Once researchers know that a new compound could be useful as a potential treatment, and it has passed safety tests in pre-clinical research, it needs to be tested thoroughly in clinical trials.
Trials for new medicines are largely funded by the pharmaceutical industry. But funding may also come from research institutions, the NHS, and publicly funded bodies, such as the Medical Research Council (MRC) (external link).
Why are trials needed?
Clinical trials are the start of the process that ends with a medicine being licensed and used for treatment.
These aim to find out if it:
- works well in people
- has an acceptable level of side effects
- is at least as effective as existing treatments
Who takes part?
Clinical trials involve healthy volunteers or patients (research participants), depending on the type of treatment under test and its stage of development. All participants must agree to take part by giving informed consent before being given any treatment.
Larger numbers of participants take part in each trial phase, to uncover side effects that have not come to light before, and confirm the effectiveness, or otherwise, of the compound.
The Northwick Park incident
Side effects are common when a new compound is tested in people for the first time. But those of the severity experienced by six people in the Northwick Park Hospital trial in 2006 are, fortunately, exceptionally rare.
These volunteers were helping to test a compound (TGN1412) for its potential to treat leukaemia, multiple sclerosis, and arthritis, but became seriously ill and had to be admitted to hospital.
The report into the incident by an independent expert scientific panel is available below:
Expert Group on Phase One Clinical Trials: Final report (external link)
The episode illustrates the unpredictability of medicines development and the need for rigorous testing of any new compound.
Trials run in phases I to IV, and a compound will only go forward to the next phase if it has passed the safety and effectiveness tests of the previous one.
- Phase I trials usually involve small numbers of healthy people. They are designed to find out how the treatment works in the body and how those treated react to it. This type of trial also aims to find out the lowest dose at which the treatment is effective, known as the minimum therapeutic dose, and the highest dose at which it can be taken without causing harm.
- Phase II trials test the treatment in several hundred people with a given disease or condition. They aim to find out how well the treatment works in larger numbers, identify common side effects, and refine the dose and length of treatment.
- Phase III trials typically compare the treatment on several thousand patients, to gather more detailed information on how well it works and in which groups of patients, as well as its safety. The results influence the prescribing and patient information of a medicine once it is marketed.
- Phase IV trials are carried out after a medicine has been licensed, put on the market and prescribed to patients. Part of the monitoring process, these trials are designed to find out more about the long term harms and benefits of a medicine, and to discover new uses for it.
The different types of trial
There are several types of clinical trials. For example:
- randomised controlled trials aim to compare doses or treatments in two or more different groups; participants are randomly assigned to their group, but matched for factors, such as age and sex, so that the results are comparable - hese trials may compare two similar treatments or an active treatment and an inactive treatment (placebo).
- blind trials aim to eliminate bias; patients don’t know what treatment they are getting - they might be given an inactive treatment, for example
- double blind trials mean that neither the treating doctors nor the participants know which treatment they are being given.
It’s possible to have a combination of trial types, such as a randomised controlled double blind trial, for example.
Quality safeguards for trials
To protect the safety and wellbeing of participants and ensure that quality standards are maintained, a clinical trial for a medicinal product must be approved by the appropriate medicines regulator before it can be given the go ahead.
For UK trials, this is the Medicines and Healthcare products Regulatory Agency (MHRA). The MHRA issues licenses for trials of new compounds and medicines that have already been marketed, but for which the manufacturers are seeking a change in use.
All UK clinical trials are legally required to meet the standards laid down by the European Union Clinical Trials Directive (May 2004). And they are regularly inspected by the MHRA to make sure they are meeting these standards.
A trial must also have ethical approval from an independent body called a Research Ethics Committee. This is to ensure that the purpose of the trial can be justified on ethical grounds, and that the rights and privacy of the participants have been fully protected.
Find out more...
If you are interested in taking part in a clinical trial, you can contact the Clinical Contract Research Association (external link) for details of trials in your area.
More information on clinical trials is available below:
The National Research Register (external link)
The UK Clinical Research Network (external link)
The UK Clinical Research Collaboration (external link)
The World Health Organization International Clinical Trial Register (external link)