title: Translating Clinical Findings into the Patient's Perspective: Post-hoc Pooled Analysis of Bowel Movement Changes as a Predictor of Improvement in Patients' Opioid-induced Constipation Symptoms and Outcomes.
abstract: Opioid-induced constipation (OIC) is a bothersome side effect of opioid use for the management of noncancer pain, affecting patients' health-related quality of life and chronic-pain management. The objective of this study was to examine the relationship between changes in the frequency of spontaneous bowel movements (SBMs) and changes in patient-reported outcomes (PROs) among patients with OIC treated with naloxegol.
  
  
  
  Post hoc analyses were conducted using pooled data from two Phase III 12-week, placebo-controlled trials of naloxegol for the treatment of OIC (NCT01309841 and NCT01323790). Patients completed the Patient Assessment of Constipation-Quality of Life (PAC-QOL) and PAC-Symptoms (PAC-SYM) at each study visit, and the Straining Scale and Bristol Stool Scale (BSS) with each bowel movement for the study duration. Four subgroups were created based on improvements from baseline in mean frequency of SBMs per week: 0 or worse (no change), +1 SBM, +2 SBMs, and +≥3 SBMs. Spearman correlations assessed the association between mean SBM changes from baseline and mean changes from baseline in PROs; analysis of covariance was used to compare changes from baseline.
  
  
  
  A total of 1337 patients with mean (SD) age of 52.2 (11.0) years were included in this analysis. The patient population was predominantly white (79.0%) and female (62.4%). At baseline, mean SBM frequency was 1.4 (1.0) per week. At study end, all 4 SBM-change subgroups experienced improvements in PAC-QOL, PAC-SYM, Straining Scale, and BSS scores, and these changes were significantly correlated with mean changes from baseline in SBMs per week. The subgroup of patients with an increase in SBMs of ≥3 per week experienced the greatest improvements in PROs.
  
  
  
  In these patients with OIC, an improvement in the frequency of SBMs by ≥3 per week was associated with consistent improvements in PROs, providing support for the use of improvements in SBMs as a clinical outcome surrogate for managing patients with OIC. Further research is needed to determine a threshold for change in SBMs that is clinically meaningful in both research and clinical settings. A key limitation was the post hoc nature of the study, which was not powered prospectively to examine these relationships.
authors.affiliation: Outcomes Research, Evidera, Bethesda, Maryland. Electronic address: karin.coyne@evidera.com.
authors.forename: Karin S
authors.initials: KS
authors.lastname: Coyne
authors.affiliation: Outcomes Research, Evidera, Bethesda, Maryland.
authors.forename: Jiat-Ling
authors.initials: JL
authors.lastname: Poon
authors.affiliation: Outcomes Research, Evidera, Bethesda, Maryland.
authors.forename: Christine
authors.initials: C
authors.lastname: Thompson
authors.affiliation: AstraZeneca, Wilmington, Delaware.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Hu
authors.affiliation: AstraZeneca, Wilmington, Delaware.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Datto
authors.affiliation: AstraZeneca, Gaithersburg, Maryland.
authors.forename: Mark
authors.initials: M
authors.lastname: Sostek
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use; D003248:Constipation / Q000139:chemically induced*; D006801:Humans; D007422:Intestines / Q000187:drug effects; D010146:Pain / Q000188:drug therapy; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic
chemical_list: D000701:Analgesics, Opioid
keywords: bowel movement changes; opioid-induced constipation; patient outcomes