Protocol design for recent duodenal ulcer maintenance trials.

The long-term efficacy and safety of ranitidine for the prevention of duodenal ulcer recurrence were studied in two sets of double-blind, randomized, multicenter clinical trials. Ranitidine 150 mg at bedtime was compared with either cimetidine 400 mg at bedtime or placebo in the United States and Europe. To meet one of the objectives of the studies (that is, to provide a mechanism for standardizing sponsored clinical research methodology on an international basis), several features were incorporated into the study protocol. These features included identical case report forms for all trials, central clinical laboratories in the United States and Europe, monitoring of all sites to ensure that the United States style was followed, and the all sites to ensure that the United States style was followed, and the completion in the United States of all data processing and analysis. Additionally, to overcome flaws in the design of earlier trials with similar drugs, patients were examined endoscopically at more frequent intervals to detect an ulcer recurrence without symptoms, and the data were analyzed for recurrence rates by the life-table method. This method more accurately reflects the true ulcer recurrence rate than the crude-rate method that was used in earlier trials.