In this article you will learn:
- What kinds of risks a clinical trial can involve for a participant
- Why a new treatment can still cause unexpected side effects even after laboratory testing
- Who checks that a trial is safe before it can start
- What happens if a safety concern comes up while the trial is already running
- What a control group is and why you might not receive the investigational treatment
- What rights you keep as a participant, including the right to withdraw
- When and how to report side effects during the trial
What risks can a clinical trial involve?
Participation in research sometimes carries risk: some studies carry very small risks, while others, particularly those involving new medications, may carry significant risks[1]. A clinical trial cannot guarantee a positive outcome, and the investigational treatment might not work or might not be better than what is already available. It might also cause side effects that currently available treatments do not[2].
Each phase of clinical research aims to learn more about the potential benefits and risks of the investigational treatment. Not all possibilities are known in advance, so there may be unexpected or unpleasant side effects. Before you decide to join, someone from the clinical trial site is required to explain these risks to you as part of informed consent[2].
Why can side effects still happen after laboratory testing?
New drugs and treatments are tested extensively in a laboratory before being given to humans. Strict regulations are in place to make sure a treatment is as safe as possible before it reaches any phase of a clinical trial[3]. Even so, an investigational treatment is still being tested, and while sponsors take steps to predict and watch closely for side effects, these can still occur[2].
An investigational treatment first tested in a clinical trial starts with a small group of people, and sponsors watch its safety closely before it is given to more people. If the treatment meets certain standards for safety and effectiveness in smaller trials, it is then tested in larger trials. This step-by-step method is designed to protect participants from investigational treatments that might carry more risks than benefits[2].
You will only be allowed to join a trial if your doctor believes the benefits outweigh the risks for you, and if you meet the eligibility requirements for that specific study[3]. Each clinical trial has inclusion and exclusion criteria, for example a certain age, sex or health condition, designed to make the trial as safe as possible for the people who take part in it[4].
Who checks that a trial is safe before it can start?
Every clinical trial has detailed documentation that multiple experts review before it can begin. This review is designed to ensure the trial is as safe as possible; if the potential risk to participants is judged too great, the trial plan will not be approved[4]. Before any trial involving people can start, it is reviewed by an independent research ethics committee to make sure it is fair, respectful and protects everyone taking part. An ethics committee also checks that the information you are given tells you everything you need to know and is easy to understand[3].
Local and national clinical trial committees also check that a trial is planned well and carried out safely, and that it is based on scientific knowledge and follows recognised guidelines and safe practices[3]. For comparison, in the United States, an Institutional Review Board must approve any study supported by federal research funds or used to apply for drug approval before any patients can be enrolled. This board includes physicians, researchers and consumers who confirm the study is ethical, that participant risks are minimised, that participant rights and welfare are protected, and that the informed consent form is understandable[1].
| Safeguard | What it checks | When it acts |
|---|---|---|
| Research ethics committee | Fairness, respect for participants, understandable information[3] | Before the trial can start |
| Clinical trial committees | Study design, adherence to guidelines and safe practices[3] | Before and during the trial |
| Doctor / study team | Whether an individual patient's benefits outweigh the risks (eligibility)[3] | Before enrolment and throughout the trial |
| Data Safety Monitoring Board (or equivalent independent committee) | Ongoing safety data while the study is in progress[1] | Throughout the trial |
What happens if a safety concern comes up while the trial is running?
While a study is being conducted, an independent committee, sometimes called a Data Safety Monitoring Board, looks at the data as it comes in to monitor safety and ensure no harm is being done. Its members can include physicians, scientists, ethicists, statistical experts and patient advocates, and they are independent of the research team running the trial. This board has the authority to pause or stop a trial if there is any concern about participant safety[1].
Researchers also build "stopping rules" into the trial design from the start: these outline the conditions under which a trial may be stopped early to protect participants, for example if one or more participants experiences a serious side effect, or if one group in the study does much better or much worse than expected. If the trial is stopped early, the new information is shared with the research team and with study participants[1].
Doctors monitor participants' health throughout the trial as a matter of course, and detailed trial documentation is reviewed to keep every participant protected from unnecessary risks[4].
What should you do if you notice a side effect?
If you experience any side effects during a trial, you should tell the clinical trial staff right away. You should also tell them about any change in how you feel, even if you do not think it is connected to the trial or the treatment. The study team is required to help with any trial complications and to try to minimise lasting effects on your health, so speaking up about even small discomforts matters, because they could signal a new risk[2].
Researchers keep records of adverse events, meaning negative changes in health occurring in participants, such as nausea, anaemia, high blood pressure or low blood counts. If one or more participants experience a serious adverse event, the independent safety monitoring committee may pause or stop the study to reassess safety. Your informed consent form includes contact information for reporting any changes in your health, so keep it accessible for the duration of the trial[1].
Why might you be assigned to a control group instead of the investigational treatment?
Many trials use a control group, which allows researchers to compare the effects of the investigational treatment against those of a currently available treatment, or against no treatment at all. Sometimes the control group is offered the investigational treatment after a period of time has passed[2].
A placebo is an intervention that looks and is administered the same way as the medication being tested, but does not contain the active ingredient. Trials are only allowed to include a placebo under certain circumstances, where doing so does not cause the patient increased risk or harm. For diseases with a well-established treatment, participants are often randomly assigned to one of two groups instead of being given a placebo alone[1].
Before you decide to join a trial, a member of the trial site team will talk to you about the investigational treatment, the possibility of a control group, and what this means for the care you will receive[2].
What rights do you keep once you have joined a trial?
Every participant in a clinical trial has the right to withdraw from it at any time, without any consequences. At any time during the trial, you also have the right to ask your doctor for information about your condition and to see your own medical records[4].
Before you agree to take part, you will be given full information about the trial, including its purpose, the potential benefits and risks, and all relevant details. You will also receive an informed consent form describing every aspect of the study, including potential side effects and the conditions of participation. If any part of this document is hard to understand, because it is written in medical and legal language, you can always ask the researcher or the research team to clarify it. Making sure you fully understand and feel comfortable with your decision is treated as essential to the whole research process[4].
All approved research studies also have plans in place for protecting the privacy of participants' medical records and any information they provide, including responses to study questionnaires[1].
Who can take part, and why are the criteria so strict?
Not everyone can take part in every trial: each study has inclusion and exclusion criteria describing who can and cannot join, for example a specific age range, sex or health condition, and these requirements exist to keep the trial as safe as possible[4]. The main reason for exclusion criteria is the need for a group of participants with minimal confounding factors, so that the results are as clear as possible[5].
Restricting who can join, however, can make results less applicable to other groups, including patients with additional health conditions who were excluded from the trial. For this reason, exclusion criteria should be clearly justified and based on the best available evidence that a given group of patients is either at higher risk of severe, unacceptable side effects, or likely to gain significantly less benefit. Updated international guidance on clinical study design states that the participant selection process should be representative of the population expected to use the treatment in future medical practice, so that particular patient groups are not excluded without good reason[5].
Are clinical trials only for people with serious illnesses?
Clinical trials cover a wide range of conditions and diseases, and may focus on improving quality of life, preventing disease or diagnosing it earlier, not only on treating advanced illness. Trials also study medical procedures, technologies, psychology, vaccines and rehabilitation, not only new medicines. There are also clinical trials designed specifically for children, since paediatric trials are needed to adjust treatments to children's specific needs[4].
When should you talk to your doctor or the research team?
Contact the clinical trial staff immediately if you notice a new symptom, a change in an existing symptom, or any change in how you feel, whether or not you think it is related to the trial[2]. Use the contact details given in your informed consent form, since these are provided specifically for reporting changes in your health during the trial[1].
You can also ask your doctor for information about your condition, or ask to see your medical records, at any point during the trial; this is your right as a participant, not a special request. If you no longer wish to continue, you can withdraw from the trial at any time, without needing to justify your decision and without facing any consequences for the medical care you receive afterwards[4].
Summary
Clinical trials involve real risk, ranging from mild, expected side effects to rarer, unpredictable ones, and no trial can guarantee that the investigational treatment will work or that you will benefit from it personally. What differs between a well-run trial and an unregulated experiment is the layered system of checks around it: careful laboratory testing before human trials begin, independent ethics review before a trial is approved, ongoing safety monitoring and stopping rules while it runs, and your own right to information, privacy and withdrawal at every stage.
None of these safeguards remove risk completely, but together they are designed to catch problems early and to keep you informed and protected throughout. If anything about a trial you are considering, or one you have already joined, feels unclear, ask the research team directly; getting a clear answer before you sign, and staying in contact with the study team throughout, is part of how the system is meant to work.
❓ Can a clinical trial be dangerous?
Some risk is always possible, and studies involving new medications may carry significant risks, but each trial is planned and reviewed to minimise the risks to participants before it is approved, and you will only be allowed to join if your doctor believes the benefits outweigh the risks for you.
❓ Who reviews a trial before it can start?
An independent research ethics committee reviews the trial to make sure it is fair, respectful and protects participants, and local or national clinical trial committees check the study design against recognised guidelines and safe practices before it begins.
❓ What happens if I have a side effect during the trial?
Tell the clinical trial staff right away, even if you are not sure the change is related to the treatment. Researchers record these as adverse events, and the study team must help manage any complications and try to minimise lasting effects on your health.
❓ Could the trial be stopped while I am taking part?
Yes. Researchers build stopping rules into the trial design, and an independent safety monitoring committee can pause or stop a trial early if a serious side effect occurs or if one group is doing much better or worse than expected. Participants are informed if this happens.
❓ Will I definitely receive the investigational treatment?
Not necessarily. Many trials use a control group, which may receive a currently available treatment, a placebo where this does not increase your risk, or the investigational treatment after a delay. The trial team will explain this to you before you decide to join.
❓ Can I leave a trial once I have signed the consent form?
Yes. Every participant has the right to withdraw from a clinical trial at any time, without any consequences, and can also ask to see their medical records or ask their doctor about their condition at any point during the study.
❓ Why don't the eligibility criteria let everyone join?
Inclusion and exclusion criteria, such as age, sex or a specific health condition, are set to keep the trial as safe as possible for participants and to keep the results clear. Exclusion should be justified by evidence of higher risk or lower expected benefit for that group.
- [1] Research & Clinical Trial Safety (accessed 2 June 2026) – https://www.facingourrisk.org/research-clinical-trials/why-enroll/clinical-trial-safety
- [2] Benefits and Risks of Participating in a Clinical Trial (accessed 2 June 2026) – https://www.clinicaltrials.astellas.com/risks-of-clinical-trials
- [3] How clinical trials are kept safe - Blood Cancer UK (accessed 2 June 2026) – https://bloodcancer.org.uk/understanding-blood-cancer/clinical-trials/understand-what-a-clinical-trial-is/how-clinical-trials-kept-safe/
- [4] MYTHS & FACTS ABOUT CLINICAL TRIALS - Fact sheet (accessed 2 June 2026) – https://abm.gov.pl/download/1/9052/Brochure-Mythsandfactsaboutclinicaltrails.pdf
- [5] Optimising clinical trials for greater inclusiveness - ESMO Daily Reporter (accessed 2 June 2026) – https://dailyreporter.esmo.org/spotlight/optimising-clinical-trials-for-greater-inclusiveness
