How does groundbreaking research become reality for men? We look into clinical trials.

There are many stages in the process of developing a new medicine or medical procedure. And before a new treatment can be widely used, researchers must test how well it works in patients and how it compares to the best treatment currently available.

This process is called a clinical trial. A new treatment has to perform well in several different clinical trials, with increasing numbers of patients, before it can be made widely available. Treatments for prostate cancer are no exception.

Clinical trials can also be a way to access the newest treatments and many men contact us to find out more about this and how they can take part. So here Sophie looks into:

• Different types and phases of clinical trials
• What it takes to get a trial off the ground
• The pros and cons of taking part in a trial
• Men's experiences of taking part in clinical trials

Clinical trial phases

Clinical trials are divided into different steps, or phases. If a new drug or procedure does well in one phase, it is tested in the next.

A phase 0 trial is the first time a drug has been used in people. The dose of drug patients receive in these types of study are too small to treat the cancer, but should tell the researchers whether the drug reaches the cancer, and how the body and the cancer cells respond. The small doses mean patients are unlikely to benefit from the treatment at this stage, but this also reduces the risk of side effects.

A phase 1 trial will generally involve a small number of patients. The patients may be people with advanced disease who have tried all other available treatments. These trials are designed to find out about the safety and side effects of a new treatment and if it could work well in humans.

A phase 2 trial often involves more patients than a phase 1. It is designed to look at how well a treatment works and to collect more information about the dose, safety and side effects. These trials may either test a new treatment against an existing treatment or against a placebo (dummy) drug.

A phase 3 trial tests a new treatment against the best existing treatment, if there is one available. These may involve thousands of patients at different hospitals and even in different countries.This is where most potential new treatments fail.

A phase 4 trial may happen after a new treatment is in use. It is intended to collect information aboutlong-term risks and benefits and find out more about the safety and side effects, as well as how well the treatment works when it’s used more widely.

Blinded trials
Sometimes, a trial might be blinded. This means that the patients don’t know which treatment they’re getting. Trials need to be blind because just knowing that you are getting a new treatment can affect how you respond to it and make the results unreliable. If a trial is doubleblinded, neither the patients nor the doctors know
which treatment each patient is getting.

Randomised trials
Most phase 3 and some phase 2 trials are randomised. This means that there are at least two groups of patients, often those who will get the treatment and those who won’t. People are put into one group or the other randomly. This is important to make sure that nothing in the way people are chosen for each group will affect the results – for example patient age, gender or even how well they feel.

What does it take to make a clinical trial happen?

We spoke to Mr Hashim Ahmed, MRC Clinician Scientist and Honorary Consultant Urological Surgeon at University College London Hospital to find out. He told us: “Having the idea is the most enjoyable, but also most difficult part of getting a clinical trial off the ground. It can then take two or three years to get from having this good idea to recruiting the first patient.”

So what are the hold ups? Well, there are a lot of approval processes to go through. This is mainly because it’s so important to make sure that patients’ safety during the trial has been properly considered.

It’s also down to the fact that clinical trials are very expensive. They can cost anything from £50,000 to more than £100million, depending on the type, length and complexity of the trial and how many hospitals are involved.

The first port of call is the ethics committee. This is a group of health professionals, patients, lawyers and members of the public, who are there to look after the best interests of patients involved in the trial. Mr Ahmed said getting approval here used to be the biggest hold up, until the Westminster Government introduced compulsory turnaround times.

“Now you can expect final approval or rejection in a maximum of 90 days, if you respond to their questions quickly. It’s the hospital R and D (Research and Development) that’s the biggest obstacle now. This can take up to six months.”

The local R and D process is one of the approval steps needed for an NHS hospital to agree to host a trial, and the time this takes can vary from hospital to hospital. In hospitals that run a lot of clinical trials, the R and D office is likely to be extremely busy, considering lots of applications for trials in all disease areas at the same time.

Trials of new medicines or experimental medical equipment will also need approval from the Medicines and Healthcare Products Regulatory Agency (MHRA), which is responsible for making sure that all medicines and medical devices in the UK work and are safe to use.

If a trial is taking place in more than one hospital, there may be more complications. They also need something called coordinated NHS permission. This means the NHS has approved the trial at a high level and should mean that local R and D permissions can be faster and less in depth, and help avoid some of the delays.

Once all the checks are complete, the researchers visit the hospital to make sure everyone involved in the trial, including doctors, researchers and nurses, knows exactly how it will work and what to expect. However there may still be delays from issues such as drug supply and staff training.

The Health Research Authority recognises that this process is not efficient. It’s attempting to streamline it by introducing a single approval method to cover all ethical, legal and practical aspects of a research study – regardless of how many hospitals are involved.This should mean each hospital will just have to decide whether they are able to host the trial. This new system is intended to be in place in all hospitals in England by the end of 2015.

Deciding to be part of a clinical trial

Taking part in a clinical trial can be a way to access the newest treatments. Not everyone is going to be suitable for every trial but, if you find that you are, deciding whether or not to take part is something to think very carefully about. It’s really important to find out as much as possible and ask questions before you sign up.

It is important to remember that not everyone will benefit from taking part in a clinical trial. And, to some people, being part of a process to test a brand new treatment can sound scary. But, as explained above, there are many checks in place to ensure clinical trials are as safe as possible. And there can be important benefits to taking part.

One recent study found that men with advanced prostate cancer that had stopped responding to hormone therapy lived for longer, on average, than they would have done 10 years ago. The men in this study had taken part in clinical trials and received experimental treatments like docetaxel, abiraterone, enzalutamide or radium 223. Since then, these treatments have become more widely available and can make a real difference to life expectancy for men with advanced prostate cancer.

You can read through all the pros and cons below and hear from two men who’ve taken part themselves.

The pros and cons of taking part in a clinical trial

To find out more on clinical trials you can also read our factsheet or call our Specialist Nurses.

Pros

• You might get early access to new, potentially more effective therapies that may not be routinely available on the NHS for years.
• You may have more regular check-ups, tests and support from doctors and nurses than usual – some people find this reassuring.
• You are helping to improve future cancer treatment for others.
• You feel you’re doing something positive about your health and taking an active role in your treatment and recovery.

Cons

• You may have more frequent testing as well as treatment, which might be inconvenient. This can go on for a long time. Some people also find this makes them more anxious about their cancer.
• There could be check-ups for many months or years afterwards, with questionnaires, tests or scans.
• You might not know in advance about all the possible side effects – the researchers themselves might not know them all yet.
• If the trial is randomised you won’t get a choice about which treatment you have, and if the trial is blinded, you won’t know which treatment you’re getting.
• The new treatment may turn out to be no better than the existing treatment.
• There is the risk that the new treatment may not help you, even if it helps others

What's it like taking part in a clinical trial?

Ian Liston and Chris Dobbs have both taken part in clinical trials for prostate cancer treatments. Find out what they have to say about their experiences.

How do I find out about trials for prostate cancer?

• You can ask your doctor or nurse if there are any local or national trials that may be suitable for you
• You can call our Specialist Nurses on our confidential helpline
• Or search online lists of trials, such as the NHS Choices clinical trials page.