Economic analysis of insulin initiation by pharmacists in a Canadian setting: The RxING study.

BACKGROUND: Conducted in Alberta, the RxING study examined the effect of a community pharmacist prescribing intervention on glycemic control in patients with uncontrolled type 2 diabetes mellitus (T2DM) using insulin glargine. The objective of this study was to assess the cost-effectiveness of pharmacists' prescribing of insulin glargine as an early intervention in uncontrolled patients with T2DM vs usual clinical practice. METHODS: The IMS CORE diabetes Markov model was used to project long-term clinical outcomes, costs and cost-effectiveness of interventions. The efficacy of insulin glargine, in terms of hemoglobin A1c reduction and hypoglycemia rates, was obtained from the RxING study. Health utility and cost data were found in Canadian publications. The base-case analyses examined the economic and clinical effects of having pharmacists initiate insulin therapy in patients with uncontrolled T2DM in comparison to a physician initiate it up to 3 years later. RESULTS: Insulin initiation by pharmacists with uncontrolled T2DM patients is cost-effective. Having pharmacists prescribe insulin 1 year earlier than usual clinical practice resulted in an incremental cost savings of $805 (CDN$) and a gain of 0.048 QALYs per patient. Pharmacists prescribing insulin 2 years earlier resulted in an incremental cost savings of $624 (CDN$) per year and a gain of 0.075 quality-adjusted life-years (QALYs). Prescribing 3 years earlier allowed for a minor increase of $26 and a gain of 0.086 QALYs. CONCLUSION: Earlier initiation of insulin by pharmacists, in uncontrolled T2DM patients, resulted in cost savings and delays in the development of diabetes-related complications, leading to an improved quality of life and increased survival rates.

Cost effectiveness of insulin glargine plus oral antidiabetes drugs compared with premixed insulin alone in patients with type 2 diabetes mellitus in Canada.

BACKGROUND: Several treatment options are available for patients with type 2 diabetes mellitus who are making the transition from oral antidiabetes drugs (OADs) to insulin. Two options currently recommended by the Canadian Diabetes Association for initiating insulin therapy in patients with type 2 diabetes who are no longer responsive to OADs alone are insulin glargine plus OADs, and premixed insulin therapy only. Because of differences in efficacy, adverse events (such as hypoglycaemia) and acquisition costs, these two treatment options may lead to different long-term clinical and economic outcomes. OBJECTIVE: To determine the cost effectiveness of insulin glargine plus OADs compared with premixed insulin without OADs in insulin-naive patients with type 2 diabetes in Canada. METHODS: Using treatment effects taken from a published clinical trial, the validated IMS-CORE Diabetes Model was used to simulate the long-term cost effectiveness of insulin glargine with OADs, versus premixed insulin. Input treatment effects for the two therapeutic approaches were based on changes in glycosylated haemoglobin A(1c) (HbA(1c)) at clinical trial endpoint, and hypoglycaemia rates. The analysis was conducted from the perspective of the Canadian Provincial payer. Direct treatment and complication costs were obtained from published sources (primarily from Ontario) and reported in $Can, year 2008 values. All base-case costs and outcomes were discounted at 5% per year. Sensitivity analyses were conducted around key parameters and assumptions used in the study. Outcomes included direct medical costs associated with both treatment and diabetes-related complications. Cost-effectiveness outcomes included total average lifetime (35 years) costs, life expectancy (LE), QALYs and incremental cost-effectiveness ratios (ICERs). RESULTS: Base-case analyses showed that, compared with premixed insulin only, insulin glargine in combination with OADs was associated with a 0.051-year increase in LE and a 0.043 increase in QALYs. Insulin glargine plus OADs showed a very slight increase in total direct costs ($Can 343 +/- 2572), resulting in ICERs of $Can 6750 per life-year gained (LYG) and $Can 7923 per QALY gained. However, considerable uncertainty around the ICERs was demonstrated by insulin glargine having a 50% probability of being cost effective at a willingness-to-pay threshold of $Can 10,000 per QALY, and a 54% probability at a $Can 20,000 threshold. Base-case results were most sensitive to assumed disutilities for hypoglycaemic events, to the assumed effect of insulin glargine plus OADs on HbA(1c), and to its assumed acquisition costs. CONCLUSIONS: These findings should be interpreted within the context of a large degree of uncertainty and of several study limitations that include a single clinical trial as the source for primary treatment assumptions and a single province as the source for most cost inputs. Under current study assumptions and limitations, insulin glargine plus OADs was projected to be a cost-effective option, compared with premixed insulin only, for the treatment of insulin-naive patients with type 2 diabetes unresponsive to OADs. Additional work is needed to examine the generalizability of the findings to individual jurisdictions of the Canadian healthcare system.

The Use of Computer Simulation Modeling to Estimate Complications in Patients with Type 2 Diabetes Mellitus: Comparative Validation of the Cornerstone Diabetes Simulation Model.

OBJECTIVE: The objective of this study was to assess the validity of the Cornerstone Diabetes Simulation (CDS), a Microsoft Excel®-based patient-level simulation for type 2 diabetes mellitus based on risk equations from the revised United Kingdom Prospective Diabetes Study Outcomes Model (UKPDS-OM2, also known as UKPDS 82). METHODS: Three levels of validation were conducted. Internal validation was assessed through independent review and model stress-testing. External validation was addressed by populating the CDS with baseline characteristics and treatment effects from three major diabetes clinical trials used in the Fifth Mount Hood Diabetes Challenge (MH5) for computer simulation models. Cross-validation of predicted outcomes was tested versus eight models that participated in the MH5. Simulated results were compared with observed clinical outcomes via the coefficient of determination (R2) for both the absolute risk of each clinical outcome and the difference in absolute risk between control and intervention arm in each trial. We ensured transparency of all model inputs and assumptions in reporting. RESULTS: The CDS could be used to predict 18 of 39 single and composite endpoints across the three trials. The model obtained an R2 of 0.637 for predicted versus observed absolute risks, and an R2 of 0.442 for predicted versus observed risk differences between control and intervention. Among the other eight models, only one obtained a higher R2 value under both definitions, albeit based on only four predicted endpoints. CONCLUSIONS: The CDS provides good predictions of diabetes-related complications when compared to observed trial outcomes and previously validated models. The model has value as a validated tool in cost-effectiveness evaluations.

Real-World Health Outcomes of Insulin Glargine 300 U/mL vs Insulin Glargine 100 U/mL in Adults With Type 1 and Type 2 Diabetes in the Canadian LMC Diabetes Patient Registry: The REALITY Study.

OBJECTIVES: This study evaluated real-world clinical outcomes of patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) initiating or transferring to insulin glargine 300 U/mL (Gla-300) vs insulin glargine 100 U/mL (Gla-100). METHODS: This is a retrospective cohort study using data from the Canadian LMC Diabetes Patient Registry. The 4 following cohorts were analyzed: 1) insulin-naïve patients with T2D who initiated Gla-300 or Gla-100, 2) patients with T2D who switched from neutral protamine Hagedorn (NPH) or detemir to Gla-300 or Gla-100, 3) patients with T2D who switched from Gla-100 to Gla-300 and 4) patients with T1D who switched from Gla-100, NPH or detemir to Gla-300. RESULTS: Of 376 propensity score-matched insulin-naïve patients, 6-month reduction in glycated hemoglobin (A1C) was similar between Gla-300 (-1.78%±1.85%; p<0.001) and Gla-100 (-1.74%±1.87%; p<0.001). In 114 propensity score-matched patients who switched from NPH or detemir, 6-month reduction in A1C was similar between Gla-300 (-0.78%±1.14%) and Gla-100 (-0.70%±1.57%). The 396 patients who switched from Gla-100 to Gla-300 had a significant reduction in A1C (-0.45%±1.39%; p<0.001). In 196 patients with T1D who switched from Gla-100, NPH or detemir to Gla-300, there was a significant reduction in A1C of -0.17%±1.19% (p=0.04). CONCLUSIONS: In a real-world clinical setting, insulin-naïve patients who initiated Gla-300 or Gla-100 showed similar changes in A1C and weight. Patients with T1D or T2D using Gla-300 transferred from another basal insulin had significant reductions in A1C with no change in weight or insulin dose.

Treatment satisfaction and quality of life using an early insulinization strategy with insulin glargine compared to an adjusted oral therapy in the management of Type 2 diabetes: the Canadian INSIGHT Study.

The objective was to compare the impact on treatment satisfaction (TS) and quality of life (QoL) of early insulinization with glargine versus adjusting oral antidiabetic drug (OAD) therapy in people with Type 2 diabetes with uncontrolled glycemia. TS and QoL were assessed at baseline, weeks 12 and 24 within the Canadian INSIGHT, a randomized 24-week trial of Type 2 patients. A total of 366 patients randomized to either the insulin glargine arm (n=182) or the adjusted OAD therapy arm (n=184) completed both questionnaires. At baseline, TS and QoL were similar in both groups. A1c reduction was greater in the insulin glargine arm. TS improved from baseline in both treatment arms; however, there was greater increase with insulin glargine+OAD. Perceived frequency of hypoglycemia and hypoglycemia were lower at week 24, with no differences between the two groups. Perceived frequency of hyperglycemia improved with glargine at week 12, and no difference was found at 24 weeks. Finally, QoL improved in both groups, but significantly more with glargine at both weeks 12 and 24. Improving glucose control by adding insulin glargine to OAD therapy had a positive impact on TS and general QoL without complaints related to hypoglycemia.

Modelling cost effectiveness of insulin glargine for the treatment of type 1 and 2 diabetes in Canada.

BACKGROUND AND OBJECTIVE: Intensive insulin therapy improves glycosylated haemoglobin (Hb(A1C)) levels and delays the onset of long-term diabetes-related complications. Current treatment guidelines recommend maintaining a glycosylated haemoglobin (Hb(A1C)) of < or = 7% in patients with type 1 and 2 diabetes mellitus. However, the risk of hypoglycaemia increases with lower Hb(A1C) levels. As such, patients often choose to settle for suboptimal glucose control in order to prevent hypoglycaemic events. At a given Hb(A1C) level, treatment with insulin glargine results in a lower risk of hypoglycaemia in type 1 and 2 diabetes compared with NPH insulin. It has been proposed that the lower hypoglycaemic risk will allow more patients to achieve target Hb(A1C) levels with insulin glargine compared with NPH insulin. The objective of this study was to assess the cost effectiveness of insulin glargine compared with NPH insulin in patients with type 1 or 2 diabetes who had inadequate glycaemic control. METHODS: A long-term, state-transition model was developed to simulate the natural history of type 1 and 2 diabetes. Risks of diabetes-related macro- and microvascular complications and mortality by Hb(A1C) levels were estimated based on the UKPDS (United Kingdom Prospective Diabetes Study). Outcome measures included complication rates and associated costs, insulin costs, life years (LYs) and QALYs. The baseline analysis was conducted for patients with type 1 and 2 diabetes (aged 27 and 53 years, respectively) with Hb(A1C) levels >7%, using a 36-year time horizon and a Canadian public payer perspective. Costs and effects were discounted at 5% per annum. Univariate sensitivity analyses were performed on key model inputs. All costs were reported in $Can (2005 values). RESULTS: The NPH insulin group had lower total costs than the insulin glargine group for patients with inadequately controlled diabetes (Hb(A1C) >7%; lifetime difference 1398 Can dollars and 1992 Can dollars, respectively, in type 1 and 2 diabetes). However, patients treated with insulin glargine had greater total and quality-adjusted life expectancy than those who received NPH insulin (incremental LY = 0.08 and QALYs = 0.07 in type 1 diabetes and incremental LY = 0.25 and QALYs = 0.23 in type 2 diabetes). The weighted incremental cost per LY gained and QALY gained were 18,661 Can dollars and 20,799 Can dollars, respectively, in type 1 diabetes and 8041 Can dollars and 8618 Can dollars, respectively, in type 2 diabetes (discounted results). CONCLUSIONS: The cost-effectiveness ratios for insulin glargine use for type 1 and 2 diabetes provide evidence for its adoption from a Canadian healthcare payer perspective.

After the diabetes care trial ends, now what? A 1-year follow-up of the RxING study.

INTRODUCTION: There is strong evidence that pharmacist care improves patients' glycaemic control. However, the sustainability and durability of such interventions beyond the research period is not known. RxING was the first trial of pharmacist prescribing in diabetes and it showed an improvement in glycated haemoglobin (HbA1c) of 1.8% over 6 months. OBJECTIVE: 1° objective: To evaluate glycaemic control in the RxING study patients 12 months after the end of the formal study follow-up. 2° objective: To assess the patients' risk of cardiovascular events in the next 10 years. METHODS: We contacted the participating pharmacists to check if the patients who participated in the RxING study are still taking insulin, the dose of insulin they are taking, and their HbA1c. There were no mandated follow-up visits with the pharmacist after the study completion. RESULTS: A total of 100 patients with poorly controlled type 2 diabetes were enrolled in the original RxING study; 93 of them completed the study, while 83 participated in the 12-month follow-up. Seventy-five patients were still taking insulin, with the average dose increasing from 31.1 units (SD 18.4) at study completion to 37.4 units (SD 30.8) (95% CI -13.3 to 0.88, p=0.085). HbA1c was reduced from 9.1% (SD 1) at baseline to 7.3% (SD 0.9) at study completion (95% CI 1.4 to 2, p <0.001), and increased to 8.1% (SD 1.3) 12 months later (95% CI -1.1 to -0.5, p <0.001 vs study completion). CONCLUSIONS: Twelve months after completing the intervention, approximately half of the glycaemic control gains were lost. This highlights the importance of structured follow-up with the pharmacist in this patient population. TRIAL REGISTRATION NUMBER: clinicaltrials.gov; Identifier: NCT01335763.

Meta-analysis and economic evaluation of LH-RH agonists' depot formulations in advanced prostatic carcinoma.

The present study compares the relative efficacy, safety and cost of therapy of the following LH-RH agonists: buserelin acetate (Suprefact(R) Depot, Hoechst Marion Roussel), goserelin acetate (Zoladex(R) LA, Zeneca Pharma Inc.), and leuprolide acetate (Lupron(R) SR Depot, Abbott Laboratories Inc.). To support the conduct of a cost-minimization analysis in patients with advanced prostatic carcinoma their comparable efficacy and safety was first assessed using a meta-analysis technique. The absence of statistically significant differences among the 2 major end points, survival and progression-free survival was confirmed. The cost-minimization analysis for the depot formulations was conducted from the perspectives of the provincial formulary and the Ministry of Health, and considered 2 time horizons: 1 year, and mean survival time of 2.5 years. Cost differences among LH-RH agonists were sensitive to changes in dosing interval and patient survival time but, even when these parameters were varied, for a general population of patients with advanced prostate cancer, buserelin remained the most cost-saving treatment alternative among LH-RH agonists.

Cost-effectiveness of insulin glargine versus sitagliptin in insulin-naïve patients with type 2 diabetes mellitus.

PURPOSE: In the EASIE (Evaluation of Insulin Glargine Versus Sitagliptin in Insulin-Naïve Patients) trial, insulin glargine found a significant reduction in glycosylated hemoglobin compared with sitagliptin in patients with type 2 diabetes who are inadequately controlled with metformin. The objective of this study was to assess the cost-effectiveness of insulin glargine compared with sitagliptin in type 2 diabetes patients, from the perspective of the publicly funded Canadian health care system. METHODS: The IMS CORE Diabetes Model, a standard Markov structure and Monte Carlo simulation model, was used. The model used a lifetime horizon to capture the long-term complications associated with type 2 diabetes. The efficacy of insulin glargine and sitagliptin in terms of glycosylated hemoglobin reduction and corresponding rates of hypoglycemia were obtained from the EASIE trial. Health utility and cost data were obtained from recently published Canadian publications. Univariate and probabilistic sensitivity analyses were conducted. FINDINGS: In the lifetime base-case analysis, treatment with insulin glargine resulted in cost savings of $1434 CAD in 2012 and a gain of 0.08 quality-adjusted life years per patient. A probabilistic sensitivity analysis found the robustness of the base-case analysis, with 88% probability of insulin glargine being dominant (ie, cost savings and more quality-adjusted life years). IMPLICATIONS: Insulin glargine is a clinically superior and cost-effective alternative to sitagliptin in patients with type 2 diabetes who are inadequately controlled with metformin.

Cost-effectiveness of dronedarone in patients with atrial fibrillation in the ATHENA trial.

BACKGROUND: The ATHENA trial randomized 4628 patients with atrial fibrillation (AF) or atrial flutter, aged ≥ 70 years with risk factors or ≥ 75 years without risk factors, to receive 400 mg dronedarone twice daily or placebo in addition to standard therapy. Our objective was to evaluate the cost-effectiveness of dronedarone from a Canadian health care perspective based on resource utilization and cardiovascular hospitalization or death in ATHENA. METHODS: Data on medical resource utilization (cardiovascular hospitalizations, hospitalization because of treatment-related adverse events, outpatient examinations and procedures, study drug and concomitant medications) were aggregated for all randomized patients during the entire trial period (mean 21 months). Effectiveness was measured using the total number of avoided cardiovascular hospitalizations and deaths from any cause, and projected survival and quality-adjusted survival using life tables adjusted for AF mortality and data on determinants of utility in AF. We used standard unit costs from Canada (2008), discounting costs and effects at 5% per year. RESULTS: Patients receiving dronedarone incurred a mean total cost (undiscounted) of CAD $7402 during the trial period, compared with CAD $6708 for patients receiving placebo. The cost of dronedarone was partly offset by savings for cardiovascular hospitalizations and concomitant medications. On average, patients taking dronedarone experienced 0.18 fewer events (cardiovascular hospitalizations or death). The cost per event avoided was CAD $3807, the cost per life-year gained was CAD $5204, and the cost per quality-adjusted life-years was CAD $7560. CONCLUSIONS: Compared with generally accepted thresholds, our results indicate that treatment with dronedarone as in ATHENA is cost-effective.

The burden of atrial fibrillation on the hospital sector in Canada.

BACKGROUND: Atrial fibrillation (AF) is a common disease that frequently requires acute hospital care; however, the cost of hospital care in Canada has not been reported. The purpose of this study was to estimate the cost of AF related to hospital-based care in Canada. METHODS: Analyses were conducted with 2 national administrative databases for the fiscal year 2007-2008. Databases included information for hospital admissions, day operations, and ambulatory care. Records with a most responsible diagnosis of AF, atrial flutter, or a diagnosis related to AF with a concomitant comorbidity of AF were included. Hospital costs were estimated, in 2010 Canadian dollars, by applying an average cost per weighted case to the resource intensity weight for each admission or visit and then adding the separate billable fee for admissions, surgical procedures, and interventions. RESULTS: In 2007-2008, the number of acute care admissions with AF as the most responsible diagnosis was 22,823, same-day surgical procedures was 5707, and emergency department visits was 58,066. The hospital costs attributable to AF were $815 million in 2010 Canadian dollars: $710 million for hospitalizations; $32 million for same-day surgical procedures; and $73 million for emergency department visits. Most of the acute care costs were for hospitalizations when AF was listed as a comorbidity ($558 million, or 69%). CONCLUSION: AF results in a substantial cost burden to the acute care hospital sector. Current hospital costs in AF patients are driven by the consequences of AF, while the costs for specific treatments for AF are relatively low.

Demographic Characteristics and Patterns of Medication in Atrial Fibrillation Patients in South West Ontario: Insights from a Large Primary Care Database.

Background: Information about current practice in primary care-based management of atrial fibrillation (AF) can help to improve care quality. Purpose: To assess the epidemiology of AF and current patterns of treatment in order to identify therapeutic trends and aspects of current practice that may allow for care-gap identification. Methods: We scrutinized the anonymized records of the South Western Ontario database (SWO) collected between July 2002 and October 2008 for information about the characteristics and management of AF patients. Results: From a population of ~168,000 patients we identified 4922 patients with a diagnosis of AF (2.9%). The recorded prevalence of AF increased with age, from <2% at age <60 years to 6% in the age range 71-75 years and 10% at age ≥81 years. AF patients were characterized by an unfavourable cardiovascular risk profile including widespread hypertension (54% of all cases), coronary artery disease (37%) and heart failure (21%), many cases of which were advanced (New York Heart Association class III or IV). Diabetes (22%) and dyslipidaemia (31%) were also widely prevalent. The most frequently prescribed anti-arrhythmic drugs (AADs) were sotolol (n=798), amiodarone (n=712) and propafenone (n=451). Recorded use of flecainide was relatively low (n=175). Rate control-agents were being prescribed for 1838 patients, beta-blockers for 1311 patients and calcium channel blockers (CCBs) for 784 patients. Use of anticoagulants was higher among patients assigned to AADs than among those assigned to rate-control drugs (>25% vs. ~10%). Overall prescription rates for other concomitant medications were >50% for ACE inhibitors/ARBs, 30-35% for statins and beta-blockers, and 27-29% for diuretics, digoxin and CCBs. Conclusions: These Canadian patients with AF were relatively elderly and had multiple concomitant cardiovascular conditions and medications.

Atrial fibrillation: a real-life observational study in the Québec population.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia and has been associated with heart failure, stroke, and mortality. The prevalence of AF is expected to rise with the aging population. Our objectives were to characterize the Québec AF patient population at the time of diagnosis of AF, quantify medical resource use prior to and after the initial diagnosis of AF, and determine overall survival. METHODS: A retrospective cohort study was undertaken using the Régie de l'Assurance Maladie du Québec databases to evaluate patients diagnosed with AF between January 1, 1998, and April 30, 2009. RESULTS: A total of 64,157 patients were included in our study population. At the time of diagnosis of AF, patients also suffered from several diseases, including heart failure (15.8%) and angina pectoris (15.1%). Compared with the year prior to AF diagnosis, in the year after AF diagnosis patients were more frequently hospitalized (1.5 vs 1.1 hospitalizations) and for longer periods (5.6 vs 3.3 days), and had more outpatient visits (12.9 vs 11.7). Survival rapidly decreased during the first 60 days (60-day mortality, 6.1%) and steadily declined thereafter, with mortality rates of 14.7% and 36.8% at 1 and 5 years, respectively. CONCLUSION: At the time of diagnosis of AF, patients often suffer from several comorbidities. Diagnosis of AF is associated with an increase in medical resource use and higher mortality rates, particularly within the first 60 days.

Cost-effectiveness of enoxaparin compared with unfractionated heparin in ST elevation myocardial infarction patients undergoing pharmacological reperfusion: a Canadian analysis of the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment - Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 trial.

OBJECTIVE: To evaluate the cost-effectiveness of enoxaparin versus unfractionated heparin in conjunction with fibrinolysis in ST elevation myocardial infarction patients within Canada. DESIGN: Based on the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment - Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 trial, a model was created to analyze the cost-effectiveness of enoxaparin compared with unfractionated heparin in conjunction with fibrinolysis among ST elevation myocardial infarction patients within Canada. Clinical outcomes were derived from published results of the main trial. Resource use costs were first assessed based on United States Diagnosis-Related Group values for hospitalizations and Current Procedural Terminology codes for outpatient visits and tests. Both were then converted using Canadian local costs. Survival and life expectancy were estimated from Framingham survival data. The incremental cost-effectiveness ratio was expressed as cost per life year gained. RESULTS: Through 30 days after random assignment, the primary composite end point favoured the enoxaparin group over the unfractionated heparin group (death or recurrent myocardial infarction rate 9.9% versus 12.0%, P<0.001), and was associated with a modest increased cost of $169.50 ($8,757.00 versus $8,587.50, respectively). Life years gained as a result of treatment with enoxaparin was increased by 0.11 years (P<0.05). Enoxaparin was found to be cost-effective, as indicated by an incremental cost-effectiveness ratio of $4,930 with a 99% probability of costing less than $20,000. CONCLUSIONS: Although associated with modest increased direct medication costs, enoxaparin following fibrinolysis improved the clinical efficacy in STEMI patients and increased the life years gained.