title: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Research and Development Center for New Medical Frontiers, School of Medicine, Kitasato University, Kanagawa, Japan. Electronic address: koba-eus@kitasato-u.ac.jp.
authors.forename: Kiyonori
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
authors.forename: Fumihito
authors.initials: F
authors.lastname: Hirai
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Naganuma
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ando
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakase
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Matsuoka
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000293:Adolescent; D000328:Adult; D026683:Advisory Committees; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology*; D003106:Colon / Q000473:pathology; D003113:Colonoscopy; D004311:Double-Blind Method; D005260:Female; D005762:Gastroenterology; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D008505:Medical Staff, Hospital; D019804:Mesalamine / Q000008:administration & dosage*; D008875:Middle Aged; D015588:Observer Variation; D012074:Remission Induction; D015203:Reproducibility of Results; D012107:Research Design; D012720:Severity of Illness Index; D013488:Suppositories; D014945:Wound Healing; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013488:Suppositories; D019804:Mesalamine
keywords: Central review; Colonoscopy; Inter-rater reliability; Mucosal findings; Ulcerative colitis