The terms phase I, II, III and IV are usually used when there is an drug being tested. There can be multiple trials in each phase. The phases usually follow one another, but can sometimes overlap. Decisions will be made at the end of each trial whether to continue testing the treatment. Let‟s consider the treatment being test is called DrugABC.
The first time DrugABC is tested in humans is called a FTIH (first time in human) or Phase I trial. The aim of Phase I trials is to find out what dose is safe in humans, how DrugABC should be given (by mouth, injected into a vein, or injected into the muscle), and how often. The researchers will watch closely for any possible side effects.
These trials are usually done on people staying in hospital so that the volunteers can be watched very closely, and there are doctors close by to help if there is a problem. These trials can take days to weeks tofinish, so can represent a big inconvenience for volunteers. This is why these are the only trials where volunteers are sometimes paid a small amount to participate.
Phase I studies are done in only a small group of 20-80 people, normally healthy people and usually men. This is because the possible effect on a women‟s reproduction system (which does not renew like the reproductive system of men) may not be well known at this early stage of development. Healthy volunteers are not used in phase I trials when a treatment is potentially toxic, such as for some cancer treatments, where it would be unethical to try these treatments on healthy people.
Volunteers are usually divided into smaller groups, called cohorts. Each cohort is treated with an increased dose of DrugABC and the highest dose with an “acceptable” level of side effects will usually be used for Phase II studies.
In phase II trials, DrugABC will be tested for the first time in people with the health condition the medicine is hoping to treat to find out if it has the desired effect, and to collect more safety information. There might also be some early comparisons with other products on the market to see if it is at least as good and safe as other medicines available. Typically these trials will involve 100-500 people in at least 2 different trials.
If DrugABC appears to work in Phase II and still has an “acceptable” safety profile, it will be tested in larger groups (from 500-5000+ people) with the target health condition. The aim of these studies is to show that DrugA works, and how safe and well it works compared with other treatments available. Researchers will continue to monitor for side effects and collect information that will allow the treatment to be used safely. Once all phase III trials are completed, if the treatment looks good, companies will submit the data to the regulatory authorities for review, and hopefully approval.
Once DrugABC is approved, regulatory authorities usually require the company to perform additional clinical studies under more “real-life” conditions to collect more information on DrugA‟s risks, benefits, and optimal use. These are called Phase IV or “post-marketing” trials.