Gastroenterology

Gastroenterology

Volume 133, Issue 2, August 2007, Pages 423-432
Gastroenterology

Clinical–alimentary tract
Development, Validation, and Evaluation of a Pediatric Ulcerative Colitis Activity Index: A Prospective Multicenter Study

https://doi.org/10.1053/j.gastro.2007.05.029Get rights and content

Background & Aims: Colonoscopic appearance, the primary measure of disease activity in adult ulcerative colitis, is less acceptable to children. Our aim was to develop a noninvasive activity index of pediatric ulcerative colitis. Methods: Item selection was performed judgmentally using a Delphi group of 36 experts in pediatric inflammatory bowel disease. Item weighting was performed by regression modeling using a prospective cohort of 157 pediatric ulcerative colitis patients. Validation was assessed on a separate prospective cohort of 48 children with ulcerative colitis undergoing complete colonoscopy. Responsiveness was evaluated at a follow-up visit of 75 children using effect size statistics and diagnostic utility approaches. Results: A list of 41 items was generated and reduced to 11 by rank order. Two physicians completed the Pediatric Ulcerative Colitis Activity Index (PUCAI) on each of the patients in the weighting cohort. Six clinical items were significant in the regression analysis; the laboratory items and an endoscopic appearance item did not improve the PUCAI performance. In the validation cohort, the PUCAI was highly correlated with the Physician’s Global Assessment (r = 0.91, P < .001), Mayo score (r = 0.95, P < .001), and colonoscopic appearance (r = 0.77, P < .001). Correlations were higher than 2 noninvasive adult indices calculated concurrently. Interobserver and test-retest reliability were excellent (intraclass correlation coefficient = 0.95; 95% CI: 0.93–0.97). Cut-off points were established using receiver operator characteristic curves on the full cohort. Excellent responsiveness was found at repeated visits (effect size = 1.9, area under the receiver operator characteristic curve = 0.97). Conclusions: The rigorously developed PUCAI is a noninvasive, valid, highly reliable, and responsive index with which to assess disease activity in pediatric ulcerative colitis.

Section snippets

Study Design and Overview

A Delphi group of pediatric IBD experts was established to aid with item generation, reduction, and gradation. A Delphi technique involves an iterative, multistep process to reach a consensus for a specified question, when the experts are not physically together. The responses of all members of the Delphi group are summarized by an expert panel, processed, and resent to the group for further comments until consensus is reached. Between November 2005 and November 2006, 2 separate prospective

Item Generation, Reduction, and Grading

Of the 48 pediatric IBD experts contacted, 36 responded and served as the Delphi group. A list of 21 potential items was generated by the expert panel, and the Delphi group added another 20. Eleven variables, which were ranked significantly higher than the others, were graded by the Delphi group from 1, important, to 11, least important (Table 1). One item, “rectal urgency,” was removed because of perceived difficulties in applying this variable to young children. C-reactive protein (CRP),

Discussion

We have developed a novel multiitem UC activity index for pediatric patients. The large Delphi group and the multicenter enrollment serve to enhance its content and face validity. The use of the PGA as the outcome measure39 judged by multiple pediatric IBD experts provided a good average estimate of disease activity for the weighting. There are multiple precedents for utilizing the PGA in this way. It has been used to weight the items of the widely accepted CDAI3 and to validate the Pediatric

References (56)

  • G.H. Guyatt et al.

    A critical look at transition ratings

    J Clin Epidemiol

    (2002)
  • R.A. Deyo et al.

    Assessing the responsiveness of functional scales to clinical change: an analogy to diagnostic test performance

    J Chronic Dis

    (1986)
  • G. Guyatt et al.

    Measuring change over time: assessing the usefulness of evaluative instruments

    J Chronic Dis

    (1987)
  • M. Seo et al.

    Correlation between endoscopic severity and the clinical activity index in ulcerative colitis

    Am J Gastroenterol

    (1998)
  • G. Stucki et al.

    Relative responsiveness of condition-specific and generic health status measures in degenerative lumbar spinal stenosis

    J Clin Epidemiol

    (1995)
  • C. Su et al.

    A meta-analysis of the placebo rates of remission and response in clinical trials of active Crohn’s disease

    Gastroenterology

    (2004)
  • B.E. Sands et al.

    Optimal Crohn’s Disease Activity Index (CDAI) response criteria is defined by decrease >100 points (abstr)

    Gastroenterology

    (2003)
  • S.L. Werlin et al.

    Severe colitis in children and adolescents: diagnosis: course and treatment

    Gastroenterology

    (1977)
  • B.E. Sands

    Biological therapies for ulcerative colitis

    Acta Gastroenterol Belg

    (2001)
  • M. Seo et al.

    An index of disease activity in patients with ulcerative colitis

    Am J Gastroenterol

    (1992)
  • S.C. Truelove et al.

    Cortisone in ulcerative colitis; final report on a therapeutic trial

    Br Med J

    (1955)
  • D. Rachmilewitz

    Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial

    BMJ

    (1989)
  • K.W. Schroeder et al.

    Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitisA randomized study

    N Engl J Med

    (1987)
  • J. Powell-Tuck et al.

    A comparison of oral prednisolone given as single or multiple daily doses for active proctocolitis

    Scand J Gastroenterol

    (1978)
  • R.S. Walmsley et al.

    A simple clinical colitis activity index

    Gut

    (1998)
  • F. Azzolini et al.

    Proposal of a new clinical index predictive of endoscopic severity in ulcerative colitis

    Dig Dis Sci

    (2005)
  • M.S. Silverberg et al.

    Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology

    Can J Gastroenterol

    (2005)
  • R.M. Beattie et al.

    Endoscopic assessment of the colonic response to corticosteroids in children with ulcerative colitis

    J Pediatr Gastroenterol Nutr

    (1996)
  • Cited by (832)

    View all citing articles on Scopus

    Supported by a research fellowship stipend (to D.T.) from the Canadian Institute of Health Research/Canadian Association of Gastroenterology/Crohn’s and Colitis Foundation of Canada.

    The authors thank the pediatric IBD experts who participated in the Delphi process.

    Conflict of interest: None.

    1

    D.T. is the recipient of a postgraduate award, University of Toronto.

    View full text