Establishing Minimal Clinically Important Differences in Quality of Life Measures in Opioid-Induced Constipation.


Journal

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
ISSN: 1542-7714
Titre abrégé: Clin Gastroenterol Hepatol
Pays: United States
ID NLM: 101160775

Informations de publication

Date de publication:
04 2022
Historique:
received: 30 03 2020
revised: 30 04 2021
accepted: 02 05 2021
pubmed: 10 5 2021
medline: 17 3 2022
entrez: 9 5 2021
Statut: ppublish

Résumé

Opioids have a role in chronic pain management. However, opioid-induced constipation may cause patients to skip or reduce opioid doses, leading to inadequate pain relief and negatively impacting quality of life. We sought to establish a minimal clinically important difference to understand whether changes in quality of life scores are of value to patients. Integrated data from the double-blind, controlled, phase 3 COMPOSE-1 and COMPOSE-2 trials of naldemedine in chronic noncancer pain and opioid-induced constipation were used to determine minimal clinically important differences using Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaires. Patients completed the questionnaires (5-point Likert scale; predose, Weeks 2, 4, and 12), kept a daily log of Bowel Movement and Constipation Assessment, and rated satisfaction at end of study. Minimal clinically important differences were computed using an anchor-based method with 6 anchors: 5 from the Bowel Movement and Constipation Assessment and 1 from patient satisfaction. Threshold values for each anchor were set to define responders versus nonresponders based on score definitions. Clinically meaningful cutoff values for changes in PAC-SYM and PAC-QOL scores were determined using receiver operating characteristic curves. Data from 1095 patients (549, naldemedine; 546, placebo) were analyzed. The area under the curve for the receiver operating characteristic curves (ranges, 0.719 to 0.798 for PAC-SYM and 0.734 to 0.833 for PAC-QOL) indicated that both instruments can discriminate responders and nonresponders for each anchor. PAC-SYM cutoff values ranged from -1.04 to -0.83; PAC-QOL cutoff values ranged from -0.93 to -0.82. Based on data derived from the anchor method, reductions in PAC-SYM and PAC-QOL scores of >1.0 in patients with chronic noncancer pain and opioid-induced constipation are clinically meaningful. gov Registration: NCT01965158; NCT01993940.

Sections du résumé

BACKGROUND & AIMS
Opioids have a role in chronic pain management. However, opioid-induced constipation may cause patients to skip or reduce opioid doses, leading to inadequate pain relief and negatively impacting quality of life. We sought to establish a minimal clinically important difference to understand whether changes in quality of life scores are of value to patients.
METHODS
Integrated data from the double-blind, controlled, phase 3 COMPOSE-1 and COMPOSE-2 trials of naldemedine in chronic noncancer pain and opioid-induced constipation were used to determine minimal clinically important differences using Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaires. Patients completed the questionnaires (5-point Likert scale; predose, Weeks 2, 4, and 12), kept a daily log of Bowel Movement and Constipation Assessment, and rated satisfaction at end of study. Minimal clinically important differences were computed using an anchor-based method with 6 anchors: 5 from the Bowel Movement and Constipation Assessment and 1 from patient satisfaction. Threshold values for each anchor were set to define responders versus nonresponders based on score definitions. Clinically meaningful cutoff values for changes in PAC-SYM and PAC-QOL scores were determined using receiver operating characteristic curves.
RESULTS
Data from 1095 patients (549, naldemedine; 546, placebo) were analyzed. The area under the curve for the receiver operating characteristic curves (ranges, 0.719 to 0.798 for PAC-SYM and 0.734 to 0.833 for PAC-QOL) indicated that both instruments can discriminate responders and nonresponders for each anchor. PAC-SYM cutoff values ranged from -1.04 to -0.83; PAC-QOL cutoff values ranged from -0.93 to -0.82.
CONCLUSIONS
Based on data derived from the anchor method, reductions in PAC-SYM and PAC-QOL scores of >1.0 in patients with chronic noncancer pain and opioid-induced constipation are clinically meaningful.
CLINICALTRIALS
gov Registration: NCT01965158; NCT01993940.

Identifiants

pubmed: 33965574
pii: S1542-3565(21)00507-3
doi: 10.1016/j.cgh.2021.05.004
pii:
doi:

Substances chimiques

Analgesics, Opioid 0

Banques de données

ClinicalTrials.gov
['NCT01993940', 'NCT01965158']

Types de publication

Clinical Trial, Phase III Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

855-863

Informations de copyright

Copyright © 2022. Published by Elsevier Inc.

Auteurs

Jan Tack (J)

Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium. Electronic address: jan.tack@kuleuven.be.

Michael Camilleri (M)

Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, Minnesota.

Martin Hale (M)

Gold Coast Research, LLC, Plantation, Florida.

Bart Morlion (B)

Leuven Center for Algology and Pain Management, University Hospital Leuven, University of Leuven, Leuven, Belgium.

Srinivas Nalamachu (S)

Mid America PolyClinic, Overland Park, Kansas.

Lynn Webster (L)

PRA Health Sciences, Salt Lake City, Utah.

James Wild (J)

Upstate Clinical Research Associates, Williamsville, New York.

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Classifications MeSH