ABSTRACT
I. BACKGROUND A few years ago, I had the responsibility of running a large-scale clinical research program of the synthetic prostaglandin (PGE2 ) analog, misoprostol. Clinical and statistical evidence from the program formed the primary basis for NDA approval in the United States of misoprostol in the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcers in osteoarthritic patients requiring NSAIDs in the management of their arthritic symptoms. Statistical aspects of the program, particularly with regard to interim analyses, are presented in this chapter. The program consisted of two identical protocols. A rationale for the program is presented in Section II. The protocols are reviewed in Section Ill. Monitoring and data management considerations are presented in Section IV. Meeting with the U.S. Regulatory agency is addressed in Section V. Interim analysis plans are outlined in Section VI. Conclusions and final remarks appear in Section VII.
