The Application of Magnetic Resonance Imaging to Phase II Trials in Multiple Sclerosis

Abstract

Before discussing the design of phase II clinical trials, it is valuable to first examine the role of phase II or preliminary trials in the testing of a new therapy in multiple sclerosis (MS). Phase II trials are often more complicated than phase III clinical trials since they may attempt to obtain several important goals within the setting of a study involving a small number of patients or of short duration. The overall goal of a phase II trial can vary considerably. The trial can be relatively large in order to provide sufficient efficacy data to determine if the treatment has sufficient merit to proceed to a costly phase III trial or to allow the phase II trial to be considered confirmatory to a subsequent, larger phase III study. Alternatively, a phase II study can be small and designed to provide only very preliminary efficacy data and possibly some proof of principle for the treatment being tested. Data from preliminary trials can also be valuable in providing background information useful in designing confirmatory, pivotal, phase III trial. Thus, information on dose and frequency of administration of the treatment being tested, some impression on the magnitude of the treatment effect and the outcome measures best suited to measure the treatment effect, and which patient populations will be most appropriate for the phase III trial may all be sought in a phase II study. Because of the range of objectives, there is no single design that will meet all of the goals. In this chapter, we will discuss elements of various trial designs and discuss the relative strengths and weaknesses of each. However, overall, the choice of design must be tailored to the particular needs of the investigators and the type of treatment being tested.