An adverse event is any untoward medical occurrence in a participant who has received a trial treatment, whether or not it is thought to be caused by that treatment. It can be a symptom, a sign, an abnormal result or a disease.
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Adverse event
noun · clinical research
Any untoward medical occurrence in a participant given a trial treatment, which does not necessarily have a causal relationship with that treatment.
Related terms
In short
Explained
The wording used in ICH guidance and in US regulation is broad on purpose: an adverse event is any untoward medical occurrence in a participant who has been given a pharmaceutical product, and it does not need a proven causal link to the treatment. The point is to capture everything first and decide about relationship afterwards. A broken ankle, a cold, a raised liver enzyme and a worsening of a pre-existing condition can all be AEs, depending on how the protocol defines reporting.
Because the definition ignores cause, an AE is a different thing from an adverse drug reaction (ADR), where there is at least a reasonable possibility that the treatment caused the event. Every ADR is an AE; most AEs are not ADRs. "Side effect" is the everyday word and is not a regulatory term.
Protocols usually set the reporting window (for example from consent or first dose until a follow-up visit) and say what counts as a reportable AE, such as whether a stable pre-existing condition or a planned procedure is recorded. Those rules matter more for data quality than the textbook definition does.
An adverse event becomes a serious adverse event when its outcome meets a seriousness criterion. The commonly used list is: death, a life-threatening event, inpatient hospitalisation or prolongation of existing hospitalisation, persistent or significant disability or incapacity, a congenital anomaly or birth defect, and an important medical event that may jeopardise the participant or need intervention to prevent one of those outcomes. Check the current ICH E2A and 21 CFR 312.32 text for the precise wording. SAEs trigger faster reporting to the sponsor and, where related and unexpected, to regulators; see SAE reporting deadlines and the SAE report form template.
Severity grades intensity, often with a scale such as CTCAE in oncology. Seriousness is a yes/no regulatory classification. Causality is the investigator's judgement of whether the treatment, another drug, the disease or something else explains the event. A mild event can be serious (a brief hospital stay for observation), and a severe event can be non-serious (a severe headache that passes). Keep all three as separate fields; see AE causality assessment.
Some protocols name adverse events of special interest (AESI) that need extra detail or faster notification whether or not they are serious. Expectedness is judged against the reference safety information, such as the investigator's brochure. An event that is serious, suspected to be related and unexpected is a SUSAR, covered by SUSAR reporting software.
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Causality is required because the event is serious.
Related terms
| Term | What it means | Needs a causal link? |
|---|---|---|
| AE | Any untoward medical occurrence in a participant given a trial treatment | No |
| SAE | An AE that meets a seriousness criterion such as death, hospitalisation or disability | No |
| ADR | A response to a medicinal product where a causal relationship is at least a reasonable possibility | Yes, suspected |
| SUSAR | A suspected, unexpected serious adverse reaction | Yes, suspected |
Simplified for learning. Regulatory definitions and timelines differ by jurisdiction and change; use the current guidance.
Build the adverse event form, enter sample events and see the audit trail record every change. No credit card.
What to record
Whatever the form looks like, a usable AE record answers the same questions.
A clear diagnosis or term rather than a vague phrase. Add a coding step if your analysis plan requires a dictionary.
Start and stop dates, or an "ongoing" flag, so duration and overlap with dosing can be seen.
Mild, moderate, severe, or the grade scale named in the protocol.
A yes/no field with the criterion ticked; a "yes" should start the SAE workflow.
Relationship to the study treatment, and what was done (none, dose changed, interrupted, stopped).
Recovered, recovering, not recovered, recovered with sequelae, fatal or unknown.
In Capture
Capture's template library includes an adverse events form and an AESI form, built as a repeating table so each event is its own row with its own audit trail. Edit checks can flag an impossible stop date as an auto-query, and every change records who made it, when, the old and new value and the reason. Exports carry an automatic data dictionary, and templates are tagged with SDTM domains such as AE.
SAE timeline
SAE reported
Day 0 · 09:12
Safety alert acknowledged
Medical monitor · 09:40
Site staff attestation
Study coordinator · 11:05
AE sign-off (PI / Sub-I)
Awaiting signature
Any untoward medical occurrence in a participant who has received a trial treatment, whether or not it is thought to be caused by that treatment. It can be a sign, symptom, abnormal test result or disease.
An SAE is an AE whose outcome meets a seriousness criterion, such as death, a life-threatening event, hospitalisation, persistent disability, a congenital anomaly or another important medical event. SAEs are reported faster.
"Side effect" is an informal term for an effect thought to be caused by a treatment. An adverse event needs no proven cause, so it is wider than a side effect. An adverse drug reaction is the regulatory term for a suspected causal effect.
Usually only if they worsen after the reporting period starts, but the protocol decides. Baseline conditions are normally recorded on a medical history form instead.
The investigator assesses causality, and the sponsor may add its own assessment. They are recorded as separate fields from severity and seriousness.
No. Severity describes intensity (mild, moderate, severe). Seriousness is a regulatory classification based on outcome and drives expedited reporting.
Keep exploring
Adverse event reporting software
Collecting and escalating AEs.
Adverse event eCRF template
A ready-made AE form.
SAE report form template
When an AE is serious.
SAE reporting deadlines
Check the reporting clock.
AE causality assessment
Recording relationship.
SUSAR reporting
Suspected unexpected reactions.
Case report form (CRF)
Where AE logs live.
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