An Adverse Event (AE) is any untoward medical occurrence in a research subject that has a temporal association with a research study.
It can be any unfavourable and unintended sign, symptom or disease that has occurred during the course of a subject’s participation in research, regardless of whether it is actually related to the research procedures / interventions / investigational products or not.
The requirement and speed with which to report an adverse event will vary according to its classification: (Click on the respective headings)
SERIOUSNESS
An adverse event is classified as ‘serious’ if it:
- results in death
- is life-threatening (the person is at risk of death at the time)
- requires inpatient hospitalization or prolongation of existing hospitalization
- results in persistent or significant disability / incapacity
- is a congenital anomaly / birth defect
- poses serious risks to a subject’s health according to medical judgement, or requires intervention to prevent one of the outcomes above
CAUSALITY
Adverse Drug Reaction (ADR)
- An adverse event is reported as an ADR when there is a reasonable possibility that it is caused by an investigational drug / medicinal product.
- ‘Reasonable possibility’ means that a causal relationship cannot be ruled out.
- In a study investigating a new drug, or a new usage of a drug, any noxious or unintended response to any dose of the drug is considered an ADR.
Adverse Device Effect (ADE)
- Similarly, an adverse event is reported as an ADE when there is a reasonable possibility that it is caused by an investigational medical device.
- This includes those resulting from inadequate instruction for use, user error, intentional misuse or malfunction of the device.
EXPECTEDNESS
The terms ‘unexpected’ and ‘expected’ are used to further categorise ADRs and ADEs.
When an ADR / ADE is classified as ‘unexpected’, this means that the nature, severity or frequency of the reaction / effect is not consistent with what was previously observed or documented about the product (drug / device).
Adapted from: ICH E2A Guideline for clinical safety data management: Definitions and standards for expedited reporting (1994) and EC MEDDEV Guidelines on medical devices - Clinical investigations: Serious adverse event reporting (2015) (18,19)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Clinical Safety Data Management: Definitions and Standards for Expedited Reporting: ICH E2A [Internet]. [cited 2019 Jan 22]. Available from: http://www.ich.org/products/guidelines/efficacy/efficacy-single/article/clinical-safety-data-management-definitions-and-standards-for-expedited-reporting.html
MEDDEV 2.7/3 revision 3 Guidelines on medical devices - Clinical investigations: Serious adverse event reporting under directives 90/385/EEC and 93/42/EEC [Internet]. European Commission; 2015. Available from: https://ec.europa.eu/docsroom/documents/16477/attachments/1/translations