Public Drug Programs Research Articles

Formulary Management of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists


 Health Canada has approved 4 sodium-glucose cotransporter-2 (SGLT2) inhibitors (ertugliflozin, dapagliflozin, canagliflozin, and empagliflozin) and 5 glucagon-like peptide-1 (GLP-1) receptor agonists (semaglutide, liraglutide, dulaglutide, lixisenatide, and exenatide), with 5 fixed-dose combination products (SGLT2 inhibitors: dapagliflozin-metformin, canagliflozin-metformin, and empagliflozin-metformin; GLP-1 receptor agonists: liraglutide–insulin degludec and lixisenatide–insulin glargine).
 Data protection has ended for all SGLT2 inhibitors in Canada as well as their fixed-dose combinations. Eleven dapagliflozin generics are currently available, and there are several canagliflozin and empagliflozin generics under review at Health Canada. Patent protection has not expired for GLP-1 receptor agonists.
 There is heterogeneity in public drug program reimbursement criteria for each SGLT2 inhibitor and GLP-1 receptor agonist ranging from restricted to unrestricted benefit.
 This Environmental Scan highlights that as SGLT2 inhibitors and GLP-1 receptor agonists have matured, additional indications (heart failure, chronic kidney disease, weight management) have been added to their initial Health Canada–approved indication (type 2 diabetes mellitus). SGLT2 inhibitors are beginning to lose their exclusivity status and are experiencing generic competition.

P672 Occurrence of malignancy among infliximab biosimilar and bio-originator initiators in Canada: a comparative population-based analysis

Abstract Background Infliximab (INF) downregulates the immune system. Given the immune system's role in deleting pre-cancerous cells, malignancy is a potential concern. Still, relatively few real-world data analyses have compared biosimilar versus bio-originator INF in terms of malignancy incidence. We aimed to compare malignancy occurrence among initiators of infliximab biosimilar (INF-B) and originator (INF-O). Methods We used data from the National Prescription Drug Utilization Information System (NPDUIS), containing pan-Canadian (except Quebec) claims-level data on prescription dispensations paid from public drug programs linked to comprehensive day surgery and inpatient care (Discharge Abstract Database, DAD) and hospital-based and community-based ambulatory care (National Ambulatory Care Reporting System, NACRS). We studied adults (≥18 years) initiating INF between January 2015 and December 2019 with no history of malignancy, HIV or organ transplant (1-year pre-baseline). Follow-up began 365 days after treatment initiation (lag period) and continued until the first cancer diagnostic code (ICD-10 C00-C97), treatment discontinuation + 365 days, or end of study period. We compared INF-B and INF-O using Cox regression models, adjusting for potential confounders/ effect modifiers: sex, age at treatment initiation, prior use of other biologics or prednisone, province (Ontario versus others), and calendar year. Results New users of INF-B (2,019) and INF-O (5,183) were about half female (52%), with a median age (interquartile range) of 45 years (28-62). Overall, the malignancy incidence rate was 10.2 (95% confidence interval, CI, 8.7-11.8) events per 1,000 person-years. Comparing INF-B to INF-O, the adjusted hazard ratio for malignancy was 0.97 (95% CI 0.63-1.48). Conclusion In this real-world dataset, we were unable to identify clear differences in malignancy comparing INF-B and INF-O. Limitations include the inability to control for residual confounders (e.g., disease severity), potential outcome misclassification, and selection bias.

Living With Type 2 Diabetes


 We conducted a custom technology review to narratively describe treatment outcomes and considerations important to people living with type 2 diabetes mellitus (T2DM) in Canada, as detailed in patient input provided to CADTH in the past. Patient groups submitted the input described in this review to inform CADTH Reimbursement Reviews, which advise reimbursement decisions made by public drug programs in Canada. CADTH staff produced this report through close engagement with representatives from patient groups that had contributed these inputs, including Diabetes Canada, Type 2 Diabetes Experience Exchange (T2DXX), and Patient Commando. This learning project provided an opportunity for CADTH to explore patient input in a new but rigorous way outside of the time constraints of Reimbursement Reviews for specific drugs.
 In past patient input, people living with T2DM emphasized that the condition demands intensive, perpetual self-management and has a profound and usually negative impact on their physical, psychosocial, and economic well-being.
 People living with T2DM want a cure for the condition. In the meantime, to improve their quality of life, they desire treatments that reduce the risk of hyperglycemia and its short- and long-term complications; facilitate weight loss; and improve their mental state, focus, and energy levels. They also desire treatments that can lessen the burden of medication administration, specifically by decreasing polypharmacy and dose frequency and allowing for easy storage, preparation, and administration. They would like medications to reduce the need for blood glucose checks, injections, and insulin, and they hope that new treatments can promote a return to normalcy by providing the freedom to eat and do what they want, when they want.
 In addition to these desired treatment outcomes, people living with T2DM want medications that cause few or no adverse effects, especially hypoglycemia, weight gain, and gastrointestinal and urogenital side effects.
 All patient input emphasized the need to increase access to and affordability of T2DM treatments in Canada. When discussing the contexts in which people living with T2DM access and use medications, patient groups also stressed the importance of respect and effective communication in therapeutic and interprofessional relationships; the need to provide and enhance knowledge to support informed decisions about and safe use of medications; and the importance of offering people with T2DM individualized treatment plans and a variety of choices.
 Patient groups reported limited demographic information on the people they surveyed and interviewed to inform their inputs. Inputs providing demographic information, however, showed that the voices of those belonging to equity-deserving groups in Canada were missing or underrepresented. The treatment outcomes and considerations emphasized in past patient input may differ from those important to members of these groups or may carry additional meaning or significance to them. Future avenues of inquiry and active engagement could focus on gaining insight into the perspectives and preferences of equity-deserving groups that include but are not limited to Black people, Indigenous people, and other people of colour; people living in poverty or with low income; people living in rural and remote communities; adolescents and adults aged 25 years or younger; and members of the LGBTQ2S+ community.

Deferiprone (Ferriprox)


 CADTH recommends that Ferriprox should be reimbursed by public drug plans for the treatment of patients with transfusional iron overload due to sickle cell disease (SCD) or other anemias if certain conditions are met.
 Ferriprox should be covered based on the criteria used by each of the public drug programs for deferasirox (DFX), the other orally administered treatment for transfusional iron overload for patients with SCD and other anemias.
 Ferriprox should only be prescribed by clinicians who have expertise managing SCD and if the cost of Ferriprox is not more than the lowest cost iron chelation therapy used to treat transfusional iron overload for SCD or other anemias.

Dupilumab (Dupixent)


 CADTH recommends that Dupixent be reimbursed by public drug plans for the treatment of patients aged 12 years and older with moderate-to-severe atopic dermatitis (AD) whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable, if certain conditions are met.
 This recommendation supersedes the CADTH Canadian Drug Expert Committee rec­om­men­dation for this drug and indication on April 24, 2020. A Request for Advice was filed in 2022 by public drug programs to address an inquiry regarding the 2020 reimbursement conditions.
 Dupixent should only be covered for patients who previously tried and did not experience improvement with or are unable to use other treatments. These treatments include the highest dose of topically applied drugs combined with phototherapy (where available), and the highest dose of topically applied drugs and at least 1 of the following: methotrexate, cyclosporine, mycophenolate mofetil, or azathioprine.
 Dupixent should only be reimbursed if prescribed by a dermatologist, allergist, clinical immunologist, or pediatrician, and if the cost of Dupixent is reduced.

Access to new medicines in Canada 2016-2021 Federal-provincial public drug programs and private sector drug plans

Access to new medicines in Canada 2016-2021: Federal-provincial public drug programs and private sector drug plans Mark Rovere, PhD candidate, Canadian Health Policy Institute (CHPI) Brett Skinner, PhD, Canadian Health Policy Institute (CHPI) ABSTRACT: Since 2013, CHPI has

Regional differences in access to direct-acting antiviral treatments for hepatitis C across Ontario: A cross-sectional study.

Direct-acting antivirals (DAAs) are curative treatments for hepatitis C virus (HCV) infection, a condition affecting over 100,000 Ontarians. Although DAAs are covered under the public drug programs in Ontario, receiving prescriptions depends on access to healthcare. The aim of this study is to understand the relationship between DAA treatment rates and distance to prescriber in Ontario, Canada. We conducted a cross-sectional study and identified patients who filled a DAA prescription through the Ontario Drug Benefit (ODB) in 2019. We calculated crude (per 100,000 ODB recipients) and adjusted (by a regional HCV infection rate) DAA treatment rates by public health unit (PHU). We reported median distances to provider for all visit types, in-person visits, virtual visits, and proportions of visits that were virtual. In 2019, the crude DAA treatment rate for Ontario is 83.0 patients per 100,000 ODB recipients. The HCV-adjusted DAA treatment rate ranges from 28.2 (Northwestern Ontario) to 188.5 (Eastern Ontario) per 100,000. In our primary analysis, patients in rural PHUs, including Northwestern and Porcupine, were among the highest median distances to prescriber for all visit types (1,195 km and 556 km, respectively). These PHUs also had the highest proportions of virtual visits (greater than 60%). Urban PHUs, such as Toronto and Ottawa, had smaller median distances for all visit types, with smaller proportions of virtual visits (10.8% and 12.4%, respectively). We observed heterogeneity in treatment rates, distance to DAA prescribers and use of virtual care in the management of HCV. Increasing use of telemedicine in regions with limited utilization of DAAs may improve access.

Biologics in Plaque Psoriasis


 Health Canada has approved 11 biologics for the treatment of adults with moderate-to-severe plaque psoriasis (PsO). These biologics can be divided into 2 groups based on mechanisms of action and market authorization dates:
 
 Old-generation biologics (5): include anti–tumour necrosis factor (TNF) agents (etanercept, adalimumab, infliximab, and certolizumab pegol) and an anti-interleukin (IL)-12/IL-23 inhibitor (ustekinumab) which were approved in Canada before 2010.
 New-generation biologics (6): include anti-IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab) and anti-IL-23 inhibitors (guselkumab, tildrakizumab, and risankizumab) which were approved in Canada in 2015 or later.
 
 
 Patent protection has expired for infliximab, certolizumab, and ustekinumab. There is no valid data protection status for all 5 older generation biologics. However, only 3 of the old-generation biologics have biosimilar versions (adalimumab, etanercept, and infliximab) that are available in the Canadian market.
 
 Biosimilar versions for adalimumab and etanercept were marketed for PsO approximately 3 years to 4 years after their initial Notice of Compliance was issued, respectively. This delay can be attributed to various factors, including litigation and global agreements between manufacturers.
 Despite the expiry of data and patent protection for both ustekinumab and certolizumab, no biosimilar versions are available in Canada. Data protection for both biologics expired more than 4 years ago, and the patents have expired in 2021. A lack of a biosimilar entrant in Canada could be attributed to various factors, including clinical trial development based on exclusivity timelines in the US, where data protection is 4 years longer for biologics versus Canada.
 
 
 CADTH has reviewed 3 of 5 of the old-generation biologics and all 6 of the new-generation biologics; all drugs received similar CADTH Canadian Drug Expert Committee (CDEC) recommendations. The clinical programs of most of the new-generation biologics included direct evidence demonstrating superiority or statistically significantly higher efficacy outcomes compared with the active comparator of the old-generation biologics. The clinical trials for new-generation biologics also incorporated more stringent primary outcome measures.
 The old-generation biologics predated the pan-Canadian Pharmaceutical Alliance (pCPA) process (except for certolizumab), which could imply disparate product listing agreements across public drug plans for these drugs. The only biologics not included on any public formularies are certolizumab, guselkumab, and tildrakizumab (although tildrakizumab has yet to begin pCPA negotiations). Listing status for biologics fell under restricted benefit, but differed in terms of active (e.g., review through special authorization forms) versus passive (e.g., Limited Use codes in Ontario) procedures across public drug plans. Moreover, 3 public drug plans employed 2-tiered formularies (i.e., Alberta, Manitoba, and Correctional Services Canada) which required a trial of new-generation biologics or old-generation biosimilars before reimbursement of old-generation originators.
 Utilization patterns of old- versus new-generation biologics within the Ontario Public Drug Programs demonstrated that a significant proportion of new patients were treated with old-generation biologics (54% in 2019 and 37% in 2020) despite the availability of multiple new-generation biologics.
 In conclusion, formulary management is warranted for biologics for PsO given the significant utilization of old-generation originators in the current context of delayed marketing of their biosimilar versions for PsO and their reimbursement predating the pCPA process. New-generation biologics underwent pCPA negotiations and direct evidence was submitted that demonstrated superiority versus old-generation biologic active comparators, which may ultimately prove to be a greater value for patients and payers.

Indicators of publicly funded prescription opioid use among persons with traumatic spinal cord injury in Ontario, Canada

Objective: To describe the proportion and identify predictors of community-dwelling individuals with traumatic spinal cord injury (TSCI) who were dispensed ≥1 publicly funded opioid in the year after injury using a retrospective cohort study. Setting: Ontario, Canada. Participants, Interventions, Outcome Measures: We used administrative data to identify predictors of receiving publicly funded prescription opioids during the year after injury for individuals who were injured between April 2004 and March 2015. Our outcome was modeled using robust Poisson multivariable regression and we reported adjusted relative risks (aRR) with 95% confidence intervals. Results: In our retrospective cohort of 934 individuals with TSCI who were eligible for the provincial drug program, 510 (55%) received ≥1 prescription opioid in the year after their injury. Most individuals were male (71%) and the median age was 63 years (interquartile range: 42–72). Being male (aRR 1.15, 95% confidence interval [CI] 1.01–1.31), having chronic obstructive pulmonary disease (aRR 1.25, 95% CI 1.05–1.50), and using prescription opioids before injury (aRR 1.46, 95% CI 1.29–1.66) were significantly associated with receiving opioids in the year after TSCI. Short durations of hospital stay after injury were also identified as being a significant risk factor of outpatient opioid use (aRR = 1.28, 95% CI = 1.08–1.51) when compared to longer hospital stays. Conclusion: This study presented evidence showing that most individuals eligible for Ontario’s public drug program who experienced a TSCI used opioids in the year following their injury. Due to the paucity of research on this population and their potential for elevated risks of adverse events, it is important for additional studies to be conducted on opioid use in this population to understand short-term and long-term risks and benefits.

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.

Drugs for Rare Diseases: A Review of National and International Health Technology Assessment Agencies and Public Payers’ Decision-Making Processes


 Drugs for rare diseases can address significant unmet therapeutic needs for patients living with seriously debilitating and life-threatening conditions; however, the high costs of these drugs can pose challenges for public drug programs and health care systems.
 There are challenges with the application of standard health technology assessment methods for the assessment of drugs for rare diseases, including uncertainty with the clinical and economic evidence due to small sample sizes, poorly characterized natural history of disease, uncertain epidemiology, absence of comparative studies, heterogenous phenotypes, and lack of diagnostic accuracy. In addition, there are challenges applying commonly accepted economic benchmarks due to the very high cost of these drugs.
 To address these challenges, agencies and public payers have established separate or modified processes and programs to review and make reimbursement recommendations for drugs for rare diseases. There is a lack of consistency across agencies with respect to how drugs for rare diseases are defined and what aspects of the process are modified to address the challenges with these drugs; however, common features include greater acceptance of uncertainty with the clinical and economic evidence and a higher willingness-to-pay threshold.
 The majority of health technology assessment agencies have highlighted that drugs for ultra-rare diseases are particularly challenging and warrant special consideration. This includes the creation of completely separate review processes for drugs indicated for use in the treatment of ultra-rare conditions in the UK (both England and Scotland).
 The majority of processes for funding drugs for rare diseases by public drug programs included in this report manage the drugs through standard formulary processes involving the use of special authorization to ensure that patients meet the eligibility criteria for the drugs. Those that have specialized formularies have largely focused on providing access to ultra-rare conditions.

Effect of listing strategies on utilization of antitumor necrosis factor biologics infliximab and etanercept: a cross-sectional analysis from Ontario, Canada

BACKGROUND: Use of costly biologic drugs for the treatment of chronic inflammatory diseases has increased significantly in recent years. However, biosimilar drugs offer an opportunity to ensure health system sustainability with robust uptake. OBJECTIVE: To study the effect of formulary listing strategies on the use of infliximab and etanercept innovator and biosimilar biologics. METHODS: This is a cross-sectional study of individuals in Ontario, Canada, dispensed a biologic prescription for infliximab or etanercept through Ontario's public drug program between January 1, 2010, and June 30, 2019. Quarterly utilization and costs were forecasted using Holt-Winters' exponential smoothing models to the second quarter (Q2) of 2022. Secondary analyses explored utilization for rheumatic conditions (RC) and inflammatory bowel disease (IBD). RESULTS: From Q1 2010 to Q2 2019, infliximab and etanercept users increased by 75.7% (n = 4,073 to 7,158), with a forecasted increase of 13.7% (n = 8,142; 95% CI = 7,438-8,847) by Q2 2022. Biosimilar users represented 13.8% (n = 539 of 3,905) of total infliximab users in Q2 2019, although this differed by indication with 6.9% for IBD (n = 187 of 2,712) and 26.6% for RC (n = 203 of 764). Etanercept biosimilar users represented 20.2% (n = 659 of 3,256) of total etanercept users for RC in Q2 2019. Biologics expenditures increased 109.7% during the study, amounting to $49.9 million in Q2 2019. CONCLUSIONS: Despite differing reimbursement restrictions between innovator infliximab and etanercept biologics, the uptake of their biosimilars was low and not noticeably different in the treatment of RC. Dynamic policy strategies are needed to improve the uptake of biosimilars, particularly for IBD. DISCLOSURES: Funding for this study was contributed by the Ontario Ministry of Health. The authors have no conflicts of interest to disclose.

Prescribing trends in direct-acting antivirals for the treatment ofhepatitis C in Ontario, Canada.

Direct-acting antivirals (DAA) offer an opportunity to cure hepatitis C. Reimbursement for DAAs has changed on two occasions since their inclusion on the Ontario public formulary. Whether these changes have appreciably modified prescribing patterns and increased access to DAAs is unknown. We conducted a repeated cross-sectional study of DAA reimbursement by the Ontario Public Drug Programs from January 1, 2012, to December 31, 2018, to summarize the use of DAAs in Ontario and describe changes in DAA prescribing physician specialties over this period. We measured the total number of users quarterly. Results are reported overall and by prescriber type. A total of 27,116 individuals received a publicly funded prescription for a DAA from the first quarter (Q1) of 2012 to the fourth quarter (Q4) of 2018. Nearly two-thirds (n = 17,813; 65.7%) of all DAAs were prescribed by gastroenterologists, hepatologists, or infectious disease specialists. Use of DAAs over time appears to have had three major phases in uptake: (1) the introduction of DAA treatments on the Ontario public drug formulary as a prior authorization benefit in Q1 2015, (2) expanded listing of all DAAs as limited-use products on the formulary in Q1 2017, and (3) the introduction of newer DAAs in Q2 2018. Changes in listing of these agents had a direct impact on the use of DAAs overall. Generally, broader listing expanded access but did not appear to shift utilization patterns to primary care prescribers. Further understanding of who is not receiving treatment is needed.

Potential Cost Implications of Mandatory Non-Medical Switching Policies for Biologics for Rheumatic Conditions and Inflammatory Bowel Disease in Canada.

In 2018, TNFα inhibitors were the highest cost drug class for Canadian public drug programs. In 2019, two Canadian provinces announced mandatory nonmedical switching policies in an attempt to reduce their costs by increasing biosimilar uptake. The national impact of similar policies across Canada is unknown. We conducted a cross-sectional analysis of monthly publicly funded prescription claims for infliximab, etanercept, and adalimumab between June 2015 and December 2019. We reported the market share of biosimilars for infliximab and etanercept in 2019 for each province and estimated the cost savings that public payers could have realized in 2019 if mandatory switching policies had been implemented across Canada, including a sensitivity analysis, which assumed that governments receive a 25% rebate on all biologics. Provincial drug programs spent CAD $991.84million on infliximab, etanercept, and adalimumab in 2019, and, when biosimilars were available, they constituted only 15.5% of national utilization of these drugs. In British Columbia, the implementation of a mandatory switching policy for patients with rheumatic conditions increased the biosimilar market share of infliximab and etanercept by 299% (from 19.7% to 78.5%). If applied nationwide to all three biologics for all indications, we estimate such policies could lead to annual savings of between CAD $179.71million and CAD $425.64million nationally. The overall market share of biosimilars remains low in all provinces where mandatory switching policies have not been introduced. The cost implications of successfully increasing biosimilar uptake would be substantial, particularly as more biosimilars reach the Canadian market.

Regulatory approval and public drug plan listing of new drugs for rare disorders in Canada and New Zealand.

A previous assessment of the alignment of health technology assessments and price negotiations for new drugs for rare disorders in Canada completed between 2014 and 2018 demonstrated that it is working for governments but has yet to lead to improved access in a timely manner for all appropriate patients in all provinces. In this analysis, drugs for rare and ultra-rare disorders with a completed price negotiation or no negotiation between 2014 and 2018 in Canada, and their reimbursement recommendations and listings in Canadian public drug programs are compared with their regulatory approval in New Zealand and listing in the New Zealand National Formulary. The results show that pharmaceutical manufacturers generally seek regulatory approval for rare disorder drugs in Canada before New Zealand, and fewer rare disorder medicines receive regulatory approval in New Zealand. One reason for this difference might be New Zealand's smaller population. However, another reason is likely the restrictive drug formulary in New Zealand. Drugs not given coverage in New Zealand are frequently made unavailable by the manufacturer. Planned changes to Canada's pricing regulations and guidelines will significantly diminish the country's attractiveness as a place in which pharmaceutical companies want to do business, which has the potential to negatively impact the health of all Canadians irrespective of whether they have private or public drug coverage.

Prescribed Drug Spending in Canada, 2019: A Focus on Public Drug Programs.

Public drug program spending accounts for 43.1% of prescribed drug spending in Canada. This report provides an in-depth look at public drug program spending in Canada, using the Canadian Institute for Health Information's (CIHI) National Prescription Drug Utilization Information System. Public drug program spending does not include spending on drugs dispensed in hospitals or on those funded through cancer agencies and other special programs.

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

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. 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. 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. 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.

Alignment of health technology assessments and price negotiations for new drugs for rare disorders in Canada: Does it lead to improved patient access?

A previous assessment of submissions for rare disorder drugs made to the Canadian Agency for Drugs and Technologies in Health (CADTH) found that, from 2012, all positive recommendations included criteria advocating a price reduction. Since 2016, CADTH and the pan-Canadian Pharmaceutical Alliance (pCPA), which conducts drug price negotiations with manufacturers for all public drug programs, have aligned their processes. This analysis examined drugs for rare and ultra-rare disorders (DRDs and DURDs)-prevalence of ≤20 to >2 and ≤2 per 100,000, respectively-with a completed pCPA negotiation or no negotiation between 2014 and 2018, together with their reimbursement recommendations and listings in public drug programs. A positive recommendation led to a successful price negotiation for 81.8% and 78.6% of the DRD and DURD submissions and a negative recommendation to no negotiation for 100.0% and 66.7%. Less than half the recommendations for DURDs reported before 2016 mentioned the need for a substantial price reduction, but this increased to 80% in those reported from 2016 onwards. A successful price negotiation led to listing in the majority of the public drug programs and a negative recommendation usually led to no listing. The CADTH-pCPA alignment is working for the governments who own and fund public drug programs but has yet to lead to coverage for all appropriate patients in all provinces. There is still a way to go to ensure that patients with unmet needs can access high-cost innovative medicines that alleviate suffering, prevent premature death, and/or significantly improve their quality of life.

Public prescription drug plan coverage for antiretrovirals and the potential cost to people living with HIV in Canada: a descriptive study.

Antiretrovirals are expensive and people living with HIV may experience a range of financial burdens when accessing these medications. Our aim was to describe the policy of all Canadian public drug insurance programs for antiretroviral drugs and illustrated how these policies might affect patients' annual out-of-pocket expenditures. In December 2017, we reviewed public drug programs offering antiretroviral coverage in Canada using government websites to summarize eligibility criteria. We estimated the annual out-of-pocket costs incurred by people living with HIV by applying the cost-sharing rules to 2 hypothetical cases, a single man and a married woman with a net household income of $39 000 and $80 000, respectively, receiving identical prescriptions in different jurisdictions. We observed substantial variation in the subsidy provided based mainly on geography, income and age. All 5 federal programs and 6 of 13 provincial and territorial jurisdictions offered universal coverage. In the remaining regions, patients spend up to several thousand dollars annually depending on income (Manitoba), age and income (Ontario, Saskatchewan) and age, income and drug costs (Quebec and Newfoundland and Labrador). We found the greatest variation for our higher income case, with out-of-pocket expenses ranging from 0 to over 50% of the antiretroviral cost. There is considerable inter- and intra-jurisdiction heterogeneity in the cost-sharing policies for antiretrovirals across Canada's public drug programs. Policy reforms that either eliminate or set national standards for copayments, deductibles or premiums would minimize variation and could reduce the risk of cost-associated non-adherence to HIV therapy.

Public Reimbursement of Prescription Drugs Used For Off-Label Indications in Ontario.

A Canadian Agency for Drugs and Technologies in Health (CADTH) therapeutic review concluded that bevacizumab and ranibizumab have similar efficacy and safety in treating retinal conditions and recommended bevacizumab be used as preferred initial therapy based on a cost-saving perspective. Such use would be off-label because bevacizumab is not approved for these conditions and has a serious safety warning (SSW) in its Product Monograph (PM) about intravitreal use. To evaluate whether the Ontario Public Drug Programs (OPDP) reimbursement is provided only for off-label use for serious, life-threatening or severely debilitating conditions and not when the drug's PM contains a SSW against such use. OPDP reimbursement criteria for non-palliative drugs from its frequently-requested Exceptional Access Program (EAP) and Limited Use (LU) lists were compared with approved indications and SSWs in the drugs' PMs. Of 125 unique frequently-requested non-palliative EAP drugs, 12 included off-label use for serious conditions for which no alternative treatment exists. Eight of the 12 had SSWs, but only one warning for orally-administered sirolimus related directly to the OPDP-reimbursed off-label use. Of 29 injectable non-palliative LU drugs, one had off-label LU criteria allowing reimbursement for an unapproved indication and a SSW unrelated to the reimbursable indication. Presently, OPDP only reimburse drugs for off-label use for the treatment of serious, life-threatening or severely debilitating conditions for which no alternative treatment exists. OPDP should not diverge from this approach by allowing cost-savings to trump appropriate drug use, which would set a unique and unprecedented example.