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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.
AE reporting is an essential aspect of conducting medical device clinical trials, but managing reporting requirements between separate legal jurisdictions can still prove challenging - especially for MedTech firms conducting clinical trials in both Europe and the USA.
In this blog post, we’re taking a deep dive into medical device adverse event reporting regulations and how they differ between Europe and the United States. You’ll find in-depth information about AE reporting and how it works in both jurisdictions, including:
What is AE reporting?
Why is AE reporting important?
What laws govern AE reporting in the US and Europe?
What kinds of AEs must be reported?
Who is responsible for reporting AEs?
How and Where should AEs be reported?
Article 2 of Regulation (EU) 2017/745 on medical devices, also known as the European Union Medical Device Regulations (EU MDR), defines an adverse event as:
“any untoward medical occurrence, unintended disease or injury or any untoward clinical signs, including an abnormal laboratory finding, in subjects, users or other persons, in the context of a clinical investigation, whether or not related to the investigational device”. -- EU MDR Article 2, paragraph 57.
In the US, adverse events are defined by the United States Food and Drug Administration (FDA) as:
“Any undesirable experience associated with the use of a medical product in a patient”. -- US FDA
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.
Regulatory authorities like 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. AE reporting laws also allow regulators to hold medical device companies accountable for being transparent about adverse events that occur during clinical investigations.
In the United States, AE 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.
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), defined as:
“any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects.” --21 CFR Part 812.3(s)
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;
Any new findings in relation to any event referred to in points (a) and (b).” -- EU MDR, Article 80, paragraph 2.
Adverse event reporting laws in the US establish specific requirements for when an applicable AE should be reported. They are found under 21 CFR Part 812.150:
Paragraph (a)(1 ) of this part requires clinical investigators to 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.
Paragraph (b)(1) of this part requires a clinical trial sponsor who conducts an evaluation of a UADE under 21 CFR Part 812.46 to report their results to both the FDA, all reviewing IRB’s, and all participating investigators within 10 working days after the sponsor first receives notice of the effect.
21 CFR Part 812.46 (b) requires clinical trial sponsors to immediately conduct an evaluation of any UADE, to terminate all investigations when a UADE is determined to present an unreasonable risk to subjects, and not to resume a terminated investigation without IRB and FDA approval.
A clinical investigation must be terminated no more than 5 days after determining unreasonable risk and no later than 15 days after the sponsor first receives notice of the UADE.
In Europe, Article 80 of the EU MDR says that 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.
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 under the EU MDR. Article 80 of the legislation requires 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.
In the US, medical device companies must submit reports of individual adverse events to the FDA in an electronic format, as per 21 CFR Parts 803.12 (a) and 803.20 - unless granted an exemption under Part 803.19.
In Europe, Article 73 of the EU MDR established that the European Commission, in collaboration with Member States, would set up and maintain an electronic system for reporting on serious adverse events and device deficiencies observed in clinical trials.
That system is EUDAMED, but as of this writing the Clinical Investigations and performance studies reporting module of the system has not been completed. 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).
The FDA does accept data from clinical investigations conducted outside the United States to support an IDE or device marketing application, but does not require clinical trial sponsors or investigators to report on AEs that happen during a European clinical trial.
Similarly, the European Commission only requires clinical trial sponsors to report on applicable AEs to the Competent Authorities in EU member states where the trial is taking place.
Medical device companies in Europe and the United States are required by law to report adverse events involving marketed devices.
In the US, the FDA MedWatch system acts as an online portal where device user facilities, importers, and manufacturers can submit both mandatory and voluntary reports on medical device adverse events.
In Europe, requirements for post-market vigilance reporting are codified under Articles 87-92 of the EU MDR. They require manufacturers to promptly report on serious incidents involving devices available on the EU market, as well as on field safety corrective actions taken in respect of devices available on the EU market.
We created a separate guide to help clinical sponsors comply with post-market follow-up requirements in Europe: The Practical Guide to Post-Market Clinical Follow-up EU MDR Compliance.
Greenlight Guru Clinical is a software Electronic Data Capture (EDC) system purpose-built for medical device clinical trials.
Along with the ability to securely create, customize, store, and share electronic case report forms (eCRF), Greenlight Guru Clinical delivers an Adverse Event Reporting Module that makes it easy for clinical investigators and trials sponsors to record and report AEs in compliance with legal frameworks in most countries around the world.
Our Adverse Event Reporting Module lets you create customized AE forms to fit your study using provided AE form templates or starting from scratch.
Talk to our sales team to schedule a free demo and learn more about using Greenlight Guru Clinical for your next clinical investigation.
Páll Jóhannesson, M.Sc. in Medical Market Access, is the founder and Managing Director of Greenlight Guru Clinical (formerly SMART-TRIAL). Páll was previously the CEO of Greenlight Guru Clinical where he led the team to create the only EDC specifically made for medical devices.