Willingness to pay for medications among patients with Rome IV Irritable Bowel Syndrome

Abstract Background Little is known about willingness to pay for medications among individuals with irritable bowel syndrome (IBS). Methods We collected demographic, gastrointestinal symptom, psychological health, quality of life, and healthcare usage data from 752 adults with Rome IV‐defined IBS. We examined willingness to pay for a hypothetical medication in return for improvement in IBS symptoms using a contingent valuation method, according to these variables. Results The median amount of money individuals was willing to pay was £1–£50 (IQR £0–£100) per month for a medication with a 100% chance of improving IBS symptoms. Women, compared with men, (92.7% willing to pay “£0,” 89.8% “£1–£50,” 87.3% “£51–£100,” 78.9% “£101–£200,” and 78.5% “more than £200,” p = 0.008) were less likely to be willing to pay for a pill with a 100% chance of improving IBS symptoms whilst those with an annual income of £30,000 or more (12.2% willing to pay “£0,” 25.2% “£1–£50,” 33.5% “£51–£100,” 40.2% “£101–£200,” and 35.1% “more than £200,” p = 0.002) were more likely. We observed a higher willingness to pay among those with lower IBS‐related quality of life (p = 0.002 for trend). Of all 752 individuals, 92.7%, 74.5%, and 58.0% would be willing to pay for a medication that would give them a 100%, 50%, or 30% chance of improving IBS symptoms, respectively. Conclusion Patients with IBS are willing to pay for medications which improve IBS symptoms. Future studies should investigate the relative importance of medication pricing, efficacy, and side effect profile among individuals with IBS.


| INTRODUC TI ON
Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction characterized by recurrent abdominal pain in association with abnormal stool form or frequency. 1 It affects between 5% and 10% of the world's population. [2][3][4] A diagnosis of IBS is reached using symptom-based criteria proposed by the Rome Foundation, the Rome IV criteria, 5 in patients with typical symptoms in the absence of red flags and limited investigations. 6,7 IBS is a chronic disorder with a relapsing and remitting course, 8 partly because of the modest efficacy of medications. [9][10][11][12][13] Current treatment strategies aim to alleviate the predominant gastrointestinal symptom(s) reported by patients. 14,15 Patients exhibit reductions in quality of life of the same magnitude as those with organic gastrointestinal disorders, such as Crohn's disease. 16 IBS affects people in their activities of daily living and at work, 17,18 and costs an estimated £1.3-£2 billion per year to the UK National Health Service (NHS). 19 In an attempt to improve their health, individuals with IBS are willing to accept substantial risks from medications. [20][21][22] In the UK, the Medicines and Healthcare products Regulatory Agency is the responsible agency to ensure medicines meet an acceptable standard of safety and efficacy. 23 In addition, the National Institute for Health and Care Excellence (NICE), considers the cost of these medications to decide whether they should be funded by the NHS using public funds. 24 Partly as a result of cost, patients' access to some drugs is limited because they can only be initiated in secondary care, rather than by general practitioners (GPs). This has led some pharmaceutical companies to cease promotion of certain drugs for IBS or even, in the case of lubiprostone and eluxadoline, withdraw them from the market.
Even though lay persons and patients are involved in decisions taken by NICE, there are a lack of data on willingness to pay to guide an acceptable threshold for cost that can be used to determine access to medications in the NHS. Additionally, because several medications for IBS are bought by patients over the counter, it is crucial to evaluate individual's willingness to pay from their own pocket for drugs.
A previous cross-sectional study reported that among individuals with IBS whose annual salary was <$75,000 (approximately £62,000), the willingness to pay for a medication to improve IBS symptoms was between $49.4 (approximately £41) and $73.3 (approximately £61) per month depending on symptoms. 22 However, the study findings were limited by the relatively small population used. In addition, the authors did not examine willingness to pay according to other demographic characteristics, IBS characteristics, or psychological factors that are commonly associated with IBS. We, therefore, examined these issues in a cross-sectional study recruiting a large cohort of individuals with IBS. We hypothesized that most individuals with IBS would be willing to pay for a hypothetical medication with a 100% chance of improving IBS symptoms, but that this may be affected by personal finances, symptom severity, psychological health, and IBS-related quality of life.

| Participants and Setting
We recruited individuals registered with ContactME-IBS, a national UK registry run by County Durham and Darlington NHS Foundation Trust, whose members have IBS and are interested in research. 25 We have reported data from this cohort previously. 17,19,20 Briefly, the registry advertises itself to individuals in the community via numerous sources including posters in primary care, specialist hospital clinics, pharmacies, or social media. Individuals enroll by completing a short questionnaire about bowel symptoms and providing contact details. Among all 4280 registrants, 2268 (53%) have seen their GP with IBS, and another 1455 (34%) a gastroenterologist.
There were no exclusion criteria for this study apart from the inability to understand written English. We contacted all registered individuals, via electronic mailshot, in July 2021, directing them to an online questionnaire and information about the study. All responses were stored in an online database and non-responders received a reminder email in August 2021. Participants were given a chance to win one of three gift cards (worth £200, £100, or £50) in return for completing the questionnaire. The University of Leeds research ethics committee approved the study in March 2021 (MREC 20-051).

| Demographic and Symptom Data
We collected basic demographic data, including age, sex, lifestyle (tobacco and alcohol consumption), ethnicity, marital status, educational level, and annual income. We defined presence of IBS according to the Rome IV questionnaires, 26 assigning the presence or absence of Rome IV-defined IBS among all individuals according to the scoring algorithm proposed for its use. 5 We categorized IBS

Key Points
• There is limited knowledge about the willingness to pay for medications in IBS. We conducted a cross-sectional study among individuals with Rome IV-defined IBS to examine their willingness to pay for a hypothetical medication.
• Participants were willing to pay a median £1-£50 per month for a hypothetical medication with a 100% chance of improving IBS symptoms. We observed several factors associated with a higher willingness to pay.
• These results have important implications for pharmaceutical companies and regulatory agencies. We used validated questionnaires, as we have described previously. 17,19,20 Briefly, we assessed severity of symptoms using the IBS severity scoring system (IBS-SSS), 27 which carries a maximum score of 500 points, with <75 points indicating remission; 75-174 points mild; 175-299 points moderate; and 300-500 points severe symptoms. We used the hospital anxiety and depression scale (HADS) to collect anxiety and depression data.

| IBS-related Resource Use
We collected data on healthcare usage related to a person's IBS over the 12 months prior to recruitment. We asked participants to report any appointments with healthcare professionals (GPs, gastroenterologists, specialist nurses, dietitians, or psychologists), including the number of appointments, number of investigations (blood tests, stool tests, endoscopies, abdominal ultrasounds, computed tomography scans, magnetic resonance imaging scans, hydrogen breath tests, or 23-seleno-25-homo-tauro-cholic acid scans), number of unplanned emergency department attendances or inpatient admissions (including length of stay), and over the counter and prescribed medication usage (in months). We applied costs for GP appointments from Unit Costs of Health and Social Care 2020, 34 and other appointments, investigations, or unplanned inpatient days in secondary care using the NHS's 2019/20 National Cost Collection Data. 35 We assumed all appointments for IBS were follow-up appointments, which cost less than a new patient appointment. We applied the lowest price for a 1-month supply of each IBS-related medication using the online version of the British National Formulary. 36

| Willingness to Pay for Improvement of IBS Symptoms
We used a contingent valuation method. This is a technique in which respondents are asked to state their preferences in a hypothetical scenario, to determine the amount of their own money they were willing to pay per month for a hypothetical medication in return for a 100% chance of improving IBS symptoms. As there is no validated questionnaire to assess IBS patient's willingness to pay for medication, we used a set of questions to examine participants' willingness to pay with potential responses on a 12-point scale from "not willing to pay anything" to "more than £500" with each response in between representing equal £50 increments (e.g., "£1-£50," "£51-100," "£101-£150"). We also examined how much money participants were willing to pay per month if the medication only had a 30% or 50% chance of improving IBS symptoms.

| Choice of pill
We asked participants to choose a pill they would prefer to take from a list of eight pills. Four pills relieved one symptom (pain, bloating, diarrhea, or constipation) almost completely, but hardly relieved other symptoms, whilst the other four pills relieved one symptom (pain, bloating, diarrhea, or constipation) well and relieved other symptoms a little.

| Statistical Analysis
Because data were skewed positively, we categorized individuals in groups of those who were willing to pay "£0," "£1-£50," "£51-£100," "£101-£200," and "more than £200." We examined characteristics of participants in each of these groups. We also examined the pill participants would prefer according to IBS subtype and most troublesome symptom. We compared categorical variables such as sex, ethnicity, IBS subtype, IBS-SSS severity, presence or absence of abnormal anxiety or depression scores, levels of somatic symptomreporting, levels of gastrointestinal symptom-specific anxiety, and levels of quality of life using a χ 2 test and continuous data such as age, mean annual cost of medications for IBS, and mean annual direct healthcare cost of IBS using one-way analysis of variance for continuous data. Statistical significance was defined as a p value <0.01. The median annual income of respondents was £20,000-£29,999 (interquartile range [IQR] £10,000-£39,999). The median amount of their own money individuals with IBS was willing to pay per month for a hypothetical medication with a 100% chance of improving their symptoms was £1-£50 (IQR £0-£100).

| Willingness to Pay for a Hypothetical Medication with Varying Chance of Improvement of IBS symptoms
We examined the proportion of individuals who were willing to pay for a hypothetical medication with a 100%, 50%, or 30% chance of improving symptoms of IBS. The median amount of money individuals was willing to pay were £1-£50 (IQR £0-£50), 1-£50 (IQR £0-£50), and 1-£50 (IQR £0-£100) for a 30%, 50%, and 100% chance of improvement of IBS symptoms respectively. Figure 1 shows the proportion of individuals with Rome IV IBS according to the amount of money they would be willing to spend per month for each medication. Of 752 people, 55 (7.3%), 192 (25.5%), and 316 (42.0%) were not willing to pay anything for a medication that would give them a 100%, 50%, or 30% chance of improving IBS symptoms respectively.
Conversely, 697 (92.7%), 560 (74.5%), and 436 (58.0%) individuals were willing to pay for a medication that would give them a 100%, 50%, or 30% chance of improving IBS symptoms, respectively. For a 100% chance of improvement of IBS symptoms, 21.3% of the 752 participants were willing to pay more than £100 per month and 13.0% were willing to pay £150 per month.

| Choice of pill
When asked about their preference out of eight pills, 602 (80.1%) individuals chose one of the four pills that relieved pain, bloating, diarrhea, or constipation well and relieved other symptoms a little (pills E to H), whereas 150 (19.9%) chose one of the other four pills that relieved pain, bloating, diarrhea, or constipation almost completely, but hardly relieved other symptoms (pills A to D) ( Figure 2).
We observed a significant difference in the choice of pill among individuals with different IBS subtypes (p < 0.001 for trend) ( Table 2) and those who reported different symptoms as their most troublesome (p < 0.001 for trend) ( Figure 3 and Table 3

| DISCUSS ION
This cross-sectional study recruited 752 individuals with Rome IV-defined IBS to examine willingness to pay for a medication that improves the symptoms of IBS. The median amount of money individuals was willing to pay was £1-£50 per month for a medication with a 100% chance of improving IBS symptoms. Men, individuals earning £30,000 or more annually, those with higher mean costs for IBS medications in the last 12 months, and those with lower IBSrelated quality of life were willing to pay more for a medication with TA B L E 1 Characteristics of individuals with Rome IV IBS according willingness to pay per month for a hypothetical medication with a 100% chance of improving symptoms a 100% chance of improving IBS symptoms. There were significantly higher proportions of individuals with more severe IBS or higher somatic symptom-reporting scores among those who were not willing to pay anything ("£0") and those who were willing to pay the most ("more than £200").    have underestimated willingness to pay. One study demonstrated willingness to pay for healthcare services increased when participants were interviewed face-to-face, rather than completing an online questionnaire. 40 As the NHS in the UK is free at the point of use and collects a fixed charge for NHS prescriptions from patients, participants in this study may be unfamiliar with costs of healthcare those not willing to pay anything ("£0") and among those willing to pay the most ("more than £200"), with a similar trend among those with higher depression scores, is interesting. One possible explanation is that in those with more severe IBS, higher levels of somatic symptom-

ACK N OWLED G M ENT
We are grateful to the patients who gave their time freely to answer our questionnaire.

FU N D I N G I N FO R M ATI O N
Unrestricted research monies were provided by Tillotts Pharma UK Ltd. The funder had no input into the concept, design, analysis, or reporting of the study.

CO N FLI C T S O F I NTE R E S T
Guarantor of the article: ACF is guarantor. All author have no conflict of interest.