A serious adverse event (SAE) in human drug trials is defined as any untoward medical occurrence that at any dose
- results in death,
- is life-threatening
- requires inpatient hospitalization or causes prolongation of existing hospitalization
- results in persistent or significant disability/incapacity,
- may have caused a congenital anomaly/birth defect, or
- requires intervention to prevent permanent impairment or damage.
The term "life-threatening" in the definition of "serious" refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe. Adverse events are further defined as “Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.”
Investigators in human clinical trials are obligated to report these events in clinical study reports. Research suggests that these events are often inadequately reported in publicly available reports. Because of the lack of these data and uncertainty about methods for synthesising them, individuals conducting systematic reviews and meta-analyses of therapeutic interventions often unknowingly overemphasise health benefit. To balance the overemphasis on benefit, scholars have called for more complete reporting of harm from clinical trials.
Serious adverse reactions are serious adverse events judged to be related to drug therapy. A SUSAR (suspected unexpected serious adverse reaction) should be reported to a drug regulatory authority under an investigational license by using the CIOMS form (or in some countries an equivalent form). "Unexpected" means that for an authorised (approved) medicinal product that the event is not described in the product's labeling, or in the case of an investigational (unapproved) product that the event is not listed in the Investigator’s Brochure.
An adverse effect is an adverse event which is believed to be caused by a health intervention.
- Expert Working Group (Efficacy) of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). (August 25, 2007). "Guideline for Industry - Clinical safety data management: definitions and standards for expedited reporting" (PDF). FDA Center for Drug Evaluation and Research.
- Expert working group (efficacy) of the international conference on harmonization of technical requirements for registration of pharmaceuticals for human use (August 25, 2007). "Guideline for Industry Structure and Content of Clinical Study Reports" (PDF). FDA Center for Drug Evaluation and Research.
- Ioannidis JP, Lau J (2001). "Completeness of safety reporting in randomized trials: an evaluation of 7 medical areas". JAMA. 285 (4): 437–43. doi:10.1001/jama.285.4.437. PMID 11242428.
- Chou R, Helfand M (2005). "Challenges in systematic reviews that assess treatment harms". Ann Intern Med. 142 (12 Pt 2): 1090–0. doi:10.7326/0003-4819-142-12_part_2-200506211-00009. PMID 15968034.
- Ioannidis JP, Evans SJ, Gøtzsche PC, O'Neill RT, Altman DG, Schulz K, Moher D, CONSORT Group (2004). "Better reporting of harms in randomized trials: an extension of the CONSORT statement". Ann Intern Med. 141 (10): 781–8. doi:10.7326/0003-4819-141-10-200411160-00009. PMID 15545678.
- Adverse event, including mild/minor
- Clinical trial
- Good clinical practice (GCP)
- Data Monitoring Committees
- EudraVigilance (European Union)
- Directive 2001/20/EC (European Union)
- TGN1412, a drug that had SAEs in a clinical trial
- BIA 10-2474, a drug that had SAEs, including a fatality, in a clinical trial