How clinical trials are carried out
Treatment-related clinical trials are usually carried out in a series of steps or phases. These phases may not be needed for other types of trials.
New cancer drugs or treatments are first tested in the laboratory (pre-clinical trials) before they’re given to people in trials. If it seems they may help to treat a particular cancer, they are tested in phase 1 trials. If these are successful, the drug is used in phase 2 and then phase 3 trials.
Manufacturers of drugs that have been shown to be safe and effective in phase 3 trials can apply for the drug to be granted a licence. This is known as a marketing authorisation. Licensed drugs are then available to be used in healthcare.
Most licences are granted by the European Medicines Agency (EMA) as the licence covers all countries in the European Union. The Medicines and Healthcare products Regulatory Agency (MHRA) can grant a licence for a drug to be used just in the UK. Drugs that are licensed may be further researched in phase 4 trials.
People who run trials involving patients (trial researchers) have to offer a treatment they believe is at least as good as, or possibly better than, the best available treatment. The trials have to be conducted following strict rules and guidelines.
Phase 1 trials test a new cancer treatment or drug that has already been tested on cancer cells in the laboratory. Phase 1 is the first stage in which the drug or treatment are used to treat people. It’s not expected that the treatment will cure the cancer, but it aims to find out:
if the treatment has an effect on the body
how much of the treatment can be given safely without causing serious side effects
what side effects it causes
whether the treatment has any effect on the cancer.
Phase 1 trials usually involve a small number of patients. They’re offered to people whose cancer has come back or spread, where there is no other standard treatment that may help them.
The first patients are given a small dose of the treatment or drug that is expected to be safe. If none of the patients have any side effects, the next group will be given a higher dose. In this way, the dose of the drug is increased until some people do have side effects. When side effects are seen that make it unsafe to increase the dose further, it’s known as the ‘maximum tolerated dose’. The dose is not increased any more after this.
Sometimes, phase 1 studies include different ways of giving the new treatment. For example, patients may be given the same drug by injection or as tablets.
It’s impossible to predict whether a new treatment will cause harmful side effects, so people in this type of trial need to be monitored very carefully. Phase 1 trials are usually carried out in clinical research units at specialist hospitals, rather than in local hospitals. Sometimes, this may involve a lot of travelling to and from the hospital.
Phase 1 trials may take from several months to a year to complete. At the end of the trial, the research team will know the major side effects of the treatment and whether it has any effect on the cancer. If the treatment is safe and does have an effect on the cancer, it will then be tested in phase 2 trials. Not all treatments tested in phase 1 trials make it to phase 2.
The aim of phase 2 trials is to find out:
if the treatment works well enough to be tested in a larger, phase 3 trial
which types of cancer it might be best used to treat
more about the side effects and how best to manage them
more about the best dose to use.
Phase 2 trials have more patients, usually about 20-40 people, and may last a couple of years. These patients will be closely monitored to see whether their cancer is responding. If the cancer shrinks, it’s known as a response to the treatment.
The trial will also look further at any side effects caused by the treatment. Although the new treatment would have been tested in a phase 1 trial, it’s still possible that it will cause side effects that haven’t been seen before.
A phase 3 trial aims to compare the effectiveness of new treatments with that of standard treatments. It also gives more information about the side effects that the new treatment may cause.
Sometimes, a phase 3 trial may test whether a new treatment will be as good as the standard treatment but cause fewer side effects. For example, a new way of giving radiotherapy may be tested and compared to the standard radiotherapy treatment used on patients.
Sometimes, a new treatment will be tested when no standard alternative treatment currently exists. In these trials, the new treatment may be compared with the current routine care that would be given. Routine care might involve regular appointments to see how well the person is and to treat any symptoms. This is sometimes called ‘observation’ or ‘best supportive care’. Sometimes, phase 3 trials may involve a placebo.
Phase 3 trials are large and may include hundreds, or sometimes thousands, of patients from many different hospitals, often from several countries. They may take many years to complete.
Researchers use these trials to find out:
how long patients stay free of cancer - this is known as disease-free survival
the number of people who are alive, with or without signs of cancer - this is known as overall survival
whether the cancer grows more slowly
how the treatment affects patients’ quality of life.
Phase 3 trials usually involve randomisation.
Phase 4 trials are carried out after a drug has been shown to be effective and has been granted a licence. They aim to find out:
how well the drug works when it’s used more widely
the long-term risks and benefits of the drug
more about possible rare side effects and the safety of the drug.