What Is a SUSAR in Clinical Trials?

Understanding the Implications of Serious Adverse Reactions

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Sometimes, during a clinical trial for a certain drug, a subject may experience serious adverse reactions. These reactions may or may not be dose-related, but they are not consistent with current information on the drug, so they are considered a "suspected unexpected serious adverse reaction," or SUSAR.

Reporting a SUSAR is an important aspect of clinical trials in drug testing or clinical care. As an example, you may see the term used in a news story like this: "Because the clinical trial subject had a serious seizure, investigators of the new drug had to file a SUSAR."

SUSAR reporting is an important part of clinical trials around the world, but the process and requirements for reporting one look different depending on where the trial is taking place.

Defining Adverse Reactions

The definition for an "adverse reaction" used by the International Conference on Harmonization (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, for example. According to the European Union, the following events constitute a "serious" adverse reaction:

  • Death
  • 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

SUSAR Reporting Requirements By Region

A SUSAR may occur during clinical trials or clinical care. Here are a few examples of reporting requirements and other regulations set forth by governing bodies:

  • The European Union: Reporting SUSARs is mandatory for clinical investigators in the EU. A report must be submitted to the national competent authority within 15 days of occurrence. In cases of death or life-threatening issues, the time frame shortens to seven days.
  • The United States: In the U.S., reporting adverse events during clinical trials is mandatory, but it is voluntary during clinical care. The U.S. FDA has a reporting system for serious adverse events (SAEs) called the Adverse Event Reporting System, or AERS (sometimes also referred to 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 any SUSARs that occurred inside or outside Canada while the drug is in clinical trials in Canada. These reports must be submitted within 15 days of the occurrence, and like in the EU, that time frame is shortened to seven days in cases of death or life-threatening issues. Within eight days of informing Health Canada of the SUSAR, another report must be submitted to Health Canada with an assessment of the importance and implication of any findings related to the SUSAR.

Efforts to Harmonize

These substantial international differences in regulations and reporting rules for SUSARs demonstrate how the processes are not fully harmonized. Different regions expect different amounts of information to be provided to investigators and regulators, and the time frames for fulfilling these obligations also vary.

The lack of harmonization between countries has been an area of concern for the ICH since at least the '90s.

Both the public and international pharmaceutical developers have vested interests in a more harmonized method of reporting SUSARs. For international pharmaceutical developers, for instance, there are operational and ethical reasons to harmonize. However, the process remains fragmented in 2020. There is still a long way to go in leveling the differences in methods and resources that makes reporting difficult.