Clinical—Alimentary TractPsychometric Evaluation of Patient-Reported Outcomes in Irritable Bowel Syndrome Randomized Controlled Trials: A Rome Foundation Report
Section snippets
Pooling Patient Level Data From Databases of IBS Clinical Trials
Prior to conducting psychometric analyses of IBS end points, we first sought to pool patient-level data from available trials. This allowed the opportunity to maximize the robustness and explanatory power of its findings and to test whether those findings can be generalized across data sets. The sections below describe the steps followed to systematically acquire, evaluate, and harmonize data from existing clinical trials.
Data Acquisition
We identified pharmaceutical companies that have previously conducted
Patient Characteristics
There were 9044 evaluable subjects in the 12 trials. The mean age was 44.3 years, and 85% were female. More than half of the sample had IBS-C (58%) and 31% IBS-D. Fifty-three percent of the cohort had received an investigational IBS treatment, whereas the rest received placebo. Using the binary response definition, 60% of the overall cohort achieved a response at the end of the study follow-up period. Table 3 displays the key descriptive statistics of patients included in the sample.
Effect of Baseline Severity on Responder Status for the Binary Responses
There were
Discussion
This pooled analysis was motivated by questions regarding the validity of traditional IBS end points, with particular focus on binary end points.6 The Rome Foundation Outcomes and Endpoints Committee combined data from over 9000 patients from 12 randomized controlled drug trials involving 5 separate investigational treatments with different mechanisms of action. Our goal was to leverage the power of this harmonized database to explicitly test key psychometric properties of binary end points and
Acknowledgments
The Rome Foundation thanks the participating pharmaceutical companies for their donated time and willingness to contribute data to this effort.
The authors thank Carlar Blackman of the Rome Foundation for her administrative and logistical support of this research project and Dr Douglas Drossman for his stewardship of the Rome Foundation and the pharmaceutical companies that donated their time and data to assist the Working Group in successfully completing this project.
Drs Emeran Mayer and Hashem
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Conflicts of interest The authors disclose the following: Dr Spiegel has served as a consultant for AstraZeneca, McNeail Consumer, Novartis, Prometheus, Takeda Pharmaceuticals, and TAP Pharmaceuticals and has received grant support from Amgen, AstraZeneca, Bristol Myers Squibb, Novartis, Salix, and Takeda. Dr Camilleri has served as a consult for GlaxoSmithKline and has received research support from Ironwood Pharmaceuticals and Novartis. Drs Fehnel and Mangel are employees of RTI Health Solutions. Dr Chey is a consultant for Novartis, GlaxoSmithKline, Solvay, and Ironwood and is on the speaker's bureau of Novartis. Dr Talley is a consultant for Astellas Pharma Inc US, AstraZeneca, Centocor, Eisai, Elsevier, Ferring Pharmaceuticals, Focus, Gilead, In2MedEd, Ironwood Pharmaceuticals, McNeil Consumer, Medscape, Meritage Pharma, Metabolic Pharma, Microbia Inc, Novartis, Optum HC, Salix, SK Life Sciences, Steigerwald, The Journal of Medicine, Therevance, and Wyeth and received grant support from GlaxoSmithKline, Dynogen, and Tioga. The remaining authors disclose no conflicts.
Funding Supported by the Rome Foundation and by a Veteran's Affairs Health Services Research and Development (HSR&D) Career Development Transition Award (RCD 03-179-2; to B.S.), the CURE Digestive Disease Research Center (NIH 2P30 DK 041301-17; to B.S.), and NIH Center Grant 1 R24 AT002681-NCCAM (to B.S.).