Synonyms: SUSAR, suspected unexpected serious adverse reaction
Definition: A SUSAR is a suspected (causality-suspected) medicinal product reaction in a clinical trial that is both serious and unexpected in relation to the reference safety information (e.g., Investigator’s Brochure or SmPC) and is therefore subject to expedited safety reporting.
Components of the definition: suspected, unexpected, serious
Suspected means that a relationship to the investigational medicinal product appears at least possible (e.g., “related” or “possibly related”). Unexpected means that the nature or severity is not consistent with the reference safety information. Serious refers to criteria such as death, life-threatening events, inpatient hospitalization/prolongation, persistent disability, congenital anomalies, or other medically important events.
Why are SUSARs regulatorily relevant?
SUSARs are signals of new, potentially serious risks. Authorities and ethics committees therefore expect rapid reporting so that protective measures (e.g., protocol amendments, updating informed consent, study interruption) can be assessed. A consistent reporting process is a core component of safety management in clinical trials.
Reporting pathways and typical timelines
In many regulatory frameworks, expedited timelines apply, e.g., 7 days for fatal or life-threatening SUSARs (with follow-up submission of additional information) and 15 days for other SUSARs. Implementation is handled via systems such as EudraVigilance/CTIS or national reporting pathways, depending on the region and study design.
Practical implementation in safety management
Classification typically follows a defined workflow: recording the event as an AE/SAE, medical assessment, causality assessment, assessment of expectedness against the reference safety information, and preparation and submission of an expedited report. Clear responsibilities between sponsor, CRO, and site, as well as robust documentation of the decision rationale, are essential.
In quality management, a clear trace between specification, method, result, and release decision has proven effective. This enables rapid assessment, in the event of deviations, of whether there is a risk to patient safety, efficacy, or data interpretation and which CAPA measures are required.
Interfaces are also relevant: when multiple parties are involved (e.g., sponsor, manufacturer, contract laboratory), responsibilities, test plans, data formats, and review steps should be aligned contractually and procedurally. This reduces the risk of inconsistent assessments.
Data integrity principles (ALCOA+) also play a role in the preparation and review of such documents: data should be attributable, legible, contemporaneous, original, and accurate. This helps to investigate deviations in a traceable manner and to ensure traceability across the lifecycle of a product or study.
Practical note: For documentation and reporting in regulated environments, definitions, roles (sponsor, CRO, site), and timelines should be clearly defined in SOPs. Consistent application improves data comparability and reduces follow-up questions during audits and inspections.
For quality assurance, it is also important that the underlying source data (e.g., raw laboratory data, medical findings, time reference, dose information) are available in a traceable manner. Summary documents are helpful, but they do not replace complete data integrity and controlled document management.
In practice, many errors arise from inconsistent use of terminology or unclear delineations. A brief definition check (What is the trigger? Which criteria apply? Who makes the final decision?) helps to stabilize processes and simplify internal communication.
If specifications, reference information, or reporting pathways change during a project, these changes should be version-controlled and communicated. This ensures it is traceable which rules applied at which time and how decisions were justified.
In quality management, a clear trace between specification, method, result, and release decision has proven effective. This enables rapid assessment, in the event of deviations, of whether there is a risk to patient safety, efficacy, or data interpretation and which CAPA measures are required.
Interfaces are also relevant: when multiple parties are involved (e.g., sponsor, manufacturer, contract laboratory), responsibilities, test plans, data formats, and review steps should be aligned contractually and procedurally. This reduces the risk of inconsistent assessments.
Data integrity principles (ALCOA+) also play a role in the preparation and review of such documents: data should be attributable, legible, contemporaneous, original, and accurate. This helps to investigate deviations in a traceable manner and to ensure traceability across the lifecycle of a product or study.
Practical note: For documentation and reporting in regulated environments, definitions, roles (sponsor, CRO, site), and timelines should be clearly defined in SOPs. Consistent application improves data comparability and reduces follow-up questions during audits and inspections.
For quality assurance, it is also important that the underlying source data (e.g., raw laboratory data, medical findings, time reference, dose information) are available in a traceable manner. Summary documents are helpful, but they do not replace complete data integrity and controlled document management.
In practice, many errors arise from inconsistent use of terminology or unclear delineations. A brief definition check (What is the trigger? Which criteria apply? Who makes the final decision?) helps to stabilize processes and simplify internal communication.
If specifications, reference information, or reporting pathways change during a project, these changes should be version-controlled and communicated. This ensures it is traceable which rules applied at which time and how decisions were justified.
FAQ
Is every SAE automatically a SUSAR?
No. A SUSAR is only present if, in addition to seriousness, there is both a suspicion of causality and the event is unexpected in nature/severity.
What is “unexpectedness” assessed against?
Against the reference safety information (RSI), typically the Investigator’s Brochure (for IMPs) or the SmPC/label information (for authorized medicinal products in certain setups).
Who decides whether a case is a SUSAR?
The sponsor (often via the medical monitor/pharmacovigilance) makes the final assessment, usually based on information from the investigator and, if necessary, follow-up queries.
Which information is important for reporting?
At a minimum: an identifiable patient, an identifiable reporter, a suspected medicinal product, and a described event. In addition, the time course, dose, concomitant medication, and relevant findings are helpful.
Sources
- ICH E6(R2): Good Clinical Practice – section on safety reporting / AE/SAE (R2 Addendum). https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf
- EMA: Clinical safety data management: definitions and standards for expedited reporting (ICH E2A). https://www.ema.europa.eu/en/ich-e2a-clinical-safety-data-management-definitions-standards-expedited-reporting
- EU CTR/CTIS overview (EU 536/2014): safety reporting in the clinical trial context. https://health.ec.europa.eu/medicinal-products/clinical-trials/clinical-trials-regulation-eu-no-5362014_en
For sponsors and sites, it is also important that coding (e.g., MedDRA), the assessment of expectedness (Investigator’s Brochure/SmPC), and timelines (e.g., 7/15 days for SUSAR) are clearly described in the Safety Management Plan. This reduces follow-up questions from authorities and improves data quality.