Study Conduct and Monitoring
The Study Conduct and Monitoring domain covers the trial lifecycle from feasibility through close-out: how sites are selected, initiated, monitored, and closed, and what the CRA must verify at each stage.
Lifecycle expectations
- Pre-study: confirm the investigator is qualified and has adequate staff, facilities, and access to a suitable subject population (ICH E6 4.1).
- Site initiation: protocol and GCP training, investigational product handling, laboratory procedures, the informed consent process, CRF completion, and SAE reporting expectations - all documented.
- Routine monitoring: source data review, CRF/eCRF review, drug accountability counts, consent documentation, protocol deviation identification, AE/SAE reporting compliance, and site file review.
- Close-out: final investigational product reconciliation, resolution of outstanding queries, collection of essential documents, and written notification of record retention requirements (ICH E6 4.9; 21 CFR 312.62(c) - at least 2 years after the marketing application is approved or the investigation is discontinued).
Worked example
At an interim monitoring visit the investigational product accountability log shows 30 kits dispensed, 12 returned, and 10 remaining, but the arithmetic should leave 8. Reasoning: the 2-unit discrepancy could reflect a dispensing error, an undocumented return, or unreported loss. The CRA queries the pharmacist, checks dispensing records against subject diaries and visit dates, and documents the resolution. If unresolved, it becomes a protocol deviation and possibly a product-loss report; if subjects may have taken the wrong dose, an AE assessment is required. Do not simply adjust the log.
Data quality frame
Source documents must be attributable, legible, contemporaneous, original, accurate, complete, consistent, enduring, and available (ALCOA+). Corrections use a single line, initials, date, and reason - never obliteration or back-dating.
Traps that cost marks
- Writing "no findings" without a monitoring report - every visit needs a documented report.
- Missing that serious unexpected suspected adverse reactions need expedited reporting: 15 calendar days, or 7 days for fatal or life-threatening events (21 CFR 312.32), with follow-up.
- Accepting a CRF as source when the protocol designates the medical record as source.
- Overlooking re-consent after a consent form revision.
- Closing a site without final drug accountability and site file reconciliation.