Claire Ervin

Understanding the patient experience with carcinoid syndrome: Exit interviews from a randomized, placebo-controlled study of telotristat ethyl

PURPOSE Telotristat ethyl, an oral tryptophan hydroxylase inhibitor, is intended to treat carcinoid syndrome by reducing serotonin production. Telotristat ethyl was evaluated in TELESTAR, a Phase III study for patients who had carcinoid syndrome with at least 4 bowel movements (BMs) per day and who were receiving somatostatin analogue therapy. This interview substudy was conducted to provide insight into the patient experience in TELESTAR and to help understand whether reductions in BM frequency (the primary end point) and other symptoms were clinically meaningful. METHODS Participating sites were asked to invite (before randomization) all eligible patients to telephone interviews scheduled at the end of the double-blind treatment period. Patients and interviewers were blinded to treatment. FINDINGS All 35 interviewed participants reported diarrhea and/or excessive BMs at baseline. Patients reported that these symptoms negatively affected emotional, social, physical, and occupational well-being. Prespecified criteria for treatment response (achieving ≥30% reduction in BM frequency for at least 50% of the days) were met by 8 of 26 patients taking telotristat ethyl and 1 of 9 patients taking placebo. All 8 patients taking telotristat ethyl described clinically meaningful reductions in BM frequency and were very satisfied with the ability of the study drug to control their carcinoid syndrome symptoms. Overall, reports of being very satisfied were observed in 12 patients taking telotristat ethyl and 0 taking placebo. IMPLICATIONS Patient interviews revealed that TELESTAR patients, at baseline, were significantly affected by their high BM frequency. Patient reports of their clinical trial experience supported the significance of the primary end point and clinical responder analysis in TELESTAR, helping identify and understand clinically meaningful change produced by telotristat ethyl.

Urgency as an endpoint in irritable bowel syndrome

Background The choice of endpoints is crucial for proper evaluation of agents in clinical trials of irritable bowel syndrome (IBS). In a recently published draft guidance for IBS from the United States Food and Drug Administration (FDA), urgency was not considered an appropriate primary endpoint. The FDA’s position is that it is not clear how patients with diarrhea-predominant IBS (D-IBS) “define or describe urgency”. The aims of this study were to evaluate the association of urgency with stool frequency and consistency in patients with D-IBS and to describe results from patient interviews on their understanding of the term urgency. Methods A retrospective analysis of clinical trial data in patients with D-IBS was conducted. Analyses focused on the relationship of urgency to stool frequency and consistency. Interviews were conducted with patients with D-IBS to test their understanding of the term urgency. Results On the days that patients reported urgency, as compared to the days that patients did not report urgency, they had more frequent bowel movements (3.9 versus 1.8) and looser stools (Bristol Stool Score: 5.4 versus 4.2). The differences for both parameters, evaluated on the days with or without urgency, were statistically significant. In patient interviews, patients with D-IBS had a clear understanding of the concept and terminology of urgency and considered it one of their two most bothersome symptoms. Conclusions Urgency should be considered a suitable co-primary endpoint in D-IBS studies.

Development of the Diary for Irritable Bowel Syndrome Symptoms to Assess Treatment Benefit in Clinical Trials: Foundational Qualitative Research

BACKGROUND Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and alterations in bowel habits. Three subtypes are defined on the basis of stool patterns: diarrhea-predominant IBS, constipation-predominant IBS, and alternating or mixed IBS. OBJECTIVES To develop patient-reported outcome measures for qualification by the Food and Drug Administration to support product approvals and labeling in IBS; the article focuses on the qualitative research that provided the foundation for the new measures. METHODS Forty-nine concept elicitation and 42 cognitive debriefing interviews were conducted with subjects meeting Rome III criteria; additional criteria were imposed to yield a sample representative of the target patient population. RESULTS Although incomplete bowel movements, abnormal stool frequency and consistency, and abdominal pain, discomfort, and bloating were reported most frequently across concept elicitation interviews, the relative importance of specific symptoms varied by subtype. Among their five symptoms most important to treat, diarrhea-predominant and alternating or mixed IBS subjects frequently identified urgency, loose/watery stools, abdominal pain, and cramping, whereas constipation-predominant IBS subjects commonly included infrequent and incomplete bowel movements, bloating, and abdominal pain. The cognitive debriefing interviews facilitated refinement of each item set, supported minor modifications following translatability assessment, and suggested improvements to the electronic interface. Furthermore, subjects reported that every item was relevant and no concepts of importance were missing. CONCLUSIONS Results support the content validity of the IBS patient-reported outcome measures. A pilot study was recently initiated to inform item reduction, develop scoring algorithms, and provide preliminary psychometric information. Comprehensive psychometric evaluation and responder definition development will follow.

Development of the Painful Periods Screening Tool for endometriosis

ABSTRACT Objectives: Diagnostic delay is common in endometriosis. There is an unmet need for a symptom-based, patient-completed screening tool to facilitate discussions between patients and physicians about potential endometriosis symptoms. The objective of this study was to develop and assess the patient-completed Painful Periods Screening Tool (PPST) to assess the presence of potential endometriosis symptoms. Methods: To develop and refine the PPST, a cross-sectional qualitative study was conducted with women with endometriosis and healthy controls. Following identification of potentially relevant concepts in the literature and input from clinical experts, a draft version of the PPST was tested during in-depth individual interviews with 16 women: 11 with endometriosis and 5 healthy controls. Results: The six draft items of the PPST were refined iteratively in two rounds of interviews, and one item was deleted following the second set of interviews. All concepts included in the final five-item PPST were found to be relevant to women with endometriosis, and all 11 participants with endometriosis endorsed at least one of the items. No core symptoms of endometriosis were noted as missing from the PPST. Conclusion: The PPST assesses the most important endometriosis-related symptoms and may help facilitate discussions between patients and physicians, promoting earlier diagnosis and treatment of endometriosis.

Su2065 Qualitative Assessment of Symptom Experience in Patients With Irritable Bowel Syndrome for the Development of Patient-Reported Outcome Instruments

for the Development of Patient Reported Outcome Instruments Mollie J. Baird, MPH1; Robyn T. Carson, MPH2, Claire Ervin, MPH3; Lin Chang, MD4; Brennan Spiegel, MD4; Nancy J. Norton5; Jeffrey Lackner, PsyD6; Karen Lasch, MD7; and Sheri E. Fehnel, PhD3 on Behalf of the Critical Path Institute PRO Consortiums Irritable Bowel Syndrome Working Group 1Ironwood Pharmaceuticals, Cambridge, MA, USA; 2Forest Research Institute, Jersey City, NJ, USA; 3RTI Health Solutions, Research Triangle Park, NC, USA; 4Division of Digestive Diseases, University of California, Los Angeles, CA, USA; 5International Foundation for Functional Gastrointestinal Disorders, Milwaukee, WI, USA; 6University of Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, USA; 7Takeda Pharmaceuticals, Chicago, IL, USA

M1345 Assessing Treatment Response in Chronic Constipation Clinical Trials: Concepts Elicited Through Qualitative Interviews With Patients

INTRODUCTION The assessment of treatment response in CC trials has historically focused on bowel symptoms; however, the FDA guidance on patient reported outcome (PRO) measures recommends that selection of appropriate endpoints for clinical trials be based upon direct patient input obtained through open-ended patient interviews or focus groups. AIMS and METHODS The study aimed to identify a comprehensive set of CC symptoms important to patients and optimal terminology to measure those symptoms. Twenty-eight in-depth qualitative interviews were conducted in two geographic locations in patients meeting modified Rome II criteria for CC. A semi-structured interview guide was used, beginning with a series of open-ended questions to ascertain all relevant symptoms. Participants were subsequently probed to identify their most bothersome CC symptoms as well as other symptoms not mentioned spontaneously. RESULTS Patients spontaneously reported bowel symptoms including infrequent stools (28/28), hard stools (22/28) straining (20/28), unsuccessful attempts to have a BM (18/28), stools too small or too large (18/28), and incomplete BMs (13/28). In addition, patients frequently reported abdominal symptoms including bloating (22/28), abdominal pain (22/28), abdominal discomfort (15/28), stomach pains/aches (14/28), abdominal cramping (13/28), and feeling of fullness/feeling stuffed (13/ 28). Other symptoms elicited were predominantly the consequence of severe bowel or abdominal symptoms. For example, patients reported rectal pain, hemorrhoids, and rectal bleeding secondary to straining and hard stools. The symptoms reported most frequently by patients as their most bothersome included bloating, rectal pain, infrequent BMs, and abdominal pain. CONCLUSIONS This study is the first published report of symptoms spontaneously identified by CC patients through open-ended interviews using the methods outlined in FDAs guidance on PROs. Although patients identified a wide variety of symptoms, symptom assessment in a clinical trial should be focused on the most relevant symptoms reported by patients. These interview results suggest that in addition to bowel symptoms, abdominal symptoms are important and bothersome to CC patients and should be considered for inclusion in the assessment of treatment response in CC clinical trials.