Situations where formal confirmatory analysis is inappropriate for clinical research

When new drugs are developed for indications where no effective therapies have been established, such as emphysema, useful measures of clinical activity have to be derived from a large number of proposed measures. It often happens that most of the proposed measures are of little use in tracking the disease and that the numbers of patients needed to establish whether the drug is effective is very large. Thus, the first study in man may be the size of the usual Phase III "confirmatory" study, and the expense and the time needed to complete it are so great that decisions about the future development of the drug will depend upon this one large study. The situation of such innovative therapies is examined, and methods for controlling the error rate when almost all analyses have to be exploratory are proposed.