Clinical trials are important. The discovery of any new medical treatments is a standard step for testing the device on human subjects in a safe, controlled environment where the results and process can be studied extensively.
Although it’s a test, it is done on humans. So this step is also done after the device is proven relatively safe for use. Additionally, while the major purpose of clinical research is to determine whether the treatment works as it should, it’s also to find out what could go wrong in clinical settings.
Since clinical trials are test runs, Adverse events (AEs) can and do occur every so often. Correctly reporting such events in the regulatory context is just as important as recording the trials themselves.
However, different countries have some differences regarding how to report them. This blog article will discuss the adverse event reporting systems in the United Kingdom, France, Germany, and Switzerland.
The basic goal of adverse event reporting is to discover and document any undesirable consequences associated with the use of investigational medications and medical devices in clinical trials. So, regardless of how the study is funded, the clinician must record any adverse event. The best way to do this is to keep a detailed list of where data analysis and statistical analysis can be conducted if required.
Clinical trials are usually overseen by the Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom. They require clinicians and clinical trial sponsors to promptly report any adverse events (AEs) that occur during clinical studies.
The reports usually should contain the following:
- Name of study and patient details, including treatment duration
- Details of the Adverse Event
- Severity, Expectedness, Relatedness, Intensity, Casualty, Frequency etc.
- A detailed explanation of the actions performed
- Result (ongoing/resolved)
- Study protocol
- Safety reference documents
Regarding serious adverse events or SAE, the standard is to report the incident within 24 hours of detection. The time limit is important to adhere to, even during the holidays or weekends. If a serious adverse event is realized on a Friday, it should be reported within Saturday, with no exceptions.
It should also have all the clinical trial data available at the moment.
The reports are submitted to national competent authorities, who then evaluate and assess them to guarantee patient safety. The ethics committees could also be notified based on the severity and type of adverse event. One can also contact the Clinical Trial Unit of MHRA directly to discuss any issue within 24 hours of the AE reporting.
Some studies do not require MHRA reporting. The adverse events should be recorded in the patient file in those cases.
In France, the French Agency for the Safety of Health Products (ANSM) ensures the safety of clinical trials. The ANSM requires Reference Safety Information and possible adverse events to be updated yearly.
Apart from this, according to French clinical trial regulations, the clinician (or investigator) should document all adverse events in detail as they happen and report them according to the study protocol. All serious adverse events have to be reported to the sponsor within 24 hours (like the UK). After the trial ends, the clinician should also report any suspected casualty related to the trial results. The investigator should also conduct a risk-benefit ratio to weigh the AEs against the benefits of the treatment.
Sponsors must report any suspected unexpected serious adverse reactions (SUSARs) to the European database. Fatal or life-threatening adverse event
s or SUSARs should be reported within seven calendar days, and non-fatal SUSARs should be reported within 15 days. Sponsors also need to submit an annual report to the national competent authority.
Swissmedic is at the top of the Swiss regulatory authorities that oversee clinical trials. Healthcare professionals must report any AE to the sponsor within 24 hours. It is important to note that this reporting is mandatory “even if they are not necessarily in a direct causal relationship with the treatment.”
Regarding suspected unexpected serious adverse reactions, the Swiss regulatory directive is that the sponsor should report all SUSARs to the agency within a certain time frame. Like the UK, an assessment of the situation based on the severity, relation, and unexpectedness of the adverse event, along with all details of the event and trial available, should be submitted.
The AEs can be reported in the annual safety reports if the clinical trial is not conducted within Switzerland. Similar to other countries, the risk-benefit ratio is also expected to be reassessed.
Germany has the Federal Institute for Drugs and Medical Devices (BfArM) as a clinical trials regulation authority. They provide those conducting clinical trials with an SAE / DD individual notification form for reporting serious adverse events.
Like other European countries, Germany requires immediate reporting of adverse events with risk of death or serious injuries. The deadline in Germany is within two calendar days of being aware of the event. For other reportable adverse events, as mentioned in MDR article 80, it follows a timeline of 7 seven days for reporting. Both timelines apply to any new/relevant information sharing, too.
All reportable Serious Adverse Events should also be included in the quarterly report.
Fortunately, the above-mentioned regulations will not apply to medical device clinical trials for long. When it is up and running, EUDAMED is expected to be the central repository for information on medical devices available on the EU market. This would provide for a more streamlined approach and centralized access to safety information, which will help the European authorities identify and respond to possible issues faster and more efficiently.
However, the development of EUDAMED is still under process. Until then, European Union countries will have to make do with the current regulation for ongoing trials.
Overall, the reporting criteria for adverse occurrences in the United Kingdom, France, Germany, Switzerland, and other EU member states are very comparable. They all have reporting requirements for SAEs and SUSARs, and they also evaluate adverse event reports with a focus on patient safety.
While there may be some discrepancies in the types of events reported due to sample sizes and experimental treatments, adverse event reporting is required for patient safety and helps maintain the benefit-risk analysis of clinical trials.
Adverse event reporting provides a fail-safe mechanism for catching and preventing adverse events, eventually leading to modifications in treatment regimens and assisting regulators in assessing whether a medicine or device is safe for human use. It’s a serious issue with both legal and clinical consequences.
For additional reading:
- Safety measures in clinical trials (swissmedic.ch)
- BfArM – SAE and DD reporting for clinical investigations