What Is a SUSAR in Clinical Trials?
Understanding Serious Adverse Reaction in Trials
A suspected unexpected serious adverse reaction is known as a SUSAR. Sometimes during a clinical trial for a certain drug, a subject may experience serious adverse reactions that may or may not be dose-related but are unexpected, as they are not consistent with current information. Reporting a SUSAR is an important aspect of clinical trials in drug testing or clinical care. Here is an example of the way the term is used:
"Because the clinical trial subject had a serious seizure, investigators of the new drug had to file a SUSAR."
Why SUSAR Matters
A SUSAR may occur during clinical trials or clinical care and reporting varies by country or region depending on the regulations set forth by the governing bodies in each area.
- The European Union: Reporting of SUSAR is mandatory for clinical investigators in the European Union. A report must be submitted to the national competent authority within 15 days of occurrence (seven days in case of death or life-threatening issue).
- The United States: In the U.S., reporting of adverse events during clinical trials is mandatory, but during clinical care it is voluntary. The U.S. FDA has a reporting system for serious adverse events (SAEs) through the AERS (FDA Adverse Event Reporting System, also known as FAERS). During the reporting process and assessment, it is decided if the adverse event was unexpected. FDA regulations require reporting within 15 days for any reactions that are both serious and unexpected.
- Canada: Clinical trial sponsors in Canada are required to report SUSARs to Health Canada. Clinical trial sponsors, also known as applicants, must report within 15 days of occurrence (seven days in case of death or life-threatening issue) to Health Canada any SUSARs that occurred inside and outside Canada while the drug is in clinical trials in Canada. Within eight days of informing Health Canada of the SUSAR, a complete report which includes an assessment of the importance and implication of any findings must be submitted to Health Canada.
Lack of Harmonization
The substantial international differences in regulations on SUSARs and rules on reporting to regulatory agencies are not fully harmonized, as different regions have different expectations on the amount of information provided to investigators and regulators and in what time frame.
The lack of harmonization between countries has been under assessment by the International Conference on Harmonization (ICH) for at least half a decade.
The definition for "Adverse Reaction" used by ICH is "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."
An adverse reaction may be a response to nonactive ingredients of a drug and the following events constitute a "serious" adverse reaction, according to the EU:
- A life-threatening episode requiring immediate intervention
- An event resulting in hospitalization or that prolongs existing hospitalization
- Events resulting in persistent or significant incapacitation or disability
- A congenital anomaly or birth defect
- An episode that requires intervention to prevent the above and/or permanent impairment or damage
Even though both the public and international pharmaceutical developers have vested interests in a more harmonized method of reporting SUSARs (for international pharmaceutical developers, there are operational and ethical reasons to harmonize) there are is still a long way to go in leveling the differences in methods and resources that makes reporting difficult.