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
ARTICLE HIGHLIGHTS
Research background

The pediatric Crohn’s disease activity index (PCDAI) is a standard tool to assess disease activity in clinical trials for pediatric Crohn’s disease. Over time, concerns over both feasibility and short-term responsiveness to change in clinical status have arisen. Based on feasibility concerns, and new guidance recommending that symptoms are scored directly from a patient, the PCDAI was reexamined.

Research motivation

In response to a call from the Food and Drug Administration our team reexamined functioning of this index.

Research objectives

The objective of this study was 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.

Research methods

We retrospectively examined data from three completed studies – one registry study and two clinical trials involving pediatric patients with Crohn’s disease. Data was collected at baseline, at 3-mo (Q1) and 1-year (Q4). Change in individual PCDAI scores from baseline to Q1 and to Q4 were examined using the non-weighted PCDAI.

Research results

Abdominal pain, well-being, weight, and stooling had the highest change scores over time. Objective markers of disease activity including weight, albumin, and abdominal exam were amongst the next group of items that changed the most over time. Subjective and objective subgroups of items predicted less variance on total PCDAI scores at Q1 and Q4 compared to the full PCDAI, or a composite scale containing significant predictors.

Research conclusions

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. However, the results do indicate that subjective items such as abdominal pain and stooling in the short-term, and well-being in a longer-term measurement are adequate indicators of disease activity and response to treatment. Reliance on subjective or objective items as stand-alone proxies for disease activity measurement could result in misclassification of disease state.

Research perspectives

Subjective or objective items alone, as currently measured on the PCDAI, do not serve as a substitute for a robust patient-reported outcome measure. Complementary subjective (i.e., patient reported outcome measures) and objective markers of disease should be used to evaluate the outcomes of treatment.