Abstract and Introduction
Background: Some drugs for irritable bowel syndrome (IBS) have serious side effects.
Aims: To examine the willingness of individuals with IBS to accept risks with medication in return for symptom cure.
Methods: We collected demographic, gastrointestinal symptoms, psychological health, quality of life and impact on work and daily activities data from 752 adults with Rome IV-defined IBS. We examined median willingness to accept death in return for cure with a hypothetical medication using a standard gamble, according to these variables.
Results: Participants would accept a median 2.0% (IQR 0.0%-9.0%) risk of death in return for a 98.0% (IQR 91.0%-100.0%) chance of permanent symptom cure. The median accepted risk of death was higher in men (5.0% vs 2.0%, P < 0.001), those with continuous abdominal pain (4.0% vs 1.0%, P < 0.001), more severe symptoms (P = 0.005 for trend), abnormal depression scores (P < 0.001 for trend), higher gastrointestinal symptom-specific anxiety (P < 0.001 for trend), and lower IBS-related quality of life (P < 0.001 for trend). Those willing to accept above median risk of death were more likely to be male (17.1% vs 9.1%, P < 0.001), take higher levels of risks in their daily life (P = 0.008 for trend), and report continuous abdominal pain (53.1% vs 39.4%, P < 0.001), and had higher depression (P = 0.004 for trend) and lower quality of life (P < 0.001 for trend) scores.
Conclusion: Patients are willing to accept significant risks in return for cure of their IBS symptoms.
Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction (DGBI) affecting 5% to 10% of the population, characterised by recurrent abdominal pain in association with abnormal stool form or frequency. Although the diagnosis is made using symptom-based criteria proposed by the Rome Foundation, the pathophysiology is complex and incompletely understood. As a result, patients with IBS form a heterogenous group of individuals possibly suffering from different underlying pathophysiological dysregulations but presenting with similar symptoms of abdominal pain and altered bowel habit.
For most patients, IBS is a chronic condition, with a relapsing and remitting course. Quality of life is affected to the same degree as organic gastrointestinal disorders, such as Crohn's disease. The condition also impacts on other aspects of daily life, such as work productivity,[6,7] social functioning,[8,9] and psychological health.[10–12] As the cause of IBS remains unclear, current treatment approaches target predominant gastrointestinal symptoms, rather than addressing specific underlying mechanisms. Most treatment trials demonstrate high placebo response rates and modest efficacy.[13–18] Although novel drugs continue to be developed, over the last 20 years several have been either withdrawn or their use restricted, due to safety concerns. Examples include ischemic colitis with alosetron, an excess of cardiovascular and cerebrovascular events with tegaserod, and episodes of acute pancreatitis with eluxadoline. Although regulatory bodies often have laypersons, including patients and carers, on their committee, they do not require formal consideration, review or quantification of the risks patients are willing to accept to relieve or cure their symptoms. In a chronic, incurable, condition like IBS, which has a huge impact on quality of life, and where most drugs have limited efficacy, it is important to determine these risks.
A previous survey established that individuals with IBS were, on average, willing to relinquish 15.1 years of their life to achieve perfect health with a new medication. In one study patients were willing to accept a 2.65% risk of bowel impaction and a 1.34% risk of bowel perforation from medication, although the use of a discrete choice experiment only allowed the authors to examine a specific set of trade-offs for a drug for use in women with IBS with diarrhoea (IBS-D). Two other studies reported that patients with IBS were willing to accept a median 1% risk of sudden death for a 99% chance of cure of their symptoms, and that patients with IBS with predominant severe diarrhoea would accept a mean 10.2% risk of sudden death for a 99% chance of cure, but these studies were relatively small and patients were recruited from referral populations. In addition, three of these previous studies used the Rome III criteria for IBS, but symptom severity appears worse with the current Rome IV criteria, so their findings may no longer be applicable. Finally, none of these examined predictors of a higher acceptance of medication-related risk among individuals with IBS. We, therefore, examined willingness to accept risks with medications in return for cure of symptoms in a cohort of individuals with IBS defined according to the Rome IV criteria.
Aliment Pharmacol Ther. 2022;55(10):1311-1319. © 2022 Blackwell Publishing