ThePAC‐SYMquestionnaire for chronic constipation: defining the minimal important difference

Abstract

SummaryBackgroundThe 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.AimTo determine the minimal important difference in PAC‐SYM score, and the optimum cut‐off value for defining responders.MethodsThe 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.ResultsData 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.ConclusionsAnchor‐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.

Patients' Self-Assessment of the Symptoms and Impact of Opioid-Induced Constipation: Results From a Prospective Observational Cohort Study of Japanese Patients With Cancer

“…The PAC-SYM is a validated, patient-rated, 12-item questionnaire that measures the severity of constipationrelated symptoms for a two-week period in patients using opioid analgesics to manage chronic pain. 23,24 PAC-QOL is a validated 28-question assessment of the burden of constipation on patients' everyday functioning and well-being during the previous two weeks based on the impact of 12 symptoms across the four subscales of worries and concerns, physical discomfort, psychosocial discomfort, and satisfaction. 25,26…”

“…19 In addition, many patients who developed OIC reported feeling embarrassed, ashamed, or uncomfortable discussing their bowel habits with HCPs, resulting in substantial underdiagnosis and patient attempts to selftreat. 15,20e22 The validated patient-reported outcome (PRO) tools Patient Assessment of Constipation Symptoms (PAC-SYM) 23,24 and Patient Assessment of Constipation Quality of Life (PAC-QOL) 25,26 are frequently used in clinical trials and provide important measures of health-related QOL for patients with constipation. PRO measures indicate that OIC is frequently associated with severe abdominal pain, bloating, cramping, frustration, anxiety, depression, and disgust.…”

Patient dissatisfaction with medical therapy for chronic constipation or irritable bowel syndrome with constipation: analysis of N‐of‐1 prospective trials in 81 patients

“…M‐PAC‐SYM is a modified 11‐item score of the Patient Assessment of Constipation Symptoms (PAC‐SYM) score, which has been used to define the symptoms severity of outpatients with CC and IBS‐C enrolled in Italian referral centres: a >0.24 decrease was the minimal difference to define improvement after treatment . Furthermore, a recent secondary analysis of four randomised controlled trials with prucalopride has defined a >0.64 decrease in the standard PAC‐SYM score as the minimal difference to define improvement …”

“…5 Furthermore, a recent secondary analysis of four randomised controlled trials with prucalopride has defined a >0.64 decrease in the standard PAC-SYM score as the minimal difference to define improvement. 10 Beyond the standardised criteria to define satisfaction with therapy, it may be very helpful in both clinical practice and clinical trials to identify outcome-predicting factors. IBS diagnosis has been demonstrated to be a factor predicting more severe disease and poorer quality of life than CC.…”

Editorial: patient assessment of constipation‐symptoms (PAC‐SYM) questionnaire has a minimal important difference

“…Yiannakou et al have provided a numeric value of the threshold for reduction in total PAC‐SYM score to define a clinical response. This was generated using three methods.…”