The science behind EB clinical trials

Find out about the science behind EB clinical trials below or download our leaflet.

What is an EB clinical trial?

A clinical trial is a planned way of providing a drug or treatment to people living with epidermolysis bullosa (EB) before it has been proven to work. EB clinical trials are vital to provide evidence that brand new or repurposed treatments will be safe (Phase 1 and 2 trials) and effective (Phase 2 and 3 trials) to reduce EB symptoms such as pain and itch. Gathering this evidence means providing the treatment, regularly checking in with the people in the trial about their symptoms and any side effects, then finally publishing the results in a peer-reviewed scientific journal.

Joining a clinical trial for EB

DEBRA UK provides funding to doctors running trials but is not responsible for running them and cannot recommend joining one. A family’s EB doctor can help people with EB to join an appropriate trial if they choose to, but nobody should be pressured to take part. The risks and benefits should be clearly explained with an opportunity to ask questions, then a consent form signed. At any point in a clinical trial, participants can decide to stop taking part without giving any reason or explanation, even after signing consent forms.

Clinical trials recruit a specific number of people, with specific EB symptoms, and offer treatment for a specific length of time. The start time for each person is often staggered, so a trial that involves treatment for 8 weeks, for example, can take considerably longer than 8 weeks for everyone taking part to complete. After the treatment finishes, there will often be a follow-up appointment to check on symptoms and conclude the clinical trial. When all participants have completed the trial, the results can be compared.

Research can be clinical, pre-clinical or non-clinical

A clinical trial generally requires attendance at a hospital or clinic and involves a doctor or nurse making examinations, giving treatments, asking questions and perhaps taking samples of blood or skin biopsies. People can only join an EB clinical trial that they are eligible for by speaking to their EB doctor or nurse and can find out before they start, what will be involved. For pre-clinical research in the laboratory, doctors may ask someone with EB for permission to use samples such as blood, DNA or skin biopsies.

For research carried out on computers to find out more about EB, doctors may ask people with EB for permission to use information saved on their digital records.

People with experience of living with EB can also choose to participate in non-clinical research without needing to go through their EB doctor. This could involve questionnaires and workshops to provide information about EB symptoms or to help guide the direction of research, called Patient Public Involvement (PPI). Information sheets about non-clinical research have the name of the lead researcher and the logo of their university or hospital to give an indication that the research has been approved by their ethics committee. This is important because anybody can circulate a survey without being part of an official research institution, and information provided by participants may not always be well-protected or contribute to good quality research.

Who can join EB clinical trials?

For each EB clinical trial, there will be a different set of ‘eligibility criteria’. These may include:

being a certain age and sex
having a certain, genetically diagnosed, type of EB or even a specific genetic change
being able to attend a specific centre or clinic
having certain EB symptoms to a defined level of severity

To provide evidence that treatments are safe and effective to be offered to anyone with EB, participants in clinical trials should include men and women from diverse backgrounds.

Benefits and risks of joining an EB clinical trial

A potential benefit may be trying out something new that could improve symptoms. However, many trials will have a ‘control group’ of participants who do not receive the new treatment and act as a comparison group to see whether those receiving the new treatment really do benefit. It is also possible that the new treatment might not help at all or may even make symptoms worse.

Extra or longer medical appointments may mean more contact with healthcare professionals, being able to speak directly to researchers, and the chance for additional health checks. These can help someone living with EB who wants to find out more about their condition and symptoms and the work going on to actively search for treatments. However, it may also mean more time spent at a clinic and potentially additional discomfort if extra samples for research are given.

It may feel positively empowering and satisfying to be helping with the development of future EB treatments and to see the importance of being involved. However, being asked to focus on and share symptoms and experiences of living with EB may bring feelings of sadness or anxiety.

Phases of EB clinical trials

Clinical trials occur in different ‘phases’:

Infographic outlining the stages of EB clinical trials from pre-clinical research to Phase 3, showing progression from lab studies to human testing and evidence for regulatory approval.

Before a clinical trial begins, pre-clinical studies are carried out in laboratories on cells, biopsy samples and animals. These are sometimes called ‘models’ of EB and are used to provide as much evidence as possible that a treatment could work safely.

In phase 1 clinical trials, a small number of healthy volunteers try out different amounts of a new treatment with close attention to safety from doctors and nurses. The results provide evidence about what dose is best to use and what side-effects the new treatment might cause.

In phase 2 clinical trials, the new treatment is given to people living with EB. The results provide evidence that people with EB can safely take the new treatment and give early evidence that it can improve EB symptoms.

In phase 3 clinical trials, the new treatment is offered to a larger group of people living with EB. The results provide evidence that the new treatment is safe for more people and improves most people’s symptoms more effectively than existing treatments.

The evidence from these trials can be used by the company that makes the treatment to apply for a licence to allow it to be prescribed for people living with EB. The effectiveness of a licensed treatment can be assessed against its price to see whether it should be provided by the NHS.

After a licensed treatment is in use, phase 4 clinical trials can continue to study the on-going safety, side-effects and effectiveness of the treatment as more and more people use it over time. This can provide more evidence of safety or discover side effects that are rare, only affect specific people, or only show up years after the treatment was used. Anyone using any licensed treatment in the UK can report side effects using the yellow card scheme.

A phase 2/3 trial of a treatment already licensed for use in another condition could provide evidence to license that treatment for EB. This is called drug repurposing. It saves time and money as the treatment is already available, and doses and side effects are already known.

Types of EB clinical trials

No clinical trial will guarantee a treatment is safe and effective for everyone, but different types of clinical trials provide stronger evidence than others.

Controlled trial

The symptoms of people receiving the new treatment should be compared to symptoms of people in a control group. The control group could be people who don’t receive any treatment at all, but evidence is stronger if they receive a placebo treatment that looks, feels, tastes and smells exactly like the treatment but doesn’t contain the ingredient being tested.

Evidence is even stronger if people in the control group receive the current best available treatment to provide evidence that the new treatment is better than what already exists.

Blinded trial

Researchers assessing the outcomes of the clinical trial shouldn’t know who is receiving the treatment and who isn’t as this could make them biased.

‘Single-blinded’ means that people don’t know whether they are in the treatment or control group, or that the people applying the treatment know, but the people rating their symptoms do not.

Evidence is stronger if the trial is ‘double-blinded’. This means that neither the participants receiving the treatment nor the healthcare professionals assessing their symptoms know who
is in the treatment or control group. The pharmacy that prepares and dispenses the treatment knows which group each participant is in.

At the end of the clinical trial, the results from both groups can be compared without researchers knowing which group is which before they are ‘unblinded’.

Randomised trial

People should be randomly chosen for the treatment or control group. This is usually done by a computer that tells the pharmacy providing the treatment which group each participant is in. This avoids researchers subconsciously putting people who look like they will do well in the treatment group or feeling pressure to put someone in the treatment group.

Reporting the results of EB clinical trials

There is no guarantee that the results of a clinical trial will provide evidence that a new treatment for EB works. The trial may show that the potential treatment is not safe, has too many side effects, is too difficult to take, doesn’t help much or at all, or even makes symptoms worse. Results like this are valuable and should be published in scientific journals as it is
important to save people with EB, doctors, and researchers from wasting time and money on something that doesn’t work by testing it again in the future.

If too few people complete a clinical trial, it will not provide good evidence that the treatment is safe or works. Any changes in symptoms may be due to chance or unique to those few people who took part and might not apply to other people with EB. Statisticians calculate how many people are needed for the results of a clinical trial to be ‘statistically significant’. Statistically significant results are probably not due to chance and provide acceptable evidence that the treatment was responsible for changes in symptoms.

A clinical trial can be stopped early if it is too difficult to recruit enough participants, or if unexpectedly frequent or severe side effects occur, and this should be reported. When a clinical trial finds evidence that a treatment for EB is safe and effective, the results should be published in peer-reviewed scientific journals so that everyone can see exactly what was done and what the results were. If the evidence is strong enough, the treatment can be licensed and made available to people living with EB.