Introduction
Participant safety is the cornerstone of all clinical research. Timely identification and reporting of adverse events, particularly serious adverse events (SAEs), are critical to ensuring compliance with regulatory standards and protecting trial participants. This guide provides a clear overview of SAE reporting requirements for both drug trials and medical device trials in the European Union (EU), with special focus on practices in the Netherlands. Since terminology, regulations, and reporting procedures differ between drug and device trials, this article breaks down these differences to help sponsors, investigators, and ethics committees navigate the process efficiently.
SAE Reporting in Drug Trials
Overview
In drug clinical trials, the main focus is on Suspected Unexpected Serious Adverse Reactions (SUSARs), which are serious events that are unexpected and likely related to the investigational medicinal product. Regulatory oversight is governed primarily by the EU Clinical Trials Regulation (CTR) No 536/2014 and the ICH-GCP E6(R2) guidelines.
Responsibilities
- Investigators: Promptly report all serious adverse events (SAEs) to the sponsor, regardless of causal relationship. Notify the Medical Ethics Review Committee (METC) only if urgent safety interventions or protocol/consent form amendments are needed.
- Sponsors: Assess each SAE for causality and expectedness. Report SUSARs to EudraVigilance, the national competent authority (CCMO in the Netherlands), and all participating investigators.
- METCs: Review SAEs that signal new or increased risk, possibly requiring protocol adjustments.
Reporting Timelines
- Urgent safety measures: immediate reporting, possibly before METC approval
- SUSARs: report without undue delay (typically within 10 working days)
- Annual Safety Report (ASR): submitted once per year
SAE Reporting in Medical Device Trials
Overview
For medical device trials, the emphasis is on Serious Adverse Device Effects (SADEs), which include serious incidents related to device performance or malfunction. The EU Medical Device Regulation (MDR) 2017/745 governs these trials, enforced at the national level by authorities such as the Dutch Health and Youth Care Inspectorate (IGJ).
Responsibilities
- Investigators: Report SADEs immediately to the sponsor and inform METCs if urgent safety actions or protocol changes are necessary.
- Sponsors: Conduct causality and risk assessments specific to the device. Report SADEs to the competent authority (e.g., IGJ) and the METC.
- METCs: Review SADE reports indicating new or increased safety risks and advise on trial modifications.
Reporting Timelines
- Urgent safety issues: immediate notification
- Unanticipated SADEs: reported promptly (typically within 10 working days)
- Annual safety updates documenting cumulative safety information
Decision Tree for METC Notification
- Is the event serious? → Yes
- Is it unexpected? → Yes
- Is it related to the investigational product or device? → Yes
- Does it present increased risk? → Yes → Notify METC
- Are protocol or consent changes required? → Yes → Notify METC
- Otherwise → Report to sponsor only
Best Practices for Compliance
- Develop clear SOPs to define SAE/SADE reporting responsibilities.
- Provide ongoing training on identification and documentation of adverse events.
- Engage proactively with METCs, especially for multi-site or international studies.
- Maintain detailed records supporting all safety communications.
Keywords: SAE reporting Netherlands, SUSAR reporting EU, Serious Adverse Device Effects, clinical trial safety, METC adverse event reporting, Dutch clinical trial regulations, medical device trial compliance, CCMO safety guidelines, EudraVigilance, CTR 536/2014, MDR 2017/745, investigator responsibilities, sponsor responsibilities.
References
- European Commission. (2014). Regulation (EU) No 536/2014 on Clinical Trials on Medicinal Products for Human Use. https://health.ec.europa.eu/system/files/2021-09/regulation536_2014_en_0.pdf
- European Parliament & Council. (2017). Regulation (EU) 2017/745 on Medical Devices. https://eur-lex.europa.eu/eli/reg/2017/745/oj
- Central Committee on Research Involving Human Subjects (CCMO). (n.d.). Safety Reporting Guidelines – Netherlands. https://english.ccmo.nl/investigators/review-procedure-for-medical-scientific-research/safety-reporting
- European Medicines Agency (EMA). (n.d.). EudraVigilance – Adverse Drug Reaction Database. https://www.ema.europa.eu/en/human-regulatory/research-development/pharmacovigilance/eudravigilance
- International Council for Harmonisation (ICH). (2016). E6(R2) Good Clinical Practice Guideline. https://www.ich.org/page/efficacy-guidelines
How Lex Clinical Can Help
At Lex Clinical, we specialize in guiding sponsors, CROs, and research teams through the complexities of SAE and SADE reporting across drug and medical device trials in the Netherlands and EU. We offer:
- Customized SAE and SUSAR reporting systems for drug trials and SADE frameworks for device trials.
- Training programs on GCP and MDR-compliant safety practices.
- Representation and liaison with Dutch regulatory bodies such as CCMO and IGJ.
- Review and drafting of essential safety documents including DSURs, ASRs, and SUSAR narratives.
- Auditing and optimization of safety reporting workflows.
Looking for tailored support to ensure your clinical trial complies fully with regulatory safety reporting? Let’s connect and discuss your project.