Whilst clinical trials are generally safe, serious adverse events (SAEs) can occur. An SAE is defined as any untoward medical occurrence that results in death or persistent or significant disability or incapacity, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, or is a congenital anomaly or congenital disability.
SAEs are considered to be events that are not necessarily related to the investigational product being studied but that occur during the clinical trial and may require medical intervention to prevent one of the outcomes listed above.
How SAE’s are determined
To ensure the safety of study participants, sponsors of clinical trials have specific safety monitoring procedures in place to identify and assess any adverse events that may occur.
Clinical trial sponsors develop these procedures in consultation with the study investigators and the regulatory authorities overseeing the trial. The clinical trial sponsor is typically a pharmaceutical company, biotechnology company, or other organisation responsible for developing and testing the investigational product being studied in the clinical trial.
To determine whether an event is an SAE, the study investigator, sponsor, or regulatory authority will consider the following information:
- The outcome of the event: Did the event result in death, hospitalisation, disability, or another significant effect?
- The event’s severity: Was the event severe enough to require medical intervention or to significantly impact the participant’s daily activities or quality of life?
- The timing of the event: Did the event occur during the clinical trial or after the trial ended?
- The event’s causality: Is it likely that the event was caused by the investigational product being studied in the clinical trial?
- The expectedness of the event: Is it expected or unexpected?
Clinical trial sponsors often use a Safety Reporting Assessment Flowchart outlined by the National Health and Medical Research Council to assist in determining SAEs. This is a tool that helps to standardise the process of identifying and reporting SAEs. The flowchart includes a series of questions that help determine whether an adverse event is serious and provides guidance on reporting the event to the appropriate regulatory authorities and other relevant parties.
What happens when a SAE is reported during a clinical trial?
When a serious adverse event is reported during a clinical trial, the priority is to ensure the safety of the study participants. The response to a SAE will depend on the event’s specific circumstances and severity.
One possibility is that the clinical trial may need to be modified in some way to address the SAE. For example, the investigators may need to change the dosing regimen or modify the inclusion or exclusion criteria for the study. The clinical trial sponsor may also need to provide additional information or documentation to the regulatory authorities overseeing the trial.
A temporary halt or “partial clinical hold” may sometimes be necessary if the SAE requires further investigation. This may involve temporarily stopping the enrollment of new participants in the study or suspending treatment with the investigational product until the issue has been resolved.
If the risks of continuing the clinical trial outweigh the potential benefits, the trial may be terminated early. The regulatory authorities overseeing the trial would typically make this decision in consultation with the study investigators and the trial’s sponsor.
In cases where an SAE poses an immediate threat to the safety of study participants, urgent safety measures (USM) may be implemented. These measures may include informing study participants and their treating clinicians about the SAE and any potential risks, suspending treatment with the investigational product or enrolling participants in an alternative treatment option.
How does reporting serious adverse events help ensure the safety of participants in clinical trials?
Reporting SAEs helps to identify potential risks to study participants and allows for timely interventions to be put in place to mitigate those risks. When a SAE is reported, the clinical trial’s sponsor and the regulatory authorities overseeing the trial can evaluate the event and determine the appropriate response.
In addition, reporting SAEs helps to provide a comprehensive understanding of the safety profile of the investigational product being studied in the clinical trial. This information is vital for determining the product’s potential benefits and risks and informing decisions about its use in clinical practice.
What White Coats Foundation does
If you want to learn more about clinical trials, check out our variety of resources including a blog post specifically about clinical trials and other clinical trial-related blog posts. These resources can help you better understand clinical trials and the role of consumer and community involvement in research.
While White Coats Foundation aims to provide access to reliable information to help guide you in understanding clinical trials, please note that our blogs are only informational. They are not meant to replace your doctor’s medical advice. Should you wish to participate in a clinical trial, please consult with a healthcare professional.