What is Phase III?
In the traditional scheme of drug development, Phase III studies are intended to 'confirm' the observations of Phase II studies and to establish the safety profile so that a benefit risk assessment can be made. Increasingly, however, Phase III studies may the first time that the endpoints needed to support registration of the drug will be assessed. Regulatory agencies are increasingly requiring that these are 'hard' endpoints, such as the incidence of myocardial infarction or survival, rather than surrogates, such as HbA1c or change in serum cholesterol. Studies that use these types of endpoint commonly require a very large number of subjects to be randomised to have sufficient power to establish confidence in the treatment effect they may demonstrate. This is driving the trend towards ever larger studies conducted across the globe (Fig 10). On the other hand, regulatory authorities are legitimately asking the extent to which the results of a global study apply to the patient population in their region. There are no simple answers to these challenges.
The results of Phase III trials usually form the basis of the information supplied in the application to the regulatory authorities for a marketing authorisation. It is always important for prescribers to examine the population sampled in these studies and consider the extent to which they are the same as those in your clinic. They should not assume that benefit observed in one population will apply to all those with the same disease.
Large-scale phase III studies will usually be supported by a number of smaller studies examining, for example, the risk of drug interactions, or the effect of renal or hepatic impairment on the elimination of the drug.
Fig 10 Phase III and Phase IV clinical trials often involve patients drawn from many populations around the world. There are also strict inclusion and exclusion criteria that may limit the extrapolation of their findings to individual patients encountered in the clinic.
