How to understand the phases of a clinical trial

The drugs that you buy at your local pharmacy are all clinically tested, meaning that they are run through trials in human subjects where the results are reviewed by the FDA. There are 4 main levels of clinical trials. This article will give a quick overview of the differences between the trial types.

~~Phase I~~

The first phase in drug development in humans is called a Phase I trial ('Phase One' trial). Prior to even conducting this earliest of trials, drugs are studied in animal models to obtain a 'safety profile' - that is, to see what the potential side effects (called Adverse Events or AEs) may be.

Phase I trials are generally very small (6-10 participants) as it's the first time that the formulation will be introduced in man so caution is a must. Data is collected on Case Report Forms (CRFs) and entered into a database and analyzed by a Data Manager. If a drug shows promise in Phase I and there are no untoward side effects, it may obtain approval from the FDA to advance to Phase II.

~~Phase II~~

A Phase II trial enrolls more participants that a Phase I trial but may still be relatively small (perhaps a few hundred people). Safety is still paramount so adverse events are studied very carefully, but, now, the study may try to focus on what is the correct dosage to give. The key is to give the lowest dose to get the desired effect (such as producing antibodies in the blood for a swine flu vaccine) while keeping down the adverse events (such as swelling, fever).

A Phase II trial may be called a 'Dose Escalation Study.' Safety data from the earlier Phase I trials and the Phase II trials may be added together to strengthen the safety profile (give a more accurate read on the adverse events uncovered). Provided that the safety is still acceptable and the target dosage has been obtained, the FDA may give a nod to proceed to a Phase III trial.

~~Phase III~~

The Phase III trial may be a very large clinical trial, involving thousands of participants - there is a current HIV trial ongoing with over 20,000 participants.. In this trial, the dose identified in Phase II is used and safety is again studied. At the end of the trial, data is analyzed, produced for review by the FDA and sent along with the Clinical Study Report (CSR) for review. After scrutiny by the FDA, the drug may be approved or the FDA may not approve the drug. The FDA may also give what is called a 'Conditional Approval' which means that the drug may be marketed but the company is responsible for collecting even more data in a Phase IV trial.

~~Phase IV~~

A Phase IV trial is also called a 'Post-Marketing Study' as the drug is on the market but this study will collect more data. Even if the number of participants in the Phase III trial was large (in the thousands), a Phase IV study may collect much more data (generally safety data) since the data is collected worldwide, from people who use the drug under doctor's prescription - the potential for the addition of millions of safety reports is possible. Data is collected, analyzed and again submitted to the FDA. Phase IV trials may go on many years.

Additional resources: Useful information about enrolling in a clinical trial