Evaluating the economic burden of acute myeloid leukemia in Canada.

Background Acute myeloid leukemia (AML) represents a significant burden for patients and their families, and to the healthcare system. This study estimated the total cost of illness associated with newly diagnosed AML patients in Canada. Methods The economic burden of AML was estimated using an incidence-based model, analyzing different types of AML cases in Canada. Direct and indirect costs were calculated using scientific literature and Canadian clinical experts' inputs. Patients were categorized depending on their eligibility for intensive chemotherapy (fit and unfit patients) as well as according to age and cytogenetic markers. Results The total average cost of AML per patient is estimated to be $178,073 with a cost of $210,983 and $145,163 for fit and unfit patients, respectively. The costs related to treatment represent half of the total average cost (52%), followed by hematopoietic stem cell transplant (23%), best supportive care (16%), productivity loss (6%) and wastage (4%) Conclusions For patients with AML, the costs associated with fit patients are higher than unfit patients. Hospitalization and best supportive care costs are key cost drivers for the total costs of fit and unfit patients, respectively. This study highlights that AML is associated with a significant economic burden in Canada.

Comparative Efficacy of Venetoclax-Based Combination Therapies and Other Therapies in Treatment-Naive Patients With Acute Myeloid Leukemia Ineligible for Intensive Chemotherapy: A Network Meta-Analysis.

OBJECTIVES: This network meta-analysis (NMA) assessed the efficacy of venetoclax (VEN) + azacitidine (AZA) and VEN + low-dose cytarabine (LDAC) compared with AZA, LDAC, and decitabine monotherapies and best supportive care (BSC) in adults with untreated acute myeloid leukemia ineligible for intensive chemotherapy. METHODS: A systematic literature review and feasibility assessment was conducted to select phase III randomized controlled trials for inclusion in the NMA. Complete remission + complete remission with incomplete blood count recovery and overall survival (OS) were compared using a Bayesian fixed-effects NMA. Treatments were ranked using surface under the cumulative ranking curves (SUCRAs) with higher values indicating a higher likelihood of being effective. RESULTS: A total of 1140 patients across 5 trials were included. VEN + LDAC (SUCRA 91.4%) and VEN + AZA (87.5%) were the highest ranked treatments for complete remission + complete remission with incomplete blood count recovery. VEN + LDAC was associated significantly higher response rates versus AZA (odds ratio 5.64), LDAC (6.39), and BSC (23.28). VEN + AZA was also associated significantly higher response rates than AZA (5.06), LDAC (5.74), and BSC (20.68). In terms of OS, VEN + AZA (SUCRA: 95.2%) and VEN + LDAC (75.9%) were the highest ranked treatments. VEN + AZA was associated with significant improvements in OS compared with AZA (hazard ratio 0.66), LDAC (0.57), and BSC (0.37), and VEN + LDAC was associated with significant improvements in OS compared with LDAC (0.70) and BSC (0.46). CONCLUSIONS: VEN + AZA and VEN + LDAC demonstrated improved efficacy compared with alternative therapies among treatment-naive patients with acute myeloid leukemia ineligible for intensive chemotherapy.

Canadian economic impact of improved workplace productivity in patients with major depressive disorder treated with vortioxetine.

OBJECTIVE: The AtWoRC study is an interventional, open-label Canadian study that demonstrated significant improvements in cognitive function and workplace productivity in patients with major depressive disorder (MDD) treated with vortioxetine for a current major depressive episode. The objective of the present analysis was to assess the Canadian economic impact of improved workplace productivity based on the AtWoRC study results. METHODS: The economic impact of improved productivity in patients with MDD treated with vortioxetine was assessed over a 52-week period considering productivity loss due to absenteeism and presenteeism using the standard human capital approach and an employer's perspective. Absenteeism was measured with the Work Productivity and Activity Impairment questionnaire; and presenteeism with the Work Limitation Questionnaire. Productivity gains following treatment initiation with vortioxetine were estimated using the difference from baseline. RESULTS: In the AtWoRC study, patients at baseline reportedly missed, in the past 7 days, an average of 8.1 h due to absenteeism and 3.0 h due to presenteeism. Following 52 weeks of treatment with vortioxetine, patients reportedly missed an average of 4.9 h due to absenteeism and 2.0 h due to presenteeism. This improved workplace productivity translated into savings of C$110.64 for 1 week of work following 52 weeks of treatment. The cumulative 52-week economic impact showed potential savings of C$4,550 when factoring in the cost of therapy. CONCLUSION: This study suggested that workplace productivity gain due to an improvement in symptoms of MDD following treatment with vortioxetine will lead to substantial cost savings for the Canadian economy.

Review of real-world evidence studies in type 2 diabetes mellitus: Lack of good practices.

OBJECTIVES: Unlike randomized controlled trials, lack of methodological rigor is a concern about real-world evidence (RWE) studies. The objective of this study was to characterize methodological practices of studies collecting pharmacoeconomic data in a real-world setting for the management of type 2 diabetes mellitus (T2DM). METHODS: A systematic literature review was performed using the PICO framework: population consisted of T2DM patients, interventions and comparators were any intervention for T2DM care or absence of intervention, and outcomes were resource utilization, productivity loss or utility. Only RWE studies were included, defined as studies that were not clinical trials and that collected de novo data (no retrospective analysis). RESULTS: The literature search identified 1,158 potentially relevant studies, among which sixty were included in the literature review. Many studies showed a lack of transparency by not mentioning the source for outcome and exposure measurement, source for patient selection, number of study sites, recruitment duration, sample size calculation, sampling method, missing data, approbation by an ethics committee, obtaining patient's consent, conflicts of interest, and funding. A significant proportion of studies had poor quality scores and was at high risk of bias. CONCLUSIONS: RWE from T2DM studies lacks transparency and credibility. There is a need for good procedural practices that can increase confidence in RWE studies. Standardized methodologies specifically adapted for RWE studies collecting pharmacoeconomic data for the management of T2DM could help future reimbursement decision making in this major public health problem.

Real-World Experience With Apremilast in the Treatment of Adults With Moderate to Severe Plaque Psoriasis in Québec: A Claims-Based Analysis of Drug Utilization and Healthcare Resource Utilization.

BACKGROUND: In Québec, targeted biologic therapies for moderate to severe plaque psoriasis are restricted to patients who have not responded to phototherapy or conventional systemic treatment, primarily due to high drug costs. Apremilast, an oral treatment for plaque psoriasis, was added to the Québec provincial health insurance plan (Régie de l'assurance maladie du Québec; RAMQ) formulary in 2015, making this the only province in Canada with public drug plan reimbursement for apremilast. OBJECTIVES: The aim of this study is to describe patients' characteristics, treatment patterns, healthcare resource utilization (HCRU), and associated costs and to measure real-world budget impact of using apremilast before biologics in plaque psoriasis. METHODS: This study was performed using RAMQ drug claims and medical services data. Patients diagnosed with psoriasis between January 2015 and December 2017 were identified. Medical services and prescription claims were categorized as all-cause and psoriasis-related. Using RAMQ database estimates, a 3-year budget impact analysis was developed comparing treatment cost with and without the addition of apremilast to the formulary. RESULTS: In all, 540 patients were identified (apremilast: n = 92; biologics: n = 448). Comorbidity burden and treatment persistence and adherence were comparable between apremilast and biologic users. The year following the index date, all-cause HCRU was lower for apremilast versus biologic users (CAN$19 763 vs CAN$28 025; P < .01), mainly driven by drug cost. Using apremilast before biologics resulted in an estimated RAMQ net savings of CAN$49 290 (2015), CAN$746 856 (2016), and CAN$1 216 512 (2017), and a total savings of CAN$2 012 658 since apremilast's addition to the formulary. CONCLUSION: Adding apremilast to the drug formulary of other Canadian provinces could result in significant healthcare savings.

Collaborative writing applications in healthcare: effects on professional practice and healthcare outcomes.

BACKGROUND: Collaborative writing applications (CWAs), such as wikis and Google Documents, hold the potential to improve the use of evidence in both public health and healthcare. Although a growing body of literature indicates that CWAs could have positive effects on healthcare, such as improved collaboration, behavioural change, learning, knowledge management, and adaptation of knowledge to local context, this has never been assessed systematically. Moreover, several questions regarding safety, reliability, and legal aspects exist. OBJECTIVES: The objectives of this review were to (1) assess the effects of the use of CWAs on process (including the behaviour of healthcare professionals) and patient outcomes, (2) critically appraise and summarise current evidence on the use of resources, costs, and cost-effectiveness associated with CWAs to improve professional practices and patient outcomes, and (3) explore the effects of different CWA features (e.g. open versus closed) and different implementation factors (e.g. the presence of a moderator) on process and patient outcomes. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and 11 other electronic databases. We searched the grey literature, two trial registries, CWA websites, individual journals, and conference proceedings. We also contacted authors and experts in the field. We did not apply date or language limits. We searched for published literature to August 2016, and grey literature to September 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs), non-randomised controlled trials (NRCTs), controlled before-and-after (CBA) studies, interrupted time series (ITS) studies, and repeated measures studies (RMS), in which CWAs were used as an intervention to improve the process of care, patient outcomes, or healthcare costs. DATA COLLECTION AND ANALYSIS: Teams of two review authors independently assessed the eligibility of studies. Disagreements were resolved by discussion, and when consensus was not reached, a third review author was consulted. MAIN RESULTS: We screened 11,993 studies identified from the electronic database searches and 346 studies from grey literature sources. We analysed the full text of 99 studies. None of the studies met the eligibility criteria; two potentially relevant studies are ongoing. AUTHORS' CONCLUSIONS: While there is a high number of published studies about CWAs, indicating that this is an active field of research, additional studies using rigorous experimental designs are needed to assess their impact and cost-effectiveness on process and patient outcomes.

Is adjunctive pharmacotherapy in attention-deficit/hyperactivity disorder cost-effective in Canada: a cost-effectiveness assessment of guanfacine extended-release as an adjunctive therapy to a long-acting stimulant for the treatment of ADHD.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder in children, with worldwide prevalence of ADHD varying from 5.9 to 7.1 %, depending on the reporter. In case of inadequate response to stimulants, combination therapy of stimulants and an adjunctive medication may improve the control of ADHD symptoms, reduce the dose-limiting adverse events, and help control comorbidities. To date, the only medication to be used for adjunctive therapy to psychostimulants is guanfacine extended release (GXR). The aim of this study was to assess the economic impact of GXR as an adjunct therapy with long-acting stimulants (GXR + stimulant) compared to long-acting stimulant monotherapy (stimulant alone) in the treatment of children and adolescents with ADHD in Canada. METHOD: A Markov model was developed using health states defined based on the clinician-reported Clinical Global Impression-Severity (CGI-S) score (normal, mild, moderate, severe). Transition probabilities were calculated based on patient-level data from a published study. Long-acting stimulants available in Canada were considered in the base-case model: amphetamine mixed salts, methylphenidate HCl formulations, and lisdexamfetamine dimesylate. Analyses were conducted from a Canadian Ministry of Health (MoH; Ontario) and a societal perspective over a 1-year time horizon with weekly cycles. RESULTS: Over a 1-year time horizon, GXR + stimulant was associated with 0.655 quality-adjusted life year (QALY), compared to 0.627 QALY with stimulant alone, for a gain of 0.028 QALY. From a MoH perspective, GXR+ stimulant and stimulant alone were associated with total costs of $CA1,617 and $CA949, respectively (difference of $CA668), which resulted in an incremental cost-effectiveness ratio (ICER) of $CA23,720/QALY. From a societal perspective, GXR + stimulant and stimulant alone were associated with total costs of $CA3,915 and $CA3,582, respectively (difference of $CA334), which resulted in an ICER of $CA11,845/QALY. Probabilistic sensitivity analysis (PSA) of GXR + stimulant showed that it remains a cost-effective strategy in 100 % of the simulations from both perspectives in numerous PSA and one-way sensitivity analyses, relative to a willingness to pay threshold of $50,000/QALY. CONCLUSIONS: This economic evaluation demonstrates that GXR + stimulant is cost-effective compared to stimulant alone in the treatment of children and adolescents with ADHD in Canada.

Economic evaluation of arsenic trioxide for treatment of newly diagnosed acute promyelocytic leukaemia in Canada.

To assess, from a Canadian perspective, the economic impact of arsenic trioxide (ATO) + all-trans retinoic acid (ATRA) for treating newly diagnosed acute promyelocytic leukaemia (APL), the cost-effectiveness of ATO + ATRA compared to ATRA + idarubicin (IDA) was assessed over a lifetime horizon using a time-dependent Markov model. The model considers four health states: complete remission, treatment failure or relapse, post-failure, and death. Markov cycle length was 1 month for the first 48 months and 1 year thereafter. Efficacy outcomes in terms of event-free survival and overall survival were taken from a head-to-head clinical trial. Costs were associated with drug and administration, adverse events (AEs), treatment of relapses, follow-up visits, and productivity losses. Utilities and disutilities associated with health states and AEs were derived from the literature. Compared to ATRA + IDA, ATRA + ATO is associated with incremental cost-effectiveness ratios (ICERs) of $CAD50,193/quality-adjusted life years (QALY) and $CAD50,338/QALY from a Canadian Ministry of Health (MoH) and societal perspectives, respectively. Results of the one-way sensitivity analysis show that ICER varied from $CAD23,045 to $CAD60,759/QALY (MoH perspective) and from $CAD23,120 to $CAD60,905/QALY (societal perspective). ATO in the first-line therapy for patients with APL can be considered a more cost-effective strategy than standard treatment from a Canadian perspective.

Economic evaluation of arsenic trioxide compared to all-trans retinoic acid + conventional chemotherapy for treatment of relapsed acute promyelocytic leukemia in Canada.

OBJECTIVES: Acute promyelocytic leukemia (APL) is an uncommon type of acute leukemia characterized by high early mortality. Current first-line treatments include all-trans retinoic acid (ATRA), anthracyclines, and other conventional chemotherapies (CTs). Although APL is generally associated with a good prognosis, about 20% of patients who achieve remission subsequently relapse and are resistant to the previously administrated treatment. The objective of this study was to assess, from a Canadian perspective, the economic impact of arsenic trioxide (ATO) compared to ATRA+CT for treatment of patients with relapsed/refractory APL. METHODS: The cost-effectiveness of ATO compared to ATRA+CT for treating patients with relapsed/refractory APL was assessed over a lifetime horizon using a Markov model. The model considers five health states: induction, second remission, treatment failure or relapse, postfailure, and death. Markov cycle length was 1 month for the first 24 months and 1 yr thereafter. The model also takes into account the incidence of grade 3-4 adverse events reported in clinical trials. Analyses were conducted from a Canadian Ministry of Health (MoH) and a societal perspective. RESULTS: Compared to ATRA+CT, ATO was associated with incremental cost-effectiveness ratios of $ 20,551/quality-adjusted life year (QALY) from a MoH perspective and $ 22,219/QALY from a societal perspective. Results of the probabilistic sensitivity analysis indicated that ATO is a cost-effective strategy in 99.27% and 98.98% of the simulations from a MoH and a societal perspective, respectively. CONCLUSIONS: This economic evaluation demonstrates that ATO is a cost-effective strategy compared to ATRA+CT for treatment of patients with relapsed/refractory APL in Canada.

Cost-utility analysis of nonalcoholic steatohepatitis screening.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. No studies have examined the cost-effectiveness of screening its advanced form, nonalcoholic steatohepatitis (NASH). METHODS: We performed a cost-utility analysis of annual noninvasive screening strategies using third-party payer perspective in a general population in comparison to screening a high-risk obese or diabetic population. Screening algorithms involved well-studied techniques, including NAFLD fibrosis score, transient elastography (TE), and acoustic radiation force impulse (ARFI) imaging for detecting advanced fibrosis (≥ F3); and plasma cytokeratin (CK)-18 for NASH detection. Liver biopsy and magnetic resonance elastography (MRE) were compared as confirmation methods. Canadian dollar (CAD or C$) costs were adjusted for inflation and discounted at 5%. Incremental cost-effectiveness ratio (ICER) of ≤C$ 50,000 was considered cost-effective. RESULTS: Compared with no screening, screening with NAFLD fibrosis score/TE/CK-18 algorithm with MRE as confirmation for advanced fibrosis had an ICER of C$ 26,143 per quality-adjusted life year (QALY) gained. Screening in high-risk obese or diabetic populations was more cost-effective, with an ICER of C$ 9,051 and C$ 7,991 per quality-adjusted life-year (QALY) gained, respectively. Liver biopsy confirmation was not found to be cost-effective. CONCLUSIONS: Our model suggests that annual NASH screening in high-risk obese or diabetic populations can be cost-effective. KEY POINTS: • This cost-utility analysis suggests that screening for nonalcoholic steatohepatitis may be cost-effective. • In particular, screening of high-risk obese or diabetic populations is more cost-effective. • Magnetic resonance elastography was more cost-effective to confirm disease compared to biopsy. • More studies are needed to determine quality of life in nonalcoholic steatohepatitis. • More management strategies for nonalcoholic steatohepatitis are also needed.

Impact of switching to long-acting injectable antipsychotics on health services use in the treatment of schizophrenia.

OBJECTIVE: To better understand the treatment patterns, persistence and compliance, resource use, and associated costs, of long-acting injectable antipsychotics (LAI-AP), using the Régie de l'assurance maladie du Québec database. METHOD: Patients with schizophrenia or schizoaffective disorder who were incident users of an LAI-AP prescribed between January 1, 2008, and March 31, 2012, were selected. Concomitant use of oral APs and treatment persistence and compliance with LAI-AP were analyzed. Patients were considered compliant if they had a medication possession ratio (MPR) of at least 0.80. Health care resource use (HCRU) and associated costs were analyzed during the year before and after LAI-AP initiation. RESULTS: A total of 1992 patients met the inclusion criteria. The average persistence with LAI-AP was 217.2 days (SD 144.2). The mean MPR with LAI-AP during the postinitiation year was 0.58 (SD 0.35), with 37.5% of patients being compliant. In the preinitiation year, 29.0% of patients were compliant with previous oral AP. In the pre- and postinitiation periods, 1484 and 958 patients had at least 1 hospitalization, and hospitalized days were reduced by one-half (P<0.001). Cost of HCRU, including medication, was significantly decreased from $24,382 (SD $27,234) to $13,090 (SD $16,987), respectively, in the pre- and postinitiation years (P<0.001). CONCLUSIONS: The initiation of an LAI-AP improved treatment compliance, compared with previous oral APs, resulted in significantly lower HCRU and costs. The primary drivers were the reduction in the occurrence and days of hospitalizations.

Rates of non-vertebral osteoporotic fractures in rheumatoid arthritis and postfracture osteoporosis care in a period of evolving clinical practice guidelines.

In 2002, guidelines for the management of osteoporosis were published by Osteoporosis Canada and widely disseminated. We aimed to assess if those guidelines had any impact on clinical practice and ultimately on fracture rates in rheumatoid arthritis (RA). This was an observational study using the Quebec healthcare databases. To quantify the use of osteoporosis drugs, hormone replacement therapy (HRT), bone mineral density (BMD) testing, and fracture rates, quarterly age-standardized rates between 1998 and 2008 were calculated. A time series approach was used to predict fracture rates from 2003 onward, based on the earlier data. The provision of postfracture osteoporosis care, as defined by the initiation of osteoporosis drugs, HRT, or BMD testing, was examined; and logistic regressions identified factors associated with care. The study population in each quarter was mainly composed of older women. The use of osteoporosis drugs and BMD testing increased over the study period. The actual fracture rates from 2003 onward fell within the projected rates and their 95 % CI indicating no reduction. A total of 1,279 subjects were included in the postfracture care analysis. Over time, the likelihood of receiving osteoporosis care increased by 64 % (OR = 1.64, 95 % CI 1.27-2.11), and the two strongest predictors of care were female gender and corticosteroid use. Over our study period, fracture rates remained stable in this RA population. However, the use of osteoporosis drugs, BMD testing, and provision of postfracture osteoporosis care improved, which may result from gradual adoption of guidelines.

Cost-effectiveness of asenapine in the treatment of bipolar disorder in Canada.

BACKGROUND: Bipolar disorder (BPD) is prevalent and is associated with a significant economic burden. Asenapine, the first tetracyclic antipsychotic approved in Canada for the treatment of BPD, has shown a comparable efficacy profile to other atypical antipsychotics. In addition, it is associated with a favourable metabolic profile and minimal weight gain potential. This study aimed to assess the economic impact of asenapine compared to olanzapine in the treatment of BPD in Canada. METHODS: A decision tree combined with a Markov model was constructed to assess the cost-utility of asenapine compared with olanzapine. The decision tree takes into account the occurrence of extrapyramidal symptoms (EPS), the probability of switching to a different antipsychotic, and the probability of gaining weight. The Markov model takes into account long-term metabolic complications including diabetes, hypertension, coronary heart diseases (CHDs), and stroke. Analyses were conducted from both a Canadian Ministry of Health (MoH) and a societal perspective over a five-year time horizon with yearly cycles. RESULTS: In the treatment of BPD, asenapine is a dominant strategy over olanzapine from both a MoH and a societal perspective. In fact, asenapine is associated with lower costs and more quality-adjusted life years (QALYs). Results of the probabilistic sensitivity analysis indicated that asenapine remains a dominant strategy in 99.2% of the simulations, in both a MoH and a societal perspective, and this result is robust to the many deterministic sensitivity analyses performed. CONCLUSIONS: This economic evaluation demonstrates that asenapine is a cost-effective strategy compared to olanzapine in the treatment of BPD in Canada.

Medication adherence and persistence in the treatment of Canadian ulcerative colitis patients: analyses with the RAMQ database.

BACKGROUND: Although high non-adherence to medication has been noticed for ulcerative colitis (UC), little is known about adherence to mesalamine treatments and determinants that can predict adherence. The objective of this study was to assess adherence and persistence to mesalamine treatments and their potential determinants in mild to moderate UC patients in a real-life setting in Quebec, Canada. METHODS: A retrospective prescription and medical claims analysis was conducted using a random sample of mesalamine users with UC. For inclusion, patients were required to initiate an oral mesalamine treatment between January 2005 and December 2009. Patients with a diagnosis of Crohn's disease were excluded. Treatment adherence (medication possession ratio [MPR]) and persistence were evaluated over a 1-year period after the index prescription using the Kaplan-Meier method with log-rank test and stepwise regression to identify potential determinants. RESULTS: A sample of 1,681 of the new oral mesalamine users (mean age = 55.3) patients was obtained. Overall, the percentage of patients with a MPR of 80% or greater at 12 months was 27.7%, while persistence was 45.5%. Among patients treated with mesalamine delayed/extended-release tablets (Mezavant®), adherence and persistence were 40.9% and 71.9%, respectively. Predictors of high adherence included, male gender (OR=1.3; 95% confidence interval [CI]=1.1-1.6), older age (>60 years; OR=1.6; 95% CI=1.3-2.0) and current use of corticosteroids (OR=1.4; 95% CI=1.1-1.8). Predictors of high persistence included male sex (OR=1.4; 95% CI=1.1-1.7), current use of corticosteroids (OR=1.4; 95% CI=1.1-1.7) and presence of hypertension or respiratory diseases (OR=1.2; 95% CI=1.01-1.55). CONCLUSIONS: The majority of patients with UC exhibited low adherence and persistence to mesalamine treatments. Various determinants of improved adherence and persistence were identified.

Rheumatoid arthritis pharmacotherapy and predictors of disease-modifying anti-rheumatic drug initiation in the early years of biologic use in Quebec, Canada.

Disease-modifying anti-rheumatic drugs (DMARDs) are the cornerstone of rheumatoid arthritis (RA) pharmacotherapy and should be initiated promptly after RA diagnosis. We examined trends in use of traditional and biologic DMARDs, and non-DMARD treatments, among overall RA patients, and factors associated with DMARD initiation in the newly diagnosed RA. RA subjects identified with the Quebec administrative databases were followed between January 1, 2002, and December 31, 2008. DMARD use was characterized on November 1 of each year using cross-sectional analyses. For a subgroup of newly diagnosed subjects, we used multivariable logistic regressions to identify predictors of DMARD initiation within 12 months of diagnosis and survival analyses to appraise time to DMARD initiation. A total of 37,399 subjects were included (65.8 % ≥65 years; 70.5 % female). The percentage of subjects using any DMARDs increased over the study period from 41.4 % [95 % confidence interval (CI) 40.8-42.0] to 43.3 % (95 % CI 42.7-43.9). Among newly diagnosed RA, being followed by a rheumatologist was the strongest predictor of DMARD initiation (odds ratio 4.31; 95 % CI 3.73-4.97). Care by an internist, increasing calendar year, use of NSAIDs, corticosteroids, or opioids, and a history of hospitalization increased the likelihood of DMARD initiation. Older age, female, higher comorbidity score, number of medical visits pre-diagnosis, care by other specialists, and the use of acetaminophen were inversely associated with DMARD initiation. The probability of any DMARD initiation at 12 months was 38.5 %. Despite the clinical practice guideline recommendations for earlier aggressive RA management, DMARD use appears to be suboptimal in Quebec.

Impact of Fixed-Duration Oral Targeted Therapies on the Economic Burden of Chronic Lymphocytic Leukemia in Canada.

BACKGROUND: Continuous oral targeted therapies (OTT) represent a major economic burden on the Canadian healthcare system, due to their high cost and administration until disease progression/toxicity. The recent introduction of venetoclax-based fixed-duration combination therapies has the potential to reduce such costs. This study aims to estimate the prevalence and the cost of CLL in Canada with the introduction of fixed OTT. METHODS: A state transition Markov model was developed and included five health states: watchful waiting, first-line treatment, relapsed/refractory treatment, and death. The number of CLL patients and total cost associated with CLL management in Canada for both continuous- and fixed-treatment-duration OTT were projected from 2020 to 2025. Costs included drug acquisition, follow-up/monitoring, adverse event, and palliative care. RESULTS: The CLL prevalence in Canada is projected to increase from 15,512 to 19,517 between 2020 and 2025. Annual costs were projected at C$880.7 and C$703.1 million in 2025, for continuous and fixed OTT scenarios, respectively. Correspondingly, fixed OTT would provide a total cost reduction of C$213.8 million (5.94%) from 2020 to 2025, compared to continuous OTT. CONCLUSIONS: Fixed OTT is expected to result in major reductions in cost burden over the 5-year projection, compared to continuous OTT.

Adherence to oral antiretroviral therapy in Canada, 2010-2020.

OBJECTIVE: To assess antiretroviral therapy (ART) adherence among people with HIV (PWH) in Canada and identify baseline characteristics associated with suboptimal adherence (<95%). DESIGN: Retrospective observational study using data from the National Prescription Drug Utilization Information System and Régie de l'assurance maladie Quebec (RAMQ) Public Prescription Drug Insurance Plan. METHODS: This analysis included PWH aged 18 years or older who initiated an ART regimen and were followed for at least 12 months (2010-2020). Patient characteristics were summarized using medical/pharmacy claims data from seven provinces (Alberta, Manitoba, New Brunswick, Newfoundland and Labrador, Ontario, Saskatchewan, and Quebec). ART regimen at index date (first dispensing of a regimen including a core agent) was defined as a single-tablet or multitablet regimen (MTR). Adherence was calculated using a Proportion of Days Covered approach, based on ART dispensing, recorded between April 2010 and the last available date. Multivariate linear regression analysis was used to determine correlations between suboptimal adherence and baseline characteristics. RESULTS: We identified 19 322 eligible PWH, 44.7% of whom had suboptimal adherence (<95%). Among 12 594 PWH with evaluable baseline data, 10 673 (84.8%) were ART-naive, 74.2% were men, mean age was 42.9 years, and 54.1% received a MTR as their ART. Based on multivariate regression analysis, suboptimal adherence was significantly associated with multitablet ART ( P  < 0.001) and younger age ( P  < 0.001) but not sex. CONCLUSION: Almost half of adult PWH in Canada had suboptimal adherence to ART. Better understanding of factors influencing adherence may help address gaps in current care practices that may impact adherence.

Cost-Effectiveness of Icosapent Ethyl (IPE) for the Reduction of the Risk of Ischemic Cardiovascular Events in Canada.

Background: Despite the use of statins, many patients with cardiovascular disease (CVD) have persistent residual risk. In a large Phase III trial (REDUCE-IT), icosapent ethyl (IPE) was shown to reduce the first occurrence of the primary composite endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina. Methods: We conducted a cost-utility analysis comparing IPE to placebo in statin-treated patients with elevated triglycerides, from a publicly funded, Canadian healthcare payer perspective, using a time-dependent Markov transition model over a 20-year time horizon. We obtained efficacy and safety data from REDUCE-IT, and costs and utilities from provincial formularies and databases, manufacturer sources, and Canadian literature sources. Results: In the probabilistic base-case analysis, IPE was associated with an incremental cost of $12,523 and an estimated 0.29 more quality-adjusted life years (QALYs), corresponding to an incremental cost-effectiveness ratio (ICER) of $42,797/QALY gained. At a willingness-to-pay of $50,000 and $100,000/QALY gained, there is a probability of 70.4% and 98.8%, respectively, that IPE is a cost-effective strategy over placebo. The deterministic model yielded similar results. In the deterministic sensitivity analyses, the ICER varied between $31,823-$70,427/QALY gained. Scenario analyses revealed that extending the timeframe of the model to a lifetime horizon resulted in an ICER of $32,925/QALY gained. Conclusion: IPE represents an important new treatment for the reduction of ischemic CV events in statin-treated patients with elevated triglycerides. Based on the clinical trial evidence, we found that IPE could be a cost-effective strategy for treating these patients in Canada.

I-SAVE study: impact of sedation, analgesia, and delirium protocols evaluated in the intensive care unit: an economic evaluation.

BACKGROUND: Intensive care units (ICUs) account for considerable health care costs. Adequate pain and sedation management is important to clinical care. OBJECTIVE: To determine whether implementing a protocol for management of analgesia, sedation, and delirium in the ICU would save costs. METHODS: With data from the I-SAVE (Impact of Sedation, Analgesia and Delirium Protocols Evaluated in the Intensive Care Unit: an Economic Evaluation) study, a prospective pre- and postprotocol design was used. Between the 2 periods, protocols for systematic management of sedation, analgesia, and delirium were implemented. Cost-effectiveness was calculated by associating the variation of cost and effectiveness measures (proportion of patients within targeted pain, sedation, and delirium goals). Total costs (in 2004 Canadian dollars), by patient, consisted of the sum of sedation, analgesia, and delirium drug acquisition costs during the ICU stay and the cost of the ICU stay. RESULTS: A total of 1214 patients, 604 in the preprotocol group and 610 in the postprotocol group, were included. The mean (SD) ICU length of stay and the duration of mechanical ventilation were shorter among patients of the postprotocol group compared with those of the preprotocol group (5.43 [6.43] and 6.39 [8.05] days, respectively; p = 0.004 and 5.95 [6.80] and 7.27 [9.09] days, respectively; p < 0.009). The incidence of delirium remained the same. The proportion of patients with Richmond Agitation and Sedation (RASS) scores between -1 and +1 increased from 57.0% to 66.2% (p = 0.001), whereas the proportion of patients with a numeric rating scale (NRS) score of 1 or less increased from 56.3% to 66.6% (p < 0.001). The mean total cost of ICU hospitalization decreased from $6212.64 (7846.86) in the preprotocol group to $5279.90 (6263.91) in the postprotocol group (p = 0.022). The cost analyses for pain and agitation management improved; the proportion of patients with RASS scores between -1 and +1 or NRS scores of 1 or less increased significantly in the postprotocol group while costing, on average, $932.74 less per hospitalization. CONCLUSIONS: Establishing protocols for patient-driven management of sedation, analgesia, and delirium is a cost-effective practice and allows savings of nearly $1000 per hospitalization.

The Impact of Hypoglycemia on Productivity Loss and Utility in Patients With Type 2 Diabetes Treated With Insulin in Real-world Canadian Practice: Protocol for a Prospective Study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) imposes a substantial burden owing to its increasing prevalence and life-threatening complications. In patients who do not achieve glycemic targets with oral antidiabetic drugs, the initiation of insulin is recommended. However, a serious concern regarding insulin is drug-induced hypoglycemia. Hypoglycemia is known to affect quality of life and the use of health care resources. However, health economics and outcomes research (HEOR) data for economic modelling are limited, particularly regarding utility values and productivity losses. OBJECTIVE: This real-world prospective study aims to assess the impact of hypoglycemia on productivity and utility in insulin-treated adults with T2DM from Ontario and Quebec, Canada. METHODS: This noninterventional, multicenter, 3-month prospective study will recruit patients from 4 medical clinics and 2 endocrinology or diabetes clinics. Patients will be identified using appointment lists and enrolled through consecutive sampling during routinely scheduled consultations. To be eligible, patients must be aged ≥18 years, diagnosed with T2DM, and treated with insulin. Utility and productivity will be measured using the EQ-5D-5L questionnaire and Institute for Medical Technology Assessment Productivity Cost Questionnaire, respectively. Questionnaires will be completed 4, 8, and 12 weeks after recruitment. Generalized estimating equation models will be used to investigate productivity losses and utility decrements associated with incident hypoglycemic events while controlling for individual patient characteristics. A total of 500 patients will be enrolled to ensure the precision of HEOR estimates. RESULTS: This study is designed to fill a gap in the Canadian evidence on the impact of hypoglycemia on HEOR outcomes. More specifically, it will generate productivity and utility inputs for the economic modeling of T2DM. CONCLUSIONS: Insulin therapy is expensive, and hypoglycemia is a significant component of economic evaluation. Robust HEOR data may help health technology assessment agencies in future reimbursement decision-making. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/35461.