When a potential new medicine is being investigated, it will always first be tested thoroughly in laboratories (‘preclinical’ trials). It is then given to a small number (typically 20-100) of healthy volunteers under carefully controlled conditions in order to detect any safety issues (‘Phase 1’).
Once Phase 1 is successfully completed, the investigational medication is given to a group of patients with the relevant condition (typically a few hundred) to find the best dose and study the effects closely (‘Phase 2’). If there are clear signs that the medication may be beneficial and does not cause any significant safety issues, a larger trial (‘Phase 3’) will be planned. Only about one-third of potential medications reach Phase 3.
Phase 3 trials often involve hundreds and sometimes even thousands of participants across several countries. If the results show that the potential new medicine is helpful and its side effects are considered acceptable (the benefits should always outweigh the risks), licensing authorities such as the European Medicines Agency (EMA) are likely to approve the medicine for doctors to prescribe in routine care. Only about 10% of investigational medications make it from Phase 1 to approval.1
Following approval, Phase 4 trials (which typically involve many thousands of patients and can be clinical trials or observational studies) may be carried out to see how well the medicine is working in the wider world and how helpful it is compared to existing options.
Clinical trial protocols, sponsors and investigators
Every clinical trial is run according to a protocol, which is a detailed document describing the reason for conducting the trial, the way it will be run, the type of people it is suitable for (and what they will need to do), the tests that will be performed and how long the trial will last.
The protocol is prepared by the trial sponsor, who is usually an academic or commercial organisation that takes responsibility for managing, and often financing, the trial and ensuring it is run in accordance with all relevant regulations and standards.
The sponsor is also responsible for appointing the trial investigators, who are usually medical doctors at one or more hospitals, medical centres or clinics. These doctors will usually be experts in the condition being studied. They will involve their own teams of nurses, pharmacists and other staff in running the trial.