Regulatory authorities in both Europe and the United States require medical device companies to report on some adverse events (AEs) that occur during clinical investigations.
Compliance with the ISO 14155:2020 Good Clinical Practices (GCP) standard also requires medical device companies to report AEs to the applicable authorities as required by law.
What is Adverse Event Reporting?
Adverse event reporting is a legally mandated process where clinical trial sponsors report to regulatory authorities on certain types of serious or unexpected adverse events that occur in medical device clinical investigations.
Importance of Adverse Event Reporting
Regulatory authorities, such as the FDA, have a mandate to protect public health by ensuring the safety and effectiveness of medical devices marketed in areas where they have jurisdiction.
They fulfill this mandate by enforcing laws that require medical device companies to demonstrate the safety and effectiveness of their products (through clinical investigations, post-market surveillance, quality management, and other activities) and by approving new medical devices before they go to market.
The adverse event reporting requirements for medical devices in clinical trials ensure that regulatory authorities are informed in a timely manner of serious or unexpected adverse events that could impact patient safety or the risk classification of the device.
In this way, adverse event reporting helps regulators make well-informed decisions about the safety and effectiveness of medical devices so they can protect the public. Adverse event reporting laws also allow regulators to hold medical device companies accountable for being transparent about adverse events that occur during clinical investigations.
Medical device adverse event reporting regulations: EU vs. US FDA
In the United States, Adverse event reporting requirements for medical device trials are codified under 21 CFR Part 812 Investigational Device Exemptions and enforced by the United States Food and Drug Administration (FDA).
In Europe, AE reporting requirements for medical device trials are codified under Article 80 of the EU MDR and enforced by the 27 member states of the EU.
Type of Adverse Events to be reported
In the United States, both clinical trial sponsors and investigators are required to keep records concerning adverse device effects, both anticipated and unanticipated, that occur during clinical investigations.
But only adverse events that are both serious and unexpected must be reported to regulatory authorities. These are known as Unanticipated Adverse Device Effects (UADEs).
In Europe, clinical trial sponsors must fully record all AEs identified in the clinical investigation plan (CIP) as being critical to the evaluation of results of the investigation, all serious adverse events, and any device deficiencies that could have triggered a serious adverse event if “appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate”.
However, clinical trial sponsors are only required to report the following kinds of adverse events:
- Any serious adverse event that has a causal relationship with the investigational device, the comparator, or the investigation procedure, or where such causal relationship is reasonably possible;
- Any device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate;
Adverse Events Reporting Timelines
In the United States, Clinical investigators must submit a report of any UADE to both the trial sponsor and reviewing IRB as soon as possible, but no later than 10 working days after the investigator first learns of the effect.
In Europe, Sponsors should report applicable AEs without delay once they have been identified to all Member States in which the clinical investigation is being conducted. The period for reporting should take account of the severity of the event.
Responsible person for reporting Adverse Events
In the United States, both clinical investigators and clinical trial sponsors have responsibilities when it comes to AE reporting. Investigators must report UADEs to sponsors and the reviewing IRB, while sponsors must evaluate UADEs and report on them to both the reviewing IRB and the FDA.
In Europe, clinical trial sponsors are responsible for compliant adverse event reporting. Clinical trial sponsors to keep records of adverse events and report on applicable AEs that occur during a clinical investigation. Sponsors must also implement and maintain a system to ensure that reportable events are promptly reported to them by clinical investigators.
How and where should Adverse Events be reported?
In the US, medical device companies must submit reports of individual adverse events to the FDA in an electronic format.
In Europe, the EU MDR established that the European Commission, in collaboration with Member States, would set up and maintain an electronic system that is EUDAMED for reporting on serious adverse events and device deficiencies observed in clinical trials. But for implementing the Clinical Investigations and performance studies reporting module of the system, the system is not fully functional. Instead, medical device companies should use the template provided in MDCG 2020-10/1 Rev 1 (Safety reporting in clinical investigations of medical devices under the Regulation (EU) 2017/745).
