The idea for a trial can come from people working in the NHS, research institutes, drug companies and other bodies such as charities. Trials are funded by industry, charities and government organisations, including the NHS.
Before treatments can be tested on humans, they will have already undergone extensive investigation in the laboratory and testing on animals. If the results from these studies are positive, the next step is to seek approval to begin trials in humans.
Approval has to be sought from the regulatory authority of the member state in which the trial is to be conducted. In the UK, this is the Medicines and Healthcare products Regulatory Agency (MHRA).
The researchers conducting the trial must draw up a plan or protocol which will include information such as who and how many will take part in the trial, what question does the trial aim to answer, what treatments will be compared and how the results will be collected. The protocol then undergoes an independent scientific review and must also be approved by an ethics committee before the trial can go ahead. These checks are to ensure that the trial design is sound and that the research will respect the rights, dignity, safety and well being of the participants.
Since May 2004, all trials are now required by UK law to meet the standards set by the European Union Clinical Trials Directive. This is designed to ensure that all trials will be carried out to the same standard wherever they take place in Europe.
Advice and guidance on good practice in clinical trials is available from bodies such as the Medical Research Council.
Clinical Trial Stages
Once the relevant scientific, regulatory and ethical bodies have approved the protocol, testing in humans can go ahead.
The first step, known as Phase I, is to check that the treatment is safe. The treatment is tested in small doses on a very small number of people, usually healthy volunteers, to check for any side effects.
Phase II trials test the treatment in a larger number of people, typically a few hundred, who have the illness that the therapy aims to treat. The purpose of these tests is both to ensure the treatment is safe and that it works.
Treatments only move into a Phase III trial if phases I and II have been successful. Phase III trials involve many more patients with the illness, often several thousands. The treatment under investigation is pitted against the treatment currently in use or a dummy drug, known as a placebo, to see how well it compares.
Often the study is designed so that neither the participants nor the investigators will know which treatment each person is getting. To further reduce the risk of bias - when incorrect conclusions are drawn due to prejudices - the participants can be allocated at random to the two treatments being compared. The researchers will also check for any side effects.
Once a drug has been through all of these stages of testing, which can take 10 to 12 years, it can be considered for licensing by the relevant body. When a licence application is submitted, the researchers must provide all results from the trial, both positive and negative. If a medicine is granted a licence it can be sold in the UK.
Sometimes Phase IV trials are carried out after a treatment has been granted a licence to find out more about the long-term risks, benefits and use, or to test the product in different populations, such as children.
The licensing body in the UK is the MHRA. It must ensure that medicines, healthcare products and medical equipment meet appropriate standards of safety, quality, performance and effectiveness. In arriving at a decision whether or not to grant a licence, the MHRA often seeks independent expert advice from bodies such as the Commission on Human Medicines (2005 -).
Experts will take into account the nature of the illness to be treated as well as the duration, dosage and formulation of the treatment. Evaluating the beneficial effects of a treatment against the possible harmful effects is complex. Serious side effects may be an acceptable trade off when the treatment can cure a condition that would otherwise be deadly but not when the disease is minor, for example.
Participating In Clinical Trials
Anyone considering whether or not to take part in a clinical trial should be advised about the potential risks and benefits of participating before they make their decision. They are also free to withdraw from the trial at any time without prejudicing their future medical care.
If the subject is a child or incapacitated adult, a legal representative must give informed consent on their behalf. Participants should be reimbursed financially for any out-of-pocket expenses that they incur through participation, such as travel expenses. However, payment should not be an inducement for a person to take part in a trial. At the end of the trial the experimental treatment might stop.
This can be a problem if the patients who received the treatment benefited from it and, therefore, wish to continue on the therapy. If the drug has been licensed it can be prescribed on the NHS or the trial's sponsor might agree to continue to provide it free of charge to the participants even after the trial has stopped. If the drug has not been licensed it can sometimes be provided on a named patient basis or by means of a doctor's exemption certificate from the MHRA.
What Are The Risks?
Any new treatment must be extensively tested to check that it works, is safe and doesn't have unacceptable side effects. A new treatment may not be better and could even be worse than existing treatment, for example. Most often the treatment is a drug, but it could be a medical device, a surgical or physical procedure, a therapy or an intervention such as health promotion.