8 Clinical trials and research

8.4 Developing a new treatment: Phase I, II, III and IV studies

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When a new drug is being developed, there are four main 'Phases' of clinical research. These studies are run in order - you have to start with Phase I, then II etc

Pre-clinical research is the term used to describe the whole range of studies, including test-tube and animal studies, that are carried out before a drug enters human trials.

Phase I studies

Phase I studies are the first human studies.

This includes single-dose studies that are often called Phase Ia trials. A small group of patients (5-10) will take one dose and be carefully monitored. 1-2 patients will usually get a placebo.

Short-term multi-dose studies, perhaps for 1-2 weeks, are called Phase Ib. This is where a slightly larger group (perhaps 10-20 patients) will take multiple doses and be carefully followed.

These studies are usually in 'healthy volunteers' - ie for an HIV drug, the first people to take it are HIV-negative.

Phase II studies

Phase II studies are usually the first study to look at activity - whether the investigational compound is actually active.

These are short-term and in HIV-positive people. Phase IIa studies usually enrol 20-50 HIV-positive people.

Phase IIb studies also look at different doses of a drug - called 'dose-finding' studies. In which case they may enrol 200-300 people.

Phase II studies

Phase III studies are the large trials that are used by regulatory agencies to decide whether a drug will be approved.

For an HIV drug this is usually 1,000 - 2,000 patients.

If the same people from the Phase II study, continue to be followed in the Phase III study, the study is sometimes called Phase II/III.

If one study leads into another study, it is called a 'roll-over' study.

Phase IV studies

Phase IV studies are usually referred to as 'post-marketing' studies.

They involve longer follow-up of patients looking at side effects and other safety concerns. Sometimes a rare side effect, or a side effect that takes years to develop, are unlikely to be seen in Phase III studies.

Phase IV studies are usually recommended by the regulatory agencies. Although, in the past, the European regulatory agency (called the EMEA) had very little power to make sure companies followed through on these commitments, recent legislation has strengthened these powers. Phase IV studies are now compulsory and the EMEA can withdraw a medication if safety commitments are not followed.