StATS: What is an adverse event?

There is no common definition of adverse event. Some of the definitions are, in fact, contradictory, though they do appear to have some common elements. Here is a haphazard sampling of some definitions:

An unexpected medical problem that happens during treatment with a drug or other therapy. Adverse events do not have to be caused by the drug or therapy, and they may be mild, moderate, or severe.

An adverse event (AE) is defined as any occurrence that has unfavorable and/or unintended effects on research subjects, regardless of severity or study-relatedness. AEs may manifest as new findings (signs, symptoms, diagnoses, laboratory results) or alterations in pre-existing conditions.

Any harm experienced by a participant (regardless of whether the event was internal (on-site) or external (off-site) and regardless of whether the event meets the FDA definition of “serious adverse event”) which in the opinion of the Investigator are both unexpected and related. o Unexpected is defined as an event whose specificity and severity are not accurately reflected in the human studies application, protocol, consent form, current investigational brochure or medical device/medication package insert. o Related to the research procedures is defined as an event which in the opinion of the Investigator, was more likely than not to be caused by the research procedures or if it more likely than not affects the right and welfare of current participants.

An undesirable and unintended, although not necessarily unexpected, result of therapy or other intervention.

The HHS regulations at 45 CFR part 46 do not define or use the term adverse event, nor is there a common definition of this term across government and non-government entities. In this guidance document, the term adverse event in general is used very broadly and includes any event meeting the following definition: Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research (modified from the definition of adverse events in the 1996 International Conference on Harmonization E-6 Guidelines for Good Clinical Practice). Adverse events encompass both physical and psychological harms. They occur most commonly in the context of biomedical research, although on occasion, they can occur in the context of social and behavioral research. 


In a study of an exercise intervention, home-based walking, among participants with or at risk for cardiovascular disease, researchers described the number of adverse events. The results were:

During 1110 person months of observation, 87 of 274 participants reported 121 adverse events. -- Adverse events among high-risk participants in a home-based walking study: a descriptive study. Goodrich DE, Larkin AR, Lowery JC , Holleman RG, Richardson CR. International Journal of Behavioral Nutrition and Physical Activity 2007, 4:20 doi:10.1186/1479-5868-4-20. [Medline] [Abstract] [Full text] [PDF]

This page was written by Steve Simon while working at Children's Mercy Hospital. Although I do not hold the copyright for this material, I am reproducing it here as a service, as it is no longer available on the Children's Mercy Hospital website. Need more information? I have a page with general help resources. You can also browse for pages similar to this one at Category: Adverse events in clinical trials or Category: Definitions.