10.1 Detecting Events, AESIs and Collection Windows
Key Takeaways
A medication change can signal a possible event but does not prove a diagnosis.
An AESI can be serious or non-serious and follows protocol-specific surveillance instructions.
Pre-dose events may require collection under the protocol.
Detecting Events, AESIs and Collection Windows
On site during Interim Monitoring Visits (IMVs), verifying safety reporting is the CRA's highest-priority obligation. Site coordinators and investigators under administrative strain frequently fail to recognize or capture adverse events.
Proactive Detection of "Hidden" Safety Events
Experienced CRAs do not merely read the completed AE log; they actively hunt for unreported events across multiple source streams:
- Concomitant Medication Logs: If a CRA notices that a subject was newly prescribed ondansetron (an antiemetic) or ciprofloxacin (an antibiotic), but the AE log contains no mention of nausea, vomiting, or infection, a potential discrepancy needs clarification. The CRA should verify the indication and investigator assessment, then follow the protocol collection rules.
- Progress Notes & Emergency Room Records: Reviewing nursing notes or physician correspondence often reveals that a patient called the clinic reporting severe dizziness or spent 8 hours in an urgent care clinic.
- Diagnostic and Laboratory Reports: Reviewing local and central laboratory reports for flagged high/low values. If a participant's creatinine jumped from 0.9 mg/dL to 2.8 mg/dL, the CRA must verify that the investigator reviewed the report, documented clinical significance, and logged an AE for acute renal insufficiency if clinically meaningful.
- Protocol-Mandated Dosing Adjustments: If an investigational product dose was withheld, reduced, or interrupted, the CRA must cross-reference the dose change against the AE log to ensure the underlying toxicity was documented.
Reviewing reporting timeliness
Reconstruct the sequence from the first site notification, investigator awareness, initial sponsor report and subsequent follow-up. Apply E6(R3)'s immediate reporting expectation and the trial's specific instructions. If a protocol specifies 24 hours, test that requirement; do not teach it as an ICH-defined universal limit. Review any protocol-defined exceptions and verify that they actually cover the event. A serious event does not become exempt because the investigator thinks it unrelated.
A medication change or abnormal result is a signal for investigator review, not proof of an AE diagnosis. A new antibiotic could represent prophylaxis; an abnormal laboratory value could be artefactual. Ask a neutral clarification question and verify the investigator's assessment. Do not direct the coordinator to invent an event merely to populate an empty log.
AESIs, pregnancy and collection windows
An AESI is a protocol-defined focus of surveillance and can require rapid communication or extra information even when it does not meet seriousness criteria. It does not automatically mean SUSAR. Evaluate seriousness, suspected relationship and expectedness separately while following the additional AESI instructions. A named risk in a safety plan can be important without being an expected adverse reaction in the designated RSI.
Pregnancy exposure is another situation that may have a separate protocol reporting and follow-up process. Pregnancy itself is not automatically an adverse event or a congenital anomaly. Record the required exposure and outcome information under the authorised process, protecting confidentiality. An adverse pregnancy outcome or other event may meet AE or seriousness criteria and needs the appropriate clinical assessment.
Do not wait for an eventual outcome to report an exposure when the protocol requires earlier notification.
The protocol defines relevant collection periods, including screening and post-treatment follow-up as appropriate. E6(R3) explicitly recognises consideration/reporting of unfavourable events before product administration if required by the protocol. A site should not omit a screening event solely because the person has not received a first dose. Conversely, a monitor should not invent an unlimited collection period beyond the agreed framework. Establish the timing, requirement and medical assessment from evidence.
Expedited Safety Reporting, SUSARs & Safety Oversight
Note
The expedited reporting of serious safety events represents the primary international mechanism for detecting emerging pharmacological risks, halting hazardous clinical investigations, and protecting human trial participants worldwide. Established under ICH E2A and operationalized through national regulatory frameworks (such as US FDA 21 CFR 312.32 and EU Clinical Trials Regulation 536/2014), strict safety escalation rules mandate that clinical trial sponsors, investigators, and monitors adhere to uncompromising timelines.
When an adverse event occurs during a clinical investigation, it enters a structured safety evaluation pipeline. While routine adverse events are captured in electronic case report forms (eCRFs) and evaluated during cumulative study analyses, safety occurrences that meet specific criteria require immediate, rapid escalation. On the CCRA examination, candidates must master the anatomical definition of a SUSAR, understand exact regulatory timelines (distinguishing calendar days from business days), grasp the independent role of Data Monitoring Committees, and execute rigorous monitoring oversight to reconcile clinical and safety databases.
Official sources
Checked October 18, 2026: ICH E6(R3), Principles and Annex 1, ICH E2A, WMA Declaration of Helsinki, 2024.
A new antibiotic appears in source records with no AE entry. What should the monitor do?
Automatically create an infection diagnosis.
Ignore it because antibiotics cannot relate to study safety.
Change the prescription record to match the empty log.
Clarify the indication and investigator assessment under the collection rules.
Sections you finish are checked off in the contents.