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What trial phases are

Medical research studies involving people are called clinical trials. They are divided into different stages, called phases. The earliest phase trials may look at whether a drug is safe or the side effects it causes. A later phase trial will aim to test whether a new treatment is better than existing treatments.

There are generally 4 phases of clinical trials – phases 1 to 4. But some trials will have an earlier stage – phase 0.

 

Phase 0 trials

Phase 1 trials are usually the earliest trials of drugs in people. But your doctor might ask if you would like to join a phase 0 study. These studies aim to find out if a drug behaves in the way researchers expect it to from their laboratory studies.

Phase 0 studies usually only involve a small number of people and they only have a very small dose of a drug. The dose of the drug is too small to treat your cancer, but the types of things researchers are looking for include

  • Whether the drug reaches the cancer
  • How the drug behaves in the body
  • How cancer cells in the body respond to the drug

You might have extra scans and give extra samples of blood and cancer tissue (biopsies) to help them work out what is happening.

Because the dose of the drug used in phase 0 trials is so small, you won’t benefit from the drug.  But this also means that you are less likely to have side effects.  

The main aim of these studies is to speed up the development of promising new drugs. Testing them in very small doses in humans rather than in animals can be more reliable and means scientists get useful information more quickly.

 

Phase 1 trials

Phase 1 is sometimes written as phase I. They are usually small trials, recruiting only a few patients. The trial may be open to people with any type of cancer.

When laboratory testing shows that a new treatment might help treat cancer, phase 1 trials are done to find out

  • The safe dose range
  • What the side effects are
  • How the body copes with the drug
  • If the treatment shrinks the cancer

Patients are recruited very slowly onto phase 1 trials. So although they don't recruit many patients, they can take a long time to complete. The first few patients to take part (called a 'cohort' or group) are given a very small dose of the drug. If all goes well, the next group have a slightly higher dose. The dose is gradually increased with each group. The researchers monitor the effect of the drug, until they find the best dose to give. This is called a dose escalation study.

In a phase 1 trial, you may have lots of blood tests, as the researchers look at how the drug is affecting you. They also look at how your body copes with, and gets rid of the drug. They record any side effects.

People taking part in phase 1 trials often have advanced cancer and have usually had all the treatment available to them. They may benefit from the new treatment in the trial, but many won't. Phase 1 trials aim to look at doses and side effects. This work has to be done first, before we can test the potential new treatment to see if it works. 

 

Phase 2 trials

Not all treatments tested in a phase 1 trial make it to a phase 2 trial. Phase 2 is sometimes written as phase II. These trials may be for people who all have the same type of cancer, or who have several different types of cancer. Phase 2 trials aim to find out

  • If the new treatment works well enough to test in a larger phase 3 trial
  • Which types of cancer the treatment works for
  • More about side effects and how to manage them
  • More about the best dose to use

Although these treatments have been tested in phase 1 trials, you may still have side effects that the doctors don't know about. Drugs can affect people in different ways.

Phase 2 trials are often larger than phase 1. There may be up to 100 or so people taking part. Sometimes in a phase 2 trial, a new treatment is compared with another treatment already in use, or with a dummy drug (placebo). If the results of phase 2 trials show that a new treatment may be as good as existing treatment, or better, it then moves into phase 3.

 

Phase 3 trials

These trials compare new treatments with the best currently available treatment (the standard treatment). Phase 3 is sometimes written as phase III. These trials may compare

  • A completely new treatment with the standard treatment
  • Different doses or ways of giving a standard treatment
  • A new way of giving radiotherapy with the standard way

Phase 3 trials usually involve many more patients than phase 1 or 2. This is because differences in success rates may be small. So, the trial needs many patients to be able to show the difference.

For example, say that 6 out of 100 more people (6%) get a remission with a new treatment compared to standard treatment. If there were 50 people in the new treatment group and 50 people in the standard treatment group, there may be 3 more people in remission in the new treatment group. The 2 groups would not look that different. But if the researchers gave each treatment to 5,000 people, there could be 300 more remissions in the new treatment group.

Sometimes phase 3 trials involve thousands of patients in many different hospitals and even different countries.

 

Randomisation

Some phase 2 trials and most phase 3 trials are randomised. This means the researchers put the people taking part into treatment groups at random. There is more about randomisation and other types of trials in this section.

 

Phase 4 trials

Phase 4 trials are done after a drug has been shown to work and has been granted a licence. Phase 4 is sometimes written as phase IV. The main reasons for running phase 4 trials are to find out

  • More about the side effects and safety of the drug
  • What the long term risks and benefits are
  • How well the drug works when it’s used more widely
 

Trials covering more than one phase

Most trials are just one phase. But some trials cover more than one phase. For example, the same trial can include both phase 1 and phase 2. The aim of phase 1 might be to work out the highest safe dose of a new drug. And the aim of phase 2 might be to see how well that dose works. So you may see trials written as phase 1/2 or phase 2/3. 

 

Multi-arm multi-stage (MAMS) trials

Many trials look at just one new treatment. But some trials compare several treatments. The people taking part are still put into groups at random but there may be 3 or more treatment groups. This is a multi-arm trial.

Some trials are designed so that they stop recruiting into a particular group if early results show that a treatment isn’t working as well as the others, or is causing more side effects. This is called a multi-arm multi-stage (MAMS) trial. A MAMS trial may also be able to add new groups to look at more treatments.

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Updated: 8 October 2013