How to report side effects during a clinical trial

What counts as an adverse event during a clinical trial?

An adverse event (AE) is any unfavourable and unintended sign, symptom, abnormal laboratory result or disease that occurs during a trial. This is true regardless of whether the event is thought to be linked to the treatment being tested, since the definition covers anything unusual observed in a participant after they have joined the study. This means a headache, a change in blood test results, or a cold you catch while enrolled can all qualify as an adverse event, even if it turns out to have nothing to do with the study treatment^[1]. This broad definition is deliberate: trial safety systems are designed to capture everything unusual first, and to work out causality afterwards, rather than filtering events at the point they are noticed^[2]. Regulators favour this "capture everything first" approach precisely because it avoids relying on a participant's or clinician's initial guess about causality, a guess that is often wrong at the moment a symptom first appears and only becomes clearer once more data accumulate^[3].

An adverse reaction (AR) is an adverse event that is judged to be causally related to the investigational medicinal product (IMP) being studied. Every adverse event you report is logged on a case report form and in your medical notes, unless the trial protocol specifies otherwise^[1]. This distinction between an event and a reaction matters because it determines how quickly, and to whom, the information must be escalated once it has been recorded^[2]. In practice, this means the same headache can end up handled very differently depending on the assessment: logged quietly as background noise in one case, or triggering a formal causality review and onward reporting in another^[1].

How is the severity of an adverse event classified?

A serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, hospitalisation or prolongation of existing hospitalisation, persistent or significant disability or incapacity, or a congenital anomaly or birth defect. A suspected serious adverse reaction (SSAR) is an adverse reaction that is consistent with the known information about the investigational medicinal product. A suspected unexpected serious adverse reaction (SUSAR) is a reaction suspected to be caused by the investigational medicinal product but which is not consistent with existing information about that product. SUSARs are the most serious category and are subject to fast-track, expedited reporting^[1]. The rationale for treating SUSARs differently from other categories is that an unexpected serious reaction may signal a previously unrecognised risk of the medicine. Regulators and sponsors therefore need to be alerted quickly enough to protect other participants still in the trial. Because the fast-track requirement exists specifically for the unexpected category, sponsors must keep the reference safety information for each product up to date; without an accurate picture of what is already known, it becomes impossible to judge reliably whether a new reaction is genuinely unexpected^[3].

Term	What it means	Linked to the study treatment?
Adverse event (AE)	Any unfavourable, unintended sign, symptom or abnormal result	Not necessarily[1]
Adverse reaction (AR)	An adverse event judged to be caused by the investigational medicinal product	Yes[1]
Serious adverse event (SAE)	Results in death, hospitalisation, persistent disability or a birth defect, at any dose	Not necessarily[1]
Suspected serious adverse reaction (SSAR)	A serious reaction consistent with known information about the product	Yes[1]
Suspected unexpected serious adverse reaction (SUSAR)	A serious reaction not consistent with known information about the product	Yes, and unexpected[1]

Who should you contact first if you notice a new symptom?

If you experience a new symptom, a worsening symptom, or an unusual laboratory result while taking part in a trial, the first point of contact is your study team — the investigator or research nurse named in your trial documents, not the general public reporting channel. The chief investigator holds specialist knowledge of the disease area and the medicinal product being tested, and is responsible for assessing whether an event is related to the treatment and whether it was expected^[4]. This assessment is not a formality: it is the step that decides whether your symptom stays as a routine entry in your notes or triggers an urgent safety procedure involving the sponsor and, in some cases, a regulator^[2]. Because this judgement carries real consequences for the running of the trial, it is generally made by the investigator or a delegated clinician rather than left to a research assistant or administrative member of the team^[4].

Your informed consent documents and patient information sheet should list a direct contact number for the study team; keep this number accessible for the whole duration of your participation, not just at enrolment. Many trial sites also provide an out-of-hours contact or an on-call arrangement, precisely because side effects rarely wait for office hours. It is worth confirming at your first visit exactly who answers the phone at night or at weekends^[4].

What information should you give when you report a side effect?

When you contact the study team, be ready to describe what happened, when it started, how severe it feels, and whether it has changed since it began^[1]. Precise, consistent descriptions matter because the way symptoms are elicited and recorded directly affects how reliably adverse effects can be detected and compared across a trial. Research into how trials collect this information has found that the method used to ask participants about symptoms — a structured checklist versus an open question, for instance — can itself change how many and which side effects are reported. This is one reason your study team may ask you the same questions in a fairly standard way at each visit. The same body of research also notes that under-reporting is a persistent risk when questioning is too open-ended or infrequent, which is part of why many trials now build structured, symptom-specific questions into every scheduled contact rather than relying on participants to volunteer problems unprompted^[5].

• What happened — the exact symptom, sign or abnormal result you noticed;
• When it started — date and, if possible, time of onset;
• What you were doing at the time — for example, shortly after a dose, after stopping the study drug, or after a dose change;
• How it has progressed — better, worse, or unchanged since it began;
• Any action you already took — for example, whether you went to a pharmacist, GP or emergency department.

Side effects can appear when you start a new medicine, stop one you have been taking, or change its dose, so tell the study team about any of these changes even if you are not sure they are connected to your symptom. It is also useful to mention any over-the-counter medicines, supplements or herbal products you have started or stopped, since these can interact with a study medicine in ways that are easy to overlook when you are focused on describing the symptom itself^[6].

What happens after you report an adverse event to the study team?

Once you report a symptom, the investigator records it on a case report form and in your medical notes, and assesses whether it is serious and whether it appears related to the study treatment. If the event meets the criteria for a serious adverse event, it must be reported to the trial sponsor immediately^[1]. The sponsor, in turn, has its own legal duty to review the report, decide whether it changes the known risk profile of the medicine, and pass that assessment on through the appropriate regulatory channel within a fixed timeframe. This chain — investigator to sponsor to regulator — is designed so that no single person's judgement is the only safeguard, and each step adds a further layer of review before any wider decision about the trial is made^[2].

For trials authorised under the EU Clinical Trials Regulation, the sponsor reports suspected unexpected serious adverse reactions to EudraVigilance, and reports other unexpected events that affect the overall balance of benefits and risks of the trial through the Clinical Trials Information System (CTIS). Sponsors also compile annual safety reports summarising safety information for each investigational medicinal product used in the trial. As a participant, you generally will not need to interact with these systems yourself. Your role is limited to reporting your symptom accurately and promptly to your study team, while the administrative and regulatory reporting is handled behind the scenes by the sponsor and investigator^[3].

If the study team, or an independent data monitoring committee overseeing the trial, identifies a safety concern that could seriously affect the balance of benefits and risks, urgent safety measures may be taken to protect participants, which can include a temporary change to the trial procedures or your treatment^[3]. If such a measure affects you, the study team should explain what has changed and why, and this explanation, together with any updated consent process, should be documented in your trial record as clearly as the original adverse event. Documenting this explanation is not just administrative housekeeping; it also gives you a clear paper trail to refer back to if you have further questions about the change later in the trial^[2].

When is a side effect serious enough to need urgent action?

A side effect is considered serious if it results in death, is life-threatening, requires or prolongs hospitalisation, causes disability or permanent damage, or — for pregnancy exposure — causes a birth defect^[6]. Any symptom that fits one of these descriptions needs to be reported to your study team the same day. If you cannot reach them, you should seek emergency medical care and mention that you are taking part in a clinical trial^[1].

• Life-threatening symptoms — chest pain, severe difficulty breathing, sudden severe allergic reaction — call emergency services first, then inform the study team as soon as possible;
• Hospitalisation or its prolongation — report to the study team as soon as you are able, and mention your trial participation to the treating hospital team;
• New disability or persistent incapacity — report promptly even if the connection to the study treatment is unclear;
• Non-serious but new or worsening symptoms — report at your next scheduled contact with the study team, or sooner if the symptom is troubling you^[6].

Whenever you receive emergency or hospital care while enrolled in a trial, tell the treating clinicians which study you are part of and share the contact details of your study team, so the two can coordinate your care and reporting. This is particularly important because emergency clinicians who are not part of the trial may not otherwise know that a symptom could be related to an investigational medicine, and that knowledge can change both your immediate treatment and the trial's safety record. Carrying a card or note with the trial name, sponsor and study team contact details, alongside your usual identification, makes it far easier for unfamiliar clinicians to act on this information quickly in an emergency^[4].

Can you report a suspected side effect yourself, outside the trial team?

Alongside reporting to your study team, you can also report a suspected side effect of a medicine directly through your country's national reporting scheme, and this route is open to any member of the public, not only healthcare professionals. In the United Kingdom, this is the Yellow Card scheme, run by the Medicines and Healthcare products Regulatory Agency (MHRA). The scheme accepts reports about any medicine, vaccine or medical device, whether or not it was taken as part of a clinical trial, and it feeds directly into the national system used to detect new safety signals^[7].

In Italy, suspected adverse drug reactions can be reported through AIFA's national pharmacovigilance network, and EU pharmacovigilance legislation requires that both healthcare professionals and citizens be able to report suspected reactions, whether serious or not, known or unknown^[8]. In the United States, side effects can be reported to the FDA's MedWatch programme, which provides a plain-language consumer reporting form (FDA 3500B) and a toll-free line for questions. These national schemes are built to gather safety signals across the whole population using a medicine, not only the relatively small number of people enrolled in any single trial. This is why your individual report — even for a mild or uncertain reaction — can still add genuine value^[6]. Because trial populations are relatively small and closely monitored, rarer effects sometimes only become visible once a medicine reaches wider use. National schemes such as these are one of the main ways such later signals get picked up^[8].

These public reporting schemes exist alongside the trial's own safety reporting procedures; using one does not replace the other. Reporting to your study team ensures your own care and the trial record are updated; reporting to a national scheme adds your experience to a wider safety-monitoring system that can detect new safety signals across many medicines and many patients^[7].

Always read the patient information leaflet supplied with any medicine, including the study medicine, since it lists known side effects and advises what to do if they occur. Keeping this leaflet, along with your consent form and study contact card, in one place at home makes it much easier to check quickly whether a new symptom is already a recognised effect of the medicine or something that should be flagged straightaway^[7].

What rights do you have if a serious adverse event occurs during a trial?

Your consent documents, agreed before you joined the trial, set out how safety information will be collected and who will contact you if a safety concern arises. Ask the study team to explain any part of this you do not understand before you sign, and again at any point during the trial^[4]. You are entitled to be told about the outcome of the assessment of an adverse event affecting you, including whether it was judged related to the study treatment and whether it was already known or unexpected^[1]. This right to feedback is not automatic in every trial design, so it is reasonable to ask your study team, early on, how and when you will be told about the outcome of any event you report. Asking this question at the outset, rather than after an event has already occurred, also gives you a clearer sense of what to expect and reduces the chance of feeling left out of decisions that directly concern your own health^[2].

You can withdraw from a clinical trial at any time, for any reason, without needing to justify your decision, and reporting a side effect does not obligate you to continue participating. If you are considering withdrawal because of a side effect, tell your study team so the event can still be properly recorded and followed up. Even after withdrawal, many protocols ask for permission to continue monitoring a serious event until it resolves, since the safety record of the trial depends on knowing the eventual outcome, not just the initial report^[2].

When should you consult your doctor or pharmacist about a trial-related symptom?

Speak to your doctor, pharmacist, or use your country's health helpline if you are worried about your health, particularly if a symptom is new, worsening, or unlike anything mentioned in your patient information leaflet^[7]. Ask your healthcare professional about possible side effects and any steps you can take to reduce your risk before starting a new medicine or changing a dose within the trial. Working with your doctor or pharmacist may also help you decide, together with the study team, whether a dosage adjustment, a switch, or a lifestyle change could ease a side effect without you having to leave the trial. Your regular doctor or pharmacist may not automatically know you are on an investigational medicine unless you tell them. It is therefore worth mentioning your trial participation at every routine appointment, not only when a problem arises, so that any advice you receive properly accounts for the study drug^[6].

Summary

Reporting a side effect during a clinical trial has two parallel purposes: protecting your own health and contributing to the safety record of the treatment being studied. The practical rule is simple — tell your study team about any new or changed symptom as soon as you notice it, and treat anything life-threatening, disabling or requiring hospitalisation as an emergency that needs same-day attention.

You are never limited to a single reporting route. Your study team handles the trial-specific record and any regulatory reporting that follows from it, while national pharmacovigilance schemes such as Yellow Card, AIFA's network or MedWatch give you an independent channel open to anyone, at any time, for any suspected medicine-related reaction. Using both channels together — the study team for your immediate care and trial documentation, and the national scheme for the wider safety picture — gives you a good chance of being properly looked after. It also helps regulators and researchers keep the overall balance of benefits and risks accurate for everyone using the medicine in the future^[3].

1. [1] Classification of Adverse Events (accessed 2 June 2026) — https://www.nbt.nhs.uk/research-innovation/researcher-zone/researcher-journey/study-management/safety-reporting/classification-adverse-events
2. [2] https://www.hra.nhs.uk/approvals-amendments/managing-your-approval/safety-reporting/
3. [3] Reporting safety information on clinical trials (accessed 2 June 2026) — https://www.ema.europa.eu/en/human-regulatory-overview/research-development/clinical-trials-human-medicines/reporting-safety-information-clinical-trials
4. [4] Safety reporting - Research and Development - Oxford University Hospitals (accessed 2 June 2026) — https://www.ouh.nhs.uk/researchers/conduct/safety-reporting/
5. [5] https://pmc.ncbi.nlm.nih.gov/articles/PMC7098080/
6. [6] Learning about Side Effects (Adverse Reactions) (accessed 2 June 2026) — https://www.fda.gov/drugs/find-information-about-drug/finding-and-learning-about-side-effects-adverse-reactions
7. [7] Yellow Card | Making medicines and medical devices safer (accessed 2 June 2026) — https://yellowcard.mhra.gov.uk/
8. [8] Adverse Reactions to medicinal products (accessed 2 June 2026) — https://www.aifa.gov.it/en/content/segnalazioni-reazioni-avverse