American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

Up-Front Endoscopy Maximizes Cost-Effectiveness and Cost-Satisfaction in Uninvestigated Dyspepsia.

BACKGROUND & AIMS: Practice guidelines promote a routine noninvasive, non-endoscopic initial approach to investigating dyspepsia without alarm features in young patients, yet many patients undergo prompt upper endoscopy. We aimed to assess tradeoffs among costs, patient satisfaction, and clinical outcomes to inform discrepancy between guidelines and practice. METHODS: We constructed a decision-analytic model and performed cost-effectiveness/cost-satisfaction analysis over a 1-year time horizon on patients with uninvestigated dyspepsia without alarm features referred to gastroenterology. A RAND/UCLA expert panel informed model design. Four competing diagnostic/management strategies were evaluated: prompt endoscopy, testing for Helicobacter pylori and eradicating if present (test-and-treat), testing for H pylori and performing endoscopy if present (test-and-scope), and empiric acid suppression. Outcomes were derived from systematic reviews of clinical trials. Costs were informed by prospective observational cohort studies and national commercial/federal cost databases. Health gains were represented using quality-adjusted life years. RESULTS: From the patient perspective, costs and outcomes were similar for all strategies (maximum out-of-pocket difference of $30 and <0.01 quality-adjusted life years gained/year regardless of strategy). Prompt endoscopy maximized cost-satisfaction and health system reimbursement. Test-and-scope maximized cost-effectiveness from insurer and patient perspectives. Results remained robust on multiple one-way sensitivity analyses on model inputs and across most willingness-to-pay thresholds. CONCLUSIONS: Noninvasive management strategies appear to result in inferior cost-effectiveness and patient satisfaction outcomes compared with strategies promoting up-front endoscopy. Therefore, additional studies are needed to evaluate the drivers of patient satisfaction to facilitate inclusion in value-based healthcare transformation efforts.

Evaluating the Impact of Cost on the Treatment Algorithm for Chronic Idiopathic Constipation: Cost-Effectiveness Analysis.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common and burdensome illness. We performed a cost-effectiveness analysis of the US Food and Drug Administration-approved CIC drugs to evaluate and quantify treatment preferences compared with usual care from insurer and patient perspectives. METHODS: We evaluated the subset of patients with CIC and documented failure of over-the-counter (OTC) osmotic or bulk-forming laxatives. A RAND/UCLA consensus panel of 8 neurogastroenterologists informed model design. Treatment outcomes and costs were defined using integrated analyses of registered clinical trials and the US Centers for Medicare and Medicaid Services-supported cost databases. Quality-adjusted life years (QALYs) were calculated using health utilities derived from clinical trials. A 12-week time horizon was used. RESULTS: With continued OTC laxatives, CIC-related costs were $569 from an insurer perspective compared with $3,154 from a patient perspective (considering lost wages and out-of-pocket expenses). CIC prescription drugs increased insurer costs by $618-$1,015 but decreased patient costs by $327-$1,117. Effectiveness of CIC drugs was similar (0.02 QALY gained/12 weeks or ∼7 healthy days gained/year). From an insurer perspective, prescription drugs (linaclotide, prucalopride, and plecanatide) seemed less cost-effective than continued OTC laxatives (incremental cost-effectiveness ratio >$150,000/QALY gained). From a patient perspective, the cost-effective algorithm started with plecanatide, followed by choosing between prucalopride and linaclotide starting at the 145-µg dose (favoring prucalopride among patients whose disease affects their work productivity). The patient perspective was driven by drug tolerability and treatment effects on quality of life. DISCUSSION: Addressing costs at a policy level has the potential to enable patients and clinicians to move from navigating barriers in treatment access toward truly optimizing treatment choice.

Price Is Right: Exploring Prescription Drug Coverage Barriers for Irritable Bowel Syndrome Using Threshold Pricing Analysis.

BACKGROUND: Prescription drug costs exert profound effects on commercial insurance coverage and access to effective therapy. AIMS: We aimed to assess threshold pricing to achieve budget neutrality of FDA-approved drugs treating irritable bowel syndrome from an insurance perspective, based on cost-savings resulting in decreased healthcare utilization through effective disease management. METHODS: We constructed a decision-analytic model from an insurance perspective to assess the budget impact of IBS prescription drugs under usual insurance coverage levels in practice: (1) unrestricted drug access or (2) step therapy in a primary care population of middle-age, care-seeking IBS patients. Budget-neutral drug prices were then calculated which resulted in $0 budget impact to insurers with a short-term, one-year time horizon. RESULTS: If used according to FDA labeling, IBS-D drugs cost between $4778 and $16,844 per year and IBS-C drugs cost between $4319 and $4955 per year. These drug costs often exceed insurance expenditures of $6999 for IBS-D and $3929 for IBS-C if left untreated. Therefore, for drugs to have $0 budget impact to insurers, their prices would need to be discounted 36.7-74.2% for IBS-D drugs and 59.3-82.5% for IBS-C. IBS drugs are already priced to support step therapy "failing one of several common, inexpensive IBS treatments with a responder rate > 30-40%," reflecting the subpopulation with more severe disease and greater healthcare costs. CONCLUSIONS: Broader prescription drug coverage for patients failing common, inexpensive IBS treatments to which at least 30-40% of patients would typically respond appears warranted to enable gastroenterologists to offer personalized approaches targeting specific mechanisms of this heterogeneous disease.

Effects of Irritable Bowel Syndrome on Daily Activities Vary Among Subtypes Based on Results From the IBS in America Survey.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is associated with significant disease burden and decreased quality of life (QOL). We investigated the effects of IBS on different areas of daily function and compared these among disease subtypes. METHODS: The Life with IBS survey was conducted by Gfk Public Affairs & Corporate Communications from September through October 2015. Respondents met Rome III criteria for constipation-predominant or diarrhea-predominant IBS (IBS-C and IBS-D, respectively). Data were collected from 3254 individuals (mean age, 47 years; 81% female; and 90% Caucasian) who met IBS criteria. RESULTS: Respondents who were employed or in school (n = 1885) reported that IBS symptoms affected their productivity an average of 8.0 days out of the month and they missed approximately 1.5 days of work/school per month because of IBS. More than half the individuals reported that their symptoms were very bothersome. Individuals with IBS-C were more likely than with IBS-D to report avoiding sex, difficulty concentrating, and feeling self-conscious. Individuals with IBS-D reported more avoidance of places without bathrooms, difficulty making plans, avoiding leaving the house, and reluctance to travel. These differences remained when controlling for symptom bothersomeness, age, sex, and employment status. In exchange for 1 month of relief from IBS, more than half of the sample reported they would be willing to give up caffeine or alcohol, 40% would give up sex, 24.5% would give up cell phones, and 21.5% would give up the internet for 1 month. CONCLUSIONS: Although the perceived effects of IBS symptoms on productivity are similar among its subtypes, patients with IBS-C and IBS-D report differences in specific areas of daily function.

Emergency Department Burden of Gastroparesis in the United States, 2006 to 2013.

BACKGROUND AND AIMS: Gastroparesis, a chronic gastrointestinal disorder defined by delayed stomach emptying in the absence of obstruction, is often associated with frequent and costly visits to the emergency department (ED). The aim of this study was to analyze trends in gastroparesis-related ED visits from 2006 to 2013. MATERIALS AND METHODS: Patients with a primary diagnosis of gastroparesis were identified from the Nationwide Emergency Department Sample (NEDS), the largest publicly available ED all-payer representative database in the United States. ED visits, admission rates, duration of hospitalizations, and charges were compiled. Patients with a secondary diagnosis of diabetes mellitus were analyzed as a subgroup. RESULTS: The number of ED visits for gastroparesis as a primary diagnosis in the United States increased from 15,459 in 2006 to 36,820 in 2013, an increase from 12.9 to 27.3 per 100,000 ED visits. The total charges associated with these ED visits and subsequent admissions increased from $286 million to $592 million. In contrast, admission rates through the ED decreased by 22%, procedure rates decreased by 6.2%, and the mean length of stay was shortened by 0.6 days. ED visits for patients with diabetic gastroparesis increased from 5696 to 14,114, an increase from 4.7 to 10.5 per 100,000 ED visits, with an increase in total associated charges for ED visits and subsequent admissions from $84 million to $182 million. CONCLUSIONS: The number of ED visits and associated charges for a primary diagnosis of gastroparesis with or without a secondary diagnosis of diabetes mellitus rose significantly from 2006 to 2013.

Characterizing Normal Bowel Frequency and Consistency in a Representative Sample of Adults in the United States (NHANES).

OBJECTIVES: Our current understanding of normal bowel patterns in the United States (US) is limited. Available studies have included individuals with both normal and abnormal bowel patterns, making it difficult to characterize normal bowel patterns in the US. The current study aims to (1) examine frequency and consistency in individuals with self-reported normal bowel habits and (2) determine demographic factors associated with self-reported normalcy. METHODS: This study used data from adult participants who completed bowel health questions as part of the National Health and Nutrition Examination Survey (NHANES) in 2009-2010 and who reported normal bowel patterns (N=4,775). Data regarding self-perceived bowel health; stool frequency; stool consistency (using the Bristol Stool Form Scale (BSFS)); and demographic factors were analyzed. RESULTS: 95.9% of the sample reported between 3 and 21 BMs per week. Among men, 90% reported a BSFS between 3 and 5, while for women it was 2-6. After controlling for age, the following demographic variables were associated with normalcy: male sex, higher education, higher income, <2 daily medications, and high daily fiber intake. Hispanic ethnicity was significantly associated with abnormal self-reported bowel habits. CONCLUSIONS: This is the first study to evaluate normal bowel frequency and consistency in a representative sample of adults in the US. The current findings bolster the common "3 and 3" metric of normal frequency (3 BMs/day to 3 BMs/week) while also suggesting different criteria for normal consistency for men and women. Finally, this study provides novel information about demographic factors associated with normal frequency and consistency.

Emergency Department Burden of Nausea and Vomiting Associated With Cannabis Use Disorder: US Trends From 2006 to 2013.

BACKGROUND AND AIMS: Chronic cannabis use is associated with nausea and vomiting that may lead to emergency department (ED) visits, multiple diagnostic tests, and procedures. The aim of this study was to analyze recent trends in ED visits for vomiting associated with cannabis use disorder between 2006 and 2013. METHODS: Data were obtained from the National Emergency Department Sample records in which vomiting (ICD-9-CM codes 787.01, 787.03, and 536.2) was a primary diagnosis in combination with cannabis abuse or dependence (304.3, 304.30, 304.31, 304.32, 304.33, 305.2, 305.20, 305.21, 305.22, and 305.23) and were seen in the ED between 2006 and 2013. The National Emergency Department Sample collects data from more than 25 million visits in over 950 EDs and is weighted to provide national estimates. RESULTS: The rate of ED visits for vomiting with cannabis use disorder from 2006 compared with 2013 increased from 2.3 to 13.3 per 100,000 ED visits, while the mean inflation-adjusted costs increased 68.5% from $2758.43 to $4647.62, respectively. Men between the ages of 20 and 29 were the most common group to present to the ED for vomiting with cannabis use disorder. The Midwest and West had the higher rates of ED visits for vomiting with cannabis use disorder compared with the Northeast and South. CONCLUSIONS: ED visits for vomiting associated with cannabis use disorder is common and is associated with significant medical costs. Further research on the role of cannabis use in nausea and vomiting is warranted.

Assessment of Anti-vinculin and Anti-cytolethal Distending Toxin B Antibodies in Subtypes of Irritable Bowel Syndrome.

BACKGROUND: Antibodies to cytolethal distending toxin B (CdtB) and vinculin are novel biomarkers that rule-in and differentiate irritable bowel syndrome with diarrhea (IBS-D) from other causes of diarrhea and healthy controls. AIM: To determine whether these antibodies can also diagnose and differentiate other IBS subtypes. METHODS: Subjects with IBS-D based on Rome III criteria (n = 2375) were recruited from a large-scale multicenter clinical trial (TARGET 3). Healthy subjects without gastrointestinal (GI) diseases or symptoms (n = 43) and subjects with mixed IBS (IBS-M) (n = 25) or IBS with constipation (IBS-C) (n = 30) were recruited from two major medical centers. Plasma levels of anti-CdtB and anti-vinculin antibodies in all subjects were determined by enzyme-linked immunosorbent assay. Optical densities of ≥1.68 and ≥2.80 were considered positive for anti-vinculin and anti-CdtB, respectively. Plasma levels of anti-CdtB and anti-vinculin antibodies were highest in IBS-D and lowest in IBS-C and healthy controls (P < 0.001). Levels in IBS-C subjects were not statistically different from controls (P > 0.1). Positivity for anti-CdtB or anti-vinculin resulted in a statistically significant negative gradient from IBS-D (58.1%) to IBS-M (44.0%), IBS-C (26.7%), and controls (16.3%) (P < 0.001). CONCLUSIONS: Anti-CdtB and anti-vinculin titers and positivity rates differ in IBS subtypes, with higher antibody levels and positivity rates in IBS-D and IBS-M, and lower levels in IBS-C subjects that are similar to those in healthy controls. These antibodies appear useful in the diagnosis of IBS-M and IBS-D, but not IBS-C. Furthermore, these findings suggest that IBS-C is pathophysiologically distinct from subtypes with diarrheal components (i.e., IBS-M and IBS-D).

Emergency Department Burden of Diverticulitis in the USA, 2006-2013.

GOALS: The aim of this study was to analyze recent trends in emergency department (ED) visits for diverticulitis between 2006 and 2013. BACKGROUND: Acute diverticulitis is a serious medical condition that frequently leads to ED visits, hospitalizations, and surgeries resulting in a significant health care burden. METHODS: Data were obtained from the National Emergency Department Sample (NEDS) records in which diverticulitis (ICD-9-CM codes 562.11 and 562.13) was the primary diagnosis in the ED between 2006 and 2013. The NEDS collects data from more than 25 million visits in over 950 hospital emergency departments and is weighted to provide national estimates. Our findings reflected patient and hospital characteristics such as demographics, geographical region, and total charges for ED and inpatient stays. RESULTS: Between 2006 and 2013, the rate of diverticulitis-related ED visits increased by 26.8% from 89.8 to 113.9 visits per 100,000 population. The aggregate national cost of diverticulitis-related ED visits increased by 105%, from approximately $822 million in 2006 to over $1.6 billion in 2013. Cost data were adjusted for inflation and reported in 2015 dollars. The percentage of individuals admitted to the same hospital from the ED decreased from 58.0 to 47.1% from 2006 to 2013, respectively, while the rate of bowel surgeries per 100,000 ED visits for diverticulitis decreased by 33.7% from 2006 to 2013. CONCLUSIONS: The number of ED visits due to diverticulitis and associated costs continued to rise between 2006 and 2013, while the rate of bowel surgeries and inpatient admissions through the ED for diverticulitis decreased.

Fecal Impaction in the Emergency Department: An Analysis of Frequency and Associated Charges in 2011.

GOALS: The aim of this study was to analyze the incidence and associated charges of fecal impaction for trends in hospital and patient demographics in emergency departments (ED) across the United States. BACKGROUND: In 2010, an ICD-9-CM code (560.32) for fecal impaction was introduced, allowing for assessment of fecal impaction incidence. STUDY: Data were obtained from the National Emergency Department Sample records in which fecal impaction (ICD-9-CM code 560.32) was first listed as a diagnosis in 2011. RESULTS: In 2011, there were 42,481 [95% confidence interval (CI), 39,908-45,054] fecal impaction ED visits, with an overall rate of 32 fecal impaction visits per 100,000 ED visits. Adjusted for inflation in 2014 dollars, the associated mean charge of a fecal impaction ED visit was $3060.47 (95% CI, $2943.02-$3177.92), with an aggregate national charge in the US of $130,010,772 (95% CI, $120,688,659-$139,332,885). All charges were adjusted for inflation and reported in 2014 dollars. Late elders (85+ y) had the highest rate of fecal impaction ED visits, followed by early elders (65 to 84 y). Medicare was the primary payer for the greatest number of fecal impaction ED visits accounting for nearly two thirds of visit payments. CONCLUSION: This study reports previously unexplored statistics on the number, frequency, and associated charges of ED visits with a primary diagnosis of fecal impaction, a condition found most commonly among elders.

Consensus Recommendations on Initiating Prescription Therapies for Opioid-Induced Constipation.

OBJECTIVE: Aims of this consensus panel were to determine (1) an optimal symptom-based method for assessing opioid-induced constipation in clinical practice and (2) a threshold of symptom severity to prompt consideration of prescription therapy. METHODS: A multidisciplinary panel of 10 experts with extensive knowledge/experience with opioid-associated adverse events convened to discuss the literature on assessment methods used for opioid-induced constipation and reach consensus on each objective using the nominal group technique. RESULTS: Five validated assessment tools were evaluated: the Patient Assessment of Constipation-Symptoms (PAC-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL), Stool Symptom Screener (SSS), Bowel Function Index (BFI), and Bowel Function Diary (BF-Diary). The 3-item BFI and 4-item SSS, both clinician administered, are the shortest tools. In published trials, the BFI and 12-item PAC-SYM are most commonly used. The 11-item BF-Diary is highly relevant in opioid-induced constipation and was developed and validated in accordance with US Food and Drug Administration guidelines. However, the panel believes that the complex scoring for this tool and the SSS, PAC-SYM, and 28-item PAC-QOL may be unfeasible for clinical practice. The BFI is psychometrically validated and responsive to changes in symptom severity; scores range from 0 to 100, with higher scores indicating greater severity and scores >28.8 points indicating constipation. CONCLUSIONS: The BFI is a simple assessment tool with a validated threshold of clinically significant constipation. Prescription treatments for opioid-induced constipation should be considered for patients who have a BFI score of ≥30 points and an inadequate response to first-line interventions.

Emergency department burden of constipation in the United States from 2006 to 2011.

OBJECTIVES: Although constipation is typically managed in an outpatient setting, there is an increasing trend in the frequency of constipation-related hospital visits. The aim of this study was to analyze trends related to chronic constipation (CC) in the United States with respect to emergency department (ED) visits, patient and hospital characteristics, and associated costs. METHODS: Data from 2006 to 2011, in which constipation (The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes 564.00-564.09) was the primary discharge diagnosis, were obtained from the National Emergency Department Sample (NEDS). RESULTS: Between 2006 and 2011, the frequency of constipation-related ED visits increased by 41.5%, from 497,034 visits to 703,391 visits, whereas the mean cost per patient rose by 56.4%, from $1,474 in 2006 to $2,306 in 2011. The aggregate national cost of constipation-related ED visits increased by 121.4%, from $732,886,977 in 2006 to $1,622,624,341 in 2011. All cost data were adjusted for inflation and reported in 2014 dollars. Infants (<1 year old) had the highest rate of constipation-related ED visits in both 2006 and 2011. The late elders (85+ years) had the second highest constipation-related ED visit rate in 2006; however, the 1- to 17-year-old age group experienced a 50.7% increase in constipation-related ED visit rate from 2006 to 2011 and had the second highest constipation-related ED visit rate in 2011. CONCLUSIONS: The frequency of and the associated costs of ED visits for constipation are significant and have increased notably from 2006 to 2011.

Inpatient burden of constipation in the United States: an analysis of national trends in the United States from 1997 to 2010.

OBJECTIVES: Constipation is one of the most common outpatient diagnoses in primary care and gastroenterology clinics; however, there is limited data on the inpatient burden of constipation in the United States. The aim of this study was to evaluate inpatient admission rates, length of stay, and associated costs related to constipation from 1997 to 2010. METHODS: We analyzed the National Inpatient Sample Database for all patients in which constipation (ICD-9 codes: 564.0-564.09) was the principal discharge diagnosis from 1997 to 2010. The statistical significance of the difference in the number of hospital discharges, length of stay, and hospital costs over the study period was determined by utilizing the Spearman's coefficient to describe various trends. RESULTS: Between 1997 and 2010, the number of hospitalizations for patients with a primary discharge diagnosis of constipation increased from 21,190 patients to 48,450 (P<0.001, GoF test), whereas the mean length of hospital stay increased only slightly from 3.0 days to 3.1 days (b=0.008 (0.003-0.014); P=0.004). The mean charges per hospital discharge for constipation increased from $8869 in 1997 (adjusted for long-term inflation) to $17,518 in 2010 (b=745.4 (685.3-805.6); P<0.001)), whereas the total costs increased from $188,109,249 (adjusted for inflation) in 1997 to $851,713,263 in 2010. Although the elderly (65-84 years) accounted for the largest percentage of constipation discharges, patients in the 1-17 years age group had the highest frequency of constipation per 10,000 discharges. CONCLUSIONS: The number of inpatient discharges for constipation and associated costs has significantly increased between 1997 and 2010.

Developing valid and reliable health utilities in irritable bowel syndrome: results from the IBS PROOF Cohort.

OBJECTIVES: A "utility" is a measure of health-related quality of life (HRQOL) that ranges between 0 (death) and 1 (perfect health). Disease-targeted utilities are mandatory to conduct cost-utility analyses. Given the economic and healthcare burden of irritable bowel syndrome (IBS), cost-utility analyses will play an important role in guiding health economic decision-making. To inform future cost-utility analyses in IBS, we measured and validated the IBS utilities. METHODS: We analyzed data from Rome III IBS patients in the Patient Reported Observed Outcomes and Function (PROOF) Cohort-a longitudinal multi-center IBS registry. At entry, the patients completed a multi-attribute utility instrument (EuroQOL), bowel symptom items, IBS severity measurements (IBS Severity Scale (IBSSS), Functional Bowel Disease Severity Index (FBDSI)), HRQOL indexes (IBS quality-of-life instrument (IBS-QOL), Center for disease control-4 (CDC-4)), and the Worker Productivity Activity Index for IBS (WPAI). We repeated assessments at 3 months. RESULTS: There were 257 patients (79% women; age=43+/-15 years) at baseline and 85 at 3 months. The mean utilities in patients with severe vs. non-severe IBS were 0.70 and 0.80, respectively (P<0.001). There were no differences in utilities among IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), and mixed IBS (IBS-M) subgroups. EuroQOL utilities correlated with FBDSI (r=0.31; P<0.01), IBSSS (r=0.36; P<0.01), IBS-QOL (r=0.36; P<0.01), CDC-4 (r=0.44; P<0.01), WPAI presenteeism (r=0.16; P<0.01), abdominal pain (r=0.43; P<0.01), and distension (r=0.18; P=0.01). The utilities in patients reporting "considerable relief" of symptoms at 3 months vs. those without considerable relief were 0.78 and 0.73, respectively (P=0.02). CONCLUSIONS: EuroQOL utilities are valid and reliable in IBS. The utility of severe IBS (0.7) is similar to Class III congestive heart failure and rheumatoid arthritis. These validated utilities can be employed in future IBS cost-utility analyses.

Adequate relief in a treatment trial with IBS patients: a prospective assessment.

OBJECTIVES: Adequate relief (AR) of irritable bowel syndrome (IBS) symptoms (IBS-AR) has been used as a primary end point in many randomized controlled trials of IBS and is considered by the Rome III committee to be an acceptable primary end point. However, controversy exists on whether baseline severity confounds the effect of the treatment outcome. The aim (1) is to compare a subjective report of IBS-AR with global assessment of improvement (IBS-GAI), change in IBS symptom severity scale (IBS-SSS), and IBS quality of life (IBS-QOL); (2) to explore whether initial IBS symptom severity influences the ability of these outcome measures to detect differences post treatment; and (3) to determine whether psychological symptoms influence the sensitivity of these measures, in a randomized controlled treatment trial. METHODS: A total of 289 adult IBS patients were recruited to a treatment trial. Baseline IBS-SSS scores were used to classify IBS severity as mild (<175), moderate (175-300), or severe (>300). Questionnaires were completed at baseline and after 3 weeks of treatment with sham acupuncture or wait-list control. RESULTS: IBS baseline severity (IBS-SSS) significantly affected the proportion of patients who reported IBS-AR at 3 weeks (mild, 70%; moderate, 49.7%; severe, 38.8%) (P<0.05). However, once the patients who reported IBS-AR at baseline (28.0%) were excluded from the analysis, baseline severity no longer affected the proportion of patients reporting IBS-AR. Baseline severity did not have a significant effect on patients reporting moderate or significant improvement on the IBS-GAI (mild, 30%; moderate, 25.3%; severe, 18.8%) (P=NS). Psychological symptoms had no significant correlations with responders after adjusting for baseline severity. CONCLUSIONS: These data suggest that IBS-AR as an end point is inversely related to baseline symptom severity. However, if patients who report AR at screening were excluded from study participation, baseline symptom severity was no longer confounded with a report of AR at the study end point.

Effectiveness of recruitment in clinical trials: an analysis of methods used in a trial for irritable bowel syndrome patients.

A successful clinical trial is dependent on recruitment. Between December 2003 and February 2006, our team successfully enrolled 289 participants in a large, single-center, randomized placebo-controlled trial (RCT) studying the impact of the patient-doctor relationship and acupuncture on irritable bowel syndrome (IBS) patients. This paper reports on the effectiveness of standard recruitment methods such as physician referral, newspaper advertisements, fliers, audio and video media (radio and television commercials) as well as relatively new methods not previously extensively reported on such as internet ads, ads in mass-transit vehicles and movie theater previews. We also report the fraction of cost each method consumed and fraction of recruitment each method generated. Our cost per call from potential participants varied from $3-$103 and cost per enrollment participant varied from $12-$584. Using a novel metric, the efficacy index, we found that physician referrals and flyers were the most effective recruitment method in our trial. Despite some methods being more efficient than others, all methods contributed to the successful recruitment. The iterative use of the efficacy index during a recruitment campaign may be helpful to calibrate and focus on the most effective recruitment methods.