Safety Reporting and Adverse Event Management
This domain tests the definitions and clocks that decide whether an event becomes an expedited report. Most errors come from confusing severity with seriousness, or from assuming the site decides what gets reported to the regulator.
Definitions that drive everything
- Adverse event: any untoward medical occurrence, whether or not related to the investigational product.
- Serious adverse event (any one of): death, life-threatening, inpatient hospitalisation or prolongation of existing hospitalisation, persistent or significant disability/incapacity, congenital anomaly/birth defect, or an important medical event requiring intervention to prevent one of these.
- Severity is intensity (mild/moderate/severe or CTCAE grade); seriousness is the regulatory category. A severe headache is not automatically serious; a mild hospitalisation for observation is serious.
Causality and expectedness
- The investigator assesses relatedness; "reasonable possibility" means the product may have caused the event.
- Expectedness is judged against the Investigator's Brochure reference safety information (or the approved label). Unexpected + suspected + serious = SUSAR, which is expedited.
Timelines
- FDA IND: 7 calendar days for unexpected fatal or life-threatening suspected adverse reactions; 15 calendar days for other serious, unexpected, suspected reactions (21 CFR 312.32).
- Sites typically must notify the sponsor within 24 hours per protocol; IRB reporting follows its own policy, including unanticipated problems involving risk to others.
- Devices: unanticipated adverse device effect to sponsor and IRB within 10 working days.
Capture and follow-up
Record start/stop dates, severity, relatedness, action taken, treatment, outcome and hospitalisation dates; capture events from consent (or first dose, per protocol) through end of study; follow ongoing events to resolution or stabilisation.
Worked example
A participant is admitted for an elective hernia repair planned before enrolment. Reasoning: this is not an SAE under the standard convention because the hospitalisation was pre-planned and not caused by an adverse event - but it must still be documented and assessed, and the sponsor's convention governs. If instead the repair followed a study-related worsening, it is an SAE.
Traps that cost marks
- Equating severe with serious, or reporting every AE as expedited.
- Missing the site's 24-hour internal clock while recalling the 7/15-day regulator clock.
- Assuming an investigator's "unrelated" assessment ends reporting - the sponsor must still evaluate all serious events.
- Failing to follow an ongoing event past study discontinuation.