Pivotal Proof-of-Efficacy Clinical Trials in the Prevention of NANSAID-Induced Gastric Ulceration

One of the positions the first author had in the pharmaceutical industry provided me the opportunity to run a large-scale clinical research program of the synthetic prostaglandin (PGE2) analogue, misoprostol. The program consisted of two identical protocols. Clinical and statistical evidence from the program formed the primary basis for FDA approval of misoprostol (Cytotec) in the prevention of gastric ulceration induced by nonaspirin, nonsteroidal, anti-inflammatory drugs (NANSAIDs) in osteoarthritic (OA) patients requiring NANSAIDs in the management of their OA symptoms. A rationale for the program is presented in Section 13.2. The protocols are reviewed in Section 13.3. Monitoring and data management considerations are presented in Section 13.4. Meeting with the U.S. Regulatory Agency is addressed in Section 13.5. Discussion and concluding remarks appear in Section 13.6.