Reporting serious adverse events (SAE) is integral to running a safe, compliant clinical development programme.
But for small to mid-sized biotechs and pharma companies — especially those working in rare diseases or oncology and running early-phase clinical trials — the operational reality of detecting, assessing and reporting SAEs can be complex.
Several factors make SAE management in rare disease and oncology studies especially challenging:
- Small patient populations. When you have tens — not thousands — of patients, every SAE can disproportionately influence safety perception and statistical signals. Distinguishing drug-related events from disease progression or comorbidity is harder.
- Complex causality. Oncology programmes and many rare diseases present overlapping serious events as part of the natural history (e.g. infections, organ dysfunction). That complicates causality assessments and increases sponsor workload to assemble supporting evidence.
- Heterogeneous investigator experience. Sites running rare-disease studies may be geographically dispersed; some clinicians are less experienced with trial reporting systems. That raises the risk of incomplete or delayed SAE capture.
- First-in-human clinical trial risks. In first-in-human or adaptive early-phase clinical trials, unexpected toxicities can emerge rapidly. You must have real-time safety review committees, stop rules and immediate reporting capability.
This blog explains your responsibilities for detecting, documenting, assessing and reporting serious adverse events and outlines practical steps you can take to remain compliant and inspection-ready, particularly during early-phase clinical trials.
What counts as a serious adverse event — the regulatory baseline
Regulators rely on the ICH definition of an SAE: events that result in death, are life-threatening, require or prolong inpatient hospitalisation, result in persistent/significant disability, cause congenital anomaly or are judged medically important.
Both investigators and sponsors must apply clinical judgment when deciding whether an event meets this threshold.
Regulatory frameworks add reporting duties: for example, fatal or life-threatening suspected adverse reactions normally trigger expedited reporting (e.g. 7 calendar days) and other unexpected serious reactions within a longer but still rapid timeframe (e.g. 15 calendar days). These timelines are embedded in FDA investigational new drug guidance and mirrored across EU and UK systems.
Timely, accurate classification at source is, therefore, essential and relies on a compliant pharmacovigilance system. Key components include:
- A documented governance structure and standard operating procedures (SOPs) that link clinical operations to safety review and regulatory submission teams.
- An appointed qualified person for pharmacovigilance (QPPV), or access to one, with the authority to oversee and certify the pharmacovigilance system. The QPPV is central to EU compliance; they are the accountable individual for the system and a touchpoint for regulators and should be embedded in SAE escalation pathways.
- A maintained pharmacovigilance system master file (PSMF) that documents PV structures, responsibilities and outsourced arrangements across the EU/UK footprint.
- Capability to assemble and submit the periodic safety update report (PSUR) and other aggregate reports on schedule.
These elements help ensure that you can move from alarm to action with confidence when an SAE occurs.
Sponsor pharmacovigilance responsibilities — step by step
Biotechs and pharma sponsors must ensure their pharmacovigilance system covers four linked activities:
1. Signal detection and capture
You are responsible for ensuring investigator sites are trained and equipped to identify serious adverse events. That starts with clear protocol language and site SOPs for immediate notification, and electronic systems that flag SAE reports in real time. In early-phase clinical trials, monitoring frequency and escalation triggers should be more conservative and tightly enforced.
2. Documentation and source verification
Every serious adverse event needs complete source documentation: onset, course, concomitant medications, lab values, imaging and the investigator’s causality opinion. This data underpins regulatory submissions and inspections. Maintain an auditable trail and ensure datasets are reconciled quickly.
3. Assessment/causality
You must review site inputs and perform your own assessment of expectedness and causality. That assessment informs whether an event is a suspected unexpected serious adverse reaction (SUSAR) and, therefore, reportable under expedited timelines. Document the rationale for your decision — your judgement may be scrutinised during inspection or safety committee reviews.
4. Serious adverse event reporting and follow-up
Expedited reporting pathways (EudraVigilance for the EU; MHRA for the UK) are mandatory for SUSARs. Follow-up information must be submitted promptly as new data arrives. You should also ensure the timely submission of periodic aggregate safety documents, such as the periodic safety update reports (PSURs), and maintain core documents like the pharmacovigilance system master file (PSMF). These documents demonstrate ongoing oversight of benefit-risk.
How an experienced partner and integrated pharma services can help
When complexity outstrips internal capacity, many biotechs and pharma companies prefer to outsource parts or all of safety operations rather than build a full in-house function for EU/UK coverage. Outsourcing can help to plug gaps quickly and keep your programme compliant and focused on patient safety.
Working with a partner that offers integrated pharma services — combining regulatory, clinical and safety services — reduces handoffs and keeps safety review tight across time zones. External support can range from single-case processing to full pharmacovigilance oversight, including QPPV services, PSMF maintenance, PSUR authoring and regulatory submissions.
TMC provides integrated pharma services — partnering with biotechs and pharma companies in Phase I–III to deliver early-phase clinical development solutions that help bring transformative therapies to patients faster. Our end-to-end clinical services span study design, trial execution, site management, data oversight and regulatory alignment — tailored to the unique demands of each molecule, modality and indication.
We specialise in early-phase clinical trials for rare disease, complex oncology and advanced therapeutic modalities, offering tailored support to meet the unique scientific, regulatory and operational demands of these next-generation therapies.
With a flexible and collaborative approach, our highly experienced teams integrate seamlessly with yours — combining responsiveness with full-service capabilities to ensure speed, precision and quality across your drug development programme as you move towards global regulatory approvals.
TMC can help you run your clinical trial safely and compliantly. Contact our team today at connect@tmcpharma.com to learn more about our integrated pharma services and specialist expertise in challenging, high-impact indications.