unblinded, they must not share subject-level treatment information with blinded team members. The reconciliation should be performed by someone with appropriate access.
2. How should the data manager ensure that the reconciliation is complete and documented?
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The data manager should maintain a reconciliation log that lists each discrepancy, the action taken, the resolution date, and the responsible person. The log should be reviewed by the safety team and the sponsor. After corrections, the data manager should re-run the reconciliation report to confirm that the databases match. Any remaining discrepancies should be explained (e.g., if an event is not an SAE per protocol). The data manager should also verify that the SAE data in the clinical database is consistent with the safety database for key fields: subject ID, event term, onset date, seriousness criteria, and outcome. The reconciliation should be repeated at regular intervals and before database lock. The data manager should ensure that the audit trail captures all changes.