US Healthcare System Perspective Research Articles

Cost-Effectiveness of Adjuvant Olaparib for Patients With Breast Cancer and Germline BRCA1/2 Mutations

The OlympiA trial found that 1 year of adjuvant olaparib therapy can improve distant disease-free survival and overall survival from early-stage breast cancer in patients with a germline BRCA1/2 mutation. However, olaparib, an oral poly-adenosine diphosphate ribose polymerase inhibitor, is estimated to cost approximately $14 000 per month in the US. To estimate the incremental cost-effectiveness of adjuvant olaparib compared with no olaparib in eligible patients. In an economic evaluation from a health care system perspective, the cost-effectiveness of adjuvant olaparib was analyzed using a Markov state-transition model. The model simulated costs and lifetime health outcomes of 42-year-old women with high-risk early-stage breast cancer and a known BRCA1/2 mutation who completed definitive primary therapy and neoadjuvant or adjuvant systemic therapy. The study was conducted from August 2021 to July 2023. The effectiveness of olaparib was based on the findings of the OlympiA randomized clinical trial, and other model parameters were identified from the literature. The model was calibrated to the 1-, 2-, 3-, and 4-year distant disease-free and overall survival observed in the OlympiA trial, and olaparib was assumed to reduce the risk of distant recurrence only in the first 4 years. One year of adjuvant olaparib or no adjuvant olaparib. Incremental cost-effectiveness ratio (ICER) in 2021 US dollars per quality-adjusted life-year (QALY) gained. All outcomes were discounted by 3% annually. In the base case, adjuvant olaparib was associated with a 1.25-year increase in life expectancy and a 1.20-QALY increase at an incremental cost of $133 133 compared with no olaparib. The resulting ICER was approximately $111 000 per QALY gained. At a willingness-to-pay threshold of $150 000 per QALY, olaparib was cost-effective at its 2021 price and in more than 92% of simulations in probabilistic sensitivity analysis. The results were sensitive to assumptions about the effectiveness of olaparib and quality of life for patients with no disease recurrence. In this study, from a US health care system perspective, adjuvant olaparib was a cost-effective option for patients with high-risk, early-stage breast cancer and a germline BRCA1/2 mutation.

Comparative value of dapagliflozin vs empagliflozin in patients with heart failure and preserved ejection fraction: A cost-effectiveness analysis.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) imposes a high disease burden on patients, primarily because of multimorbidity and frequent hospitalizations. Recently, the American College of Cardiology Expert Consensus recommended treating all patients diagnosed with HFpEF with a sodium-glucose cotransporter 2 inhibitor, such as dapagliflozin or empagliflozin, to reduce the risk of cardiovascular death and hospitalization and improve health status. However, managing HFpEF can be expensive, highlighting the need to assess therapeutic alternatives that can minimize health care costs while optimizing patient outcomes. OBJECTIVE: To compare the cost-effectiveness of dapagliflozin vs empagliflozin in managing patients with HFpEF from the US health care system perspective. METHODS: We developed a Markov model to simulate a cohort of patients with HFpEF (defined as having a left ventricular ejection fraction ≥ 50%) treated with dapagliflozin or empagliflozin. Transition probabilities between 3 health states (HFpEF, hospitalization for heart failure, and death), costs, and quality of life weight input variables were obtained from the literature. In the base-case analysis, we estimated total expected costs, quality-adjusted life-years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) over a lifetime horizon. All future expected costs and QALYs were discounted at the annual rate of 3%. We conducted sensitivity analyses to demonstrate the robustness of the cost-effectiveness model findings. RESULTS: Dapagliflozin had an incremental expected lifetime cost of $29,896 compared with empagliflozin, resulting in an ICER of $36,902/QALY. Value-based price threshold analysis suggested that for empagliflozin to be cost-effective, it would need a 29% discount on its annual price. In a probabilistic sensitivity analysis, dapagliflozin would be the most preferred cost-effective option at willingness-to-pay thresholds of $50,000/QALY about 72% of the time. CONCLUSIONS: This cost-effectiveness analysis showed that, from the US health care system perspective, dapagliflozin was more cost-effective than empagliflozin, and its uptake may enhance long-term outcomes in patients with HFpEF.

Estimating the Lifetime Medical Cost Burden of an Allogeneic Hematopoietic Cell Transplantation Patient

Allogeneic hematopoietic cell transplantation (allo-HCT) has the potential for curative outcomes for a variety of hematologic malignancies. Current allo-HCT studies often describe the outcomes and costs in the near term; however, research on the lifetime economic burden post-allo-HCT remains limited. This study was conducted to estimate the average total lifetime direct medical costs of an allo-HCT patient and the potential net monetary savings from an alternative treatment associated with improved graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS). A disease-state model was constructed using a short-term decision tree and a long-term semi-Markov partitioned survival model to estimate the average per-patient lifetime cost and expected quality-adjusted life years (QALYs) for an allo-HCT patient from a US healthcare system perspective. Key clinical inputs included overall survival, GRFS, incidence of both acute and chronic GVHD, relapse of the primary disease, and infections. Cost results were reported as ranges based on varying the percentage of chronic GVHD patients that remained on treatment after 2 years (15% or 39%). Over a lifetime, the average per-patient medical cost of allo-HCT was estimated to range from $942,373 to $1,247,917. The majority of the costs were for chronic GVHD treatment (37% to 53%), followed by the allo-HCT procedure (15% to 19%). The expected lifetime QALYs of an allo-HCT patient were estimated as 4.7. Lifetime per-patient treatment costs often exceed $1,000,000 for allo-HCT patients. Innovative research efforts focused on the reduction or elimination of late complications, particularly chronic GVHD, may provide the greatest value to improved patient outcomes.

EE219 Cost-Effectiveness of Dapagliflozin Vs. Empagliflozin in Patients with Heart Failure and Preserved Ejection Fraction

To compare the cost-effectiveness of dapagliflozin vs. empagliflozin in managing patients with HFpEF from the US healthcare system perspective.

Cost-Effectiveness of Humidified High-Flow Therapy (HHFT) for COPD Patients on Long-Term Oxygen Therapy.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality, and is associated with significant respiratory impairment, decreased quality of life, and high health care costs. Recent evidence indicates significant clinical benefit results from adding humidified high-flow therapy (HHFT) to standard long-term oxygen therapy (LTOT) as a home-based therapy in persons with severe COPD. The objective was to evaluate the cost-effectiveness of adding HHFT to standard treatment of COPD patients using LTOT with US healthcare cost estimates. A Markov state-transition model was developed using data from a prospective clinical trial of adding HHFT to standard therapy for persons with severe COPD using LTOT. The analysis was conducted from the US health care system perspective using a 5-year time horizon and 3% discount rate. QALYs and downstream healthcare costs were modeled. One-way and probabilistic sensitivity analyses were used to examine the impact of input parameters on the incremental net monetary benefit (NMB). Incremental QALYs accrued were 0.058 (2.047 vs 1.989 QALYs for HHFT and standard therapy groups respectively). Incremental total costs were -$3939 ($47,516 vs $51,455 for HHFT and standard therapy groups respectively). Thus, HHFT was the dominant treatment in the analysis, resulting on both better health and lower total costs. Varying utility and cost inputs individually never resulted in NMB approaching 0. Probabilistic analyses indicate that HHFT is cost-effective in 84% of simulations. Our results indicate that the reductions in acute exacerbations of COPD (AECOPDs) that result from adding HHFT for persons with COPD on LTOT will produce both health benefit (QALYs) and cost savings. Cost savings occur because the HHFT device costs are more than offset by reductions in costly COPD exacerbations. Health care systems and payors can benefit from wider implementation of HHFT with existing treatments.

Evaluating cost per remission and cost of serious adverse events of advanced therapies for ulcerative colitis

BackgroundDetermining the relative cost-effectiveness between advanced therapeutic options for ulcerative colitis (UC) may optimize resource utilization. We evaluated total cost per response, cost per remission, and cost of safety events for patients with moderately-to-severely active UC after 52 weeks of treatment with advanced therapies at standard dosing.MethodsAn analytic model was developed to estimate costs from the US healthcare system perspective associated with achieving efficacy outcomes and managing safety outcomes for advanced therapies approved for the treatment of UC. Numbers needed to treat (NNT) for response and remission, and numbers needed to harm (NNH) for serious adverse events (SAEs) and serious infections (SIs) were derived from a network meta-analysis of pivotal trials. NNT for induction and maintenance were combined with drug regimen costs to calculate cost per clinical remission. Cost of managing AEs was calculated using NNH for safety outcomes and published costs of treating respective AEs.ResultsCosts per remission were $205,240, $249,417, $267,463, $365,050, $579,622, $750,200, and $787,998 for tofacitinib 10 mg, tofacitinib 5 mg, infliximab, vedolizumab, golimumab, adalimumab, and ustekinumab, respectively. Incremental costs of SAEs and SIs collectively were $136,390, $90,333, $31,888, $31,061, $20,049, $12,059, and $0 for tofacitinib 5 mg, golimumab, adalimumab, tofacitinib 10 mg, infliximab, ustekinumab, and vedolizumab (reference), respectively.ConclusionsTofacitinib was associated with the lowest cost per response and cost per remission, while vedolizumab had the lowest costs related to SAEs and SIs. Balancing efficacy versus safety is important when evaluating the costs associated with treatment of moderate-to-severe UC.

Modeling the Cost and Health Impacts of Diagnostic Strategies in Patients with Suspected Transthyretin Cardiac Amyloidosis.

Background Transthyretin cardiac amyloidosis (ATTR-CMP) is an increasingly recognized and treatable cause of heart failure with preserved ejection fraction. Multimodality cardiac imaging is recommended for ATTR-CMP diagnosis, but its cost-effectiveness in current clinical practice has not been well studied. Methods and Results Using a microsimulation model, we compared the cost-effectiveness of a combination of strategies involving 99mtechnetium pyrophosphate (PYP), cardiac magnetic resonance imaging, and endomyocardial biopsy for the diagnosis of ATTR-CMP. We developed a decision analytic model to project health care costs and lifetime quality-adjusted life years for symptomatic, older patients who present with congestive heart failure, with an increased left ventricular wall thickness and a 13% prevalence of ATTR-CMP. Rates of clinical events, costs, and quality-of-life values were estimated from published literature. The analysis was conducted from a US health care system perspective with health and cost outcomes discounted annually at 3%. In the base-case scenario, using a fixed tafamidis price of $16 000 annually (previously identified cost-effective price), total health care costs per person were lowest for the PYP-only strategy ($209 415) and highest for endomyocardial biopsy strategy ($215 881). Of the 7 strategies examined, the PYP-only strategy had the highest net monetary benefit using a willingness-to-pay threshold of $100 000/quality-adjusted life year. Results were sensitive to variations in model inputs for PYP and cardiac magnetic resonance imaging specificity, cost of tafamidis, and willingness-to-pay thresholds. Conclusions Our model-based analyses showed that a PYP-only strategy to diagnose ATTR-CMP is the most cost-effective strategy, at willingness-to-pay threshold of $100 000/quality-adjusted life year. At higher threshold ($150 000/quality-adjusted life year), sequential tests involving PYP and cardiac magnetic resonance imaging may be considered cost effective.

Cost-Effectiveness Analysis of Olaparib in Combination with Bevacizumab Compared with Bevacizumab Monotherapy for the First-Line Maintenance Treatment of Homologous Recombination Deficiency-Positive Advanced Ovarian Cancer.

BackgroundIn the PAOLA-1 trial, olaparib plus bevacizumab demonstrated significant clinical benefit following partial or complete response to platinum-based chemotherapy in homologous recombination deficiency (HRD)-positive ovarian cancer. Our study evaluated the cost effectiveness of olaparib plus bevacizumab compared with bevacizumab alone as a maintenance treatment for women in this population.MethodsOur model was a cohort-level partitioned survival model with a lifetime horizon from a US healthcare system perspective. Its four health states were progression-free, post first progression, post second progression, and death, modeled using time to first progression (PFS1), second progression (PFS2), and overall survival (OS) from PAOLA-1. We modeled PFS1 through mixture survival modeling, and PFS2 and OS by fitting standard parametric models. Time-on-treatment was sourced directly from PAOLA-1, with treatment capped at 24 months for olaparib and 15 months for bevacizumab. Costs included drug acquisition and administration, adverse events, disease management, biomarker testing, and subsequent treatments. Deterministic and probabilistic sensitivity analyses tested the results.ResultsCompared with bevacizumab alone, olaparib plus bevacizumab increased quality-adjusted life-years (QALYs; +2.89) and life-years (LYs; +3.43) at an incremental cost of $164,209, leading to an incremental cost-effectiveness ratio of $56,863 per QALY. Olaparib plus bevacizumab had a 97.0% probability of being cost effective compared with bevacizumab alone at a willingness-to-pay threshold of $100,000 per QALY.ConclusionThe addition of olaparib to bevacizumab led to clinically significant increases in progression-free survival, resulting in substantial predicted LYs and QALYs gained, while being cost effective in the maintenance treatment of advanced ovarian cancer with HRD in the US.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41669-022-00338-2.

Economic potential of abbreviated breast MRI for screening women with dense breast tissue for breast cancer

ObjectivesAbbreviated breast MRI (AB-MRI) was introduced to reduce both examination and image reading times and to improve cost-effectiveness of breast cancer screening. The aim of this model-based economic study was to analyze the cost-effectiveness of full protocol breast MRI (FB-MRI) vs. AB-MRI in screening women with dense breast tissue for breast cancer.MethodsDecision analysis and a Markov model were designed to model the cumulative costs and effects of biennial screening in terms of quality-adjusted life years (QALYs) from a US healthcare system perspective. Model input parameters for a cohort of women with dense breast tissue were adopted from recent literature. The impact of varying AB-MRI costs per examination as well as specificity on the resulting cost-effectiveness was modeled within deterministic sensitivity analyses.ResultsAt an assumed cost per examination of $ 263 for AB-MRI (84% of the cost of a FB-MRI examination), the discounted cumulative costs of both MR-based strategies accounted comparably. Reducing the costs of AB-MRI below $ 259 (82% of the cost of a FB-MRI examination, respectively), the incremental cost-effectiveness ratio of FB-MRI exceeded the willingness to pay threshold and the AB-MRI-strategy should be considered preferable in terms of cost-effectiveness.ConclusionsOur preliminary findings indicate that AB-MRI may be considered cost-effective compared to FB-MRI for screening women with dense breast tissue for breast cancer, as long as the costs per examination do not exceed 82% of the cost of a FB-MRI examination.Key Points• Cost-effectiveness of abbreviated breast MRI is affected by reductions in specificity and resulting false positive findings and increased recall rates.• Abbreviated breast MRI may be cost-effective up to a cost per examination of 82% of the cost of a full protocol examination.• Abbreviated breast MRI could be an economically preferable alternative to full protocol breast MRI in screening women with dense breast tissue.

Cost-effectiveness of pembrolizumab for the first-line treatment of patients with unresectable or metastatic MSI-H/dMMR colorectal cancer in the United States

Aims Approximately, 4% of Stage IV colorectal cancers (CRC) are microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) tumors. Patients with metastatic MSI-H/dMMR CRC receiving conventional therapies experience lower response rates and tend to have worse overall survival compared with patients with microsatellite stable (MSS)/proficient mismatch repair (pMMR) CRC. Pembrolizumab received FDA approval in 2020 for first-line treatment of Stage IV MSI-H/dMMR CRC based on significantly longer progression-free survival versus standard of care (SoC, 5-fluorouracil-based therapy with or without bevacizumab or cetuximab). This study evaluated the cost-effectiveness of pembrolizumab vs. SoC as per KEYNOTE-177 and other first-line treatments for MSI-H/dMMR CRC from a US healthcare system perspective. Methods A three-health-state partitioned-survival model was built using progression-free and overall survival data from KEYNOTE-177 and a network meta-analysis. Utilities were derived from KEYNOTE-177 EQ-5D-3L data. Drug acquisition, administration, AE, surgery, monitoring, subsequent treatment, and terminal care costs were included. Sensitivity and scenario analyses were performed, including utilizing a state-transition model structure and adopting a societal perspective. Results Over a lifetime time horizon, pembrolizumab and SoC were associated with total QALYs of 4.85 and 3.23, and total costs of $381,735 and $370,465, respectively, resulting in an ICER of $6,984 per QALY. QALY gains were mainly driven by extended survival with pembrolizumab. Pembrolizumab incurred higher drug acquisition costs relative to SoC but was cost-saving in terms of drug administration, AE, monitoring, subsequent treatment, and terminal care. Pembrolizumab dominated FOLFOX + panitumumab, FOLFOXIRI, and FOLFOXIRI + bevacizumab, and presented ICERs of $35,220 and $276 against XELOX and XELOX + bevacizumab. Results were robust to sensitivity and scenario analyses. Conclusion Pembrolizumab is highly cost-effective for the first-line treatment of unresectable or metastatic MSI-H/dMMR CRC in the US at a willingness-to-pay threshold of $100,000/QALY. Key messages Pembrolizumab is a highly cost-effective option for the first-line treatment of patients with unresectable or metastatic MSI-H/dMMR colorectal cancer in the United States at a willingness-to-pay threshold of $100,000. Compared with the current standard of care for these patients, pembrolizumab: Increases survival due to delaying and preventing progression; Increases QALYs due to longer survival, improvement in HRQoL in the progression-free health state, and fewer Grade 3+ adverse events; Reduces costs associated with administering treatment, managing adverse events, monitoring post-progression disease, providing subsequent treatment, and providing terminal care; and Reduces indirect health care costs when taking a societal perspective due to productivity gains from delaying and preventing progression and death, less frequent treatment administration and less frequent Grade 3+ adverse events.

Comparison of Guidelines for Evaluation of Suspected Pulmonary Embolism in Pregnancy: A Cost-effectiveness Analysis

Pulmonary embolism (PE) remains a leading cause of maternal mortality, yet diagnosis remains challenging. International diagnostic guidelines vary significantly in their recommendations, making it difficult to determine an optimal policy for evaluation. Which societal-level diagnostic guidelines for evaluation of suspected PE in pregnancy are an optimal policy in terms of its cost-effectiveness? We constructed a complex Markov decision model to evaluate the cost-effectiveness of each identified societal guidelines for diagnosis of PE in pregnancy. Our model accounted for risk stratification, empiric treatment, diagnostic testing strategies, as well as short- and long-term effects from PE, treatment with low-molecular-weight heparin, and radiation exposure from advanced imaging. We considered clinical and cost outcomes of each guideline from a US health care system perspective with a lifetime horizon. Clinical effectiveness and costs were measured in time-discounted quality-adjusted life years (QALYs) and US dollars, respectively. Strategies were compared using the incremental cost-effectiveness ratio (ICER) with a willingness-to-pay threshold of $100,000/QALY. One-way, multiway, and probabilistic sensitivity analyses were performed. We identified six international societal-level guidelines. Base-case analysis showed the guideline proposed by the American Thoracic Society and Society of Thoracic Radiology (ATS-STR) yielded the highest health benefits (22.90 QALYs) and was cost-effective, with an ICER of $7,808 over the guidelines proposed by the Australian Society of Thrombosis and Haemostasis and the Society of Obstetric Medicine of Australia and New Zealand (ASTH-SOMANZ). All remaining guidelines were dominated. The ATS-STR guideline-recommended strategy yielded an expected additional 2.7 QALYs/100 patients evaluated over the ASTH-SOMANZ. Conclusions were robust to sensitivity analyses, with the ATS-STR guidelines optimal in 86%of probabilistic sensitivity analysis scenarios. The ATS-STR guidelines for diagnosis of suspected PE in pregnancy are cost-effective and generate better expected health outcomes than guidelines proposed by other medical societies.

Cost-Effectiveness Analysis of Durvalumab Plus Chemotherapy in the First-Line Treatment of Extensive-Stage Small Cell Lung Cancer.

In the CASPIAN trial, durvalumab + chemotherapy demonstrated significant improvements in overall survival compared with chemotherapy alone in patients with extensive-stage small cell lung cancer (SCLC). We aimed to assess the cost-effectiveness of durvalumab in patients with extensive-stage SCLC from the US healthcare system perspective. A comprehensive Markov model was adapted to evaluate cost and effectiveness of durvalumab combination versus platinum/etoposide alone in the first-line therapy of extensive-stage SCLC based on data from the CASPIAN study. The main endpoints included total costs, life years (LYs), quality-adjusted life-years (QALYs), and incremental cost-e-ectiveness ratios (ICERs). Model robustness was assessed with sensitivity analysis, and additional subgroup analyses were also performed. Durvalumab + chemotherapy therapy resulted in an additional 0.27 LYs and 0.20 QALYs, resulting in an ICER of $464,711.90 per QALY versus the chemotherapy treatment. The cost of durvalumab has the greatest influence on this model. Subgroup analyses showed that the ICER remained higher than $150,000/QALY (the willingness-to-pay threshold in the United States) across all patient subgroups. Durvalumab in combination with platinum/etoposide is not a cost-effective option in the first-line treatment of patients with extensive-stage SCLC.

Impact of specificity on cost-effectiveness of screening women at high risk of breast cancer with magnetic resonance imaging, mammography and ultrasound

PurposeAim of this study was to analyze the comparative cost-effectiveness of MR-mammography vs conventional imaging in a screening setting for women with high risk of breast cancer, with particular focus on the impact of specificity of MRM. MethodDecision analytic modelling and Markov Modelling were applied to evaluate cumulative costs of each screening modality and their subsequent treatments as well as cumulative outcomes in quality adjusted life years (QALYs). For the selected time horizon of 30 years, false positive and false negative results were included. Model input parameters for women with high risk of breast cancer were estimated based on published data from a US healthcare system perspective. Major influence factors were identified and evaluated in a deterministic sensitivity analysis. Based on current recommendations for economic evaluations, a probabilistic sensitivity analysis was conducted to test the model stability. ResultsIn a base-case analysis, screening with XM vs. MRM and treatment resulted in overall costs of $36,201.57 vs. $39,050.97 and a cumulative effectiveness of 19.53 QALYs vs. 19.59 QALYs. This led to an incremental cost-effectiveness ratio (ICER) of $ 45,373.94 per QALY for MRM. US and XM + US resulted in ICER values higher than the willingness to pay (WTP). In the sensitivity analyses, MRM remained a cost-effective strategy for screening high-risk patients as long as the specificity of MRM did not drop below 86.7 %. ConclusionIn high-risk breast cancer patients, MRM can be regarded as a cost-effective alternative to XM in a yearly screening setting. Specificity may be an important cost driver in settings with yearly screening intervals.

Cost-Utility Analysis of Pembrolizumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small Cell Lung Cancer With Different PD-L1 Expression Levels.

To evaluate the cost–utility of pembrolizumab versus chemotherapy as the first-line setting for metastatic non-small cell lung cancer (NSCLC) from the US health care system perspective, a Markov model was developed to compare the lifetime cost and effectiveness of pembrolizumab versus chemotherapy for untreated metastatic NSCLC, based on the clinical data derived from phase III randomized controlled trial (KEYNOTE-042; ClinicalTrials.gov; NCT02220894). Weibull distribution was fitted to simulate the parametric survival functions. Drug costs were collected from official websites, and utility values were obtained from published literature. Total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were computed as primary output indicators. The impact of different PD-L1 expression levels on ICER was also evaluated. One-way and probabilistic sensitivity analyses were performed to assess the model uncertainty. Compared with chemotherapy, patients treated with pembrolizumab provided an additional 1.13, 1.01, and 0.59 QALYs in patients with PD-L1 expression levels of ≥50%, ≥20%, and ≥1%, with corresponding incremental cost of $53,784, $47,479, and $39,827, respectively. The resultant ICERs of pembrolizumab versus chemotherapy were $47,596, $47,184, and $68,061/QALY, in three expression levels of PD-L1, respectively, all of which did not exceed the WTP threshold of 180,000/QALY. Probability sensitivity analysis outcome supported that pembrolizumab exhibited evident advantage over chemotherapy to be cost-effective. One-way sensitivity analysis found that ICERs were most sensitive to utility value of pembrolizumab in progression survival state. All the adjustment of parameters did not qualitatively change the result. For treatment-naive, metastatic NSCLC patients with PD-L1+, pembrolizumab was estimated to be cost-effective compared with chemotherapy for all PD-L1 expression levels at a WTP threshold of $180,000/QALY in the context of the US health care system.

A cost-effectiveness analysis of pretreatment DPYD and UGT1A1 screening in patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI+bevacizumab (FOLFIRI+Bev).

168 Background: Variants in DPYD and UGT1A1 impact toxicities experienced by patients being treated with FOLFIRI+bev. Testing allows providers to preemptively adjust dosing, reducing the toxicity that patients experience. We assessed the cost-effectiveness of pre-treatment testing for variants in DPYD and UGT1A1 in patients with mCRC receiving FOLFIRI+bev. Methods: We developed a six-state Markov model to compare pre-treatment genetic testing to no testing. The genetic testing arm screened for UGT1A1 and DPYD using a multi-gene panel. Patients were dosed per proposed guidelines (Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group) and allowed dose reductions based on toxicity. In the no-test arm, patients received full doses of FOLFIRI+bev, and dose reductions based on toxicity. Costs included medications, clinic visits, and hospitalizations to treat the disease and adverse events, and were obtained from the literature, adjusted to 2019 $US. Quality-adjusted life years (QALYs) were used to assess effectiveness. We used a US health care system perspective with a 16 week horizon, the average length of time patients were exposed to FOLFIRI+bev in clinical trials. We conducted sensitivity analyses to determine the impact of uncertainty on outcomes. Results: Genetic testing cost $25,563, generating 0.21 QALYs. Standard of care cost $25,515, generating 0.20 QALYs. This resulted in an incremental cost-effectiveness ratio (ICER) of $4963 per QALY gained. Results were sensitive to costs of post-progression care, the probability of carrying UGT1A1 variants, and the impact of low-functioning DPYD variants on side effects. Conclusions: Pre-treatment testing for DPYD and UGT1A1 in patients receiving FOLFIRI+bev for mCRC is cost-effective, well below typical oncology ICERs of $50,000-100,000 per QALY. Further work is needed to characterize the impact of post-progression treatment and supportive care medications.

Cost-Effectiveness of Cabozantinib in the Second-Line Treatment of Advanced Hepatocellular Carcinoma

Treatment options are limited for patients with advanced hepatocellular carcinoma (HCC) that progresses after treatment with sorafenib. Cabozantinib, an oral small molecule inhibitor of multiple tyrosine kinase receptors, recently showed improved overall survival (OS) compared with placebo in sorafenib-pretreated patients with advanced HCC in the CELESTIAL trial. This study assessed the cost-effectiveness of cabozantinib for second-line treatment of patients with advanced HCC from a US healthcare system perspective. Cost and utility data were extracted from the CELESTIAL trial and used to determine the cost-effectiveness of cabozantinib compared with placebo plus best supportive care. The main outcome of this study was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY) gained by using cabozantinib compared with placebo plus best supportive care in sorafenib-pretreated HCC. In the base-case analysis using data from the CELESTIAL trial, the incremental QALY and ICER were 0.067 and $1,040,675 for cabozantinib compared with placebo and best supportive care. OS reported in the CELESTIAL trial (hazard ratio, 0.76; 95% CI, 0.63-0.92) had the strongest association with the ICER. In one-way sensitivity analyses, there were no scenarios in which cabozantinib was cost-effective. In a cost-threshold analysis, cabozantinib would have to be priced at least $50 per pill to be cost-effective considering a willingness to pay of $100,000 per QALY. Although the CELESTIAL trial demonstrated that cabozantinib improves OS compared with placebo in patients with HCC that progresses after treatment with sorafenib, our analysis shows that cabozantinib is not a cost-effective therapy in this scenario. At current costs, cabozantinib is not cost-effective for second-line therapy of HCC in the United States.

CULTURAL DETERMINANTS OF HEALTH AND HEALTHY AGING FOR OLDER ADULTS WITH LIMITED-ENGLISH PROFICIENCY

The absence of “culture” when discussing social determinants of health has created barriers to healthy aging for older adults with limited-English proficiency (LEP). Cultural determinants of health are critical to the study of aging and health, given that today’s unprecedented number of older adults (65 years plus) are also the most diverse than any time in our history. Our rapidly aging population includes a growing LEP immigrant and refugee sub-population who experience significant health disparities compared to English-proficient older adults. This paper is a secondary analysis from a parent study that explored barriers and facilitators to preventive cancer screenings for Hmong and Spanish-speaking LEP patients in a large healthcare system in the Midwest (N=20). Three themes emerged regarding LEP older adults’ health behavior: (1) adherence to cultural beliefs about health and illness, (2) differential attitudes between traditional healing practices and western medicine, and (3) a general distrust of western healthcare. Results suggest language barriers led to stronger adherence to their cultural attitudes about health in part because of their limitation to understand American culture. The LEP patient present unique challenges, especially since a language barrier is not an isolated situation. It is critical to understand how the combination effect of language and culture create cross-cultural barriers on health outcomes because their perspective on health and illness does not align with the US healthcare system perspective. Understanding the cultural determinants of health is an important factor to consider as this aging LEP population are at greater risk for age-related health complications.

Cost Utility of Voretigene Neparvovec for Biallelic RPE65-Mediated Inherited Retinal Disease

ObjectiveThe gene therapy voretigene neparvovec (VN) is the first Food and Drug Administration–approved treatment for vision loss owing to the ultra-rare RPE65-mediated inherited retinal disorders. We modeled the cost-utility of VN compared with standard of care (SoC). Study DesignA 2-state Markov model, alive and dead, with a lifetime horizon. MethodsVisual acuity (VA) and visual field (VF) were tracked to model quality-adjusted life-years (QALYs). VN led to an improvement in VA and VF that we assumed was maintained for 10 years followed by a 10-year waning period. The cost of VN was $850 000, and other direct medical costs for depression and trauma were included for a US healthcare system perspective. A modified societal perspective also included direct nonmedical costs and indirect costs. ResultsVN provided an additional 1.3 QALYs over the remaining lifetime of an individual. The average total lifetime direct medical cost for individuals treated with VN was $1 039 000 compared with $213 400 for SoC, leading to an incremental cost-effectiveness ratio (ICER) of $643 800/QALY from the US healthcare system perspective. Direct nonmedical costs totalled $1 070 900 for VN and $1 203 300 for SoC, and indirect costs totalled $405 400 for VN and $482 900 for SoC, leading to an ICER of $480 100/QALY from the modified societal perspective. ConclusionsAt the current price, VN was unlikely to reach traditional cost-effectiveness standards compared with SoC. VN has important implications for both development and pricing of future gene therapies; therefore clinical and economic analyses must be carefully considered.

Cost-Utility Analysis of Apixaban versus Warfarin in Atrial Fibrillation Patients with Chronic Kidney Disease.

Warfarin use for stroke prevention in atrial fibrillation (AF) patients with chronic kidney disease is debated. Apixaban was shown to be safer than warfarin, with superior reduction in the risk of stroke, systemic embolism, mortality, and major bleeding irrespective of kidney function. To evaluate the cost-utility of apixaban compared with warfarin in AF patients at different levels of kidney function. A Markov model was used to estimate the cost effectiveness of apixaban compared with warfarin in AF patients at three levels of kidney function: estimated glomerular filtration rate (eGFR) of more than 80 ml/min, 50 to 80 ml/min, and 50 ml/min or less. Event rates and associated utilities were obtained from previous literature. The model adopted the US health care system perspective, with hospitalization costs extracted from the Healthcare and Utilization Project. Treatment costs were obtained from official price lists. Univariate and probabilistic sensitivity analyses were performed to evaluate the robustness of results. Apixaban was a dominant treatment strategy compared with warfarin in AF patients with eGFR levels of 50 ml/min or less and 50 to 80 ml/min. In patients with an eGFR of more than 80 ml/min, apixaban was cost-effective compared with warfarin, costing $6307 per quality-adjusted life-year gained. Results were consistent assuming anticoagulant discontinuation after major bleeding events. Compared with dabigatran and rivaroxaban, apixaban was the only cost-effective anticoagulant strategy relative to warfarin in both mild and moderate renal impairment settings. Apixaban is a favorably cost-effective alternative to warfarin in AF patients with normal kidney function and potentially cost-saving in those with renal impairment.

PCV40 - Cost-Effectiveness Of Edoxaban Compared With Low Molecular Weight Heparin/Vitamin K Antagonist For The Treatment Of Venous Thromboembolism

This study aimed to determine the cost-effectiveness of Edoxaban versus low-molecular-weight heparin (LMWH) /vitamin K antagonist (VKA) from the US healthcare system perspective. A markov state-transition model was developed to evaluate the cost and quality adjusted life years(QALY) for treatment of Venous Thromboembolism(VTE) with Edoxaban and LMWH/VKA for 10 cycles of 3 months each. Clinical event rates and utilities of Edoxaban and LMWH/VKA treatments were modelled using the Hokusai-VTE trial, AMPLIFY and AMPLIFY-EXT trials respectively. The outcomes of this simulation were: recurrent deep-vein thrombosis(DVT), recurrent pulmonary embolism (PE), intracranial hemorrhage(ICH) major bleed, Non-ICH major bleed, clinically relevant nonmajor bleeding(CRNM) and treatment discontinuations. All costs were derived from real-world databases and published sources. The drug acquisition cost was currently derived (2018) and were as follows: Edoxaban -$13.47, LMWH -$23.86 and VKA- $0.58 per day. Edoxaban therapy for up to 30 months was associated with $378.2 per patient higher total health care costs and a 0.015 QALY increase versus LMWH/VKA. Edoxaban was found to be cost-effective compared with LMWH/VKA at an incremental cost-effectiveness ratio (ICER) of $25,213 per QALY gained, well below the high economic value threshold of $50,000 per QALY gained. One-way sensitivity analyses found that the cost of Edoxaban and the probability of recurrent deep-vein thrombosis as well as recurrent pulmonary embolism when taking either Edoxaban or LMWH/VKA had a considerable impact on the model outcomes. Varying Edoxaban daily cost by ±20% resulted in ICERs ranging from $16,674.3 to $31,194.3/QALY. Based on current analysis, the assessment of costs and effectiveness of Edoxaban and LMWH/VKA found that despite the higher drug acquisition cost Edoxaban, it is a cost-effective alternative to LMWH/VKA for 30 months of treatment of Venous Thromboembolism.