Preparation and Submission Support of a Full Qualification Package (FQP) for the Diary for Irritable Bowel Syndrome Symptoms—Diarrhea (DIBSS-D) (DDT #000148) - ABSTRACT Irritable bowel syndrome (IBS) is a chronic, oftentimes disabling gastrointestinal disorder characterized by recurrent abdominal pain associated with alterations in bowel habits (diarrhea and/or constipation). Three subtypes of IBS have been defined based on stool patterns: IBS with predominant diarrhea (IBS-D), IBS with predominant constipation (IBS-C), and alternating or mixed IBS (IBS-M). Approximately 10% to 15% of adults in the United States are affected by IBS, with IBS-D estimated to account for roughly a third of the cases. Due to the disruptiveness of the abdominal and bowel movement-related symptoms in their daily lives, IBS is among the top 10 reasons people consult a primary care physician. Although several global and symptom-specific PRO measures have been used to support approval of treatments for IBS, FDA encouraged the development of comprehensive subtype- specific symptom severity measures that meet its regulatory expectations. The PRO Consortium formed the IBS Working Group to meet this unmet measurement need. To begin the development of the Diary for Irritable Bowel Syndrome Symptoms–Diarrhea (DIBSS-D) and measures for the 2 other subtypes, the IBS Working Group reviewed the literature and conducted concept elicitation interviews to identify a comprehensive set of symptoms experienced by people with IBS. Based on these results and input from a patient representative and advisory panelists, a set of IBS symptoms was identified, and draft items were generated to assess the core symptoms of each subtype. Then, 3 rounds of cognitive interviews were conducted with 16 participants with IBS-D to ensure that the DIBSS-D addressed the IBS symptoms of greatest importance to participants and to optimize the item wording and response scales. The developmental DIBSS-D was subsequently tested in a cross-sectional observational study conducted at 10 clinical sites across the US that included 133 participants with IBS-D. Aim 1 of this proposed project is to analyze the data collected from participants with IBS-D in our cross-sectional observational study in accordance with the QP and its accompanying statistical analysis plan currently under QRT review. Aim 2 is to prepare a Full Qualification Package (FQP) in accordance with the most current version of FDA’s COA FQP content outline, and Aim 3 is to submit the DIBSS-D FQP to FDA. The intended result of this project will be a qualified, publicly available PRO measure for the assessment of abdominal and bowel- movement-related symptom severity in persons with IBS-D. Qualifying the DIBSS-D will fill a critical gap in the measurement of patient-reported clinical benefit in IBS-D treatment trials.
