In the UK, before a clinical trial is conducted, clearance must first be given by two independent bodies:

a Research Ethics Committee, and
the Medicines and Healthcare Products Regulatory Agency (MHRA)

These two bodies will look at all aspects of the trial to ensure it is well-organised and safe, with any potential risks minimised. The trial may also need to be authorised by internal ethics committee at whichever institution or organisation is carrying out the trial.

Once approval is granted, a pre-clinical trial on human and animal cell cultures, and often directly on animals, is carried out to test for safety. This is a legal requirement in order to decrease the likelihood of serious adverse reactions when the treatment is tested in humans.

There are then four key stages, or phases, to a clinical trial.

Phase 1
This phase is usually conducted in healthy volunteers, and is concerned with testing the product for safety and side effects.

Phase 2
This phase is conducted in a small number of people who have the condition for which the treatment is being tested. Phase 2 continues to test for side effects and also for signs of effectiveness of the treatment. It is also used to determine the optimal dose for the treatment.

Phase 2 trials are sometimes split into two parts, phase 2a and phase 2b.

Phase 3
This phase is conducted in a large number of people (200-300) who have the condition. Phase III continues to gather information about the effectiveness of the treatment and any side effects.

Phase 4
If a product is shown to be safe and effective following a successful phase 3 clinical trial, it may (but not always) proceed to phase 4, when it will become licensed. During this phase, more data are collected to further monitor for side effects and long term risks and benefits. Effectiveness is also compared against other similar treatments on the market.

Even treatments shown to be safe and effective may not make it on to the market. This could be for a number of reasons, for example lack of funding to continue the trial.

The length of time from preclinical trials to a licensed product can vary greatly, and may take several years.

Key terms relating to clinical trials

Randomised controlled trials (RCTs)
A randomised controlled trial is simply a trial in which participants are allocated at random a different treatment, e.g., a placebo, or the drug being tested. Randomised controlled trials are designed to ensure that the results of the trial are as sound as possible, and any potential bias on the part of the patients or researchers is eliminated. Most phase 2 trials are RCTs.

Blind / double blind trial
If a trial is referred to as 'blind' it means that the participant does not know whether they are receiving the treatment being tested, or a placebo. A 'double blind' trial is one in which neither the patient nor those administering the treatment know whether the patient is receiving the treatment or the placebo. In a double blind trial, only those analysing the data will know which patients received the treatment. Blind trials (sometimes called 'blinded trials') are also designed to eliminate bias and further ensure accurate results.

Placebo
A placebo is an inactive or 'dummy' drug given to patients in a clinical trial. A placebo has no medical effect and is used to determine the effectiveness of the real drug which is being tested.

Read Clinical Trials in Cystic Fibrosis: Information for Patients, produced by the European Cystic Fibrosis Clinical Trials Network.