Measuring symptoms in the irritable bowel syndrome: development of a framework for clinical trials.

BACKGROUND: There is uncertainty about how to measure patient-reported outcomes (PROs) in IBS. The Food and Drug Administration (FDA) emphasizes that PROs must be couched in a conceptual framework, yet existing IBS PROs were not based on such a framework. AIM: To perform qualitative analyses to inform a new conceptual framework for IBS symptoms. METHODS: Following FDA guidance, we searched the literature for extant IBS questionnaires. We then performed interviews in IBS patients to learn about the illness experience in their own words. We cultivated vocabulary to inform a conceptual framework depicted with domains, sub-domains, and item categories, per FDA guidance. RESULTS: We identified 13 questionnaires with items encompassing 18 symptoms. We recruited 123 IBS patients for cognitive interviews. Major themes included: pain and discomfort are different - asking about discomfort is nonspecific and should be avoided in future PROs; bowel urgency is multifaceted - PROs should measure bowel immediacy, controllability, and predictability; and PROs should divide bloating into how it feels vs. how it looks. Symptom experience may be determined by 35-item categories within five domains: (i) pain; (ii) gas/bloat; (iii) diarrhoea; (iv) constipation; and (v) extraintestinal symptoms. CONCLUSIONS: We applied FDA guidance to develop a framework that can serve as the foundation for developing a PRO for IBS clinical trials.

Characterizing abdominal pain in IBS: guidance for study inclusion criteria, outcome measurement and clinical practice.

BACKGROUND: Although irritable bowel syndrome (IBS) is a multisymptom disorder, abdominal pain drives illness severity more than other symptoms. Despite consensus that IBS trials should measure pain to define study entry and determine efficacy, the optimal method of measuring pain remains uncertain. AIM: To determine whether combining information from multiple pain dimensions may capture the IBS illness experience more effectively than the approach of measuring 'pain predominance' or pain intensity alone. METHODS: Irritable bowel syndrome patients rated dimensions of pain, including intensity, frequency, constancy, predominance, predictability, duration, speed of onset and relationship to bowel movements. We evaluated the impact of each dimension on illness severity using multivariable regression techniques. RESULTS: Among the pain dimensions, intensity, frequency, constancy and predictability were strongly and independently associated with illness severity; the other dimensions had weaker associations. The clinical definition of 'pain predominance', in which patients define pain as their most bothersome symptom, was insufficient to categorize patients by illness severity. CONCLUSIONS: Irritable bowel disease pain is multifaceted; some pain dimensions drive illness more than others. IBS trials should measure various pain dimensions, including intensity, constancy, frequency and predictability; this may improve upon the customary use of measuring pain as a unidimensional symptom in IBS.

Measuring irritable bowel syndrome patient-reported outcomes with an abdominal pain numeric rating scale.

BACKGROUND: Controversy exists on how to measure patient-reported outcomes in irritable bowel syndrome (IBS) clinical trials effectively. Pain numeric rating scales (NRS) are widely used in the non-IBS pain literature. The Food and Drug Administration has proposed using the NRS in IBS. AIM: To test the psychometrics of an abdominal pain NRS in IBS. Methods We analysed data from a longitudinal cohort of Rome III IBS subjects. At entry, subjects completed a 10-point NRS, bowel symptoms, IBS severity measurements (IBS-SSS, FBDSI), health-related quality of life indices (IBS-QOL, EQ5D), and the Worker Productivity Activity Index (WPAI). We repeated assessments at 3 months along with a response scale to calculate the minimal clinically important difference. RESULTS: There were 277 subjects (82% women; age = 42 +/- 15) at baseline and 90 at 3 months. The NRS correlated cross-sectionally with IBS-SSS (r = 0.60; P < 0.0011), FBDSI (r = 0.49; P < 0.0001), IBS-QOL (r = 0.43; P < 0.0001), EQ5D (r = 0.48; P < 0.0001), presenteeism (r = 0.39; P < 0.0001), absenteeism (r = 0.17; P = 0.04) and distension (r = 0.46; P < 0.0001), but not stool frequency or form. The minimal clinically important difference was 2.2 points, correlating with a 29.5% reduction over time. CONCLUSIONS: An abdominal pain NRS exhibits excellent validity and can be readily interpreted with a minimal clinically important difference in patients with IBS. These data support the use of the NRS in IBS clinical trials.

Adherence to best practice guidelines in dyspepsia: a survey comparing dyspepsia experts, community gastroenterologists and primary-care providers.

BACKGROUND: Although 'best practice' guidelines for dyspepsia management have been disseminated, it remains unclear whether providers adhere to these guidelines. AIM: To compare adherence to 'best practice' guidelines among dyspepsia experts, community gastroenterologists and primary-care providers (PCPs). METHODS: We administered a vignette survey to elicit knowledge and beliefs about dyspepsia including a set of 16 best practices, to three groups: (i) dyspepsia experts; (ii) community gastroenterologists and (iii) PCPs. RESULTS: The expert, community gastroenterologist and PCP groups endorsed 75%, 73% and 57% of best practices respectively. Gastroenterologists were more likely to adhere with guidelines than PCPs (P < 0.0001). PCPs were more likely to define dyspepsia incorrectly, overuse radiographic testing, delay endoscopy, treat empirically for Helciobacter pylori without confirmatory testing and avoid first-line proton pump inhibitors (PPIs). PCPs had more concerns about adverse events with PPIs [e.g. osteoporosis (P = 0.04), community-acquired pneumonia (P = 0.01)] and higher level of concern predicted lower guideline adherence (P = 0.04). CONCLUSIONS: Gastroenterologists are more likely than PCPs to comply with best practices in dyspepsia, although compliance remains incomplete in both groups. PCPs harbour more concerns regarding long-term PPI use and these concerns may affect therapeutic decision making. This suggests that best practices have not been uniformly adopted and persistent guideline-practice disconnects should be addressed.

Evaluating the process of care in nonvariceal upper gastrointestinal haemorrhage: a survey of expert vs. non-expert gastroenterologists.

BACKGROUND: When faced with the same facts, physicians often make different decisions. Aim To perform a survey to measure the process of care and variations in decision-making in nonvariceal upper gastrointestinal tract haemorrhage (NVUGIH) and compare results between experts and non-experts. METHODS: We administered a vignette survey to elicit knowledge and beliefs about NVUGIH, including 13 'best practice' guidelines. We compared guideline compliance between experts and non-experts. RESULTS: One hundred and eighty-eight gastroenterologists responded (46%). Experts endorsed more 'best practices' than non-experts (93% vs. 85%; P = 0.002). Non-experts were more likely to endorse incorrectly bolus dosing vs. continuous infusion of intravenous proton pump inhibitors (PPIs; 92% vs. 64%; P = 0.005) and to select standard-channel vs. large-channel endoscopes in high-risk bleeding (100% vs. 85%; P = 0.04). There were wide variations within groups regarding the timing of nasogastric lavage, use of promotility agents, use of hemoclips and appropriateness of snaring clots overlying ulcers. CONCLUSIONS: Experts are more likely to comply with NVUGIH guidelines. Non-experts diverge from experts in the dosing of PPIs and choice of endoscope in high-risk bleeding. Moreover, there are wide variations in key practices even within groups. This suggests that best practices have been generally well disseminated, but that persistent disconnects exist that should be further investigated.

Differences in the management of Crohn's disease among experts and community providers, based on a national survey of sample case vignettes.

BACKGROUND: When faced with the same set of facts, healthcare providers often make different diagnoses, employ different tests and prescribe disparate therapies. AIM: To perform a national survey to measure process of care and variations in decision-making in Crohn's disease, and the compared results between experts and community providers. METHODS: We constructed a survey with five vignettes to elicit provider beliefs regarding the appropriateness of diagnostic tests and therapies in Crohn's disease. We measured agreement between community gastroenterologists and Crohn's disease experts, and measured variation within each group using the RAND Disagreement Index (DI), which is a validated measure of provider variation. RESULTS: We received 186 responses (42% response rate). Experts and community providers generally agreed on diagnostic testing decisions in Crohn's disease. However, there was a significant disagreement between groups for several decisions (use of 5-aminosalicylate in particular), and there was evidence of 'extreme variation' (defined as DI > 1.0) within groups across a range of decisions. CONCLUSIONS: Although experts and community providers are in general consensus about diagnostic decision-making in Crohn's disease, extreme variation exists both between and within groups for key therapeutic decisions in Crohn's disease. We must understand and decrease this variation prior to future efforts of creating explicit quality indicators in Crohn's disease.

The cost-effectiveness and budget impact of competing therapies in hepatic encephalopathy - a decision analysis.

BACKGROUND: Treatment options for hepatic encephalopathy have disparate risks and benefits. Non-absorbable disaccharides and neomycin are limited by uncertain efficacy and common dose-limiting side effects. In contrast, rifaximin is safe and effective in hepatic encephalopathy, but is more expensive. METHODS: We conducted a decision analysis to calculate the cost-effectiveness of six strategies in hepatic encephalopathy: (i) no hepatic encephalopathy treatment, (ii) lactulose monotherapy, (iii) lactitol monotherapy, (iv) neomycin monotherapy, (v) rifaximin monotherapy and (vi) up-front lactulose with crossover to rifaximin if poor response or intolerance of lactulose ('rifaximin salvage'). The primary outcome was cost per quality-adjusted life-year gained. RESULTS: Under base-case conditions, 'do nothing' was least effective and rifaximin salvage was most effective. Lactulose monotherapy was least expensive, and rifaximin monotherapy was most expensive. When balancing cost and effectiveness, lactulose monotherapy and rifaximin salvage dominated alternative strategies. Compared to lactulose monotherapy, rifaximin salvage cost an incremental US$2315 per quality-adjusted life-year-gained. The cost of rifaximin had to fall below US$1.03/tab in order for rifaximin monotherapy to dominate lactulose monotherapy. CONCLUSIONS: Rifaximin monotherapy is not cost-effective in the treatment of chronic hepatic encephalopathy at current average wholesale prices. However, a hybrid salvage strategy, reserving rifaximin for lactulose-refractory patients, may be highly cost-effective.