Crohn's Disease Patients' Risk-Benefit Preferences: Serious Adverse Event Risks Versus Treatment Efficacy

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doi:10.1053/j.gastro.2007.04.075 Copyright © 2007 AGA Institute Published by Elsevier Inc.

Clinical–alimentary tract

Crohn’s Disease Patients’ Risk-Benefit Preferences: Serious Adverse Event Risks Versus Treatment Efficacy

Presented in part at the International Society for Pharmacoeconomics and Outcomes Research, Philadelphia, Pennsylvania, May 2006, and at the annual meeting of the American Gastroenterological Association, Los Angeles, California, May 2006.

F. , , , Semra Özdemir, Carol Mansfield, Hass‡, W. ‡, Corey A. Siegel§ and Bruce E. Sands ‡Elan Pharmaceuticals, San Diego, CaliforniaResearch Triangle Institute/RTI International, Research Triangle Park, North CarolinaMGH Crohn’s and Colitis Center and Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts§IBD Center, Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire Received 2 November 2006; accepted 19 April 2007. Available online 3 May 2007.

Background & Aims: Regulatory assessments of drug risks do not routinely consider patient preferences, despite evidence that some patients are willing to accept increased side-effect risk in exchange for therapeutic benefits. The aim of this study is to estimate the willingness of Crohn’s disease (CD) patients to accept life-threatening adverse event risks in exchange for CD symptom relief. Methods: Patients with CD completed choice-format conjoint trade-off tasks involving hypothetical treatments with varying efficacy and risk levels. The treatment features included daily symptoms and activity limitations, serious complications (fistulas, abscesses, bowel obstructions), time between flare-ups, oral steroid use and risk of 3 serious adverse events (SAEs) known to be associated with CD treatment (progressive multifocal leukoencephalopathy (PML), serious infections, and lymphoma). The mean maximum acceptable annual risk (MAR) for each of the SAEs was calculated for various levels of clinical benefit. Results: Daily symptom severity was the most important factor in treatment preferences. Higher MAR was observed for trade-off tasks involving higher levels of clinical benefit. The MAR was similar across the 3 SAEs. For improvements from severe daily symptoms to remission and from moderate daily symptoms to remission, the MARs ranged from 0.69% to 0.81% and from 0.39% to 0.55%, respectively. Conclusions: Patients with CD have well-defined preferences among treatment attributes and are willing to accept tradeoffs among attributes. The patients indicated they are willing to accept elevated SAE risks in exchange for clinical efficacy. The perspective of the patients on the benefit versus risk balance can assist in making treatment and regulatory decisions. Abbreviations: CD, Crohn’s disease; IBD, inflammatory bowel disease; IBDQ, Inflammatory Bowel Disease Questionnaire; MAR, maximum acceptable annual risk; PML, progressive multifocal leukoencephalopathy; RTI, Research Triangle Institute; SAE, serious adverse event; SIBDQ, Short Inflammatory Bowel Disease Questionnaire

Support for this study was provided by Elan Pharmaceuticals, San Diego, California, and BiogenIdec, Cambridge, Massachusetts. Dr Sands has also received research funding and/or honoraria from Centocor, UCB Pharma, and Abbott Immunology. Dr Siegel has received honoraria from Abbott Immunology and UCB. Dr Hass and Dr are employees of Elan Pharmaceuticals and hold stock interests in the company. Each author participated in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the report for publication. As the supervisor for the study, F. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.Address requests for reprints to: F. , PhD, RTI Health Solutions, 200 Park Drive, PO Box 12194, Research Triangle Park, North Carolina 27709-2194. fax: .

Gastroenterology Volume 133, Issue 3, September 2007, Pages 769-779