Estimating the Impact of Delayed Access to Oncology Drugs on Patient Outcomes in Canada.

INTRODUCTION: New requirements in Canada's pricing processes for patented drugs may exacerbate delays in regulatory and reimbursement reviews. This study seeks to better understand the impact of any additional delays on non-small cell lung cancer (NSCLC) patients by measuring the following: (a) durations and outcomes of regulatory and reimbursement reviews of NSCLC drugs in Canada and reference countries; (b) delays in Canada's reviews of three NSCLC drugs (nivolumab, afatinib, and pemetrexed [NAP]); and (c) estimating clinical, patient, and economic impacts of delays in Canada's reviews on access to NAP. METHODS: Information from the Context Matters database and the literature (2005-2020) was used to evaluate the durations and outcomes of reimbursement reviews of NSCLC drugs in Canada and comparator countries. Public information was used to assess delays in Canada's reviews of NAP. Empirical modeling with data from the literature and the Southern Alberta Lung Cancer database was used to estimate the impact of delays in Canada's NAP reviews on patients (i.e., as losses in person-years of life and quality-adjusted life-years [QALYs]). RESULTS: Regulatory and reimbursement reviews in countries of interest take 12-18 months. In Canada, reviews of NSCLC drugs took 216 days (median), with a 24% rejection rate (mean = 19%). Delays in NAP reviews ranged from 5 to 94 days at Health Canada, 0-80 days at CADTH/pCODR, and 12-797 days in Canadian provinces. These delays may have affected 6400 patients, who lost up to 1740 person-years of life and 1122 QALYs (valued at CA$112 million). CONCLUSION: Changes to Canada's prescription drug pricing processes may prolong reviews.

Increasing Prevalence and Incidence of Atherosclerotic Cardiovascular Disease in Adult Patients in Ontario, Canada From 2002 to 2018.

BACKGROUND: Cardiovascular disease is the second-leading cause of death in Canada. However, limited data are available on the prevalence of atherosclerotic cardiovascular disease (ASCVD) in Canada. The study objective was to describe the incidence and prevalence of ASCVD in adult patients in Ontario, Canada, and to evaluate temporal trends for subsequent ASCVD events among those with new-onset ASCVD. METHODS: This retrospective, observational study identified ASCVD incidence and prevalence data from the Institute for Clinical Evaluative Sciences Data Repository for adults from Ontario. Overall prevalence was established for the period from 2002 to 2018. Incident cases from April 1, 2005 to March 2016 were then identified, and followed up to 2018. Primary outcomes were date and type of index event/procedure, patient characteristics/baseline demographics, and comorbidities. Secondary outcomes assessed were time from first to second ASCVD event, subsequent event(s) and/or mortality, and type of subsequent event(s) relative to the type of index/primary event. RESULTS: A total of 1,042,621 eligible prevalent ASCVD cases were identified; of these, 743,309 patients (69%) were newly diagnosed with incident ASCVD. The 10-year prevalence rates for all ASCVD subtypes increased over the study period. Overall event incidence rates per 1000 person-years were mostly stable or increased. Among incident cases, 50% experienced subsequent events over the study period. CONCLUSIONS: This observational study demonstrated increasing prevalence and high incidence of new ASCVD diagnoses in adults from Ontario, over the study period. These data, together with the substantial number of subsequent events in ASCVD patients, demonstrate significant clinical burden of this disease in Ontario.

CONTEXTE: Les maladies cardiovasculaires constituent la deuxième cause de décès au Canada. Toutefois, on dispose de peu de données sur la prévalence de la maladie cardiovasculaire athéroscléreuse (MCVAS) au Canada. L'étude avait pour objectifs de décrire l'incidence et la prévalence de la MCVAS chez les patients adultes en Ontario (Canada) et d'évaluer les tendances temporelles des manifestations subséquentes de MCVAS chez les personnes ayant une MCVAS d'apparition récente. MÉTHODOLOGIE: Cette étude observationnelle rétrospective a permis de colliger les données sur l'incidence et la prévalence de la MCVAS chez les adultes ontariens consignées dans le référentiel de l'Institut des sciences cliniques évaluatives. La prévalence globale a été établie pour la période allant de 2002 à 2018. Les cas incidents survenus du 1er avril 2005 à mars 2016 ont ensuite été recensés et suivis jusqu'en 2018. Les paramètres d'évaluation principaux étaient : date et nature de la manifestation index et de l'intervention; caractéristiques des patients et données démographiques initiales; comorbidités. Les éléments suivants constituaient les paramètres d'évaluation secon-daires : temps écoulé entre la première et la deuxième manifestation de MCVAS, la ou les manifestations subséquentes et/ou le décès; nature de la ou des manifestations subséquentes par rapport à celle de la manifestation index ou primaire. RÉSULTATS: En tout, 1 042 621 cas de MCVAS prévalents admissibles ont été dénombrés; parmi ceux-ci, il y avait 743 309 (69 %) cas incidents de MCVAS nouvellement diagnostiqués. Les taux de prévalence à 10 ans de tous les sous-types de MCVAS ont augmenté au cours de la période étudiée. Les taux globaux d'incidence des manifestations par 1000 années-personnes étaient généralement stables ou accrus. Cinquante pour cent des cas incidents ont été associés à des manifestations subséquentes au cours de la période étudiée. CONCLUSIONS: Cette étude observationnelle a démontré une prévalence croissante et une incidence élevée de nouveaux diagnostics de MCVAS chez les adultes en Ontario au cours de la période étudiée. Les données à cet égard, ainsi que le grand nombre de manifestations subséquentes de la maladie, démontrent que la MCVAS constitue un fardeau clinique considérable en Ontario.

New View on the Canadian Burden of Stroke: Productivity Loss in Adults Who Return to Work.

An often overlooked facet of the indirect costs affecting working-age stroke survivors is the challenges experienced by those who return to work. This study quantified the productivity loss in 20 stroke survivors who returned to work which amounted to 53.0 missed work days and an average indirect cost of $10,298 (CAD) in the year following a stroke. Despite the quantified productivity loss, 75% of patients reported no significant disability and a high proportion were self-employed compared to the Canadian population, indicating that socioeconomic factors may be driving patient decisions to return to work.

Treatment and Low-Density Lipoprotein Cholesterol Management in Patients Diagnosed With Clinical Atherosclerotic Cardiovascular Disease in Alberta.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is an important indicator in the development and management of atherosclerotic cardiovascular disease (ASCVD). Herein, we describe the management of LDL-C with lipid-lowering therapy, among patients diagnosed with clinical ASCVD in Alberta, Canada. METHODS: A retrospective study was conducted by linking multiple health system databases to examine clinical characteristics, treatments, and LDL-C assessments. Patients with ASCVD were identified using a specific case definition on the basis of International Classification of Diseases, Ninth Revision, Clinical Modification/International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Canada codes between 2011 and 2015. LDL-C was assessed at the first measurement (index test) and second measurement (follow-up test) during the study period. LDL-C levels were evaluated on the basis of the 2016 Canadian Cardiovascular Society guideline recommendations for achieving < 2.0 mmol/L or a 50% reduction. Statin therapies were categorized as low-, moderate-, and high-intensity. RESULTS: Among the 281,665 individuals identified with ASCVD during the study period, 219,488 (77.9%) had an index LDL-C test, whereas 120,906 (55.1%) and 144,607 (65.9%) were prescribed lipid-lowering therapy before and after their index test, respectively. Most patients who received any lipid-lowering therapy were receiving moderate-/high-intensity statins (n = 133,029; 60.6%). Among the study cohort who had 2 LDL-C tests (n = 91,841; 32.6%), 48.5% of patients who received any lipid-lowering therapy did not achieve LDL-C levels < 2.0 at index date, whereas 36.6% did not achieve LDL-C levels < 2.0 or a 50% reduction at the follow-up test. CONCLUSIONS: The current study revealed that only two-thirds of patients with ASCVD were receiving pharmacotherapy and of those, a significant proportion did not reach recommended LDL-C levels. A remarkable treatment gap was identified for at-risk ASCVD patients. Further implementation strategies are required to address this undermanagement.

The value and consequences of using public health technology assessments for private payer decision-making in Canada: one size does not fit all.

BACKGROUND: Both public and private insurers provide drug coverage in Canada. All payers are under pressure to contain costs. It has recently been proposed that private plans leverage the public health technology assessment (HTA) evaluation process in their decision-making. OBJECTIVES: The objectives of the current study were to examine use of public health technology assessments (HTAs) for private payer decision-making in the literature, to gather the perspectives of experts from both public and private insurers on this practice, and to summarize which value parameters of public evaluations can be used for private payer decision-making. METHODS: A targeted literature review was conducted to identify publications on the use of public HTA or cost-effectiveness data for private payer decision-making on pharmaceutical reimbursement. Concurrently, a roundtable meeting was organized with invited panelists, including private payer representatives and health economic consultants (total n = 9). The findings from both were synthesized and expressed in qualitative terms using the PICO framework. RESULTS: The targeted review identified 20 studies meeting the inclusion criteria, primarily originating from the US and Canada. The panelists felt that, despite some similarities, there were substantial differences between both systems. The PICO framework highlighted the issues with transferability between the two systems. Most of the value parameters were either not applicable, needed to be added, needed to be adjusted, or their applicability to private payer systems needed to be confirmed. CONCLUSION: Some components of public HTA may be relevant for private payers, however there are reservations that still exist on whether the HTA process in Canada, designed for a public system, can address the informational needs of private payers. Private insurers need to use caution in assessing which value parameters from public HTAs can be used and which need to be confirmed, ignored, enhanced, or adjusted. One size HTA does not fit all applications.

Loss of health related quality of life following low-trauma fractures in the elderly.

BACKGROUND: To estimate the long-term change in health related quality of life (HRQoL) following low-trauma fractures among individuals receiving home care (HC) services or living in long-term care (LTC) facilities using linked healthcare administrative data from Ontario, Canada. METHODS: HRQoL was estimated using the Health Utility Index (HUI-2) with the InterRai Minimum Data Set (MDS), a mandatory questionnaire for LTC and HC in the province of Ontario (population 14 million). The HUI-2, a validated HRQoL instrument, allows the calculation of health utility where 0 represents death and 1 the best imaginable health state. For reference, the HUI-2 utility value for Canadians aged 80-84 years is 0.61 and the minimal clinically important difference is 0.03. The MDS was linked to Ontario acute care databases for fiscal years 2007-2011 to identify low-trauma fractures using ICD-10-CA codes. Regression models were used to identify predictors of change in HRQoL from pre-fracture levels to 3 years post fracture for several populations. Low-trauma fractures included hip, humerus, vertebral, wrist, multiple and other. RESULTS: Twenty-three thousand six-hundred fifty-five unique patients with low-trauma fractures were identified with pre- and post-fracture HRQoL assessments, of which 5057 individuals had at least 3 years of follow-up. Compared to patients receiving HC services (N = 3303), individuals residing in LTC (N = 1754) were older, taking more medications, and had more comorbidities. LTC patients had more hip fractures (49 % of total versus 29 %). For all fracture types, HRQoL decreased immediately following fracture. Although levels rebounded after the first month, HRQoL up to 36 months never returned to pre-fracture levels even for non-hip fracture. For both HC and LTC cohorts, clinically important and statistically significant decreases in HUI-2 utility scores were observed 36 months post fracture. Of the 6 HUI-2 domains, mobility had the largest impact on change in HRQoL. Regression analysis indicated that living with a musculoskeletal disorder or a neurological condition and living in LTC were associated with greater decrements in utility following a fracture. CONCLUSIONS: Based on the analysis of one of the largest studies on HRQoL to date, among individuals living in LTC facilities or receiving HC services, fractures have a significant permanent impact on HRQoL up to 3 years following fracture.

Patient-reported utilities in advanced or metastatic melanoma, including analysis of utilities by time to death.

BACKGROUND: Health-related quality of life is often collected in clinical studies, and forms a cornerstone of economic evaluation. This study had two objectives, firstly to report and compare pre- and post-progression health state utilities in advanced melanoma when valued by different methods and secondly to explore the validity of progression-based health state utility modelling compared to modelling based upon time to death. METHODS: Utilities were generated from the ipilimumab MDX010-20 trial (Clinicaltrials.gov Identifier: NCT00094653) using the condition-specific EORTC QLQ-C30 (via the EORTC-8D) and generic SF-36v2 (via the SF-6D) preference-based measures. Analyses by progression status and time to death were conducted on the patient-level data from the MDX010-20 trial using generalised estimating equations fitted in Stata®, and the predictive abilities of the two approaches compared. RESULTS: Mean utility showed a decrease on disease progression in both the EORTC-8D (0.813 to 0.776) and the SF-6D (0.648 to 0.626). Whilst higher utilities were obtained using the EORTC-8D, the relative decrease in utility on progression was similar between measures. When analysed by time to death, both EORTC-8D and SF-6D showed a large decrease in utility in the 180 days prior to death (from 0.831 to 0.653 and from 0.667 to 0.544, respectively). Compared to progression status alone, the use of time to death gave similar or better estimates of the original data when used to predict patient utility in the MDX010-20 study. Including both progression status and time to death further improved model fit. Utilities seen in MDX010-20 were also broadly comparable with those seen in the literature. CONCLUSIONS: Patient-level utility data should be analysed prior to constructing economic models, as analysis solely by progression status may not capture all predictive factors of patient utility and time to death may, as death approaches, be as or more important. Additionally this study adds to the body of evidence showing that different scales lead to different health state values. Further research is needed on how different utility instruments (the SF-6D, EORTC-8D and EQ-5D) relate to each other in different disease areas.

Indirect treatment comparison of abatacept with methotrexate versus other biologic agents for active rheumatoid arthritis despite methotrexate therapy in the United kingdom.

OBJECTIVE: To compare the efficacy of abatacept and alternative biologic disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) in the United Kingdom. METHODS: A systematic literature search identified 11 individual studies investigating the efficacy of abatacept, infliximab, adalimumab, etanercept, certolizumab pegol, and golimumab in adult patients with RA that did not respond to MTX. The clinical trials included in this analysis were similar in trial design, baseline patient characteristics, and background therapy (i.e., MTX). The key clinical endpoints of interest were the Health Assessment Questionnaire (HAQ) change from baseline (CFB) and the American College of Rheumatology (ACR) responses at 6 months (24-28 weeks). Results were analyzed using Bayesian network metaanalysis methods, and were expressed as differences in HAQ CFB and ACR20/50/70 relative risks, with 95% credible limits (CrL). RESULTS: Analysis of HAQ CFB at 6 months showed that abatacept is more efficacious than placebo [mean difference in HAQ CFB: -0.30 (95% CrL -0.42; -0.16)] and comparable to all other biologic agents, in patients receiving MTX as background treatment. Abatacept is also expected to result in a higher proportion of ACR responders compared to placebo, with relative risks ranging from 1.90 (95% CrL 1.24; 2.57) for ACR20 to 3.72 (95% CrL 1.50; 10.52) for ACR70, and to result in comparable proportions of ACR responders as other biologic agents, at 6 months. CONCLUSION: Abatacept is expected to result in improvement in functional status comparable to other recommended biologic agents in patients with RA who are unresponsive to MTX in the UK.

Abatacept with methotrexate versus other biologic agents in treatment of patients with active rheumatoid arthritis despite methotrexate: a network meta-analysis.

INTRODUCTION: The goal of this study was to compare the efficacy in terms of Health Assessment Questionnaire change from baseline (HAQ CFB), 50% improvement in American College of Rheumatology criterion (ACR-50) and Disease Activity Score in 28 joints (DAS28) defined remission (< 2.6) between abatacept and other biologic disease modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX-IR). METHODS: A systematic literature review identified controlled trials investigating the efficacy of abatacept (three studies), etanercept (two studies), infliximab (two), adalimumab (two), certolizumab pegol (two) ritixumab (three), and tocilizumab (two) in MTX-IR patients with RA. The clinical trials included in this analysis were similar with respect to trial design, baseline patient characteristics and background therapy (MTX). The key clinical endpoints of interest were HAQ CFB, ACR-50 and DAS28 < 2.6 measured at 24 and 52 weeks. The results were analysed using network meta-analysis methods that enabled calculation of an estimate for expected relative effect of comparative treatments. Analysis results were expressed as the difference in HAQ CFB score and odds ratio (OR) of achieving an ACR-50 and DAS28 response and associated 95% credible intervals (CrI). RESULTS: The analysis of HAQ CFB at 24 weeks and 52 weeks showed that abatacept in combination with MTX is expected to be more efficacious than MTX monotherapy and is expected to show a comparable efficacy relative to other biologic DMARDs in combination with MTX. Further, abatacept showed comparable ACR-50 and DAS28 < 2.6 response rates with other biologic DMARDs at 24 and 52 weeks, except for ACR-50 compared to certolizumab pegol at 52 weeks and for DAS28 < 2.6 compared to tocilizumab at 24 weeks. Sensitivity analyses confirmed the robustness of the findings. CONCLUSIONS: Abatacept in combination with MTX is expected to result in a comparable change from baseline in HAQ score and comparable ACR-50 and DAS28 < 2.6 response rates in MTX-IR patients compared to other approved biologic agents.