Objectives:Many fecal incontinence (FI) studies define primary efficacy outcome as a decrease from baseline of ≥50% in the number of FI episodes; this threshold has never been validated. We aimed to establish the validity and responsiveness of ≥50% reduction in FI episodes (responder50) as the threshold indicative of clinically meaningful response.Methods:Adults with a Cleveland Clinic Florida fecal incontinence score ≥10 were randomized to receive nonanimal stabilized hyaluronic acid/dextranomer (NASHA/Dx) injection or sham treatment in a 6-month trial. Validity and responsiveness of the primary end point were evaluated post hoc. The data were compared using different thresholds for defining a responder for a number of end points.Results:Data from 206 patients (NASHA/Dx, n=136; sham, n=70) were evaluated. Incremental patient response threshold increases showed that although the percentage of patients who achieved response decreased with increasing threshold, the difference between treatments remained significant up to an 80% response threshold (NASHA/Dx, 23% sham, 10% P=0.02). Response thresholds between 40% and 80% demonstrated evidence for convergent validity, with the strongest correlation with the number of FI episodes, the number of FI episodes when the patient was awake, and the number of FI-free days observed at ≥40% and ≥50% thresholds. Further examination of the responder50 threshold indicated that, regardless of treatment (NASHA/Dx or sham), responders performed significantly better than nonresponders on nearly all secondary efficacy end points.Conclusion:This study demonstrates the responsiveness, validity, and clinical applicability of the ≥50% response threshold in clinical studies of patients with FI receiving treatment with NASHA/Dx.

Purpose: Chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) are common functional gastrointestinal disorders. The prevalence of constipation-related issues tends to increase with age. This analysis pooled data from Phase III trials in CIC and IBS-C to assess the safety and efficacy of plecanatide in patients aged 65 years. Methods: Patients randomized to receive plecanatide (3 or 6 mg) or placebo from two CIC and two IBS-C trials were pooled. Efficacy end points common to all trials included changes in stool consistency (Bristol Stool Form Scale), changes in weekly frequency of complete spontaneous bowel movements (CSBMs) and spontaneous bowel movements (SBMs), and time to first CSBM and SBM. Efficacy and safety profile results are reported per age group (65 and <65 years of age). Findings: The pooled intention-to-treat population comprised 451 patients aged 65 years (mean age, 70 years) and 4364 patients aged <65 years (mean age, 41.9 years), of whom 287 and 2914, respectively, were randomized to receive plecanatide. Compared with placebo, plecanatide produced statistically significant improvements in stool consistency from baseline at week 12 (both age groups), CSBM and SBM frequency from baseline at week 12 (plecanatide 3 mg group aged 65 years and both plecanatide groups aged <65 years), and time from start of therapy to first CSBM (both age groups) and SBM (plecanatide 6 mg group aged 65 years and both plecanatide groups aged <65 years). No new safety issues were observed. Implications: Plecanatide is a well-tolerated and effective treatment option for patients aged 65 years with CIC or IBS-C.

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