Gastroenterology

Gastroenterology

Volume 137, Issue 6, December 2009, Pages 1944-1953.e3
Gastroenterology

Clinical—Alimentary Tract
Psychometric Evaluation of Patient-Reported Outcomes in Irritable Bowel Syndrome Randomized Controlled Trials: A Rome Foundation Report

https://doi.org/10.1053/j.gastro.2009.08.047Get rights and content

Background & Aims

There is debate about how best to measure patient-reported outcomes (PROs) in irritable bowel syndrome (IBS). We pooled data to measure the psychometric properties of IBS end points, including binary responses (eg, “adequate relief”) and 50% improvement in symptom severity.

Methods

We pooled data from 12 IBS drug trials involving 10,066 participants. We tested the properties of binary response and 50% improvement end points, including the impact of baseline severity on performance, and measured construct validity using clinical anchors.

Results

There were 9044 evaluable subjects (age, 44 years; 85% female; 58% IBS constipation-prominent [IBS-C]; 31% IBS diarrhea-prominent [IBS-D]). Using the binary end point, the proportion responding in the mild, moderate, and severe groups was 42%, 40%, and 38%, respectively (P = .0008). There was no effect of baseline severity on binary response (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.99–1.0; P = .07). The proportions reaching 50% improvement in pain were 45%, 41%, and 41%, respectively; there was a small, yet significant, impact of baseline severity (OR, 1.04; 95% CI, 1.03–1.05; P < .0001) that did not meet clinical relevance criteria. Both end points revealed strong construct validity and detected “minimally clinically important differences” in symptoms. Both provided better discriminant spread in IBS-D than IBS-C.

Conclusions

Both the traditional binary and 50% improvement end points are equivalent in their psychometric properties. Neither is impacted by baseline severity, and both demonstrate excellent construct validity. They are optimized for the IBS-D population but also appear valid in IBS-C.

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

References (20)

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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.).

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