Understanding SUSAR (Suspected Unexpected Serious Adverse Reaction) and its Reporting in Clinical Trials

In clinical trials and pharmacovigilance, monitoring and reporting adverse events are of utmost importance to ensure patient safety and the accurate evaluation of investigational drugs or medical interventions. Among the various types of adverse events, one crucial category is the SUSAR (Suspected Unexpected Serious Adverse Reaction). As a follow up to my last blog on TEAE/TRAE/SAE/SAR definitions, this article gives an overview of what SUSARs are, how they are identified, and the process of reporting them during clinical trials.

What is a SUSAR?

A SUSAR (Suspected Unexpected Serious Adverse Reaction) refers to an adverse event in a clinical trial that meets three specific criteria:

1. Suspected: The event is suspected to be caused by the investigational product, but its causal relationship has not been definitively established.

   
   

2. Unexpected: The event is not consistent with the known safety profile of the investigational product based on available data and information.

   
   

3. Serious: The event results in one or more of the following outcomes: death, life-threatening situations, hospitalization or prolongation of hospitalization, significant disability or impairment, or congenital anomaly/birth defect.

Identifying SUSARs:

During a clinical trial, investigators and sponsors carefully monitor all adverse events reported by trial participants. If an adverse event meets the criteria for seriousness, it is designated as a Serious Adverse Event (SAE). Next, the clinical trial data and safety monitoring board or safety committee assess whether the SAE is "related" and therefore an SAR and if it is "unexpected" based on the known safety profile of the investigational product.

An SAE determined to be an SAR, or Serious Adverse Reaction, is a serious unexpected event that may be related to the investigational medicinal product (IMP). The term "unexpected" refers to the fact that the event was not previously observed in clinical trials or known to be associated with the IMP from other sources.

If the SAE is deemed "unexpected," meaning it is not consistent with the known safety information, it is classified as a SUSAR. This determination is made through a rigorous process of reviewing available data from the trial and other relevant sources such as the Reference Safety Information in the Investigator's Brochure.

Reference Safety Information:

The Reference Safety Information (RSI) is a document that provides information about the known safety profile of an investigational medicinal product (IMP). It is used by sponsors and investigators to assess the expectedness of serious adverse reactions (SARs) that occur in clinical trials.

The RSI includes information about the following:

• The known safety profile of the IMP, including the frequency, severity, and reversibility of adverse reactions.
• The expectedness of SARs, based on the known safety profile of the IMP and the patient population being studied.
• The reporting criteria for SUSARs, including the severity, timing, and causality of the adverse reaction.

The RSI is used to determine whether a SAR is unexpected and therefore warrants reporting as a SUSAR. If the SAR is not included in the RSI, or if it is included in the RSI but is considered unexpected, then it must be reported as a SUSAR.

SUSAR reporting is an important part of the safety monitoring of clinical trials. By reporting SUSARs, sponsors and investigators can help to identify and mitigate risks to patients.

Reporting SUSARs:

The reporting of SUSARs is subject to strict timelines and regulations to ensure timely evaluation and response to potential safety concerns. Reporting requirements for SUSARs are outlined in international guidelines and regulations, such as the International Council for Harmonisation (ICH) guidelines for Good Clinical Practice (GCP) and the European Medicines Agency (EMA) regulations.

Key steps in reporting SUSARs include:

Expedited Reporting: Once identified, SUSARs must be reported to the relevant regulatory authorities and ethics committees within specific timelines, typically within 7 to 15 days, depending on the severity of the event.

• Fatal or Life-threatening SUSARs need to be reported within 7 calendar days
• All other SUSARs need to be reported within 15 calendar days

1. Investigator and Sponsor Responsibilities: Investigators and sponsors collaborate in the reporting process. The investigator provides initial information, while the sponsor ensures all relevant details are included in the report.

   
   

2. Causality Assessment: The sponsor conducts a thorough causality assessment to determine the likelihood of the investigational product's involvement in the adverse event.

   
   

3. Follow-up Reporting: Follow-up reports may be required to provide additional information and updates on the SUSAR to regulatory authorities and ethics committees.

Conclusion:

SUSARs play a critical role in ensuring the safety and integrity of clinical trials. By identifying and reporting suspected unexpected serious adverse reactions promptly, investigators and sponsors can take necessary actions to protect trial participants and make well-informed decisions about the investigational product's safety profile. Adhering to stringent reporting timelines and regulatory requirements helps maintain transparency and accountability throughout the clinical trial process, ultimately contributing to the development of safe and effective medical interventions for patients in need.