OBJECTIVE: Linaclotide, a minimally absorbed peptide agonist of the intestinal guanylate cyclase type-C receptor, is an investigational treatment for irritable bowel syndrome with constipation (IBS-C) and chronic constipation (CC). Analyses of two Phase 3 clinical trials of linaclotide were conducted to provide evidence of the psychometric properties of patient-reported outcome (PRO) measures assessing changes in the severity of abdominal and bowel symptoms of IBS-C.
METHODS: 1602 adult patients with IBS-C in the pooled ITT population who participated in two Phase 3 multicenter, double-blind, placebo-controlled, clinical trials of linaclotide were randomized to 290 lg or placebo administered orally once daily. Nine daily PRO measures addressing abdominal symptoms (pain, discomfort, bloating, fullness, cramping) and bowel symptoms (spontaneous bowel movement [SBM]/complete SBM [CSBM] frequency, stool consistency, straining) and four weekly PRO measures (constipation severity, IBS symptom severity, degree of relief, adequate relief) were administered using interactive voice response system technology. Test-retest reliability (intra-class correlation coefficients), construct validity (Pearson correlations), discriminating ability (known-groups Ftests), and responsiveness (Guyatt’s statistics) were evaluated.
RESULTS: The IBS-C PRO items showed highly satisfactory test-retest reliability, ranging from a minimum of 0.75 for Stool Consistency and Adequate Relief to a maximum of 0.95 for Abdominal Fullness. Correlation analyses supported the construct validity of the IBS-C PRO items (see Table). All hypothesis tests based on a variety of responder status groups were statistically significant and in the predicted direction, substantiating the discriminating ability of the IBS-C PRO items. With few exceptions, responsiveness statistics were highly satisfactory, demonstrating that the items were easily capable of detecting change.
CONCLUSION: In two large Phase 3 trials of IBS-C patients, linaclotide significantly improved patientreported measures of abdominal symptoms, bowel symptoms, and global assessments. The psychometric analyses strongly support the reliability, validity, responsiveness, and usefulness of these IBS-C PRO items.
