How are clinical trials carried out?

Before new cancer treatments or drugs are given to people in trials they are first tested in laboratories using cancer cells. They then go through 3 stages (phases) of being tested in trials before they are approved for use.

Phase 1 trials

The treatment is given to a small number of people. The trial is to see how the treatment effects the body and how much of the treatment can be given without causing serious side effects.

Phase 2 trials

The treatment is tested on a larger number of people to see which cancers it would be best used for. The researchers also learn more about potential side effects and the best dose to use.

Phase 3 trials

The treatment is tested on a very large number of people. It is compared to the standard treatment already available to find out if it works better. Manufacturers can apply for a licence for the drug or treatment after phase 3 trials, if the drug is seen to be safe and effective.

Phase 4 trials

This phase happens after approval, to research the long-term benefits and risks.

Different phases of a clinical trial

Treatment-related clinical trials are usually carried out in a series of steps or phases.

Potential 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 what are called phase 1 trials. If these are successful, the drug is used in phase 2 trials and then phase 3 trials. Phase 4 trials test drugs that are already licensed.

Feasibility studies and pilot studies may be carried out before a planned clinical trial. A feasibility study is designed to see how possible a clinical trial is. For example, it will look at how easy it will be to recruit people to the trial, how many people the trial might need and how long the trial could take to complete.

Pilot studies are a smaller ‘test’ version of the main clinical trial. They are done before the main study to check whether the ideas behind the trial and the suggested methods (the ‘trial design’) work in practice.

Researchers who run trials involving patients have to offer a treatment they believe is at least as good as, or possibly better than, the best treatment that is currently available. The trials have to be carried out following strict rules and guidelines.

Phase 1 trials

Phase 1 trials test a possible new cancer treatment or drug that has only been tested on cancer cells in the laboratory. This is the first stage in which the drug or potential treatment is used in patients.

Phase 1 trials may involve chemotherapy or targeted therapies.

A phase 1 trial aims to find out:

  • whether the medicine has an effect on the body
  • how much of the medicine can be given safely without causing serious side effects
  • what side effects the medicine causes.

How does the trial work?

The first patients are given a small dose of the 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. The dose is gradually increased with each group. This is called dose-escalation.

The researchers look carefully at the effects of the drug until they find the dose at which side effects are acceptable. This is known as the maximum tolerated dose.

For targeted therapies, it may be necessary to test a biopsy specimen first. This is to see whether the patient is likely to benefit from the new treatment. A biopsy is a sample of cells that may have been removed when you were diagnosed. The cells can be looked at and tested under a microscope to find out whether the patient is likely to benefit from the new treatment.

In a phase 1 trial, it’s likely that most people won’t benefit from the new treatment. But it’s possible that some people will.

Finding out the best dose and the side effects of the drug is a very important stage before testing how effective the drug is. Sometimes, phase 1 studies include different ways of giving the new drug or medicine. For example, patients may be given the same drug by injection or as tablets.

Who can take part?

Phase 1 trials involve very few patients. These trials are only open to people whose cancer has come back or spread. They have already had treatment and there is currently no other standard treatment available.

It’s difficult to know whether a new medicine will cause harmful side effects, so people in this type of trial need to be selected and checked very carefully. For example, people need to be feeling reasonably well to take part in these sorts of trials. This is because the trials are specifically looking at side effects. It would not be safe or fair to have people who were already feeling unwell taking medicines which might possibly make them feel worse – particularly with no proof yet that the medicine is effective.

Where do the trials take place?

Phase 1 trials are usually carried out in clinical research units. These are often based at specialist hospitals, rather than in local hospitals. Sometimes, this may involve some travelling to and from the hospital.

How long does the trial last?

Phase 1 trials can take from several months to a year to finish.

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 shown to be safe and looks like it 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.

Phase 2 trials

A phase 2 trial aims to find out:

  • whether the drug 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 followed up 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. This is because it is being tested in a larger group of patients.

Phase 3 trials

A phase 3 trial aims to compare what looks like promising new treatments with 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.

Sometimes a new treatment will be tested when no standard treatment currently exists. In these trials, the new treatment may be compared with the current routine ‘standard of care’ that would be given. This 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.

A phase 3 trial aims 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 a randomisation process.

Manufacturers of drugs that have been shown to be safe and effective in phase 3 trials can then 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.

I took part in a clinical trial of a new chemotherapy drug. I'd already had treatment so my progress was measured against the new one.

Ron, clinical trial participant

Phase 4 trials

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.

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