Canadian Healthcare System Perspective Research Articles

The Economic Impact of Treatment Sequencing in Chronic Lymphocytic Leukemia in Canada Using Venetoclax plus Obinutuzumab.

Bruton tyrosine kinase inhibitors (BTKis) represent an advancement in chronic lymphocytic leukemia; however, these agents are administered continuously until disease progression or unacceptable toxicity, raising concerns about their affordability. Venetoclax in combination with obinutuzumab (VO) is a fixed-duration (12-month) treatment, approved in Canada in 2020. This study estimated the total cumulative cost of different treatment sequences and evaluated the economic impact of introducing treatment sequences with/without VO, from a Canadian health care system perspective. A 10-year partitioned survival model was developed, considering key clinical parameters and direct medical costs. Results were stratified by TP53 aberration. Treatment sequences starting with first-line (1L) VO resulted in lower 10-year cumulative costs compared to sequences starting with BTKis administered until disease progression, across both TP53 aberration subgroups. With a maximum of three lines of treatment over a 10-year period, cumulative costs were largely determined by the first two lines of treatment. When comparing sequences with the same 1L treatment, sequences with BTKis in second-line incurred greater costs compared to fixed-duration regimens. Overall, the economic impact of treating all patients with VO led to 10-year cumulative savings of CAD 169,341 and CAD 293,731 per patient, without and with TP53 aberration, respectively. These savings are mainly due to reductions in treatment costs associated with fixed treatment duration.

D.2 Cost-effectiveness analysis of efgartigimod vs chronic IVIg for treatment of patients with generalized myasthenia gravis in Canada

Background: Efgartigimod is a human IgG1 antibody Fc fragment recently approved by Health Canada for patients with acetylcholine receptor antibody positive (AChR-Ab+) generalized myasthenia gravis (gMG). We assessed cost-effectiveness of efgartigimod vs chronic IVIg for adult patients with AChR-Ab+ gMG. Methods: A Markov model estimated costs (treatment and administration, disease monitoring, complications from chronic corticosteroid use, exacerbation and crisis management, adverse events, end-of-life care) and benefits (quality-adjusted life-years [QALYs]). The analysis was conducted from the Canadian healthcare system perspective. Health state transition probabilities were estimated using data from ADAPT, ADAPT+, and a network meta-analysis comparing efgartigimod with chronic IVIg. Utility values were obtained from MyRealWorld MG. Patients with MG-ADL ≥5 who did not die/discontinue were assumed to receive treatment every 4 weeks or every 3 weeks over the lifetime horizon. Results: Over the lifetime horizon, efgartigimod and chronic IVIg were predicted to have total discounted QALYs of 16.80 and 13.35, and total discounted costs of $1,913,294 and $2,170,315, respectively. Efgartigimod dominated chronic IVIg with incremental QALYs of 3.45 and cost savings of $257,020 over the lifetime horizon. Conclusions: Efgartigimod may provide greater benefit at lower costs than chronic IVIg for Canadian patients with AChR-Ab+ gMG, with substantial healthcare system savings over the lifetime horizon.

The Economic Impact of Treatment Sequencing in the Management of Chronic Lymphocytic Leukemia in Canada Using Venetoclax Plus Obinutuzumab

Introduction: In the management of patients with chronic lymphocytic leukemia (CLL), oral targeted therapies (OTT) represent a significant advancement. However, for most Canadian public and private payers, their high cost raises concerns about financial impact & affordability. In part, this burden is associated with new expensive OTT that are used on a continuous basis until disease progression or unacceptable toxicity. The introduction of venetoclax-based combinations administered for a fixed duration offers new options for CLL patients with the potential to achieve long remission with manageable side effects for a limited period, and most importantly time off therapy. From a Canadian healthcare system perspective, fixed treatment duration would have the potential to offer better budget predictability and reduced costs. Venetoclax in combination with obinutuzumab (VO) is a fixed duration treatment (12 months) recently approved in Canada, with the potential to reduce the cost burden of treating CLL. The primary objective of this project was to estimate the total cumulative cost per patient of different treatment sequences for adults with CLL, considering first line (1L) and subsequent treatments, over a 10-year time horizon, from a Canadian healthcare system perspective. A secondary objective was to evaluate the economic impact of introducing sequences of treatment with VO in 1L, compared to other sequences of treatment without VO. Methods: A 10-year partitioned survival model was developed to assess the economic impact of different treatment sequences in CLL. Five health states were included: 1L, second line (2L), third line (3L), supportive care and death. The total number of treatment sequences considered was limited to 100. Key clinical parameters, including progression-free survival and overall survival data, were extracted from pivotal clinical trials of each selected treatment. Analyses were conducted from a Canadian health-care system perspective; accordingly, only direct medical costs were considered, including treatment acquisition costs, administration costs, follow-up and monitoring costs, cost of tumour lysis syndrome prophylaxis, cost of adverse events as well as cost of supportive care. All results were stratified by TP53 aberration. Results: Total 10-year cumulative costs of treatment sequences starting with each 1L treatment are summarized in Table 1. Overall, treatment sequences starting with VO had lower 10-year cumulative costs compared to sequences starting with other novel agents (i.e., ibrutinib [IBRU] or acalabrutinib [ACAL]). Among patients without TP53 aberration, cumulative costs per patient of sequences starting with VO ranged from $327,574 to $418,213, whereas sequences starting with IBRU or ACAL monotherapy ranged from $772,127 to $930,700 [Figure 1]. Similarly, in adults with TP53 aberration, cumulative costs per patient of sequences starting with VO ranged from $500,639 to $536,507, and sequences starting with IBRU or ACAL monotherapy ranged from $770,737 to $862,554. Cumulative costs for treatment sequences were largely determined by the first two lines of treatment. When comparing treatment sequences with the same 1L therapy, sequences with continuous novel therapies in 2L (e.g., ACAL monotherapy) resulted in higher costs compared to sequences with fixed duration (e.g., venetoclax in combination with rituximab). For patients without TP53 aberration, the economic impact of treating all patients with VO led to savings of $169,341 per patient, over 10 years compared to any other 1L treatment, for the Canadian healthcare system. Savings over 10 years were even higher ($293,731) for patients with TP53 aberration. Although TP53 patients are preferably treated with expensive continuous OTT, VO, a fixed duration OTT, also demonstrates a clear and indisputable therapeutic value in this patient population, with a progression-free survival of 40.6% at 60 months; therefore, making VO available to all patients considerably increases cost savings. Conclusions: Treatment sequences starting with VO regimen in 1L resulted in lower costs compared to sequences starting with other novel agents administered until disease progression. These savings are mainly due to substantial reductions in treatment costs associated with a fixed treatment duration. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

POSA148 Cost Effectiveness of Ofatumumab in Comparison with Other Disease Modifying Therapies and Best Supportive Care for the Treatment of Relapsing-Remitting Multiple Sclerosis in Canada

Ofatumumab is a high-efficacy, first-line disease-modifying therapy (DMT) with a favourable benefit-risk profile recently approved in Canada to treat relapsing-remitting Multiple Sclerosis (RRMS) with active disease. This research evaluates the cost effectiveness of ofatumumab against other DMTs and best supportive care (BSC) for the treatment of adult patients with RRMS from a Canadian healthcare system perspective.

PET-Based Staging Is Cost-Effective in Early-Stage Follicular Lymphoma.

The objective was to assess the cost-effectiveness of staging PET/CT in early-stage follicular lymphoma (FL) from the Canadian health-care system perspective. Methods: The study population was FL patients staged as early-stage using conventional CT imaging and planned for curative-intent radiation therapy (RT). A decision analytic model simulated the management after adding staging PET/CT versus using staging CT alone. In the no-PET/CT strategy, all patients proceeded to curative-intent RT as planned. In the PET/CT strategy, PET/CT information could result in an increased RT volume, switching to a noncurative approach, or no change in RT treatment as planned. The subsequent disease course was described using a state-transition cohort model over a 30-y time horizon. Diagnostic characteristics, probabilities, utilities, and costs were derived from the literature. Baseline analysis was performed using quality-adjusted life years (QALYs), costs (2019 Canadian dollars), and the incremental cost-effectiveness ratio. Deterministic sensitivity analyses were conducted, evaluating net monetary benefit at a willingness-to-pay threshold of $100,000/QALY. Probabilistic sensitivity analysis using 10,000 simulations was performed. Costs and QALYs were discounted at a rate of 1.5%. Results: In the reference case scenario, staging PET/CT was the dominant strategy, resulting in an average lifetime cost saving of $3,165 and a gain of 0.32 QALYs. In deterministic sensitivity analyses, the PET/CT strategy remained the preferred strategy for all scenarios supported by available data. In probabilistic sensitivity analysis, the PET/CT strategy was strongly dominant in 77% of simulations (i.e., reduced cost and increased QALYs) and was cost-effective in 89% of simulations (i.e., either saved costs or had an incremental cost-effectiveness ratio below $100,000/QALY). Conclusion: Our analysis showed that the use of PET/CT to stage early-stage FL patients reduces cost and improves QALYs. Patients with early-stage FL should undergo PET/CT before curative-intent RT.

Is SABR Cost-Effective in Oligometastatic Cancer? An Economic Analysis of the SABR-COMET Randomized Trial

<h3>Purpose</h3> The phase 2 randomized study SABR-COMET demonstrated that in patients with controlled primary tumors and 1 to 5 oligometastatic lesions, SABR was associated with improved progression-free survival (PFS) compared with standard of care (SoC), but with higher costs and treatment-related toxicities. The aim of this study was to assess the cost-effectiveness of SABR versus SoC in this setting. <h3>Methods and Materials</h3> A Markov model was constructed to perform a cost-utility analysis from the Canadian health care system perspective. Utility values and transition probabilities were derived from individual-level data from the SABR-COMET trial. One-way, 2-way, and probabilistic sensitivity analyses were performed. Costs were expressed in 2018 CAD. A separate analysis based on US payer's perspective was performed. An incremental cost-effectiveness ratio (ICER) at a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY) was used. <h3>Results</h3> In the base case scenario, SABR was cost-effective at an ICER of $37,157 per QALY gained. This finding was most sensitive to the number of metastatic lesions treated with SABR (ICER: $28,066 per QALY for 2, increasing to $64,429 per QALY for 5), difference in chemotherapy use (ICER: $27,173-$53,738 per QALY), and PFS hazard ratio (HR) between strategies (ICER: $31,548-$53,273 per QALY). Probabilistic sensitivity analysis revealed that SABR was cost-effective in 97% of all iterations. Two-way sensitivity analysis demonstrated a nonlinear relationship between the number of lesions and the PFS HR. To maintain cost-effectiveness for each additional metastasis, the HR must decrease by approximately 0.047. The US cost analysis yielded similar results, with an ICER of $54,564 (2018 USD per QALY) for SABR. <h3>Conclusions</h3> SABR is cost-effective for patients with 1 to 5 oligometastatic lesions compared with SoC.

Economic evaluation of an absorbable antibiotic envelope for prevention of cardiac implantable electronic device infection

Recent evidence suggests that an antibiotic impregnated envelope inserted at time of cardiac implantable electronic device (CIED) implantation may reduce risk of subsequent CIED infection compared with standard of care (SoC). The objective of the current work was to perform a cost-effectiveness analysis comparing an antibiotic impregnated envelope with SoC at time of CIED insertion. Decision analytic models were used to project healthcare costs and benefits of two strategies, an antibiotic impregnated envelope plus SoC (Env+SoC) vs. SoC alone, in a cohort of patients undergoing CIED implantation over a 1-year time horizon. Evidence from published literature informed the model inputs. Probabilistic and deterministic sensitivity analyses were performed. The primary outcome was the incremental cost per infection prevented, assessed from the Canadian healthcare system perspective. Envelope plus SoC was associated with fewer CIED infection (7 CIED infections/1000 patients) at higher total costs ($29 033 000/1000 patients) compared with SoC (11 CIED infections and $27 926 000/1000 patients). The incremental cost per infection prevented over 1 year was $274 416. Use of Env+SoC was cost saving only when baseline CIED infection risk was increased to 6% (vs. base case of 1.2%). A strategy of Env+SoC was not economically favourable compared with SoC alone, and the opportunity cost of widescale implementation should be considered. Future work is required to develop validated risk stratification tools to identify patients at greatest risk of CIED infection. The value proposition of Env+SoC improves when applying this intervention to patients at greatest infection risk.

Cost-effectiveness of fingolimod versus interferon-β1a for the treatment of pediatric-onset multiple sclerosis in Canada

Aims To evaluate the cost-effectiveness of fingolimod versus interferon (IFN)-β1a at a dose of 30 μg per week for the treatment of relapsing pediatric-onset multiple sclerosis (POMS) in Canada. Material and methods A discrete-time Markov model was developed to compare fingolimod with IFN β-1a over a time horizon of two years representing patients followed up to mean age of 18 years from a Canadian health care system perspective. Twenty-one health states based on the Expanded Disability Status Scale (EDSS) were considered: EDSS 0‒9 for relapsing multiple sclerosis (MS), EDSS 0‒9 for secondary progressive MS, and “Death.” Relative treatment efficacy for fingolimod versus IFN-β1a was estimated from the PARADIGMS study. Costs and resource use were obtained from published literature and Canadian sources. Utilities were estimated by mapping the Pediatric Quality of Life inventory data onto the Child Health Utility Index-9 Dimension using a published mapping algorithm. Future costs and benefits were discounted at 1.5% per annum. Results Compared with IFN β-1a, fingolimod led to an increase in quality-adjusted life-years (QALYs) (0.125) with incremental costs (Canadian dollars [CAD] 2,977) and to an incremental cost-effectiveness ratio (ICER) of CAD 23,886/QALY over a time horizon of two years representing patients followed up to mean age of 18 years. The monetary benefits of fingolimod treatment versus IFN β-1a at a willingness-to-pay (WTP) threshold of CAD 50,000 per QALY gained were higher than the costs. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) both confirmed the robustness of the results. Limitations The main limitations of this analysis primarily stem from the limited data availability in POMS. Conclusions Fingolimod is cost effective compared with IFN β-1a for the treatment of POMS over a time horizon of two years representing patients followed up to a mean age of 18 years in Canada.

Cost-effectiveness of low-dose colchicine after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT)

AimsIn the randomized, placebo-controlled Colchicine Cardiovascular Outcomes Trial (COLCOT) of 4745 patients enrolled within 30 days after myocardial infarction (MI), low-dose colchicine (0.5 mg once daily) reduced the incidence of the primary composite endpoint of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularization. To assess the in-trial period and lifetime cost-effectiveness of low-dose colchicine therapy compared to placebo in post-MI patients on standard-of-care therapy.Methods and resultsA multistate Markov model was developed incorporating the primary efficacy and safety results from COLCOT, as well as healthcare costs and utilities from the Canadian healthcare system perspective. All components of the primary outcome, non-cardiovascular deaths, and pneumonia were included as health states in the model as both primary and recurrent events. In the main analysis, a deterministic approach was used to estimate the incremental cost-effectiveness ratio (ICER) for the trial period (24 months) and lifetime (20 years). Over the in-trial period, the addition of colchicine to post-MI standard-of-care treatment decreased the mean overall per-patient costs by 47%, from $502 to $265 Canadian dollar (CAD), and increased the quality-adjusted life years (QALYs) from 1.30 to 1.34. The lifetime per-patient costs were further reduced (69%) and QALYs increased with colchicine therapy (from 8.82 to 11.68). As a result, both in-trial and lifetime ICERs indicated colchicine therapy was a dominant strategy.ConclusionCost-effectiveness analyses indicate that the addition of colchicine to standard-of-care therapy after MI is economically dominant and therefore generates cost savings.

Cost-Effectiveness of Pharmacist-Led Deprescribing of NSAIDs in Community-Dwelling Older Adults.

Older adults are often prescribed potentially inappropriate medications associated with adverse health outcomes and increased health services utilization. Developing Pharmacist-led Research to Educate and Sensitize Community Residents to the Inappropriate Prescriptions Burden in the Elderly (D-PRESCRIBE), a pragmatic randomized clinical trial, demonstrated how a community pharmacist-led evidence-based educational intervention successfully empowered community-dwelling older adults and their physicians to reduce chronic use of inappropriate medications. The objective of this study was to evaluate the cost-effectiveness of the D-PRESCRIBE intervention for discontinuing nonsteroidal anti-inflammatory drugs (NSAIDs). Cost-effectiveness analysis. Canada. Community-dwelling adults aged 65 years and older. Decision analysis combining decision tree and Markov state transition modeling was developed to estimate the cost-effectiveness of D-PRESCRIBE (NSAIDs) compared with usual care from a Canadian healthcare system perspective with a time horizon of 1 year. Data from the D-PRESCRIBE trial and published literature were used to calculate effectiveness, utilities, and costs. Reference case and scenario analyses were conducted using probabilistic modeling. Sensitivity analyses assessed the robustness of the reference case model. D-PRESCRIBE (NSAIDs) was less costly (-$1008.61) and more effective (.11 quality-adjusted life-years [QALYs]) than usual care and was the dominant strategy. At willingness-to-pay thresholds of $50 000 per QALY and $100 000 per QALY, D-PRESCRIBE (NSAIDs) incurred a positive incremental net benefit compared with usual care, suggesting it is cost-effective. Compared with the reference case, scenario analyses gave comparable QALYs with modest variation in cost estimates. For community-dwelling older adults, D-PRESCRIBE (NSAIDs) provides greater benefits at lower system costs, making it a compelling strategy to reduce the use and harms associated with chronic NSAID consumption. Our findings support reimbursing community pharmacists' clinical professional services for deprescribing inappropriate NSAIDs in community-dwelling older adults. J Am Geriatr Soc 68:1090-1097, 2020.

Cost-effectiveness analysis of rituximab with methotrexate, cytarabine and thiotepa for the treatment of patients with primary central nervous system lymphoma

The International Extranodal Lymphoma Study Group-32 (IELSG32) randomized patients with primary central nervous system lymphoma (PCNSL) for induction treatment with methotrexate-cytarabine, methotrexate-cytarabine-rituximab, or methotrexate-cytarabine-thiotepa-rituximab (MATRix) and reported significantly improved complete remission with the MATRix regimen. This study assessed cost-effectiveness among these three induction strategies for PCNSL. A Markov model was developed based on the IELSG32 trial over a 20 year time horizon from the Canadian health care system perspective. Costs for induction, consolidation, inpatient treatment administration, follow-up, adverse events, relapsed disease, and palliative care were included. Methotrexate-cytarabine-rituximab was subject to extended dominance by the other two strategies. The MATRix regimen compared to methotrexate-cytarabine produced 3.05 quality-adjusted life year (QALY) gains at added costs of $75,513, resulting in an incremental cost-effectiveness ratio of $24,758/QALY gained. The MATRix regimen was the optimal strategy in the majority of simulations (98% probability at willingness-to-pay of $50,000/QALY gained) and results appeared robust across sensitivity analyses.

Cost-Effectiveness of Extended Thromboprophylaxis in Patients Undergoing Colorectal Surgery from a Canadian Health Care System Perspective.

There is increasing evidence to support extended thromboprophylaxis after colorectal surgery to minimize the incidence of postdischarge venous thromboembolic events. However, the absolute number of events is small, and extended thromboprophylaxis requires significant resources from the health care system. This study aimed to determine the cost-effectiveness of extended thromboprophylaxis in patients undergoing colorectal surgery for malignancy or IBD. An individualized patient microsimulation model (1,000,000 patients; 1-month cycle length) comparing extended thromboprophylaxis (28-day course of enoxaparin) to standard management (inpatient administration only) after colorectal surgery was constructed. The sources for this study were The American College of Surgeons National Surgical Quality Improvement Project Participant User File and literature searches. Costs (Canadian dollars), quality-adjusted life-years, and venous thromboembolism-related deaths prevented over a 1-year time horizon starting with hospital discharge were determined. The results were stratified by malignancy or IBD. In patients with malignancy, extended prophylaxis was associated with higher costs (+113$; 95% CI, 102-123), but increased quality-adjusted life-years (+0.05; 95% CI, 0.04-0.06), resulting in an incremental cost-effectiveness ratio of 2473$/quality-adjusted life-year. For IBD, extended prophylaxis also had higher costs (+116$; 95% CI, 109-123), more quality-adjusted life-years (+0.05; 95% CI, 0.04-0.06), and an incremental cost-effectiveness ratio of 2475$/quality-adjusted life-year. Extended prophylaxis prevented 16 (95% CI, 4-27) venous thromboembolism-related deaths per 100,000 patients and 22 (95% CI, 6-38) for malignancy and IBD. There was a 99.7% probability of cost-effectiveness at a willingness-to-pay threshold of 50,000$/quality-adjusted life-year. To account for statistical uncertainty around variables, sensitivity analysis was performed and found that extended prophylaxis is associated with lower overall costs when the incidence of postdischarge venous thromboembolic events reaches 1.8%. Significant differences in health care systems may affect the generalizability of our results. Despite the rarity of venous thromboembolic events, extended thromboprophylaxis is a cost-effective strategy. See Video Abstract at http://links.lww.com/DCR/A976. COSTO-EFECTIVIDAD DE LA TROMBOPROFILAXIS EXTENDIDA EN PACIENTES SOMETIDOS A CIRUGÍA COLORRECTAL DESDE UNA PERSPECTIVA DEL SISTEMA DE SALUD CANADIENSE:: Cada vez hay más pruebas que apoyen la tromboprofilaxis extendida después de la cirugía colorrectal para minimizar la incidencia de eventos tromboembólicos venosos después del alta hospitalaria. Sin embargo, el número absoluto de eventos es pequeño y la tromboprofilaxis extendida requiere recursos significativos del sistema médico.Determinar la rentabilidad (relación costo-efectividad) de la tromboprofilaxis extendida en pacientes sometidos a cirugía colorrectal por neoplasia maligna o enfermedad inflamatoria intestinal.Un modelo de microsimulación de paciente individualizado (1,000,000 de pacientes; ciclo de 1 mes) que compara la tromboprofilaxis extendida (curso de enoxaparina de 28 días) con el tratamiento estándar (solo para pacientes hospitalizados) después de la cirugía colorrectal.Archivo de usuario participante del Proyecto de Mejoramiento de la Calidad Quirúrgica del Colegio Nacional de Cirujanos Americanos (ACS-NSQIP) y búsquedas bibliográficas.Costos (en dólares Canadienses), años de vida ajustados por la calidad y muertes relacionadas con el tromboembolismo venoso prevenidas en un horizonte temporal de 1 año a partir del alta hospitalaria. Los resultados fueron estratificados por malignidad o enfermedad inflamatoria intestinal.En pacientes con neoplasias malignas, la profilaxis extendida se asoció con costos más altos (+113 $; IC del 95%, 102-123), pero con un aumento de la calidad de vida ajustada por años de vida (+0.05; IC del 95%, 0.04-0.06), lo que resultó en un incremento de relación costo-efectividad de 2473 $/año de vida ajustado por calidad. Para la enfermedad inflamatoria intestinal, la profilaxis extendida también tuvo costos más altos (+116 $; 95% IC, 109-123), más años de vida ajustados por calidad (+0.05; 95% IC, 0.04-0.06) y una relación costo-efectividad incremental de 2475 $/año de vida ajustado por calidad. La profilaxis prolongada evitó 16 (95% IC, 4-27) muertes relacionadas con tromboembolismo venoso por cada 100,000 pacientes y 22 (95% IC, 6-38) por malignidad y enfermedad inflamatoria intestinal, respectivamente. Hubo un 99.7% de probabilidad de costo-efectividad en un límite de disposición a pagar de 50,000 $/año de vida ajustado por calidad. Para tener en cuenta la incertidumbre estadística en torno a los variables, se realizó un análisis de sensibilidad y se encontró que la profilaxis extendida se asocia con menores costos generales cuando la incidencia de eventos tromboembólicos venosos después del alta hospitalaria alcanza 1.8%.Las diferencias significativas en los sistemas de salud pueden afectar la generalización de nuestros resultados.A pesar de la escasez de eventos tromboembólicos venosos, la tromboprofilaxis extendida es una estrategia rentable. Vea el video del resumen en http://links.lww.com/DCR/A976.

Development, validation and results from the impact of treatment evolution in non-small cell lung cancer (iTEN) model

ObjectivesTreatment of advanced NSCLC (aNSCLC) is rapidly evolving, as new targeted and immuno-oncology (I-O) treatments become available. The iTEN model was developed to predict the cost and survival benefits of changing aNSCLC treatment patterns from a Canadian healthcare system perspective. This report describes iTEN model development and validation. Materials & methodsA discrete event patient simulation of aNSCLC was developed. A modified Delphi process using Canadian clinical experts informed the development of treatment sequences that included commonly used, Health Canada approved treatments of aNSCLC. Treatment efficacy and the timing of progression and death were estimated from published Kaplan–Meier progression free and overall survival data. Costs (2018 CDN$) included were: drug acquisition and administration, imaging, monitoring, adverse events, physician visits, best supportive care, and end-of-life. Results and conclusionClinical validity of the iTEN model was assessed by comparing model survival predictions to published real-world evidence (RWE). Four RWE studies that reported the overall survival of patients treated with a broad sampling of common aNSCLC treatment patterns were used for validation. The validation coefficient of determination was R2 = 0.95, with the model generally producing estimates that were neither optimistic nor conservative. The model estimated that current Canadian practice patterns yield a median survival of almost 13 months, a five-year survival rate of 3% and a life-time per-treated-patient cost of $110,806. Cost and survival estimates are presented and were found to vary by aNSCLC subtype. In conclusion, the iTEN model is a reliable tool for forecasting the impact on cost and survival of new treatments for aNSCLC.

Is SABR Cost-Effective in Oligometastatic Cancer? An Economic Analysis of SABR-Comet

The phase II randomized study SABR-COMET demonstrated that in patients with a controlled primary tumor and 1-5 oligometastatic lesions, SABR was associated with an improvement in both progression free survival and overall survival compared to standard of care. SABR is associated with higher costs and treatment-related toxicity. The aim of this study was to assess the cost-effectiveness of SABR versus standard of care in patients with oligometastatic disease. A Markov model was constructed to perform a cost-effectiveness analysis from the Canadian health care system perspective comparing SABR to standard of care. The model included the following health states: 1) Pre-progression; 2) Post-progression; 3) Death from cancer; 4) Death from adverse event; and 5) Non-cancer death. Utility values and transition probabilities were derived from individual-level data from the SABR-COMET trial. Overall survival and progression outcomes were internally and externally validated. Costs were obtained from the published literature and adjusted to 2018 Canadian dollars. Deterministic sensitivity analyses were performed to obtain thresholds at which each strategy would be preferred. Probabilistic sensitivity analysis was performed to assess the robustness of model. A lifetime horizon was used with a cycle length of 3 months. A willingness-to-pay threshold of $100,000/QALY was used. Quality adjusted life years (QALYs) and costs were discounted at a rate of 1.5%, as recommended in the Guidelines for the Economic Evaluation of Health Technologies: Canada. In the base case scenario, the SABR strategy provided 2.77 QALYs at a cost of $169,697 in comparison to 1.85 QALYs at a cost of $135,452 with the standard of care. SABR was therefore cost-effective in the base case, at an incremental cost-effectiveness ratio (ICER) of $37,250 / QALY. This finding was most sensitive to the number of metastatic lesions treated with SABR (ICER $28,137 – 64,587/QALY), the chemotherapy regimen (ICER $27,242-53,870/QALY), and hazard ratio of progression free survival between strategies (ICER $31,763-$53,908/QALY). Probabilistic sensitivity analysis revealed that SABR was a cost-effective strategy in 97% of the iterations. Based on this decision-analytic model created from a combination of literature and individual-patient clinical trial data, administering SABR is cost-effective for patients with 1-5 oligometastatic lesions compared to the standard of care.

Economic evaluation of aerobic exercise training in older adults with vascular cognitive impairment: PROMoTE trial

Background/objectivesEvidence suggests that aerobic exercise may slow the progression of subcortical ischaemic vascular cognitive impairment (SIVCI) by modifying cardiovascular risk factors. Yet the economic consequences relating to aerobic training (AT)...

Cost-effectiveness of pazopanib compared with sunitinib in metastatic renal cell carcinoma in Canada.

In Canada and elsewhere, pazopanib and sunitinib-tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptors-are recommended as first-line treatment for patients with metastatic renal cell carcinoma (mrcc). A large randomized noninferiority trial of pazopanib versus sunitinib (comparz) demonstrated that the two drugs have similar efficacy; however, patients randomized to pazopanib experienced better health-related quality of life (hrqol) and nominally lower rates of non-study medical resource utilization. The cost-effectiveness of pazopanib compared with sunitinib for first-line treatment of mrcc from a Canadian health care system perspective was evaluated using a partitioned-survival model that incorporated data from comparz and other secondary sources. The time horizon of 5 years was based on the maximum duration of follow-up in the final analysis of overall survival from the comparz trial. Analyses were conducted first using list prices for pazopanib and sunitinib and then by assuming that the prices of sunitinib and pazopanib would be equivalent. Based on list prices, expected costs were CA$10,293 less with pazopanib than with sunitinib. Pazopanib was estimated to yield 0.059 more quality-adjusted life-years (qalys). Pazopanib was therefore dominant (more qalys and lower costs) compared with sunitinib in the base case. In probabilistic sensitivity analyses, pazopanib was dominant in 79% of simulations and was cost-effective in 90%-100% of simulations at a threshold cost-effectiveness ratio of CA$100,000. Assuming equivalent pricing, pazopanib yielded CA$917 in savings in the base case, was dominant in 36% of probabilistic sensitivity analysis simulations, and was cost-effective in 89% of simulations at a threshold cost-effectiveness ratio of CA$100,000. Compared with sunitinib, pazopanib is likely to be a cost-effective option for first-line treatment of mrcc from a Canadian health care perspective.

PCN99 - A Global Economic Model to Assess the Cost Effectiveness of New Treatments for Advanced Breast Cancer in Canada

Objective Considering the increasing number of treatment options for metastatic breast cancer (MBC), it is important to develop high-quality methods to assess the cost-effectiveness of new anti-cancer drugs. This study aims to develop a global economic model that could be used as a benchmark for the economic evaluation of new therapies for MBC. Methods The Global Pharmacoeconomics of Metastatic Breast Cancer (GPMBC) model is a Markov model that was constructed to estimate the incremental cost per quality-adjusted life years (QALY) of new treatments for MBC from a Canadian healthcare system perspective over a lifetime horizon. Specific parameters included in the model are cost of drug treatment, survival outcomes, and incidence of treatment-related adverse events (AEs). Global parameters are patient characteristics, health states utilities, disutilities, and costs associated with treatment-related AEs, as well as costs associated with drug administration, medical follow-up, and end-of-life care. The GPMBC model was tested and validated in a specific context, by assessing the cost-effectiveness of lapatinib plus letrozole compared with other widely used first-line therapies for post-menopausal women with hormone receptor-positive (HR+) and epidermal growth factor receptor 2-positive (HER2+) MBC. Results When tested, the GPMBC model led to incremental cost-utility ratios of CA$131 811 per QALY, CA$56 211 per QALY, and CA$102 477 per QALY for the comparison of lapatinib plus letrozole vs letrozole alone, trastuzumab plus anastrozole, and anastrozole alone, respectively. Results of the model testing were quite similar to those obtained by Delea et al., who also assessed the cost-effectiveness of lapatinib in combination with letrozole in HR+/HER2 + MBC in Canada, thus suggesting that the GPMBC model can replicate results of well-conducted economic evaluations. Conclusions The GPMBC model can be very valuable as it allows a quick and valid assessment of the cost-effectiveness of any new treatments for MBC in a Canadian context.

A global economic model to assess the cost-effectiveness of new treatments for advanced breast cancer in Canada

Objective Considering the increasing number of treatment options for metastatic breast cancer (MBC), it is important to develop high-quality methods to assess the cost-effectiveness of new anti-cancer drugs. This study aims to develop a global economic model that could be used as a benchmark for the economic evaluation of new therapies for MBC.Methods The Global Pharmacoeconomics of Metastatic Breast Cancer (GPMBC) model is a Markov model that was constructed to estimate the incremental cost per quality-adjusted life years (QALY) of new treatments for MBC from a Canadian healthcare system perspective over a lifetime horizon. Specific parameters included in the model are cost of drug treatment, survival outcomes, and incidence of treatment-related adverse events (AEs). Global parameters are patient characteristics, health states utilities, disutilities, and costs associated with treatment-related AEs, as well as costs associated with drug administration, medical follow-up, and end-of-life care. The GPMBC model was tested and validated in a specific context, by assessing the cost-effectiveness of lapatinib plus letrozole compared with other widely used first-line therapies for post-menopausal women with hormone receptor-positive (HR+) and epidermal growth factor receptor 2-positive (HER2+) MBC.Results When tested, the GPMBC model led to incremental cost-utility ratios of CA$131 811 per QALY, CA$56 211 per QALY, and CA$102 477 per QALY for the comparison of lapatinib plus letrozole vs letrozole alone, trastuzumab plus anastrozole, and anastrozole alone, respectively. Results of the model testing were quite similar to those obtained by Delea et al., who also assessed the cost-effectiveness of lapatinib in combination with letrozole in HR+/HER2 + MBC in Canada, thus suggesting that the GPMBC model can replicate results of well-conducted economic evaluations.Conclusions The GPMBC model can be very valuable as it allows a quick and valid assessment of the cost-effectiveness of any new treatments for MBC in a Canadian context.

Cost effectiveness of dabrafenib as a first-line treatment in patients with BRAF V600 mutation-positive unresectable or metastatic melanoma in Canada.

To evaluate the cost effectiveness of dabrafenib versus dacarbazine and vemurafenib as first-line treatments in patients with BRAF V600 mutation-positive unresectable or metastatic melanoma from a Canadian healthcare system perspective. A partitioned-survival analysis model with three mutually exclusive health states (pre-progression, post-progression, and dead) was used. The proportion of patients in each state was calculated using survival distributions for progression-free and overall survival derived from pivotal trials of dabrafenib and vemurafenib. For each treatment, expected progression-free, post-progression, overall, and quality-adjusted life-years (QALYs), and costs were calculated. Costs were based on list prices, a clinician survey, and published sources. A 5-year time horizon was used in the base case. Costs (in 2012 Canadian dollars [CA$]) and QALYs were discounted at 5% annually. Deterministic and probabilistic sensitivity analyses were conducted. Dabrafenib was estimated to yield 0.2055 more QALYs at higher cost than dacarbazine. The incremental cost-effectiveness ratio was CA$363,136/QALY. In probabilistic sensitivity analyses, at a threshold of CA$200,000/QALY, there was an 8.2% probability that dabrafenib is cost effective versus dacarbazine. In deterministic sensitivity analyses, cost effectiveness was sensitive to survival distributions, utilities, and time horizon, with the hazard ratio for overall survival for dabrafenib versus dacarbazine being the most sensitive parameter. Assuming a class effect for efficacy of BRAF inhibitors, dabrafenib was dominant versus vemurafenib (less costly, equally effective), reflecting its assumed lower daily cost. Assuming no class effect, dabrafenib yielded 0.0486 more QALYs than vemurafenib. At a threshold of CA$200,000/QALY, dabrafenib is unlikely to be cost effective compared with dacarbazine. It is not possible to make reliable conclusions regarding the relative cost effectiveness of dabrafenib versus vemurafenib based on available information.

Clinical and economic consequences of vancomycin and fidaxomicin for the treatment of Clostridium difficile infection in Canada.

Clostridium difficile infection (CDI) represents a public health problem with increasing incidence and severity. To evaluate the clinical and economic consequences of vancomycin compared with fidaxomicin in the treatment of CDI from the Canadian health care system perspective. A decision-tree model was developed to compare vancomycin and fidaxomicin for the treatment of severe CDI. The model assumed identical initial cure rates and included first recurrent episodes of CDI (base case). Treatment of patients presenting with recurrent CDI was examined as an alternative analysis. Costs included were for study medication, physician services and hospitalization. Cost effectiveness was measured as incremental cost per recurrence avoided. Sensitivity analyses of key input parameters were performed. In a cohort of 1000 patients with an initial episode of severe CDI, treatment with fidaxomicin led to 137 fewer recurrences at an incremental cost of $1.81 million, resulting in an incremental cost of $13,202 per recurrence avoided. Among 1000 patients with recurrent CDI, 113 second recurrences were avoided at an incremental cost of $18,190 per second recurrence avoided. Incremental costs per recurrence avoided increased with increasing proportion of cases caused by the NAP1/B1/027 strain. Results were sensitive to variations in recurrence rates and treatment duration but were robust to variations in other parameters. The use of fidaxomicin is associated with a cost increase for the Canadian health care system. Clinical benefits of fidaxomicin compared with vancomycin depend on the proportion of cases caused by the NAP1/B1/027 strain in patients with severe CDI.