Treatment training manual

8. 4 Developing a new drug: phase I, II, III and IV studies

When a new drug is being developed, there are four main ‘phases’ of research.

These studies are run in chronological order. You have to start with phase I, befre moving on to phase 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 people (ie 5-10) will take one single dose and be carefully monitored. 1-2 participants will usually get a placebo (an inactive dummy pill).

Phase Ib studies are short-term multi-dose studies, perhaps for 1-2 weeks. This is where a slightly larger group (perhaps 10-20 people) take multiple doses and are carefully monitored.

Phase I studies are usually in so-called ‘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 studies to look at whether the compound is actually active. They are run in HIV positve people.

Phase II studies can last a day, a week or two, or several months. Phase IIa studies usually enrol 20-100 people.

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

Phase III studies

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

Two important agencies are the European Medicines Agency (EMA) in Europe and the Food and Drug Administrations (FDA) in the U.S. 

Phase III studies for an HIV drug usually enroll 800 – 2,000 participants.

If the same people from a 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, this is called a ‘roll-over’ study.

Phase IV studies

Phase IV studies are also referred to as ‘post-marketing’ studies. This is because they are run after a drug is already approved and licensed.

Phase IV studies involve longer follow-up and look at side effects and other safety concerns. Rare side effects, or side effects that takes years to develop, are often only seen after a drug is approved.

Phase IV studies are usually recommended by regulatory agencies like the EMA or FDA, often as par of the approval process.

Although, the EMA used to have very little power to make sure companies followed through on these commitments, legislation has strengthened their authority.

Phase IV studies are now compulsory and the EMA can withdraw a medication if safety commitments are not followed.

Last updated: 1 December 2015.