National Cooperative Crohn's Disease Study: study design and conduct of the study.

The design and execution of the National Cooperative Crohn's Disease Study are described in this paper. The Study incorporated several noteworthy features developed to meet specific demands of the disease and its therapy. A standard clinical grading system, the Crohn's Disease Activity Index (CDAI) was developed to allow uniform decentralized clinical evaluation and decision-making throughout the 5 yr of the study. All three drugs in widespread clinical use in Crohn's disease were studied both for suppressive and prophylactic efficacy and for toxicity. The study employed a scheme for double-blind evaluation of patient progress which allowed adjustment of prednisone dose according to the degree of illness and ensured continuous monitoring for serious toxicity of any study drug. Results were analyzed primarily by ranking the clinical outcome of every patient according to a uniform and detailed scheme and applying Wilcoxon nonparametric statistics. Outcome was also analyzed by life-table methods. Eleven hundred nineteen patients were entered and 604 patients were randomized at 14 study centers during the 5-yr duration of the study. Twenty patients were eliminated from analysis as not meeting diagnostic criteria for Crohn's disease, and another 15 patients were eliminated as not meeting other preestablished criteria for analysis. Nine percent of randomized patients, equally distributed in the four treatment groups, withdrew as noncompliant. Ninety percent of patients completed all or all but one protocol-specified visits, and 95% completed the final radiologic and sigmoidoscopic evaluation.