Phase – in drug trials
What is the difference between Phase 1, Phase 2 and Phase 3 when it comes to drug trials?
New therapies for treating disease need to be tested, mainly to ensure that they do what they claim to do and that there are no unwelcome side effects. Drug trials in humans are preceded by a pre-trial / preclinical phase where the drug is tested in animals.
Some trials may have a Phase 0, where the therapy is tested on a very small number of people while it is still in development.
Phase 1 trials are used to check that the therapy works, does it have any side effects, what is the correct dose and how the body interacts with the therapy. Phase 1 trials usually involve just a few patients. Patients are recruited into the trial in small batches. The first patients are given a low dose and the dosage is gradually increased for new recruits. These used to be described as ‘first in human’ trials.
In phase 2 trials, the number of patients in the trial is higher – maybe around 100 people. They are used to refine the results of the phase 1 trial.
They might sometimes be used to check whether the new therapy works better or has less side effects than an existing therapy – so patients might be split into two groups, one on the old therapy and one on the new. The patients might be assigned to these two groups on a randomised basis (to avoid doctors skewing the results of the trial).
Alternatively, the new therapy might be compared to a placebo (a harmless, inactive substance). In such a trial, the patient is unaware of which therapy they are taking.
In the Phase 3 trial, the new therapy is compared against the standard treatment for the condition using the methodology we outlined for phase 2 but using a much larger group of patients.
Once a therapy has succeeded in a phase 3 trial it may be put forward to be approved for use. In the US, approval is granted (or not) by the FDA, in Europe the licencing authority is the European Medicines Agency (EMA).
Sometimes testing will continue even after a licence has been granted. This would then be described as phase 4. These are useful in assessing a drug’s long-term effects.
Some trials will test more than one therapy and/or more than one dosage at a time – each with its own group of patients. These are termed multi-arm trials. Sometimes parts of multi arm trials are abandoned (usually because the therapy isn’t working) and sometimes a new patient group is added to the trial. These are termed multi stage trials.