What are Phase IV and post-marketing studies?
Phase IV trials are carried out after a drug has been granted a marketing authorisation (license) by the appropriate regulatory body. They vary enormously in scale from a small study to illustrate a particular feature of a drug to a very large long-term studies to examine the effect of the drug on mortality (Fig 11).
When a drug is licensed, it may have only one licensed indication, for example, a beta-blocker licensed for the treatment of hypertension. A commercial company may then sponsor a number of other trials to evaluate its use in myocardial infarction, heart failure, etc. The licensing authority may consider these, and, if accepted, extend the license to cover these additional indications. A Phase IV trial may be required for a new formulation of a drug (e.g. a fast-melt sublingual tablet) if it is thought that the kinetic properties of the new formulation might alter its therapeutic effect. Otherwise, a phase I or phase II study, showing that both formulations provide equivalent exposure to the drug, may suffice.
Despite the duration and expense of drug development, the number of patients exposed to a drug in clinical trials to support marketing authorisation is relatively small. The safety profile of a new drug is therefore something that is incompletely understood when it first reaches the market. Regulatory authorities may require companies to conduct additional safety studies as a condition of the granting of a marketing authorisation. These may be larger in scale even than the Phase III studies.
A randomised Phase IV clinical trial
Fig 11 A randomised Phase IV trial of a new cardiovascular drug to explore its effects on 'hard' clinical endoints (myocardial infarction and stroke) in 8,076 patients at high risk of cardiovascular disease. The same study will also reveal the rate of common adverse effects of the drug.
