The Costs of Industry-Sponsored Medical Device Clinical Trials in Alberta.

OBJECTIVE: Our objective was to describe the costs of industry-sponsored clinical trials for medical devices in Northern Alberta, Canada. METHODS: We used centralized data to identify all industry-sponsored medical device clinical trials initiated in Northern Alberta from 2012 to 2016. For each arm of each trial, we calculated the price of devices provided by the sponsor and the cost of clinical and administrative services that were incurred to clinically operationalize the treatment. RESULTS: Our sample consisted of 18 device trials initiated between January 2012 and January 2016. The overall cost (Canadian dollars [$Can], year 2018 values) per enrolee was $Can18,243 for the experimental arm and $Can13,827 for the control arm. Devices were the highest cost component, at $Can13,446 per enrollee in the experimental arm. Clinical costs in the control arms were higher on average ($Can7202 vs. 2504) than those in the experimental arms. CONCLUSION: Data from industry-sponsored clinical trials can provide important information on the full costs of device-related interventions. As device costs rise, and as policy makers require more evidence on device-related treatments, the cost of medical device-driven interventions should be documented along with their effectiveness.

Early Initiation of Tumor Necrosis Factor Antagonist-Based Therapy for Patients With Crohn's Disease Reduces Costs Compared With Late Initiation.

BACKGROUND & AIMS: Antagonists of tumor necrosis factor (TNF) are effective for induction and maintenance of remission of Crohn's disease (CD) and are generally prescribed when patients do not respond to conventional, less-costly medical therapies. Early initiation of anti-TNF therapy reduced rates of surgery and dose escalation due to loss of response. However, these drugs are expensive, so studies are needed on the cost effectiveness of early initiation. We aimed to determine the cost effectiveness of initiating treatment early in the disease course (within 2 years of CD diagnosis) vs later in the disease course (more than 2 years after diagnosis). METHODS: We constructed a Markov model of a hypothetical cohort of patients with CD in Canada to simulate disease progression after initiation of infliximab or adalimumab therapy. We used published loss-of-response rates to compare the lifetime cost effectiveness of early vs late initiation of anti-TNF therapies. Transition probabilities and utilities were obtained through a literature search, and costs were obtained from the Alberta Ministry of Health. Sensitivity analysis was used to characterize uncertainty. RESULTS: Early initiation of infliximab yielded an additional 0.72 quality-adjusted life-years (QALYs) and saved $50,418 compared with late initiation. Early initiation of adalimumab yielded an additional 0.54 QALYs and saved $43,969. At a willingness-to-pay threshold of $50,000, early initiations of infliximab or adalimumab therapy had a 74% chance of being cost effective compared with late initiation. CONCLUSIONS: In a Markov model analysis, we found initiation of either infliximab or adalimumab within 2 years of CD diagnosis to provide significant cost savings and QALYs compared with later initiation (more than 2 years after diagnosis).

Real-Life Treatment Paradigms Show Adalimumab Is Cost-Effective for the Management of Ulcerative Colitis.

Background. Adalimumab is effective for the maintenance of remission in patients with moderate-to-severe ulcerative colitis (UC). Currently, biologic therapies are used in cases where patients fail conventional medical therapies. If biologic therapies are not available, patients often choose to remain in an unwell state rather than undergo colectomy. Objective. The aim of the study was to evaluate the cost-effectiveness of adalimumab in patients with UC where adalimumab was readily available compared to not available. Methods. A previously validated Markov model was used to simulate disease progression of patients with UC who are corticosteroid-dependent and/or did not respond to thiopurine therapy. Utility scores and transition probabilities between health states were determined by using data from randomized controlled trials and real-life observational studies. Costs were obtained from the Ontario Case Costing Initiative and the Alberta Health Schedule of Medical Benefits. Results. The incremental cost-effectiveness ratios for readily available adalimumab treatment of UC were $40,000 and $59,000 per quality-adjusted life year, compared with ongoing medical therapy in an unwell state, at 5-year and 10-year treatment time horizons, respectively. Conclusion. Considering real-life patient preferences to avoid colectomy, adalimumab is cost-effective according to a willingness-to-pay threshold of $80,000 for treatment of UC.

Living with inflammatory bowel disease: A Crohn's and Colitis Canada survey.

BACKGROUND: Despite improvements in therapies for inflammatory bowel diseases (IBDs), patient quality of life continues to be significantly impacted. OBJECTIVE: To assess the impact of IBD on patients and families with regard to leisure, relationships, mental well-being and financial security, and to evaluate the quality and availability of IBD information. METHODS: An online survey was advertised on the Crohn's and Colitis Canada website, and at gastroenterology clinics at the University of Alberta Hospital (Edmonton, Alberta) and University of Calgary Hospital (Calgary, Alberta). RESULTS: The survey was completed by 281 IBD patients and 32 family members. Among respondents with IBD, 64% reported a significant or major impact on leisure activities, 52% a significant or major impact on interpersonal relationships, 40% a significant or major impact on financial security, and 28% a significant or major impact on planning to start a family. Patient information needs emphasized understanding disease progression (84%) and extraintestinal symptoms (82%). There was a strong interest in support systems such as health care insurance (70%) and alternative therapies (66%). The most common source of information for patients was their gastroenterologist (70%); however, most (70%) patients preferred to obtain their information from the Crohn's and Colitis Canada website. CONCLUSIONS: The impact of IBD on interpersonal relationships and leisure activities was significant among IBD patients and their families. Understanding the disease, but also alternative treatment options, was of high interest. Currently, there is a discrepancy between interest in information topics and their availability. Respondents reported a strong desire to obtain information regarding disease progression, especially extraintestinal symptoms.

Real-life treatment paradigms show infliximab is cost-effective for management of ulcerative colitis.

BACKGROUND & AIMS: Infliximab is effective for induction and maintenance of response in patients with moderate to moderately severe ulcerative colitis. Previous cost analyses of infliximab treatment for ulcerative colitis used models of colectomy vs infliximab and response rates derived from early clinical trials. In real life, therapeutic options are more complex; patients frequently choose to remain in an unwell state rather than undergo colectomy, and rates of response to infliximab are generally higher than those reported from clinical trials. We evaluate the real-life cost-effectiveness of infliximab for treatment of ulcerative colitis where infliximab was readily available compared with not available, causing patients to remain in unwell states. METHODS: We constructed a Markov model to simulate disease progression of patients with moderate or moderately severe ulcerative colitis who depended on corticosteroids and/or did not respond to thiopurine therapy. Utility scores and transition probabilities between health states were determined by using data from randomized controlled trials and real-life rates published by expert inflammatory bowel disease centers. Health care costs were obtained from the Ontario Case Costing Initiative and the Alberta Health Schedule of Medical Benefits documents. RESULTS: The incremental cost-effectiveness ratios for infliximab treatment of ulcerative colitis were $79,000 and $64,000 per quality-adjusted life year, compared with ongoing medical therapy, at 5-year and 10-year treatment time horizons, respectively. CONCLUSIONS: By using real-life response rates and patients' preference to avoid colectomy, infliximab therapy is a cost-effective strategy at a willingness-to-pay threshold of $80,000 for treatment of ulcerative colitis.

Distance management of inflammatory bowel disease: systematic review and meta-analysis.

AIM: To review the effectiveness of distance management methods in the management of adult inflammatory bowel disease (IBD) patients. METHODS: A systematic review and meta-analysis of randomized controlled trials comparing distance management and standard clinic follow-up in the management of adult IBD patients. Distance management intervention was defined as any remote management method in which there is a patient self-management component whereby the patient interacts remotely via a self-guided management program, electronic interface, or self-directs open access to clinic follow up. The search strategy included electronic databases (Medline, PubMed, CINAHL, The Cochrane Central Register of Controlled Trials, EMBASE, KTPlus, Web of Science, and SCOPUS), conference proceedings, and internet search for web publications. The primary outcome was the mean difference in quality of life, and the secondary outcomes included mean difference in relapse rate, clinic visit rate, and hospital admission rate. Study selection, data extraction, and risk of bias assessment were completed by two independent reviewers. RESULTS: The search strategy identified a total of 4061 articles, but only 6 randomized controlled trials met the inclusion and exclusion criteria for the systematic review and meta-analysis. Three trials involved telemanagement, and three trials involved directed patient self-management and open access clinics. The total sample size was 1463 patients. There was a trend towards improved quality of life in distance management patients with an end IBDQ quality of life score being 7.28 (95%CI: -3.25-17.81) points higher than standard clinic follow-up. There was a significant decrease in the clinic visit rate among distance management patients mean difference -1.08 (95%CI: -1.60--0.55), but no significant change in relapse rate or hospital admission rate. CONCLUSION: Distance management of IBD significantly decreases clinic visit utilization, but does not significantly affect relapse rates or hospital admission rates.

Canadian Digestive Health Foundation Public Impact Series 5: Pancreatitis in Canada. Incidence, prevalence, and direct and indirect economic impact.

The Canadian Digestive Health Foundation initiated a scientific program to assess the incidence, prevalence, mortality and economic impact of digestive disorders across Canada in 2009. The current article presents the updated findings from the study concerning pancreatitis.

Canadian Digestive Health Foundation Public Impact Series 4: celiac disease in Canada. Incidence, prevalence, and direct and indirect economic impact.

The Canadian Digestive Health Foundation initiated a scientific program to assess the incidence, prevalence, mortality and economic impact of digestive disorders across Canada in 2009. The current article presents the updated findings from the study concerning celiac disease.

Canadian Digestive Health Foundation Public Impact Series 3: irritable bowel syndrome in Canada. Incidence, prevalence, and direct and indirect economic impact.

The Canadian Digestive Health Foundation initiated a scientific program to assess the incidence, prevalence, mortality and economic impact of digestive disorders across Canada in 2009. The current article presents the updated findings from the study concerning irritable bowel syndrome.

Health care resource use and costs in Crohn's disease before and after infliximab therapy.

BACKGROUND: Infliximab therapy in patients with Crohn's disease decreases resource use; however, the overall impact on health-related expenditures is unclear, especially beyond one year of study. METHODS: A retrospective analysis of economic data one and two years before and after infliximab therapy was performed using patients who served as their own controls. Total health care resource use and direct health care costs were compared for patients with or without fistulae. RESULTS: Patients with one (n=66) and two (n=39) years of economic data before and after infliximab treatment had their resource use and direct health care costs estimated. In the year following initiation of infliximab therapy, there were significant decreases in health care use, reflected in total hospital days (495 to 155 [P<0.05]), inpatient colonoscopies (46 to 24 [P<0.05]), outpatient colonoscopies (58 to 33 [P<0.05]) and major surgeries (10 to 2 [P<0.05]). Direct health care costs of inpatient costs for luminal (-$1,747 [P<0.05]) and fistulizing disease (-$2,530 [P<0.05]), major surgeries (-$1240 [P<0.05]) and outpatient colonoscopies (-$184 [P<0.05]) were also significantly reduced before and after infliximab therapy. Total direct health care costs, including the drug cost of infliximab, increased ($21,416 [P<0.05]). In general, the trends in health care costs analyzed over four consecutive years paralleled the two consecutive-year analysis.  CONCLUSION: Infliximab therapy in patients with Crohn's disease resulted in a significant decrease in both resource use and health care costs, but an increase in total direct health care costs once the cost of infliximab was added.

Canadian Digestive Health Foundation Public Impact Series. Inflammatory bowel disease in Canada: Incidence, prevalence, and direct and indirect economic impact.

The Canadian Digestive Health Foundation initiated a scientific program to assess the incidence, prevalence, mortality and economic impact of digestive disorders across Canada in 2009. The current article presents the updated findings from the study concerning inflammatory bowel diseases - specifically, Crohn's disease and ulcerative colitis.

Canadian Digestive Health Foundation Public Impact Series: gastroesophageal reflux disease in Canada: incidence, prevalence, and direct and indirect economic impact.

The Canadian Digestive Health Foundation initiated a scientific program to assess the incidence, prevalence, mortality and economic impact of digestive disorders across Canada. The current article presents the updated findings from the study concerning gastroesophageal reflux disease - a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications (Montreal definition).

Thiopurine methyltransferase enzyme activity determination before treatment of inflammatory bowel disease with azathioprine: effect on cost and adverse events.

BACKGROUND: Azathioprine (AZA), used to treat inflammatory bowel disease (IBD), is metabolized by thiopurine methyltransferase (TPMT). The accumulation of individual metabolites varies because humans display genetic polymorphism for TPMT expression. Deficiencies in TPMT result in accumulation of toxic metabolites, followed by neutropenia and hepatic inflammation. Concern over acute toxicity frequently leads to under dosing and frequent monitoring tests and visits. OBJECTIVE: To determine whether assessment of TPMT activity before the administration of AZA would predict acute toxicity and, thus, allow for reductions in health care costs related to biochemical screening for, and management of, AZA-induced adverse events. METHODS: Before AZA treatment, 29 patients with IBD were prospectively randomized to one of two groups: group 1, in which no TPMT assay was performed, was started on AZA at 1 mg/kg/day and then titrated every two weeks to a target dose of 2.5 mg/kg/day; and group 2, in which TPMT assays were performed, was started on AZA at the target dose of 2.5 mg/kg/day. For both groups, complete blood count and liver enzymes were monitored weekly for six weeks and at monthly intervals thereafter. Additional tests and health care interventions were undertaken at the discretion of the attending physicians. RESULTS: Of the 29 patients in the study, 15 were randomly assigned to group 1 and 14 to group 2. Demographics and disease activity were similar for both groups. Mean follow-up time was 7.1 months (range 3.5 to 10.7 months). Eight patients from group 1 and six patients from group 2 withdrew as a result of AZA-induced adverse events. There was no correlation between the TPMT activity and the development of AZA-induced adverse events. The direct health care costs for group 1 (300.11 dollars per patient) were lower than in group 2 (348.87 dollars per patient). CONCLUSION: The prospective assessment of TPMT enzyme activity before initiating AZA therapy in IBD patients incurred additional cost and did not predict AZA-induced toxicity.