1. Assessing expectedness of an adverse event

2. Assessment of Adverse Events (AEs)
Once identified an AE requires up to 4 assessments:
Seriousness
Severity
Causality
Expectedness
Assessment of AEs should always be made according to the study protocol

3. Assessing AEs NO Adverse Event (AE)
Any untoward medical occurrence in a clinical trial participant, which does not necessarily have a causal relationship with an IMP/intervention.
Is it serious?
Any AE that at any dose:
Results in death of the clinical trial participant
Is life-threatening
Requires hospitalisation or prolongation of existing hospitalisation
Results in persistent or significant disability or incapacity
Consists of congenital anomaly or birth defect
Other significant medical event
3. Was it caused by the IMP/Intervention?
Using clinical judgement, knowledge of scientific action and available product information is the AE/SAE possibly to be related to the IMP, NIMP or intervention? AE
YES
4. Is it expected?
Expected adverse reactions are listed in the Reference safety information (RSI). Only reactions listed in the RSI are expected.
(S)AE
Unexpected AR/Suspected unexpected SAR
(SUSAR)
(Serious) Adverse Reaction
(AR/SAR)
AR/SAR
2. How severe is it?
Mild – Easily tolerated causing minimal discomfort
Moderate – Sufficiently discomforting to interfere with everyday activities
Severe – Prevents everyday activities
Serious AE (SAE)

4. Assessment of expectedness
Expectedness assessment is only required if the event is an adverse reaction (possibly related to the IMP/intervention)
Expectedness should be assessed according to the approved Reference Safety Information (RSI)
There may be more than one RSI if you have more than one medicinal product/intervention in you study

5. What is RSI?
RSI is a list of expected events for the IMP/device/intervention used in the trial
What constitutes the RSI for a study should be clear in the safety section of the approved study protocol
For CTIMPs the RSI is approved by the MHRA

6. Examples of RSI
For products with a marketing authorisation the RSI is often section 4.8 of the approved summary of product characteristics (SPC)
For products without marketing authorisation the RSI is normally contained within a specific section of the Investigators Brochure
For medical devices the risk analysis report is often used as the source of expected events

7. How to assess expectedness
Compare the adverse reaction to the approved RSI
If the AR is:
Not listed in the RSI
Listed in the RSI but more severe, common or different in nature to the listed reaction
Then it is an UNEXPECTED event

8. Why is this important?
Suspected unexpected serious adverse reactions (SUSARs) are reported by the Sponsor to the MHRA/Research Ethics Committee
This allows safety oversight of drugs/devices in use across all clinical trials
Incorrect assessment of expectedness can lead to under reporting of SUSARs which could potentially put patients at risk

9. Require more information?
Consult your study protocol
If ACCORD sponsor your study consult the safety reporting SOPs on the ACCORD website
CR005 – Safety reporting for CTIMPs
CR006 – Safety Reporting for non-CTIMPs
CR012 – Safety reporting for medical devices
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