Quantifying women's stated benefit-risk trade-off preferences for IBS treatment outcomes.
BACKGROUND
The Food and Drug Administration, currently, is exploring quantitative benefit-risk methods to support regulatory decision-making. A scientifically valid method for assessing patients' benefit-risk trade-off preferences is needed to compare risks and benefits in a common metric.


OBJECTIVE
The study aims to quantify the maximum acceptable risk (MAR) of treatment-related adverse events (AEs) that women with diarrhea-predominant irritable bowel syndrome (IBS) are willing to accept in exchange for symptom relief.


METHODS



METHODS
A stated-choice survey was used to elicit trade-off preferences among constructed treatment profiles, each defined by symptom severity and treatment-related AEs. Symptom attributes included frequency of abdominal pain and discomfort, frequency of diarrhea, and frequency of urgency. AE attributes included frequency of mild-to-moderate constipation and the risk of four possible serious AEs.


METHODS
A Web-enabled survey was administered to 589 female US residents at least 18 years of age with a self-reported diagnosis of diarrhea-predominant IBS.


METHODS
Preference weights and MAR were estimated using mixed-logit methods.


RESULTS
SUBJECTS were willing to accept higher risks of serious AEs in return for treatments offering better symptom control. For an improvement from the lowest to the highest of four benefit levels, subjects were willing to tolerate a 2.65% increase in impacted-bowel risk, but only a 1.34% increase in perforated-bowel risk.


CONCLUSIONS
Variation in MARs across AE types is consistent with the relative seriousness of the AEs. Stated-preference methods offer a scientifically valid approach to quantifying benefit-risk trade-off preferences that can be used to inform regulatory decision-making.
RTI International, Research Triangle Park, NC 27709-2194, USA. frjohnson@rti.org
F Reed
FR
Johnson
A Brett
AB
Hauber
Semra
S
Ozdemir
Larry
L
Lynd
D000328:Adult; D002243:Carbolines / Q000009:adverse effects*; D004335:Drug and Narcotic Control; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D057240:Patient Preference; D011788:Quality of Life; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data*; D012720:Severity of Illness Index; D014481:United States
D002243:Carbolines; D005765:Gastrointestinal Agents; C090840:alosetron