Cost-effectiveness of everolimus for the treatment of advanced neuroendocrine tumours of gastrointestinal or lung origin in Canada.

BACKGROUND: In 2016, everolimus was approved by Health Canada for the treatment of unresectable, locally advanced or metastatic, well-differentiated, non-functional, neuroendocrine tumours (NET) of gastrointestinal (GI) or lung origin in adult patients with progressive disease. This analysis evaluated the cost-effectiveness of everolimus in this setting from a Canadian societal perspective. METHODS: A partitioned survival model was developed to compare the cost per life-year (LY) gained and cost per quality-adjusted life-year (QALY) gained of everolimus plus best supportive care (BSC) versus BSC alone in patients with advanced or metastatic NET of GI or lung origin. Model health states included stable disease, disease progression, and death. Efficacy inputs were based on the RADIANT-4 trial and utilities were mapped from quality-of-life data retrieved from RADIANT-4. Resource utilization inputs were derived from a Canadian physician survey, while cost inputs were obtained from official reimbursement lists from Ontario and other published sources. Costs and efficacy outcomes were discounted 5% annually over a 10-year time horizon, and sensitivity analyses were conducted to test the robustness of the base case results. RESULTS: Everolimus had an incremental gain of 0.616 QALYs (0.823 LYs) and CA$89,795 resulting in an incremental cost-effectiveness ratio of CA$145,670 per QALY gained (CA$109,166 per LY gained). The probability of cost-effectiveness was 52.1% at a willingness to pay (WTP) threshold of CA$150,000 per QALY. CONCLUSIONS: Results of the probabilistic sensitivity analysis indicate that everolimus has a 52.1% probability of being cost-effective at a WTP threshold of CA$150,000 per QALY gained in Canada.

Burden of illness for metastatic melanoma in Canada, 2011-2013.

BACKGROUND: Detailed epidemiology for patients with advanced metastatic melanoma in Canada is not well characterized. We conducted an analysis of patients with this disease in the province of Ontario, with the aim being to study the presentation, disease characteristics and course, and treatment patterns for malignant melanoma. METHODS: In this Canadian observational prospective and retrospective study of patients with malignant melanoma, we used data collected in the Canadian Melanoma Research Network (cmrn) Patient Registry. We identified patients who were seen at 1 of 3 cancer treatment centres between April 2011 and 30 April 2013. Patient data from 2011 and 2012 were collected retrospectively using chart records and existing registry data. Starting January 2013, data were collected prospectively. Variables investigated included age, sex, initial stage, histology, mutation type, time to recurrence, sites of metastases, resectability, and previous therapies. RESULTS: A cohort of 810 patients with melanoma was identified from the cmrn registry. Mean age was 58.7 years, and most patients were men (60% vs. 40%). Factors affecting survival included unresectable or metastatic melanoma, initial stage at diagnosis, presence of brain metastasis, and BRAF mutation status. The proportion of surviving patients decreased with higher initial disease stages. CONCLUSIONS: Using registry data, we were able to determine the detailed epidemiology of patients with melanoma in the Canadian province of Ontario, validating the comprehensive and detailed information that can be obtained from registry data.

Preferences of Canadian patients and physicians for adjuvant treatments for melanoma.

Background: Past research suggests that patients with early- and late-stage melanoma will endure adverse events and inconvenient treatment regimens for improved survival. Evidence about the preferences of Canadian patients and physicians for novel adjuvant treatments for melanoma is unavailable. Methods: Patient and physician preferences for adjuvant treatments for melanoma were assessed in an online discrete choice experiment (dce). Treatment alternatives were characterized by 8 attributes with respect to dosing regimen, efficacy, and toxicities, with levels corresponding to those for dabrafenib-trametinib, nivolumab, pembrolizumab, and interferon. For patients, the effects of melanoma on quality of life and ability to work and perform activities of daily living were also assessed. Patients were recruited by Canadian melanoma patient advocacy groups through e-mail and social media. Physicians were recruited by e-mail. Results: Of 94 patients who started the survey, 51 completed 1 or more dce questions. Of 166 physicians sent the e-mail invitation, 18 completed 1 or more dce questions. For patients, an increased probability of remaining cancer-free over 21 months was the most important attribute. For physicians, an increased chance of the patient's remaining alive over 36 months was the most important attribute. Patients and physicians chose active treatment over no treatment 85% and 86% of the time respectively and a treatment with attributes consistent with dabrafenib-trametinib 71% and 67% of the time respectively. A substantial proportion of patients reported worrying about future diagnostic tests and their cancer coming back. Conclusions: Canadian patients and physicians are generally concordant in their preferences for adjuvant melanoma treatments, preferring active treatment to no treatment and dabrafenib-trametinib to other options.

Erratum: Cost-effectiveness of everolimus for the treatment of advanced neuroendocrine tumours of gastrointestinal or lung origin in Canada.

[This corrects the article on p. 32 in vol. 25, PMID: 29507481.].

Systematic review and meta-analysis: The incidence and prognosis of post-infectious irritable bowel syndrome.

BACKGROUND: Individual studies suggest that post-infectious irritable bowel syndrome is common, but symptoms gradually improve. AIM: To review evidence for an association between intestinal infection and development of irritable bowel syndrome, assess the prognosis of post-infectious irritable bowel syndrome and explore factors that increase the risk. METHODS: MEDLINE (1966-2007) and EMBASE (1980-2007) databases were searched to identify the studies of post-infectious irritable bowel syndrome epidemiology. Data were extracted by two independent reviewers. Pooled odds ratios (POR) and corresponding 95% CI for incidence of irritable bowel syndrome were estimated among the exposed and unexposed groups. RESULTS: Eighteen of 26 studies identified were eligible for inclusion. Intestinal infection was associated with increased odds of developing irritable bowel syndrome at study end (POR = 5.86; 95% CI: 3.60-9.54). In subgroup analysis, the odds of developing irritable bowel syndrome was increased at 3 months (POR = 7.58; 95% CI: 4.27-13.45), 6 months (POR = 5.18; 95% CI: 3.24-8.26), 12 months (POR = 6.37; 95% CI: 2.63-15.40) and 24-36 months (POR = 3.85; 95% CI: 2.95-5.02). Among all studies (controlled and uncontrolled), the pooled incidence of irritable bowel syndrome at study conclusion was 10% (95% CI: 9.4-85.6). Subjects with post-infectious irritable bowel syndrome were younger and more anxious and depressed than those without post-infectious irritable bowel syndrome. CONCLUSION: The odds of developing irritable bowel syndrome are increased sixfold after acute gastrointestinal infection. Young age, prolonged fever, anxiety and depression are risk factors for post-infectious irritable bowel syndrome.

Intestinal permeability in patients with irritable bowel syndrome after a waterborne outbreak of acute gastroenteritis in Walkerton, Ontario.

BACKGROUND: Post-infectious irritable bowel syndrome is a common clinical phenomenon of uncertain aetiology. AIM: To test the association between intestinal permeability and irritable bowel syndrome symptoms 2 years after a large waterborne outbreak of bacterial gastroenteritis. METHODS: Consecutive adults with Rome I irritable bowel syndrome and controls without irritable bowel syndrome attending a community clinic were enrolled. Intestinal permeability was measured as the ratio of fractional urinary excretions of lactulose and mannitol, and compared among cases vs. controls and predictors of abnormal intestinal permeability were assessed. RESULTS: A total of 218 subjects (132 irritable bowel syndrome cases and 86 non-irritable bowel syndrome controls) completed the study protocol. About 27 (12%) had been diagnosed with the irritable bowel syndrome before the outbreak and 115 (53%) had been ill during the outbreak. Lactulose-mannitol ratios were increased among cases vs. controls (Mann-Whitney mean rank 118.8 vs. 95.3, P = 0.007), and cases were more likely to have a ratio >0.020 (P = 0.007). Among cases, those with increased intestinal permeability were more likely to report increased stool frequency. Both irritable bowel syndrome symptoms and male gender, but not diarrhoeal illness during the outbreak, were significant predictors of abnormal permeability. CONCLUSIONS: Irritable bowel syndrome symptoms are associated with a subtle increase in intestinal permeability irrespective of prior gastroenteritis. This may improve understanding of the aetiology of both sporadic and post-infectious irritable bowel syndrome.

Clustering and stability of functional lower gastrointestinal symptom after enteric infection.

BACKGROUND: Current diagnostic criteria for functional gut disorder are based on symptom clusters observed after sporadic onset. It remains unclear whether symptoms group similarly in functional disorders of postinfectious etiology. We utilized observational data from the Walkerton Health Study (WHS) to: (i) determine groupings of functional gastrointestinal symptoms among patients exposed to acute gastroenteritis (GE), and (ii) assess the stability of these symptoms grouping over time. METHODS: WHS participants 16 years of age and older at the time of the outbreak were included, if they had completed a modified Talley's Bowel Disease Questionnaire (BDQ) and responded 'yes' to a screening question as to whether they had experienced abdominal pain in the last 2 weeks. Exploratory factor analysis (EFA) using tetrachoric correlations was undertaken to identify symptom constructs. Hierarchical cluster analysis using the k-means method was used to create cluster groupings of patients based on these factors. Confirmatory factors analysis using responses to BDQ questionnaire administered at 4, 6, and 8 years after the outbreak was performed to assess stability of symptom domains over time. KEY RESULTS: A total of 773 participants were eligible for inclusion [62.2% female, mean age 43.1 years (SD = 16.9)]. Eighty-four percent were exposed to acute GE during the outbreak. Two symptom groupings of abdominal pain with either diarrhea or constipation together explained 85.7% of the total variance. Cluster analysis identified four patients groupings based on these factors. These clusters could be qualitatively described as diarrhea- and constipation-predominant, mixed bowel pattern, and no predominance of bowel movements abnormalities. Results of the confirmatory factor analysis validating symptom domains identified in Year 1 showed that the baseline model was acceptable at 4 and 6 years after the outbreak and approached acceptability at 8 years. Values of root mean square error of approximation were 0.071 (90% CI: 0.053, 0.089) at 4 and 0.071 (90% CI: 0.049, 0.092) at 6 years and 0.089 (90% CI: 0.065, 0.114) at 8 years. CONCLUSIONS & INFERENCES: The majority of subjects with postinfectious functional bowel disorders belong to groups with symptoms of abdominal pain and either diarrhea or constipation. These symptom groupings were stable across time.