Source-to-ECRF Discrepancies Before a Sponsor Audit
During a routine monitoring visit for a Phase III hypertension trial, the CRA compares five subject files with the eCRF. In subject 014, the source note from visit 3 documents 'mild headache since Tuesday, no medication, resolved' but the eCRF has 'no adverse events.' The visit date in the eCRF is 12 June; the source note is dated 14 June. In subject 022, the eCRF records a blood pressure of 128/78, but the source worksheet shows 148/92 with a note 'repeat 128/78 after 5 minutes.' The coordinator says she entered the repeat value because it was 'more accurate' and that she deleted the first value from the eCRF to avoid a query. The PI signed the eCRF at the end of the visit. The CRA asks for an explanation before the sponsor's audit in two weeks.
1. Identify the data integrity issues and explain the correct source-to-eCRF approach for each.
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There are three separate issues. First, the headache is an adverse event that was documented in the source but not entered in the eCRF. The coordinator must enter it with the onset date, severity, relationship, action taken, and outcome, and notify the PI and sponsor per the AE reporting plan. A resolved mild headache still belongs in the AE log; 'no adverse events' is inaccurate.
Second, the visit date discrepancy must be corrected to match the source. If the visit actually occurred on 14 June, the eCRF should say 14 June, with a documented reason for the correction. If the 12 June date was a data-entry error, correct it through the eCRF audit trail; do not leave two conflicting dates.
Third, the blood pressure entries must preserve both the initial and repeat readings if the protocol requires them. The source worksheet shows 148/92 followed by 128/78 after 5 minutes; entering only the repeat value and deleting the first value changes the clinical record and removes the reason a repeat was done. The eCRF should capture both values as the protocol defines, or the source should document which value is protocol-required. Deleting data to avoid a query is data manipulation. Corrections must be made with an audit trail, reason for change, date, and identity; the original value must remain visible.
2. What corrective and preventive actions and audit-preparation steps should the coordinator take now?
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The coordinator should stop making unilateral changes, inform the PI, and correct the eCRF transparently. Enter the headache as an AE, correct the visit date to the source, and restore or accurately represent the blood pressure data according to the protocol. Each correction needs an audit-trail reason, and the coordinator should not backdate or delete the original entry. Create a source-documentation memo explaining what happened and what was corrected, and attach it to the study file. Notify the sponsor monitor before the audit; hiding the issue until the audit is worse.
Review all subjects enrolled by the same coordinator for similar problems: missing AEs, date mismatches, selectively entered lab or vital-sign values, and deleted data. Retrain the coordinator and any backup staff on ALCOA principles, source-to-eCRF verification, and the prohibition on deleting data to avoid queries. Have the PI review and sign a CAPA and an oversight attestation. For audit preparation, organize the regulatory binder, delegation log, training records, source worksheets, eCRF audit trails, AE log, and query history. The site should be able to explain the discrepancy, show the correction, and demonstrate that the PI provided meaningful oversight rather than signing without review.