Serious Adverse Events (SAE) vs Severe Adverse Events

Professionals who are new to the clinical trial field are often confused with the concept of 'Serious Adverse Events (SAEs)' and 'Severe Adverse Events". Severity is not synonymous with seriousness. SAE is based on patient/event outcome or action criteria usually associated with events that pose a threat to a patient's life or functioning. Seriousness (not severity) serves as a guide for defining regulatory reporting obligations. In other words, the SAEs need to be filfill additional reporting process (reported to corporate global drug safety group or pharmacovigilence group, regulatory authorities, EC/IRBs). Severe AE is one class of AEs with severity (old term intensity) classified as 'severe'. Severe AE is one of the AE classifications – AE severity (other classifications are relationships/causality).

The FDA defines a serious adverse event (SAE) as one when the patient outcome is one of the following:

• Death
• Life-threatening
• Hospitalization (initial or prolonged)
• Disability - significant, persistent, or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities or quality of life.
• Congenital anomaly
• Requires intervention to prevent permanent impairment or damage

On the other hand, Severity of an AE is a point on an arbitrary scale of intensity of the adverse event in question. The terms "severe" and "serious" when applied to adverse events are technically very different. They are easily confused but can not be used interchangeably, require care in usage.

 

A headache is severe, if it causes intense pain. There are scales like "visual analog scale" that help us assess the severity. On the other hand, a headache is not usually serious (but may be in case of subarachnoid haemorrhage, subdural bleed, even a migraine may temporally fit criteria), unless it also satisfies the criteria for seriousness listed above. Similarly, a severe rash is not likely to be an SAE. However, mild chest pain may result in a day’s hospitalization and thus is an SAE.

 

Classifications of the AE sevirity often include the following:

• Mild: Awareness of signs or symptoms, but easily tolerated and are of minor irritant type causing no loss of time from normal activities. Symptoms do not require therapy or a medical evaluation; signs and symptoms are transient.
• Moderate: Events introduce a low level of inconvenience or concern to the participant and may interfere with daily activities, but are usually improved by simple therapeutic measures; moderate experiences may cause some interference with functioning
• Severe: Events interrupt the participant’s normal daily activities and generally require systemic drug therapy or other treatment; they are usually incapacitating

The guidelines for AE severity assessment is based on:

• Common Terminology Criteria for Adverse Events (CTCAE) CTC criteria, 4.03)
• It is also available as iPhone App. Here is the link.
• Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials

Other sources about this topic may be useful:

• Wikipedia
• HHS The Office for Human Research Protections (OHRP): Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events
• NIH National Institute of Aging: Adverse Event and Serious Adverse Event Guidelines