The Truth About Clinical Trials (It’s Not What You Think)

By Dr Ava Easton MBE, Encephalitis International

While clinical trials are designed with participant safety as the highest priority, there are occasions when unexpected adverse events can occur. However there is a very important ‘but’ to this statement—so please read on.  The important ‘but’ is that these events are carefully monitored, thoroughly investigated, and used to improve our understanding of treatments and their risks. This continual learning is one of the reasons clinical trials remain the cornerstone of developing safer, more effective medicines for future generations.

But first, let’s be clear what a clinical trial is.  The World Health Organization defines it as: Any research study that prospectively assigns human participants or groups of humans to one or more health‑related interventions to evaluate the effects on health outcomes[1].

It might surprise you to learn that in diseases or syndromes such as encephalitis we are really poor at launching new treatments and interventions because we often cannot find enough people to join what are potentially life-changing and exciting new treatments[2][3][4].

I have been involved in more than one trial relating to encephalitis that has failed because we simply weren’t able to meet what we call ‘recruitment targets’ – that means we weren’t able to secure enough patients to participate in the trial and had to shut the trial down.  More recently these include trials looking at the efficacy of drugs and immunomodulatory interventions in various forms of autoimmune encephalitis.  Furthermore, it is a true shame for those patients who did participate as both they, and we, will never know if the intervention would have worked for future patients or not!

In encephalitis we have insufficient medicines and therapies available.  Where they do exist we are often using very few evidence-based treatments i.e. in some cases we are using treatments on patients when we have not in fact conducted any clinical trials on them – so we don’t actually have proven data to say they work!  In addition, it might be that some of the treatments we are testing, or hoping to test in potential clinical trials, could in fact be less toxic than some of the treatments in current use[5].  Of course, without appropriate trials we will never know, nor will we ever find new evidence-based treatments and interventions.

When a patient or trial volunteer experiences a side-effect in a trial this is know as an adverse event (AE).   A serious adverse event is known as a SAE.  AEs are not uncommon in clinical trials – especially non-serious ones, and particularly in early phase one trials[6].

Serious or fatal events are much less common, but they do happen and their frequency varies significantly by phase and trial type.  The literature suggests that some later phase and condition-specific studies (one example is oncology trials) can report more, and more serious, adverse events.

Having said that, there undoubtedly remains a very strong argument that the benefits of being involved in a clinical trial outweighs the often small risks associated with them for many patients.

Clinical trials are essential for advancing medical knowledge, finding new and unique preventative interventions such as vaccines, improving existing treatments, and developing new therapies where none or few exist.  I know, for sure, that if I were diagnosed with a life-limiting illness, or someone I loved was, I would be scouring the internet to identify any potential clinical trials.  I am not naïve enough to think they might cure me but I do know that a few more months of life would be gift enough.  Having said this, the reality of being invited to participate in a clinical trial often presents itself when we least expect it and often at our greatest times of vulnerability, anguish, and distress…times when our heads feel like we aren’t part of reality and when making critical decisions is extremely difficult.

Imagine the parents at the bedside of a child, unexpectedly struck down with encephalitis – it is touch and go and no-one in the medical team is able to offer you the reassurances you so desperately seek – that they are going to be OK.  Instead, people are reluctant to raise your expectations, to give you false hope, so they say nothing other than ‘we are doing our best’.  Fast forward a few hours and they return…. “…but there is one thing…. we are involved in a clinical trial for a new drug that we think might help in reducing the injury to the brain, BUT we don’t know if it does yet and if you participate in the trial your child may or may not be given the trial drug……Now what do you do?  What if it makes them worse?  If they get the placebo (fake treatment) then they aren’t getting the drug – what was the point??  And worse, does that mean they aren’t getting anything that might help them?  Maybe, we should just ‘stick’ with the existing treatment and if we don’t do the trial then they wouldn’t be worse off than anyone else in this situation and some of those kids have lived!

However amongst all of this noise are some misconceptions about the realities of participating in clinical trials.  Understanding these myths—and the reality behind them—can help patients make informed decisions and appreciate the potential benefits of being part of a clinical trial.

Common Misconceptions

I/they will be treated like a ‘guinea pig.

Many people worry they or their loved one will be experimented on without care for their safety.
Reality: Your safety comes first. Clinical trials follow strict rules and guidelines reviewed by independent ethics committees to protect you. You’ll be given full information about what’s involved.  Patient safety and informed consent are protected by law.  You can say no, withdraw or stop at any time. You will receive close monitoring and high-quality care often with more regularity than if one were not in a clinical trial.

I/They might get the placebo (fake treatment) instead of real treatment.

People fear they may receive no treatment at all.
Reality: In many trials—especially for serious conditions—participants receive either the best standard treatment available and/or the treatment under investigation in the trial. Placebos are typically only used in addition to the existing best standard of treatment or when no proven treatment exists, and the potential use of a placebo is always explained to you in advance.  So being in a trial often still means you are getting the best treatment available.  It does not mean you are not getting any treatment in most cases.

Clinical trials are only for people who are really sick or who have run out of options.

Some people believe clinical trials are a ‘last resort.’
Reality: Many trials involve early interventions, prevention studies, or to test improved versions of existing treatments. Participation can be appropriate at all stages of a condition, not just in the case of advanced or life-limiting illness.  In fact, some trials are even for healthy volunteers who want to help find new ways to prevent disease.

It’s too dangerous or risky to be in a clinical trial.

People often overestimate the dangers.
Reality: All medical treatments, including standard care, carry some risks. In clinical trials, potential risks and benefits are carefully assessed, monitored, and clearly communicated. Your health is checked more closely than in normal care, so any problems are spotted and dealt with quickly.

I won’t have control over my treatment.

Some people think they lose the right to make decisions.
Reality: Participation is always voluntary and you make any final decisions. You can withdraw from a trial at any time, for any reason, without affecting your standard of care.

Now that we have considered some of the risks and misconceptions surrounding clinical trials, let’s have a look at some of the positives! There are a range of benefits to consider.  First you might receive access to promising new therapies before they are available to anyone else.  As mentioned above, trial patients are often monitored more closely than in standard care, with more frequent check-ups and tests, and some patients experience improved results with investigational treatments compared to current or existing options.  In addition to these, many participants find satisfaction in being on a trial with potential treatment that may help others in the future and there is always the possibility that because of the high ethical standards around the conduct of clinical trials, you actually may end up feeling more informed about your condition and more involved in the decision-making surrounding it.

So being in a clinical trial can be a positive experience. While there are always risks and uncertainties in clinical trials, as there are in the rest of life, the reality is that clinical trials are designed to protect patients in parallel with exploring new preventions, treatments, and care options.

Maybe you are reading this and wondering if there is a clinical trial you can join.  Don’t be afraid to explore with your clinical team if there are any trials running that might be relevant to you.  You can also reach out to patient organisations relevant to your condition who often know about clinical trials running in the illness or syndrome you might be affected by.

The bottom line is that joining a clinical trial is your choice. It’s a chance to get high-quality care, possibly try new treatments, and make a real difference for future patients.

By participating you may contribute to a breakthrough that changes lives, even your own.

Supplemental FAQ

Will I have to pay to be in a trial?

Usually, no. The study often covers treatment and extra test costs.

Can I still see my regular doctor?

Yes. Your regular care continues alongside the trial.

What if I change my mind?

You can stop at any time — no questions asked.

Will I find out the results?

Yes, you can usually request a summary of the study results once it’s finished.

Are there any other downsides to being in a clinical trial?

Well you may be disappointed if the arm of the trial you were in didn’t help you, and there may be demands in terms of your time and travel, or some tests or paperwork to complete.

Where can I find out more information or go to talk to someone?

You can speak to your doctor and the research team to discuss joining a clinical trial, as well as patient support organisations who can provide general information and guidance. Your healthcare team is the best starting point because they know your medical history and can determine if a trial is suitable for you.

If your trial relates to encephalitis then you can talk to one of our team – www.encephalitis.info

References

[1] World Health Organization. International Clinical Trials Registry Platform (ICTRP) – Glossary. World Health Organization. Available at: https://www.who.int/clinical-trials-registry-platform/about/glossary (Accessed July 2025).

[2] Dubey D, Britton J, McKeon A, Gadoth A, Zekeridou A, Lopez Chiriboga SA, Devine M, Cerhan JH, Dunlay K, Sagen J, Ramberger M, Waters P, Irani SR, Pittock SJ. Randomized Placebo-Controlled Trial of Intravenous Immunoglobulin in Autoimmune LGI1/CASPR2 Epilepsy. Ann Neurol. 2020 Feb;87(2):313-323. doi: 10.1002/ana.25655. Epub 2019 Dec 14. PMID: 31782181; PMCID: PMC7003900.

[3] Blackburn KM, Denney DA, Hopkins SC, Vernino SA. Low Recruitment in a Double-Blind, Placebo-Controlled Trial of Ocrelizumab for Autoimmune Encephalitis: A Case Series and Review of Lessons Learned. Neurol Ther. 2022 Jun;11(2):893-903. doi: 10.1007/s40120-022-00327-x. Epub 2022 Feb 7. PMID: 35129803; PMCID: PMC9095811.

[4] Iro MA, Sadarangani M, Absoud M, Cantrell L, Chong WK, Clark C, Easton A, Gray V, Hill M, Kneen R, Lim M, Liu X, Pike M, Solomon T, Vincent A, Willis L, Yu LM, Pollard AJ; IgNiTE Study Team. Intravenous immunoglobulin treatment for encephalitis in children aged 6 months to 16 years: the IgNiTE RCT. Southampton (UK): National Institute for Health and Care Research; 2024 Apr. PMID: 38652789.

[5] Abboud H, Clardy SL, Dubey D, Wickel J, Day GS, Geis C, Gelfand JM, Irani SR, Lee ST, Titulaer MJ. The Clinical Trial Landscape in Autoimmune Encephalitis: Challenges and Opportunities. Neurology. 2025 Apr 22;104(8):e213487. doi: 10.1212/WNL.0000000000213487. Epub 2025 Mar 27. PMID: 40146951; PMCID: PMC11966526.

[6] Sibille M, Deigat N, Janin A, Kirkesseli S, Durand DV. Adverse events in phase-I studies: a report in 1015 healthy volunteers. Eur J Clin Pharmacol. 1998 Mar;54(1):13-20. doi: 10.1007/s002280050413. PMID: 9591924.