Assessment of treatment response in chronic constipation clinical trials

Abstract

Claire M Ervin,1 Sheri E Fehnel,1 Mollie J Baird,2 Robyn T Carson,3 Jeffrey M Johnston,2 Steven J Shiff,3 Caroline B Kurtz,2 Allen W Mangel11RTI Health Solutions, Research Triangle Park, NC, USA; 2Ironwood Pharmaceuticals, Inc., Cambridge, MA, USA; 3Forest Research Institute, Jersey City, NJ, USABackground: While chronic constipation (CC) clinical trials have focused primarily on bowel symptoms (symptoms directly related to bowel movements), abdominal symptoms are also prevalent among patients. The United States Food and Drug Administration’s (FDA’s) guidance on the use of patient-reported outcome measures to support product approvals or labeling claims recommends that endpoints be developed with direct patient input and include all symptoms important to patients.Aim: To identify a comprehensive set of CC symptoms that are important to patients for measurement in clinical trials.Methods: Following a targeted literature review to identify CC symptoms previously reported by patients, 28 patient interviews were conducted consistent with the FDA’s guidance on patient-reported outcomes. Subsequent to open-ended questions eliciting descriptions of all symptoms, rating and ranking methods were used to identify those of greatest importance to patients.Results: All 67 studies reviewed included bowel symptoms; more than half also addressed at least one abdominal symptom. Interview participants reported 62 potentially distinct concepts: 12 bowel symptoms; 21 abdominal symptoms; and 29 additional symptoms/impacts. Patients’ descriptions revealed that many symptom terms were highly related and/or could be considered secondary to CC. The rating and ranking task results suggest that both bowel (for example, stool frequency and consistency) and abdominal symptoms (for example, bloating, abdominal pain) comprise patients’ most important symptoms. Further, improvements in both bowel and abdominal symptoms would constitute an improvement in patients’ CC overall.Conclusion: Abdominal symptoms in CC patients are equal in relevance to bowel symptoms and should also be addressed in clinical trials to fully evaluate treatment benefit.Keywords: abdominal symptoms, straining, infrequent bowel movements, incomplete bowel movements, patient-reported outcomes