Primary Endpoints for Irritable Bowel Syndrome Trials: A Review of Performance of Endpoints
The choice of primary endpoint for a clinical trial is one of the most important determinants of the ability of a clinical trial to demonstrate efficacy of therapeutic agents. Although there are still no clear, universally accepted guidelines on the definition of clinical benefit for irritable bowel syndrome (IBS), consensus guidelines stress the importance of using validated endpoints. This article reviews the evidence available in the literature on the psychometric validation and performance of the 3 endpoints recommended by the Rome III Committee for use as primary endpoints in treatment trials of IBS. The Rome III Committee recommends 2 types of measures: binary endpoints addressing the construct of relief (that is, adequate relief and satisfactory relief) and an integrative symptom questionnaire that addresses the change in severity of a representative group of symptoms of IBS (that is, the IBS Severity Scale). The current evidence suggests that at present, adequate relief should be recognized by regulatory authorities as an acceptable primary endpoint in clinical trials. This analysis also suggests that data from individual clinical trials should be pooled and undergo meta-analysis, and that prospective studies should be considered to further characterize the performance of available endpoints as outcome measures in pharmacotherapeutic trials in IBS.
Abbreviations used in this paper: FDA, Food and Drug Administration, FGID, functional gastrointestinal disorder, HMO, health maintenance organization, HRQOL, health-related quality of life, IBS, irritable bowel syndrome, IBS-SS, IBS Severity Scale, ICC, intraclass correlation, OTC, over the counter, PRO, patient-reported outcome, VAS, visual analog scale.
Drs Camilleri (RO1 DK54681, K24 DK02638), Drossman (R24 DK067674), Mayer (P50 DK64539, R24 AT002681, R01 DK58173, R01 DK48351), and Talley (UO1 DK 65713) receive grants for studies in the field of functional gastrointestinal disorders from the National Institutes of Health. The authors received support from RTI, a not-for-profit research institute, for travel to a face-to-face meeting. Dr Camilleri receives current research support for single center pharmacodynamic studies from GlaxoSmithKline, Johnson and Johnson, and Bristol-Myers Squibb and serves as a consultant for Astellas, Dynogen, GlaxoSmithKline, Novartis, Theravance, and Zeria. Dr Drossman receives research support from Novartis Pharmaceuticals, Microbia, and Procter & Gamble pharmaceuticals and is a consultant for Novartis, Procter & Gamble, Microbia, Astellas, and Tioga. Dr Fehnel is a consultant for Microbia, Novartis, and Tioga. Dr Mangel is a consultant for Tioga, Vela, Bristol-Myers Squibb, Astellas, GlaxoSmithKline, Trine, Napo, Microbia, Novartis, Boehringer Ingelheim, Pharmos, and Theravance. Dr Mayer receives research support for single center pharmacodynamic studies from Avera, GlaxoSmithKline, Johnson & Johnson, Lilly, and Novartis and serves as a consultant for GlaxoSmithKline, Novartis, Avera, Allergan, AstraZeneca, and Sanofi. Dr Talley is a consultant for AstraZeneca, Axcan, Chugai, EBMed, Giaconda, GlaxoSmithKline, Kosan, KV Pharmaceuticals, Medscape, ProEd Communication, Renovis, Inc, Solvay, Strategic Consultants International, Takeda Pharmaceuticals, Inc, TAP Pharmaceutical Products, Inc, Therapeutic Gastrointestinal Group, Theravance, Yamanouchi and receives research support from Merck KGaA, Novartis, TAP Pharmaceuticals, Axcan, Boehringer-Ingelheim, and Forest.
PII: S1542-3565(07)00242-X
doi:10.1016/j.cgh.2007.03.004
© 2007 AGA Institute. Published by Elsevier Inc. All rights reserved.
