Clinical trials try to find new treatment options to improve symptoms for people with a particular health condition. A treatment is most commonly in the form of a medicine but could also be in the form of a medical device, or an intervention (such as a change in diet or physical activity). A clinical trial could also test a treatment that has already shown to be effective in one health condition, in people with a different condition. For people with various forms of alopecia, we need more treatments to be available, so that everyone can find something that works for them. But before these new treatments are on the market, clinical trials need to show that they are safe and effectively improve symptoms.

What makes a good clinical trial? 

A clinical trial is a research study conducted at one or more hospitals or research centres. The researchers running the trial must show that the trial is designed in a fair and ethical way, and this is reviewed by a Research Ethics Committee (REC). When you are testing a new treatment, there are always some risks, such as unforeseen side effects from the treatment. The researchers must show that safeguards are in place to minimise these risks, and that the benefits of doing the trial outweigh these risks.

It is also important that the trial is designed in a way that the results are not able to be influenced by the participants or researchers themselves. We need to objectively test what effect the treatment under investigation has on a condition, without bias affecting the results. To do this, the ‘gold standard’ for clinical trial designs is as a ‘randomised controlled trial’ (RCT).

Randomised

People who volunteer to take part in a clinical trial will be assigned to a group. In a randomised trial, people are assigned to a group randomly. There are always at least 2 groups: the treatment under investigation, and a control group to compare with. Additional groups may be needed to test different doses of the treatment or to compare with existing treatments. Assigning people to a group randomly means we can be more confident that the observed results are because of the treatment, and not existing differences between the people taking part. This randomisation can be done by a computer program so that the groups are still balanced in terms of age, sex, disease severity and overall health.

Controlled

People who believe they are receiving a medicine can sometimes feel better or experience improvements in their symptoms, even if they are not actually receiving an active medicine. This is called the placebo effect. So, to see if a treatment that is being investigated in a clinical trial really has a positive effect, it needs to be compared to a placebo. This is a dummy drug that looks, feels and/or tastes the same as the real one but does not have any of the active ingredient in it. If there is no difference between the real medicine and the placebo, there is no benefit in taking it. A clinical trial needs to have a placebo or control group to prove that the treatment works, and the observed improvements are not due to luck or random chance. 

Blinded

Blinding means that participants do not know what the treatment is that they are receiving. People in one group will receive treatment A while people in the other group receive treatment B. Only after the trial is finished will it be revealed whether they were receiving the real medicine or the placebo. Double-blinding means that the participants and the investigators both don't know what treatment is being given. The goal of this is to protect against bias – this way neither the investigators nor the participants can influence the results of the trial, be it intentionally or unintentionally.

Why do clinical trials need to happen?

Researchers are always looking for new ways to treat health problems. In some cases, no effective treatments may be available at all for a condition. In other cases, the treatments that are available may not be suitable for someone, or they may have tried them, and they haven’t worked. Until recently, alopecia treatment had mostly relied on medications generally targeting inflammation or immune activity, without a specific target. We are now learning more and more about the genes and processes involved in the various forms of alopecia, which allow more targeted medications to be developed. We are also learning from other dermatological and autoimmune conditions, which share similar mechanisms. 

But before new treatments can be used in people with alopecia, we need to know they are safe and do not cause any unwanted effects. And we need to know they really are effective at improving symptoms. Regulatory bodies such as the Medicines and Healthcare Regulatory Agency (MHRA, UK), European Medicines Agency (EMA, Europe) or the Food and Drug Administration (FDA, USA), need to see evidence of this before they can approve a treatment for people to use. These agencies want to avoid people being harmed or spending money on treatments that have no benefit. In the UK, once a treatment is approved by the MHRA, it can be sold and used privately. However, for it to be available on the NHS, it also needs to be recommended by the National Institute for Health and Care Excellence (NICE). In addition to evidence of safety and efficacy, they also want to see the treatment is a cost-effective use of taxpayer money.

What are the phases of clinical trials?

The process of developing a new treatment happens in phases. When scientists in the laboratory find that a mechanism or gene in the body is part of the reason why people develop a disease, this means that they now have a target they can try to change with a medicine or intervention. The early stage of medicine development, which aims to find targets for treatment, is called pre-clinical or phase 0. By studying cells, animals, or human blood or skin samples, researchers try to find molecules or processes to target with treatment. 

Once they have come up with a treatment, and they have decided how to deliver it (for example via pill, cream or injection), they will first give it to a small amount of healthy people in a phase 1 clinical trial. This lets them see how the body handles it, and whether there are any side effects. 

If it is safe, it can go to a phase 2 clinical trial, testing it in a larger number of people with a particular health condition. This can include different hospitals and health centres across the UK, and sometimes other countries. In this phase there will typically be two or more groups receiving different amounts of the active ingredient. This is called the dose or dosage of the treatment. There will also be a control or placebo group to compare against. The aim of this phase is to find the best dose of the treatment, see if it is effective in improving symptoms, and does not cause any serious side effects. The treatment will be given for a set amount of time, and they will check up on people at regular points to see how they are doing.

The best dose of the treatment will then be taken forward to a phase 3 trial, where they will test it in many hundreds of people. People taking part in this phase will also be asked to fill in questionnaires about how they are feeling and how well they function in their daily work and social life. This is to see if the treatment can improve aspects of the person's life other than the physical symptoms.

After a treatment has been approved by a regulatory body, a phase 4 trials is sometimes done to better understand the long-term effects and side effects in a wider population. This is to make sure it is safe when used in a real-world setting and there are no rare but serious side effects that were not picked up in phase 1-3 trials. 

Clinical Trial Phases Explained

Phase	Number of participants	Aim of trial
Phase 0	No human participants.                                    Laboratory study of cells, animals or human samples.	Learn what mechanism we can target to improve symptoms, and to develop a treatment.
Phase 1	10-20                                                                          Small number of healthy people.	First test in humans to see how the body handles it, and if it is safe.
Phase 2	30-150                                                                            People with a specific health condition.	Find the best dose of treatment, and if it is effective in improving symptoms, without causing serious side effects.
Phase 3	300-1500                                                                         Hundreds of people with a specific health condition.	Gather more information on how well it works and side effects. In some cases, to see if the treatment is better than what is available already.
Phase 4	10-1500+                                                                           Wider population in real-world setting. Tens up to several thousands of people.	Learn more about long term benefits and rarer side effects after a treatment has been licenced. Not all treatments undergo a phase 4 trial.

Trial phases may sometimes be written in Roman numerals as phase I, II, III or IV.  A phase can also be divided into a and b, for example a phase 2a or phase 2b trial, to reflect whether the focus is on an earlier or later stage of the investigation. In some cases, a trial may span multiple phases. You may see a trial described as phase 2b/3, for example. If a treatment is already used in another health condition, it may skip the early phases and go straight to a phase 2 trial, as it has already shown to be safe in humans. However, they will still want to check there are no unforeseen side effects in this new group of people who may have different characteristics, alongside testing for effectiveness and best dose. 

How do I find a clinical trial to take part in? 

Head over to our clinical trials page to see if there are any active clinical trials looking for participants in the UK, or speak to your doctor the next time you see them. 

Other resources

• What should I expect from a clinical trial?
  

Read our 'What should I expect from a clinical trial?' webpage which explains the things to consider if you are interested in taking part in a clinical trial, and why you might want to take part. 

• Clinicaltrials.gov – database of trials

For more information about individual clinical trials, the United States National Institutes of Health holds a database of clinical trials, on the clinicaltrials.gov website. You can search by condition, location and/or treatment to find trials that may be of interest to you. It includes information on previous and current clinical trials from around the world. They also have a webpage which gives more explanation about clinical trials. 

• Be part of research

The ‘Be part of research’ website by the UK National Institute of Health and Care Research (NIHR) is another place for people to find out about clinical research happening in the UK. You can search by condition and sign up to receive alerts when studies matching your interest become available. 

• People-centred research

The UK Health Research Authority have recently published new guidance on best practice for conducting ‘people-centred’ clinical research. It is important that everyone in the UK can safely take part in clinical research trials, within an environment of openness, trust and respect. The HRA have now created recommendations to make clinical research more accessible to everyone. We encourage investigators to implement these recommendations to ensure clinical research is representative of the whole UK population.