A randomized clinical trial of mesalazine suppository: the usefulness and problems of central review of evaluations of colonic mucosal findings

Abstract

Background: The methods of evaluating endoscopic mucosal findings and the definition of mucosal healing in inflammatory bowel disease have not been standardized.

Aim: To examine a third-party central review of colonic mucosal evaluations.

Methods: A double-blind, placebo-controlled, parallel-group trial was performed for 4weeks, which involved continuous administration of a 1-g mesalazine suppository to 129 patients with mild to moderate ulcerative colitis and active rectal inflammatory findings. Mucosal findings were evaluated by using a 4-grade score (0, 1, 2, 3). Reviews by attending physicians were considered the primary evaluations. Concurrently, a central review committee of 7 gastroenterologists served as the third party.

Results: The endoscopic remission induction rate from the attending physicians' evaluations was 82.8% in the mesalazine suppository group and 31.1% in the placebo suppository group, whereas the respective rates from the central review committee were 90.6% and 59.0%. However, there was a difference of 27.9 percentage points between the remission induction rates of the placebo group found by the two groups of raters. Differences in the evaluations of mucosal finding scores were also found among the third-party reviewers.

Conclusions: The evaluations of the attending physicians were consistent with those of the central review committee in showing the effectiveness of mesalazine suppository through the index of mucosal healing. However, differences were observed among the raters in their evaluations of mucosal finding scores. Therefore, standardizing evaluation criteria and improving review methods for mucosal findings would enable the more effective use of third-party central reviews in clinical drug trials.

Keywords: Central review; Colonoscopy; Inter-rater reliability; Mucosal findings; Ulcerative colitis.