Projected impact of biosimilar substitution policies on drug use and costs in Ontario, Canada: a cross-sectional time series analysis.

BACKGROUND: Several Canadian provinces have introduced reimbursement policies mandating substitution of innovator biologics with lower-cost biosimilars. We estimated the number of patients affected and cost implications if such policy changes were to be implemented in Ontario, Canada. METHODS: We conducted a cross-sectional time series analysis of Ontarians dispensed publicly funded biologics indicated for inflammatory diseases (rheumatic conditions, inflammatory bowel disease: infliximab, etanercept, adalimumab) between January 2018 and December 2019, and forecasted trends to Dec. 31, 2020. The primary source of data was pharmacy claims data for all biologics reimbursed by the public drug program. We modelled the number of patients affected and government expenditures (in nominal Canadian dollars) of several biosimilar policy options, including mandatory nonmedical biosimilar substitution, substitution in new users, introduction of a biosimilar for adalimumab, and price negotiations. In a secondary analysis, we included insulin glargine. RESULTS: In 2018, 14 089 individuals were prescribed a publicly funded biologic for inflammatory diseases. A mandatory nonmedical biosimilar substitution would potentially have affected 7209 patients and saved $238.6 million from 2018 to 2020. A new-user substitution would have affected 757 patients and saved $34.2 million. If an adalimumab biosimilar were to become available, 12 928 patients would be affected by a mandatory nonmedical substitution and the 3-year savings would increase to $645.9 million (all biosimilars priced at 25% of innovator biologics). Finally, an expanded nonmedical substitution policy including insulin glargine would affect 115 895 patients and save $288.7 million (not including adalimumab). INTERPRETATION: Policies designed to curb rising costs of biologics can have substantially different effects on patients and government expenditures. Such analyses warrant careful consideration of the balance between cost savings and effects on patients.

Assessment of Stimulant Use and Cardiovascular Event Risks Among Older Adults.

Importance: Use of stimulants continues to increase among older adults for a variety of indications. An association between stimulant use and increased risk of cardiovascular (CV) events has been established among children and young adults, but few studies have explored the risk of CV events among older patients, a group with increased baseline risk. Objective: To evaluate the association between stimulant use and risk of CV events among older adults. Design, Setting, and Participants: This propensity score-matched cohort study, with 4 nonusers per 1 user, was conducted from July 1, 2017, to June 27, 2019, using data from population-based health care databases from Ontario, Canada, from January 1, 2002, to December 31, 2016. Included individuals were outpatients aged 66 years or older. Exposures: Initiation of a prescription stimulant. Main Outcomes and Measures: The primary outcome was a CV event, defined as a composite of emergency department visit or hospitalization for myocardial infarction, stroke or transient ischemic attack (TIA), or ventricular arrhythmia. Risk of CV event was assessed at 30 days, 180 days, and 365 days after initiation of stimulants from Cox proportional hazard models. A secondary analysis assessed each component of the primary outcome separately. Results: Among 6457 older adults who initiated a prescription stimulant (ie, the exposed group) and 24 853 older adults who did not initiate such treatment (ie, the unexposed group), the distribution of baseline patient characteristics was well balanced after matching (sex: 3173 [49.1%] men vs 12 112 [48.7%] men; standardized difference, 0.01; median [IQR] age: 74 [69-80] years vs 74 [69-80] years; standardized difference, 0.01). Within this cohort, there were 932 CV events during the 365-day follow-up (5.11 events per 100 person-years among individuals who initiated stimulants). In the primary analysis, stimulant initiation was associated with increased risk of CV events at 30 days (hazard ratio [HR], 1.4; 95% CI, 1.1-1.8) but not at 180 days (HR, 1.2; 95% CI, 0.9-1.6) or 365 days (HR, 1.0; 95% CI, 0.6 to 1.8). In the secondary analysis, stimulant initiation was associated with increased risk of ventricular arrhythmias (HR, 3.0; 95% CI, 1.1-8.7) and stroke or TIA (HR, 1.6; 95% CI, 1.1-2.1) at 30 days. Conclusions and Relevance: This cohort study found that stimulant use was associated with an early increase in CV events among older adults with no association for long-term use.

Impact of a Publicly Funded Herpes Zoster Immunization Program on the Burden of Disease in Ontario, Canada: A Population-based Study.

BACKGROUND: In September 2009, a live attenuated herpes zoster vaccine (ZVL) became available in Canada. Beginning in September 2016, ZVL was made available to all Ontario residents aged 65-70 through a publicly funded immunization program. We assessed the impact of ZVL availability and its subsequent public funding on herpes zoster burden in this population. METHODS: A population-based study of Ontario residents aged 65-70 between January 2005 and September 2018. We used interventional autoregressive integrated moving average models to examine the impact of ZVL market availability and the publicly funded ZVL program on monthly incidence rate of medically attended herpes zoster, defined as an outpatient visit for herpes zoster with a prescription for a herpes zoster antiviral dispensed ≤5 days before or after the visit, or a herpes zoster-related emergency department (ED) visit or hospitalization. In secondary analyses, we examined impacts on any herpes zoster-related ED visits and hospitalizations. RESULTS: We found no association between ZVL market availability and monthly incidence of herpes zoster (P = .32) or monthly rates of ED visits and hospitalizations (P = .88). Conversely, the introduction of publicly funded ZVL reduced the monthly rate of medically attended herpes zoster by 19.1% (from 4.8 to 3.8 per 10 000 population; P < .01) and herpes zoster-related ED visits and hospitalizations by 38.2% (from 1.7 to 1.0 per 10 000 population; P < .05). CONCLUSIONS: The introduction of a publicly funded immunization program for herpes zoster was associated with reduced disease burden and related acute healthcare service use.

Characteristics of high-drug-cost beneficiaries of public drug plans in 9 Canadian provinces: a cross-sectional analysis.

BACKGROUND: Drugs are the fastest growing cost in the Canadian health care system, owing to the increasing number of high-cost drugs. The objective of this study was to examine the characteristics of high-drug-cost beneficiaries of public drug plans across Canada relative to other beneficiaries. METHODS: We conducted a cross-sectional study among public drug plan beneficiaries residing in all provinces except Quebec. We used the Canadian Institute for Health Information's National Prescription Drug Utilization Information System to identify all drugs dispensed to beneficiaries of public drug programs in 2016/17. We stratified the cohort into 2 groups: high-drug-cost beneficiaries (top 5% of beneficiaries based on annual costs) and other beneficiaries (remaining 95%). For each group, we reported total drug costs, prevalence of high-cost claims (> $1000), median number of drugs, proportion of beneficiaries aged 65 or more, the 10 most costly reimbursed medications and the 10 medications most commonly reimbursed. We reported estimates overall and by province. RESULTS: High-drug-cost beneficiaries accounted for nearly half (46.5%) of annual spending, with an average annual spend of $14 610 per beneficiary, compared to $1570 among other beneficiaries. The median number of drugs dispensed was higher among high-drug-cost beneficiaries than among other beneficiaries (13 [interquartile range (IQR) 7-19] v. 8 [IQR 4-13]), and a much larger proportion of high-drug-cost beneficiaries than other beneficiaries received at least 1 high-cost claim (40.9% v. 0.6%). Long-term medications were the most commonly used medications for both groups, whereas biologics and antivirals were the most costly medications for high-drug-cost beneficiaries. INTERPRETATION: High-drug-cost beneficiaries were characterized by the use of expensive medications and polypharmacy relative to other beneficiaries. Interventions and policies to help reduce spending need to consider both of these factors.

Comprehensive Drug-Class Review Framework for improved evidence-based drug policy and formulary modernization.

Formularies are used by payers to optimize access and ensure the appropriate use of medications. Lack of follow-up and re-evaluation can lead to outdated formularies that are not reflective of current evidence. Formulary modernization, an approach to re-align formularies with current evidence has proven successful. The Ontario Drug Policy Research Network (ODPRN) launched a framework for conducting comprehensive drug-class reviews. This commentary describes the individual components of this framework and lessons learned through completion of 12 reviews between 2013 and 2016. We present the ODPRN drug-class review of treatments for chronic hepatitis B as a case example to illustrate the components and impact. The incorporation of foundational health technology assessment components such as economic evaluations and knowledge synthesis with contextualizing evidence such as patient and clinician perspectives (through qualitative studies), real-world evidence (through data analytics), and cross-jurisdictional comparisons (through environmental scans and data analytics), successfully developed jurisdictionally specific policy recommendations grounded in up-to-date evidence. The ODPRN framework for conducting comprehensive drug-class reviews is a robust and feasible approach to conduct formulary modernization. This framework allows for actionable and specific policies which are likely to be considered by decision makers. Adoption of similar frameworks in other jurisdictions may improve uptake of evidence-informed policy recommendations.

Tramadol and the risk of seizure: nested case-control study of US patients with employer-sponsored health benefits.

OBJECTIVES: Tramadol is a widely prescribed analgesic that influences both opioid and monoamine neurotransmission. While seizures have been reported with its use, the risk in clinical practice has not been well characterised. We examined risk of seizure with tramadol relative to codeine, a comparable opioid analgesic. DESIGN: Retrospective nested case-control study. For each case, we identified up to 10 controls matched on age, sex, US state of residence and date of cohort entry (±365 days). We calculated ORs to determine the association between seizure and exposure to tramadol, codeine (≥15 mg), both or neither, in the preceding 30 days. SETTING: Cohort of patients, who had continuous health coverage and resided in the same state for≥3 years, identified from linked administrative health data in US MarketScan databases from 2009 to 2012. PARTICIPANTS: We identified 96 753 patients with seizure and 888 540 matched controls. PRIMARY AND SECONDARY OUTCOME MEASURES: In the primary analysis, we defined cases using a broad definition of seizure (based on either an outpatient physician claim for seizure disorder or a seizure-related emergency department visit or hospitalisation). In a secondary analysis, we used a more specific definition of seizure restricted to a hospital visit with a principal diagnosis of seizure. RESULTS: In the primary analysis, we found no association between risk of seizure and exposure to tramadol compared with codeine (OR 1.03, 95% CI 0.93 to 1.15). However, in the secondary analysis (using a more specific definition of seizure), this association was statistically significant (OR 1.41, 95% CI 1.11 to 1.79). CONCLUSIONS: Tramadol was not associated with an increased risk of seizure defined by inpatient and outpatient diagnoses. However, this finding was sensitive to the outcome definition used and requires further study.

Impact of delisting high-strength opioid formulations from a public drug benefit formulary on opioid utilization in Ontario, Canada.

PURPOSE: High-strength opioid formulations were delisted (removed) from Ontario's public drug formulary in January 2017, except for palliative patients. We evaluated the impact of this policy on opioid utilization and dosing. METHODS: We conducted a longitudinal study among patients receiving publicly funded, high-strength opioids from August 2016 to July 2017. The primary outcome measure was weekly median daily opioid dose (in milligrams of morphine or equivalent; MME) of (1) publicly funded and (2) all opioid prescriptions irrespective of funding source, evaluated using interrupted time series analyses and stratified by palliative care status. RESULTS: Following policy implementation, the weekly median daily dose of publicly funded opioids decreased immediately among non-palliative patients by 10 MME (95% confidence limit [CL], -16.8 to -3.1) from a pre-intervention dose of 424.5 MME (95% CL, 417.8-431.2) and fell gradually among palliative patients by 3.9 MME per week (95% CL, -5.5 to -2.3) from a pre-intervention dose of 450.1 MME (95% CL, 432.5-467.7). In contrast, among all opioid prescriptions, gradual reductions in weekly median daily doses were observed only for non-palliative patients, which decreased by 0.7 MME per week (95% CL, -1.3 to -0.2) from a pre-intervention dose of 426.2 MME (95% CL, 420.9-431.5). CONCLUSION: The delisting of publicly-funded, high-strength opioids was accompanied by changes in funding source and small reductions in the weekly median daily doses dispensed. Although observed dose reductions of less than 1 MME weekly are likely not clinically relevant, safety implications of these changes require further monitoring.

Large care gaps in primary care management of asthma: a longitudinal practice audit.

OBJECTIVES: Care gaps in asthma may be highly prevalent but are poorly characterised. We sought to prospectively measure adherence to key evidence-based adult asthma practices in primary care, and predictors of these behaviours. DESIGN: One-year prospective cohort study employing an electronic chart audit. SETTING: Three family health teams (two academic, one community-based) in Ontario, Canada. PARTICIPANTS: 884 patients (72.1% female; 46.0±17.5 years old) (4199 total visits; 4.8±4.8 visits/patient) assigned to 23 physicians (65% female; practising for 10.0±8.6 years). MAIN OUTCOME MEASURES: The primary outcome was the proportion of visits during which practitioners assessed asthma control according to symptom-based criteria. Secondary outcomes included the proportion of: patients who had asthma control assessed at least once; visits during which a controller medication was initiated or escalated; and patients who received a written asthma action plan. Behavioural predictors were established a priori and tested in a multivariable model. RESULTS: Primary outcome: Providers assessed asthma control in 4.9% of visits and 15.4% of patients. Factors influencing assessment included clinic site (p=0.019) and presenting symptom, with providers assessing control more often during visits for asthma symptoms (35.0%) or any respiratory symptoms (18.8%) relative to other visits (1.6%) (p<0.01). SECONDARY OUTCOMES: Providers escalated controller therapy in 3.3% of visits and 15.4% of patients. Factors influencing escalation included clinic site, presenting symptom and prior objective asthma diagnosis. Escalation occurred more frequently during visits for asthma symptoms (21.0%) or any respiratory symptoms (11.9%) relative to other visits (1.5%) (p<0.01) and in patients without a prior objective asthma diagnosis (3.5%) relative to those with (1.3%) (p=0.025). No asthma action plans were delivered. CONCLUSIONS: Major gaps in evidence-based asthma practice exist in primary care. Targeted knowledge translation interventions are required to address these gaps, and can be tailored by leveraging the identified behavioural predictors. TRIAL REGISTRATION NUMBER: NCT01070095; Pre-results.

Analysis of Trends in Insulin Utilization and Spending Across Canada From 2010 to 2015.

OBJECTIVES: To describe insulin utilization and spending across Canada and investigate how interprovincial variations in long-acting insulin uptake impact provincial spending. METHODS: We conducted a cross-sectional time-series analysis of insulin products dispensed nationally from January 1, 2010, to December 31, 2015, using data from IQVIA (Durham, North Carolina, United States). Analysis was stratified according to insulin type, payer and province. We report annual numbers for national insulin dispensing and spending and provincial numbers for publicly funded long-acting insulin dispensing and spending rates that are standardized by public drug beneficiary enrolment and diabetes prevalence. We report the percent of change of an annual provincial cost-to-utilization index of total insulin spending to total insulin dispensing between 2010 and 2015. RESULTS: Between 2010 and 2015, total insulin utilization increased 21% (4.4 million to 5.3 million prescriptions), and total insulin costs increased 54% ($345 million to $530 million) nationally. The national dispensing rate of long-acting insulin (+96%) and rapid-acting insulin (+38%) increased, while the national dispensing rate for intermediate-acting (-23%), short-acting (-37%) and premixed (-28%) insulins declined. Large interprovincial variation was observed for the rate of long-acting insulin uptake (range, Alberta, +1,505%; British Columbia, +27%) and the rate of long-acting insulin spending (Alberta, +2,177%; British Columbia, +44%) between 2010 and 2015 after standardization. Provinces with higher rates of long-acting insulin uptake experienced faster increases in their cost-to-utilization index (Alberta, +78%; British Columbia, +24%). CONCLUSIONS: Overall, the rate of uptake of long-acting insulins has increased nationally. Uptake varies widely among provinces and is likely to be associated with differential cost increases across public payers in Canada.

Publicly Funded Oral Chronic Hepatitis B Treatment Patterns in Ontario over 16 Years: An Ecologic Study.

BACKGROUND: Reimbursement for the use of hepatitis B virus (HBV) treatments has not been previously reported for public payers. OBJECTIVE: To describe the number of users and total cost of HBV treatments over the last 16 years among residents of Ontario, Canada, who were covered by the public drug program. METHODS: We conducted a repeated cross-sectional study for HBV treatments reimbursed by the public drug program in Ontario from January 1, 2000, to December 31, 2015. We projected total spending to 2020 based on current utilization trends. RESULTS: HBV drug users per year increased 30-fold, from 132 users in 2000 to 4,035 users in 2015. Total spending on HBV treatments increased 150-fold, from $136,368 annually in 2000 to $21.0 million in 2015. The spending on HBV agents is projected to increase by 65%, with an estimated drug cost of $34.6 million by 2020. CONCLUSIONS: Although not reimbursed as first-line therapy, tenofovir disoproxil fumarate has become the most commonly reimbursed HBV treatment and was associated with an increase in HBV treatment use and total spending. Results of this study found that rapid growth of HBV treatments led to a sustained increase in spending for public payers in Ontario. DISCLOSURES: This study was funded by grants from the Ontario Ministry of Health and Long-Term Care (MOHLTC) and Ontario Strategy for Patient-Orientated Research (SPOR) Support Unit, which is supported by the Canadian Institutes of Health Research and the Province of Ontario. This study was also supported by the Institute for Clinical Evaluative Sciences (ICES), a non-profit research institute sponsored by the Ontario MOHLTC. The opinions, results, and conclusions reported in this article are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. Parts of this material are based on data and information compiled and provided by the Canadian Institute for Health Information (CIHI). However, the analyses, conclusions, opinions and statements expressed herein are those of the authors and not necessarily those of CIHI. Mamdani has received honoraria from Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, and Bayer. Janssen has received research support, consulting, and/or speaking fees from Gilead, Roche, Merck, AbbVie, Bristol-Myers Squibb, Arbutus, Janssen, and MedImmune. No other authors have any conflicts of interest to declare.

Real-world health care utilization and effectiveness of omalizumab for the treatment of severe asthma.

BACKGROUND: Omalizumab is indicated for the treatment of moderate to severe asthma. There is limited observational evidence on the costs and effectiveness of omalizumab. OBJECTIVE: To examine the costs and effectiveness of omalizumab for treatment of severe asthma relative to nonusers. METHODS: We conducted a within-person repeated-measures matched cohort study in Ontario, Canada from April 1, 2012 to March 31, 2014. Continuous users of omalizumab were matched with up to 4 nonusers according to age, sex, recent specialist visits, oral corticosteroid use, asthma severity, and Charlson comorbidity score. The primary outcome was direct health care costs. Secondary outcomes were asthma-related hospitalizations or emergency department visits and oral corticosteroid use. The association between omalizumab use and each outcome was assessed using mixed-effects models adjusting for confounders. RESULTS: Ninety-five omalizumab users and 352 nonusers were matched. Among users, there was a significant increase in health care costs of $1,796 per person owing to the cost of the medication at treatment initiation (P < .0001). Costs did not change significantly among nonusers ($85 increase in average monthly costs per person; P = .59). We found no significant changes in the rates of asthma-related hospitalizations or emergency department visits among omalizumab users (P = .44) or nonusers (P = .99) between pre- and postintervention periods. CONCLUSION: The use of omalizumab was associated with increased costs but no evidence of lower rates of clinically important outcomes. These results suggest omalizumab had limited effectiveness in our study population. Future studies should further explore subsets of patients most likely to benefit from omalizumab therapy.

Protocol for a randomised controlled trial evaluating the effects of providing essential medicines at no charge: the Carefully seLected and Easily Accessible at No Charge Medicines (CLEAN Meds) trial.

INTRODUCTION: Cost-related non-adherence to medicines is common in low-income, middle-income and high-income countries such as Canada. Medicine non-adherence is associated with poor health outcomes and increased mortality. This randomised trial will test the impact of a carefully selected list of essential medicines at no charge (compared with usual medicine access) in primary care patients reporting cost-related non-adherence. METHODS AND ANALYSIS: This is an open-label, parallel two-arm, superiority, individually randomised controlled trial conducted in three primary care sites (one urban, two rural) in Ontario, Canada, that was codesigned by a community guidance panel. Adult patients (≥18 years) who report cost-related non-adherence to medicines are eligible to participate in the study. Participants will be randomised to receive free and convenient access to a carefully selected list of 125 essential medicines (based on the WHO's Model List of Essential Medicines) or usual means of medicine access. Care for patients in both groups will otherwise be unchanged. The primary outcome of this trial is adherence to appropriately prescribed medicines. Secondary outcomes include medicine adherence, appropriate prescribing, blood pressure, haemoglobin A1c, low-density lipoprotein cholesterol, patient-oriented outcomes and healthcare costs. All participants will be followed for at least 12 months. ETHICS AND DISSEMINATION: Ethics approval was obtained in all three participating sites. Results of the main trial and secondary outcomes will be submitted for publication in a peer-reviewed journal and discussed with members of the public and decision makers. TRIAL REGISTRATION NUMBER: NCT02744963.

Self-Monitoring of Blood Glucose: Impact of Quantity Limits in Public Drug Formularies on Provincial Costs Across Canada.

OBJECTIVES: For most patients with diabetes, routine use of blood glucose test strips (BGTS) has not been shown to be beneficial, yet the economic implications of broad publicly funded reimbursement for BGTS are substantial. We assessed the potential impact of BGTS quantity limits on utilization and costs for 6 publicly funded drug plans across Canada. METHODS: A cross-sectional analysis was conducted in 6 provinces (Alberta, Saskatchewan, Manitoba, Nova Scotia, Newfoundland and Labrador and Prince Edward Island) for patients who received at least 1 prescription for BGTS in 2014 through the public drug program. We determined the number of BGTS that would have exceeded the quantity limits and the associated costs to the provincial drug program. RESULTS: A total of $38,051,026 was spent on BGTS reimbursed through public drug programs among the 6 provinces. In provinces where BGTS use is largely restricted to patients using insulin, the potential annual savings were minimal, ranging from 0.4% to 2.3%, whereas in provinces with more liberal listings, potential savings ranged from 12.4% to 19.8%. Combining these results with data from a previous analysis in Ontario and British Columbia, the cost savings associated with BGTS quantity limits for 8 provinces across Canada (capturing approximately three-quarters of the Canadian population) is estimated to be $30.3 million annually. CONCLUSIONS: The national implementation of a quantity limit policy for BGTS that aligns with evidence of efficacy, optimal prescribing and patient safety can lead to considerable savings for most public drug plans across Canada.

The appropriateness and persistence of testosterone replacement therapy in Ontario.

PURPOSE: To examine the concordance between testosterone replacement therapy (TRT) use and established reimbursement criteria, as well as compare the persistence of use among available formulations (injectable, oral, topical gel, transdermal patch) among elderly men in Ontario, Canada. METHODS: We conducted a retrospective cohort study of men aged 66 years or older in Ontario newly treated with testosterone between 1 January 2009 and 31 December 2012 using linked health administrative data. Continuous use was defined on the basis of prescription refills issued within 180 days of the preceding prescription. We studied men who received at least two consecutive TRT prescriptions. We estimated the prevalence of hypogonadism, human immunodeficiency virus, specialist visits and lab tests for serum testosterone prior to initiation of TRT to investigate concordance with prescribing criteria. We also performed a Kaplan-Meier analysis to test for differences in the median time to discontinuation among formulations. RESULTS: Among the 4797 men who received at least two TRT prescriptions, only 38.7% met the reimbursement criteria for use prior to initiating therapy. The median time to discontinuation differed significantly among formulations and was longest among recipients of oral TRT products (383 days), and lower for recipients of topical gels (319 days), injectable (283 days) and transdermal patches (160 days; Log-rank test p < 0.001). CONCLUSIONS: A large proportion of older men in Ontario do not appear to meet reimbursement criteria prior to commencing therapy, and many discontinue TRT within a year of initiation. Copyright © 2016 John Wiley & Sons, Ltd.

Association of a Blood Glucose Test Strip Quantity-Limit Policy With Patient Outcomes: A Population-Based Study.

Importance: Given their high costs, payers have considered implementing quantity limits for reimbursement of blood glucose test strips. The effect of these limits on patient outcomes is unknown. Objective: To determine whether the introduction of quantity limits for blood glucose test strips in August 2013 was associated with changes in clinical outcomes. Design, Setting, and Participants: Cross-sectional time series analysis from April 2008 to March 2015 of residents of Ontario, Canada, aged 19 years and older with diabetes who were eligible for public drug coverage. In a sensitivity analysis, we studied high-volume users of test strips, who were most likely to be affected by the quantity limits. Exposures: Eligible patients were stratified into 4 mutually exclusive groups based on diabetes therapy: insulin, hypoglycemia-inducing oral diabetes agents, nonhypoglycemia-inducing oral diabetes agents, and no drug therapy. Main Outcomes and Measures: The primary outcome was emergency department visits for hypoglycemia or hyperglycemia, and the secondary outcome was mean hemoglobin A1c (HbA1c) levels. Outcomes were measured for all patients in each quarter, stratified by age group (<65 vs ≥65 years) and diabetes therapy. Results: By the end of the study period, 834 309 people met inclusion criteria. Among those younger than 65 years, the rate of hypoglycemia and hyperglycemia declined over the study period (from 4.9 to 3.0 visits per 1000 Ontario drug benefit [ODB]-eligible patients and from 4.2 to 3.6 visits per 1000 ODB-eligible patients, respectively) and was not significantly associated with the introduction of quantity limits (P = .67 and P = .37, respectively). Similarly, among those aged 65 years and older, rates of hypoglycemia and hyperglycemia declined over the study period (from 2.9 to 1.3 visits per 1000 eligible patients and from 0.8 to 0.5 visits per 1000 eligible patients, respectively) and was not significantly associated with the introduction of quantity limits (P = .12 and P = .24, respectively). Results were consistent for the secondary outcome of mean HbA1c levels and in the sensitivity analysis of high-volume test strip users. Conclusions and Relevance: The imposition of quantity limits for blood glucose test strips was not associated with worsening short-term outcomes, suggesting that these policies can reduce costs associated with test strips without causing patient harm.

The Characteristics of Treated Pulmonary Arterial Hypertension Patients in Ontario.

Background. There are no Canadian prevalence studies on pulmonary arterial hypertension (PAH) to date. We described the characteristics of treated PAH patients and the healthcare utilization and costs associated with PAH in a population of public drug plan beneficiaries in Ontario, Canada. Methods. A retrospective cross-sectional analysis was conducted between April 2010 and March 2011 to identify treated PAH patients using population-based health administrative databases. We investigated demographic and clinical characteristics of treated PAH patients and conducted a cohort study to determine treatment patterns, healthcare utilization, and associated costs, over a one-year follow-up period (March 2012). Results. We identified 326 treated PAH cases in Ontario's publicly funded drug plan. Overall mean age was 59.4 years (±20.3 years) and over 77% of cases were women (n = 251). Combination therapy was used to treat 22.9% (n = 69) of cases, costing an average of $4,569 (SD $1,544) per month. Median monthly healthcare costs were $264 (IQR $96-$747) for those who survived and $2,021 (IQR $993-$6,399) for those who died over a one-year period, respectively (p < 0.01). Conclusions. PAH care in Ontario is complex and has high healthcare costs. This data may help guide towards improved patient management.

Trends in the use and cost of antipsychotics among older adults from 2007 to 2013: a repeated cross-sectional study.

BACKGROUND: Recently, several new atypical antipsychotic agents have been introduced in Ontario, and regulatory warnings have been issued regarding use of atypical antipsychotics in older adults. We sought to establish the impact of newer atypical antipsychotics on prescribing rates and costs. METHODS: We performed a population-based cross-sectional study of Ontario adults aged 65 years or more using atypical antipsychotics from Jan. 1, 2007, to Mar. 31, 2013. These people have universal access to publicly funded drugs through the Ontario Health Insurance Plan and the Ontario Drug Benefit. We conducted time-series analysis to assess the impact of the introduction of new atypical antipsychotics on rates of use of atypical antipsychotics and associated expenditures. RESULTS: Rates of atypical antipsychotic use increased following the introduction of new agents in 2009, from 27.6 users per 1000 older adults in the third quarter of 2009 to 29.1 users per 1000 older adults at the end of the study period (p = 0.04). Although prescribing rates for the newer atypical agents (paliperidone, ziprasidone and aripiprazole) remained low relative to their older counterparts (risperidone, olanzapine and quetiapine), rates of aripiprazole use rose to 1.0 user per 1000 older adults by the end of the study period. The proportion of prescriptions that were for brand-name agents fell from 57.5% in the second quarter of 2007 to 6.1% in the second quarter of 2009, and then rose to 11.7% by the end of the study period. By the first quarter of 2013, newer atypical antipsychotic agents were used by 4.4% of atypical antipsychotic users but accounted for 14.1% ($1.2 million of $8.5 million) of atypical antipsychotic expenditures. INTERPRETATION: Although the overall prevalence of use of new atypical antipsychotic agents remains low, their introduction has led to increased prescribing of this class of drugs in older adults. Given the potential cost implications, further study of these trends would be prudent.

Self-Monitoring of Blood Glucose Levels: Evaluating the Impact of a Policy of Quantity Limits on Test-Strip Use and Costs.

OBJECTIVES: To evaluate the impact of new quantity limits for blood glucose test strips (BGTS) in August 2013 on utilization patterns and costs in the elderly population of Ontario, Canada. METHODS: We conducted a population-based, cross-sectional time series analysis of all individuals 65 years of age and older who received publically funded BGTSs between August 1, 2010, and July 31, 2015, in Ontario, Canada. The number of BGTSs dispensed and the associated costs were measured for 4 diabetes therapy subgroups-insulin, hypoglycemia-inducing oral agents, non-hypoglycemia-inducing oral agents, and no drug therapy-each month during the study period. We used interventional autoregressive integrated moving average (ARIMA) models to assess the impact of Ontario's policy change on test strip use and costs. RESULTS: In the course of the study period, 657,338,177 test strips were dispensed to elderly patients in Ontario, at a total cost of CAN$482.3 million. Introduction of quantity limits was associated with significant reductions in the number of monthly strips dispensed and the associated costs (p<0.0001). In the year following the policy's implementation, test strip use decreased by 22.2% compared with the prior year (from 145,232,024 test strips to 113,007,795 test strips, a net decrease of 32,224,229 strips), resulting in a 22.5% reduction in costs (from $106.5 million to $82.6 million, a net cost reduction of approximately $24 million). CONCLUSIONS: The introduction of quantity limits, aligned with guidance from the Canadian Diabetes Association, led to immediate significant reductions in BGTS dispensing and costs. More research is needed to assess the impact of this policy on patient outcomes.

Variations in costs and use of provincially-funded testosterone replacement therapy across Canada: a population-based study.

INTRODUCTION: Provincial drug-program policies for the reimbursement of testosterone replacement therapy (TRT) vary across Canada, which may result in marked regional variability in use. METHODS: We conducted a population-based cross-sectional analysis of provincially funded TRT spending and utilization in eight provinces across Canada in 2012. We reported the annual cost per user, total cost, and rate of use of TRT overall and by formulation. RESULTS: We identified 23,544 provincially-funded recipients of TRT in 2012 in the eight provinces studied. Average annual cost per person varied by 3-fold, ranging from $173 (Prince Edward Island) to $485 (Ontario). Ontario also had the highest rate of use (1,105 users per 100,000 eligible) and the most liberal listing. Provinces with more restricted access (Alberta, British Columbia, and PEI) had lower annual costs per user ($293, $206, $173, respectively). CONCLUSIONS: Differing reimbursement policies for TRT products across Canada are likely contributing to variation in the rate of use and cost per recipient.

The Influence of Socioeconomic Status on Selection of Anticoagulation for Atrial Fibrillation.

IMPORTANCE: Without third-party insurance, access to marketed drugs is limited to those who can afford to pay. We examined this phenomenon in the context of anticoagulation for patients with nonvalvular atrial fibrillation (NVAF). OBJECTIVE: To determine whether, among older Ontarians receiving anticoagulation for NVAF, patients of higher socioeconomic status (SES) were more likely to switch from warfarin to dabigatran prior to its addition to the provincial formulary. DESIGN, SETTING AND PARTICIPANTS: Population-based retrospective cohort study of Ontarians aged 66 years and older, between 2008 and 2012. EXPOSURE: Socioeconomic status, as approximated by median neighborhood income. MAIN OUTCOMES AND MEASURE: We identified two groups of older adults with nonvalvular atrial fibrillation: those who appeared to switch from warfarin to dabigatran after its market approval but prior to its inclusion on the provincial formulary ("switchers"), and those with ongoing warfarin use during the same interval ("non-switchers"). RESULTS: We studied 34,797 patients, including 3183 "switchers" and 31,614 "non-switchers". We found that higher SES was associated with switching to dabigatran prior to its coverage on the provincial formulary (p<0.0001). In multivariable analysis, subjects in the highest quintile were 50% more likely to switch to dabigatran than those in the lowest income quintile (11.3% vs. 7.3%; adjusted odds ratio 1.50; 95% CI 1.32 to 1.68). Following dabigatran's addition to the formulary, the income gradient disappeared. CONCLUSIONS AND RELEVANCE: We documented socioeconomic inequality in access to dabigatran among patients receiving warfarin for NVAF. This disparity was eliminated following the drug's addition to the provincial formulary, highlighting the importance of timely reimbursement decisions.