Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2021; 27(30): 5100-5111
Published online Aug 14, 2021. doi: 10.3748/wjg.v27.i30.5100
Assessing disease activity using the pediatric Crohn’s disease activity index: Can we use subjective or objective parameters alone?
Amy Grant, Trudy Lerer, Anne M Griffiths, JS Hyams, Anthony Otley
Amy Grant, Anthony Otley, Division of Pediatrics, IWK Health, Halifax, NS B3K6R8, Canada
Trudy Lerer, Division of Research, Connecticut Children's Medical Center, Hartford, CT 06106, United States
Anne M Griffiths, Division of Gastroenterology Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON M5G1X8, Canada
JS Hyams, Division of Gastroenterology, Connecticut Children's Medical Center, Hartford, CT 06106, United States
Anthony Otley, Division of Pediatrics, Dalhousie University, Halifax, NS B3H4C3, Canada
Author contributions: Grant A acts as guarantor of this article; all authors contributed to the conception of the study; Grant A analyzed the data and wrote the manuscript; all other authors provided critical insight into analysis, interpretation of results, and revision of the manuscript; all authors approved the final version of the article, including the authorship list.
Institutional review board statement: Each individual study received institutional ethics review at each study site. Local Institutional Review Board approval was obtained by the IWK Health Center (Approval Nos: 3899, 2631, 2163).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Grant A and Lerer T have no conflicts of interest to disclose. Otley A is on the Advisory Board for Janssen Canada and AbbVie Canada, has received unrestricted educational grants from Janssen Canada and AbbVie Canada, has received research funding from AbbVie Global, and his centre is involved in an AbbVie clinical trial. Hyams J is on the Advisory Board for Janssen and Abbvie, and is a consultant for Pfizer, Boehringer Ingelheim, Lilly, Celgene, Allergan, and Roche. Griffiths A has served as a speaker or consultant or advisory board member for AbbVie, Amgen, Bristol Meyers Squibb, Celgene, Janssen, Lilly, Merck, Nestle, Pfizer, and Roche, and has received a research grant from AbbVie. None of the above conflicts are related to the current study.
Data sharing statement: Participants did not give informed consent for data sharing. Data is not available from the study authors.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Anthony Otley, FRCPC, MD, Doctor, Professor, Division of Pediatrics, Dalhousie University, 5850/5980 University Avenue Halifax, Halifax, NS B3H4C3, Canada. arotley@dal.ca
Received: February 20, 2021
Peer-review started: February 20, 2021
First decision: May 1, 2021
Revised: May 22, 2021
Accepted: July 27, 2021
Article in press: July 27, 2021
Published online: August 14, 2021
Processing time: 170 Days and 11.5 Hours
Abstract
BACKGROUND

The pediatric Crohn’s disease activity index (PCDAI) is used as a standard tool to assess disease activity in clinical trials for pediatric Crohn’s disease.

AIM

To examine which items on the PCDAI drive assessment of disease activity, and how subgroups of subjective and objective items reflect change in disease state over time.

METHODS

Selective raw data from three prospectively collected datasets were combined, including 703 children with full PCDAI data at baseline, at 3-mo (Q1, n = 670), and 1-year (Q4, n = 474). Change in individual PCDAI scores from baseline to Q1 and to Q4 were examined using the non-weighted PCDAI.

RESULTS

Abdominal pain, well-being, weight, and stooling had the highest change scores over time. Objective indicators including albumin, abdominal exam, and height velocity followed. Change scores for well-being and abdominal exam did not explain significant variance at Q1 but were significant predictors at Q4 (P < 0.001 and P < 0.05). Subjective and objective subgroups of items predicted less variance (18% and 22%) on total PCDAI scores at Q1 and Q4 compared to the full PCDAI, or a composite scale (both 32%) containing significant predictors.

CONCLUSION

Although subjective items on the PCDAI change the most over time, the full PCDAI or a smaller composite of items including a combination of subjective and objective components classifies disease activity better than a subgroup of either subjective or objective items alone. Reliance on subjective or objective items as stand-alone proxies for disease activity measurement could result in misclassification of disease state.

Keywords: Crohn’s disease; Pediatric Crohn’s disease activity index; Patient reported outcome measurement; Disease activity; Clinical trials; Pediatric

Core Tip: The pediatric Crohn’s disease activity index (PCDAI) is commonly used to assess disease activity in clinical trials. The PCDAI is a multi-item index incorporating subjective (e.g., patient well-being) and objective (e.g., laboratory tests) items. In response to a call from the Food and Drug Administration our team reexamined functioning of this index. Although subjective items on the PCDAI changed the most over time, the full PCDAI or a smaller composite of items that includes both subjective and objective components better classifies disease activity. Use of subjective or objective items on their own may result in misclassification of disease state.