NATIONAL COOPERATIVE CROHN DISEASE STUDY - STUDY DESIGN AND CONDUCT OF THE STUDY

Abstract

The design and execution of the National Cooperative Crohn''s Disease Study are described. 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 study. All 3 drugs in widespread clinical use in Crohn''s disease were studied both for suppressive and prophylactic efficacy and for toxicity. A scheme for double-blind evaluation of patient progress was employed 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. A total of 1119 patients were entered and 604 patients were randomized at 14 study centers during the 5-yr study. Twenty patients were eliminated from analysis as not meeting diagnostic criteria for Crohn''s disease, another 15 patients were eliminated as not meeting other pre-established criteria for analysis and 9% of randomized patients, equally distributed in the 4 treatment groups, withdrew as noncompliant. Of the patients, 90% completed all or all but protocol-specified visits, and 95% completed the final radiologic and sigmoidoscopic evaluation.