Unsupported Eligibility Value in Source and EDC
During source data verification for Subject 012-005 in a Phase I/II oncology trial, you find that the protocol requires a screening eGFR ≥50 mL/min/1.73 m². The central laboratory printout in the source file reports 47. The electronic data capture (EDC) entry reports 52. When asked, the CRC says the 47 was 'a lab error' and that a repeat value of 52 was obtained, but there is no repeat lab report, requisition, or progress note in the source. The subject was randomized on 14 April and has received two doses of study drug. The subject is 71 years old with type 2 diabetes and baseline creatinine 1.5 mg/dL. The investigator says the subject is 'clinically fine' and wants to continue. The EDC entry was made by the CRC, and the investigator signed the eligibility checklist without documenting the discrepancy. The site has not reported a protocol deviation. You are at the site with the monitor's worksheet and must decide next steps.
1. Was there an eligibility violation, and what immediate actions should you take?
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Treat the 47 as the source value unless a valid repeat lab report is produced. A verbal claim of lab error is not source documentation. The protocol requires eGFR ≥50 at screening, so 47 is below threshold and the subject was likely enrolled in violation. Immediate actions: inform the investigator and sponsor medical monitor the same day; ask for the actual repeat lab report if it exists; and do not alter EDC to match an undocumented value. Assess subject safety: two doses have been received, and the subject is 71 with diabetes and creatinine 1.5 mg/dL. Ask the medical monitor whether additional renal monitoring or dose modification is needed. Whether to continue dosing is an investigator and medical monitor decision based on protocol and safety; the CRA should ensure the decision is documented. Do not let the site simply 'correct' the EDC without a source.
2. How should the data discrepancy be handled from a data-integrity perspective?
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The EDC value of 52 is unsupported and should be queried. If no source exists, correct EDC to 47 and document the correction with the audit trail. The investigator's signed eligibility checklist is inaccurate; require a note explaining the review and the deviation. The CRC's entry may be an error or may indicate fabrication; assess whether other subjects have similar discrepancies. This is a data-integrity issue, not just a typo. Preserve original records and do not overwrite them. Report the discrepancy in the monitoring report and consider a targeted review of screening labs at the site. If fabrication is suspected, escalate to sponsor quality or compliance and avoid confronting staff accusingly without evidence.
3. What reporting and communication steps are required, and who decides whether the subject continues treatment?
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Report as a protocol deviation and potential eligibility violation to the sponsor within its timeline, and to the IRB if required by policy or if it affects subject rights and welfare. The investigator should document the deviation and any safety follow-up. The sponsor and medical monitor decide whether the subject may continue or must discontinue, with input from the investigator; the CRA must not decide unilaterally. Communicate in writing that no further EDC changes may be made for this subject without source documentation. Confirm that the site understands the difference between a data correction and an undocumented value change. Follow up to verify that the deviation is reported and that the subject's safety monitoring is completed.