Adverse event

An adverse event (AE) is any adverse change in health or "side-effect" that occurs in a person who participates in a clinical trial while the patient is receiving the treatment (study medication, application of the study device, etc.) or within a pre-specified period of time after their treatment has been completed.

AEs in patients participating in clinical trials must be reported to the local Institutional Review Board (IRB) and the study sponsor. Adverse events categorized as "serious" (for example death, illness requiring hospitalization, events deemed life-threatening, or involving cancer or fetal exposure) must be reported to the regulatory authorities immediately, whereas minor adverse events are merely documented in the annual summary sent to the regulatory authority.

The sponsor collects AE reports from the local researchers, and notifies all participating sites of the AEs at the other sites, as well as both the local investigators' and the sponsors' judgment of the seriousness of the AEs. This process allows the sponsor and all the local investigators access to a set of data that might suggest potential problems with the study treatment while the study is still going on.

Types of adverse events
All clinical trials have the potential to produce AEs. AEs are classified as serious or minor; expected or unexpected; and study-related, possibly study-related, or not study-related.

For example, while a study that tests the effectiveness of a new blood pressure cuff for a period of 10 minutes might seem innocuous, the potential exists for the patient's skin to be irritated by the device. Patients in that study might also die during that 10 minute period. Both skin irritation and sudden death would be considered AEs. In this case the skin irritation would be classified as not serious, unexpected, and possibly study-related. The death would be classified as serious and unexpected (unless the patient was already at death's door). The local researcher would use his/her medical judgment to determine whether the death could have been related to the study device.

Both the skin irritation and the death are unexpected events, and should alert the researcher to the potential existence of a problem with the device (for instance, it could have malfunctioned and shocked the patient). The researcher would report these AEs to the local IRB and to the sponsor, and await direction on whether to stop the study. If the researcher feels there is an imminent danger posed by the device, he or she can use medical discretion to stop patients from participating in the study.

An adverse event can also be declared in the normal treatment of a patient which is suspected of being caused by a medical device used in the treatment of the patient.

Reporting of adverse events
Researchers participating in a clinical trial must report all adverse events to the Food and Drug Administration (FDA) or the relevant regulatory authority in the country where the drug or device is to be registered. Serious AEs must be reported immediately; minor AEs are 'bundled' by the sponsor and submitted later.

Database of adverse events
The FDA provides a database for reporting of adverse events call the Manufacturer and User Facility Device Experience Database. (MAUDE)[1] The data consists of voluntary reports since June 1993, user facility reports since 1991, distributor reports since 1993, and manufacturer reports since August 1996 and is open for public view.