The PAC-SYM questionnaire for chronic constipation: defining the minimal important difference
Y Yiannakou, J Tack, H Piessevaux, D Dubois, E M M Quigley, M Y Ke, S Da Silva, A Joseph, R Kerstens, Y Yiannakou, J Tack, H Piessevaux, D Dubois, E M M Quigley, M Y Ke, S Da Silva, A Joseph, R Kerstens
Abstract
Background: The Patient Assessment of Constipation-Symptoms (PAC-SYM) questionnaire is frequently used in clinical trials of constipation. However, the threshold for reduction in total PAC-SYM score used to define a clinical response on this 0-4 point scale has not undergone formal appraisal, and its relationship with clinical benefit as perceived by patients has not been defined.
Aim: To determine the minimal important difference in PAC-SYM score, and the optimum cut-off value for defining responders.
Methods: The minimal important difference was estimated using data from six international phase 3/4, double-blind, randomised controlled trials of prucalopride in patients with chronic constipation (NCT01147926, NCT01424228, NCT01116206, NCT00485940, NCT00483886, NCT00488137), with anchor- and distribution-based approaches. Five appropriate patient-reported outcomes were selected as anchors. In addition, receiver operating characteristics (ROC) curve analyses were used to investigate responder discrimination for each anchor.
Results: Data from 2884 patients were included. Minimal important difference estimates ranged from -0.52 to -0.63 across the five anchors. Estimates were not affected by study location but were consistently lower for rectal symptoms than for abdominal and stool symptoms. Distribution-based estimates were considerably lower than anchor-based estimates. ROC curve analyses showed optimum cut-off scores for discriminating responders to be similar to anchor-based minimal important difference estimates.
Conclusions: Anchor-based methods gave consistent results for the minimal important difference, at approximately -0.6, and this value was close to the ROC-determined optimal cut-off scores for responder discrimination. This value could be considered in clinical practice. A slightly more conservative threshold (eg -0.75) could be used in clinical trials to reduce the placebo response rate.
© 2017 Shire International GMBH. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
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Source: PubMed