Cost-Effectiveness Analysis of Local Treatment in Oligometastatic Disease

BackgroundIn certain malignancies, patients with oligometastatic disease benefit from radical ablative or surgical treatment. The SABR-COMET trial demonstrated a survival benefit for oligometastatic patients randomized to local stereotactic ablative radiation (SABR) compared to patients receiving standard care (SC) alone. Our aim was to determine the cost-effectiveness of SABR.Materials and MethodsA decision model based on partitioned survival simulations estimated costs and quality-adjusted life years (QALY) associated with both strategies in a United States setting from a health care perspective. Analyses were performed over the trial duration of six years as well as a long-term horizon of 16 years. Model input parameters were based on the SABR-COMET trial data as well as best available and most recent data provided in the published literature. An annual discount of 3% for costs was implemented in the analysis. All costs were adjusted to 2019 US Dollars according to the United States Consumer Price Index. SABR costs were reported with an average of $11,700 per treatment. Deterministic and probabilistic sensitivity analyses were performed. Incremental costs, effectiveness, and cost-effectiveness ratios (ICER) were calculated. The willingness-to-pay (WTP) threshold was set to $100,000/QALY.ResultsBased on increased overall and progression-free survival, the SABR group showed 0.78 incremental QALYs over the trial duration and 1.34 incremental QALYs over the long-term analysis. Treatment with SABR led to a marginal increase in costs compared to SC alone (SABR: $304,656; SC: $303,523 for 6 years; ICER $1,446/QALY and SABR: $402,888; SC: $350,708 for long-term analysis; ICER $38,874/QALY). Therapy with SABR remained cost-effective until treatment costs of $88,969 over the trial duration (i.e. 7.6 times the average cost). Sensitivity analysis identified a strong model impact for ongoing annual costs of oligo- and polymetastatic disease states.ConclusionOur analysis suggests that local treatment with SABR adds QALYs for patients with certain oligometastatic cancers and represents an intermediate- and long-term cost-effective treatment strategy.

Cost-utility analysis: Mechanical thrombectomy plus thrombolysis in ischemic stroke due to large vessel occlusion in the public sector in Chile

Introduction Several studies demonstrate the therapeutic superiority of thrombolysis plus mechanical thrombectomy versus thrombolysis alone to treat stroke. Objective To analyze the cost-utility of thrombolysis plus mechanical thrombectomy versus thrombolysis in patients with ischemic stroke due to large vessel occlusion. Methods Cost-utility analysis. The model used is blended: Decision Tree (first 90 days) and Markov in the long term, of seven health states based on a disease-specific scale, from the Chilean public insurance and societal perspective. Quality-Adjusted Life-Years and costs are evaluated. Deterministic (DSA) and probabilistic (PSA) analyses were carried out. Results From the public insurance perspective, in the base case, mechanical thrombectomy is associated with lower costs in a lifetime horizon, and with higher benefits (2.63 incremental QALYs, and 1.19 discounted incremental life years), at a Net Monetary Benefit (NMB) of CLP 37,289,874, and an Incremental Cost-Utility Ratio (ICUR) of CLP 3,807,413/QALY. For the scenario that incorporates access to rehabilitation, 2.54 incremental QALYs and 1.13 discounted life years were estimated, resulting in an NMB of CLP 35,670,319 and ICUR of CLP 3,960,624/QALY. In the scenario that incorporates access to long-term care from a societal perspective, the ICUR falls to CLP 951,911/QALY, and the NMB raises to CLP 43,318,072, improving the previous scenarios. In the DSA, health states, starting age, and relative risk of dying were the variables with the greatest influence. The PSA for the base case corroborated the estimates. Conclusions Thrombolysis plus mechanical thrombectomy adds quality of life at costs acceptable for decision-makers versus thrombolysis alone. The results are consistent with international studies.

Public Health and Cost Benefits of Successful Reperfusion After Thrombectomy for Stroke

Background and Purpose— The benefit that endovascular thrombectomy offers to patients with stroke with large vessel occlusions depends strongly on reperfusion grade as defined by the expanded Thrombolysis in Cerebral Infarction (eTICI) scale. Our aim was to determine the lifetime health and cost consequences of the quality of reperfusion for patients, healthcare systems, and society. Methods— A Markov model estimated lifetime quality-adjusted life years (QALY) and lifetime costs of endovascular thrombectomy–treated patients with stroke based on eTICI grades. The analysis was performed over a lifetime horizon in a United States setting, adopting healthcare and societal perspectives. The reference case analysis was conducted for stroke at 65 years of age. National health and cost consequences of improved eTICI 2c/3 reperfusion rates were estimated. Input parameters were based on best available evidence. Results— Lifetime QALYs increased for every grade of improved reperfusion (median QALYs for eTICI 0/1: 2.62; eTICI 2a: 3.46; eTICI 2b: 5.42; eTICI 2c: 5.99; eTICI 3: 6.73). Achieving eTICI 3 over eTICI 2b reperfusion resulted on average in 1.31 incremental QALYs as well as healthcare and societal cost savings of $10 327 and $20 224 per patient. A 10% increase in the eTICI 2c/3 reperfusion rate of all annually endovascular thrombectomy–treated patients with stroke in the United States is estimated to yield additional 3656 QALYs and save $21.0 million and $36.8 million for the healthcare system and society, respectively. Conclusions— Improved reperfusion grants patients with stroke additional QALYs and leads to long-term cost savings. Procedural strategies to achieve complete reperfusion should be assessed for safety and feasibility, even when initial reperfusion seems to be adequate.

P195 Cost-effectiveness of a 17-gene classifier to guide initial treatment choice in Crohn’s disease in the UK

Background PredictSURE IBD™ is a CE-marked whole blood-based biomarker test that predicts long-term clinical outcomes in inflammatory bowel disease (Crohn’s disease, CD and ulcerative colitis, UC). PredictSURE IBD™ uses a 17-gene qPCR-based classifier to stratify patients into two prognostic subgroups, high and low risk. High-risk patients experience significantly more aggressive disease than low-risk patients, with the need for earlier and more frequent treatment escalation over time. Early stratification could enable personalised treatment strategies, such as ‘top-down’ use of biologics in high-risk patients. Our objective was to examine the cost-effectiveness of PredictSURE IBD™ in guiding the use of early biologic therapy in newly diagnosed CD patients in the UK. Methods A decision tree leading into a Markov state-transition model was constructed in MS Excel to compare two treatment approaches: (1) standard of care therapy following established UK clinical guidelines, consisting of sequences of immunomodulator followed by biologic upon relapse (‘step-up’ treatment), (2) targeted therapy guided by PredictSURE IBD™, whereby patients identified as high-risk receive sequences of anti-TNF biologic treatment followed by other biologic classes upon relapse (‘top-down’ treatment), Figure 1. Parameters were informed by patient data from PredictSURE IBD™ clinical studies and the literature. Results Top-down treatment guided by PredictSURE IBD™ resulted in an incremental cost-effectiveness ratio (ICER) of £7,179 per quality-adjusted life-year (QALY), with £1,852 incremental costs and 0.258 incremental QALYs vs. standard of care generated over a 15-year time horizon. Additional costs relating to earlier biologic use were offset by reductions in the costs of flares, hospitalisations and surgery. Incremental QALYs were driven by increased time spent in remission and improved quality of life from reduced flares and surgery. The model was most sensitive to the time horizon, rates of mucosal healing on top-down vs. step-up therapy, the costs of hospitalisation and the costs and quality of life in the severe disease health state. Conclusion Modelling shows that upfront use of biologic guided by PredictSURE IBD™ could substantially improve clinical outcomes for high-risk patients by increasing remission rates and reducing flares, surgery and treatment escalations. The ICER for PredictSURE IBD™ was well below the £20–£30k/QALY threshold used by the UK National Institute for Health and Care Excellence (NICE). Top-down treatment guided by PredictSURE IBD™ would not only represent a treatment paradigm shift for CD patients but would also be a highly cost-effective use of resources in the UK National Health Service.

Clinical and cost-effectiveness of the Ross procedure versus conventional aortic valve replacement in young adults

ObjectivesIn young and middle-aged adults, there are three current options for aortic valve replacement (AVR), namely mechanical AVR (mechAVR), tissue AVR (biological AVR) and the Ross operation, with no clear guidance on the best option. We aim to compare the clinical effectiveness and cost-effectiveness of the Ross procedure with conventional AVR in young and middle-aged adults.MethodsThis is a systematic literature review and meta-analysis of AVR options. Markov multistate model was adopted to compare cost-effectiveness. Lifetime costs, quality-adjusted life years (QALYs), net monetary benefit (NMB), population expected value of perfect information (EVPI) and expected value of partial perfect information were estimated.ResultsWe identified 48 cohorts with a total number of 12 975 patients (mean age 44.5 years, mean follow-up 7.1 years). Mortality, bleeding and thromboembolic events over the follow-up period were lowest after the Ross operation, compared with mechAVR and biological AVR (p<0.001). Aortic reoperation rates were lower after Ross compared with biological AVR, but slightly higher when compared with mechAVR (p<0.001). At a willingness-to-pay threshold of £20effective. At a willingness-to-pay threshold of £20, 000 per QALY000 per QALY, the Ross procedure is more cost-effective compared the Ross procedure is more cost-effective compared withwith conventional AVR, with a lifetime incremental NMB of £60 conventional AVR, with a lifetime incremental NMB of £60 952 (952 (££3030 236236 to to ££7979 464). Incremental costs were £12464). Incremental costs were £12 323 (323 (££61086108 to to ££1515 972) and incremental QALYs 3.66 (1.81972) and incremental QALYs 3.66 (1.81 to to 4.76). The population EVPI indicates that a trial costing up to £2.03 million could be cost 4.76). The population EVPI indicates that a trial costing up to £2.03 million could be cost--effective.At a willingness-to-pay threshold of £20 000 per QALY, the Ross procedure is more cost-effective compared with conventional AVR, with a lifetime incremental NMB of £60 952 (£30 236 to £79 464). Incremental costs were £12 323 (£6108 to £15 972) and incremental QALYs 3.66 (1.81 to 4.76). The population EVPI indicates that a trial costing up to £2.03 million could be cost-effective.ConclusionsIn young and middle-aged adults with aortic valve disease, the Ross procedure may confer greater quality of life and be more cost-effective than conventional AVR. A high-quality randomised trial could be warranted and cost-effective.

CAR-T Therapy Displays Favorable Gains in Health Outcomes and Competitive Cost-Effectiveness When Compared with Past Innovative Cancer Treatments

Background: Recent literature provides conflicting views on whether there is a negative value trend in pharmaceutical oncology treatments. A previous study (J Econ Perspect 2015;29:1) found that the price of pharmaceutical oncology treatments has outpaced the improvements in survival benefits over time, with most treatments developed since 1995 offering marginal improvements in survival with significant increases in costs. In contrast, other literature suggests pharmaceutical oncology treatments have produced significant value. Chimeric antigen receptor t-cell (CAR-T) therapy represents a novel approach for treating particular hematologic cancers-including pediatric acute lymphoblastic leukemia and diffuse large b-cell lymphoma-but a remaining question is whether CAR-T represents a continued trend of low-value innovation, or a significant break from past trends. In this study, we investigate three key questions: (i) what are the trends over the past 10 to 20 years in incremental quality-adjusted life years (QALYs) and incremental cost per incremental quality-adjusted life year (cost/QALY) for newly approved anti-cancer innovations? (ii) how do innovations for hematologic cancers differ from those for other cancers in terms of this value trend? and (iii) how does CAR-T therapy compare with the recent history of innovations for both hematologic and non-hematologic cancers? Methods: We identified all analyses of pharmaceutical treatments for cancer published since 2007 that appear in the Tufts Medical Center Cost-Effectiveness Analysis (CEA) Registry, a comprehensive database focusing on a subset of CEAs called cost-utility analyses (CUAs), which quantify health benefits in terms of QALYs. CUA results on CAR-T therapies came from an analysis conducted by the Institute for Clinical and Economic Review (2018). We limited the CUAs in our study to those conducted in the US context with at least one of the following measures of value: incremental QALYs or cost/QALY, and with intervention/indication approval year 1995 or later. We measured linear trend in the value measures as a function of approval year and compared interventions for non-hematologic cancers with non-CAR-T interventions for hematologic cancers and, in turn, with CAR-T therapy. Regression analysis was used to control for the potential influence of characteristics of a CUA such as discount rate chosen, time horizon, number of years between publication and approval of the intervention for the indication in question, and an indicator for rare diseases as defined by the Genetic and Rare Diseases Information Center of the NIH. Indicators for CAR-T therapy and for non-CAR-T treatments for hematologic cancers were included to test for differences from innovations for other cancer types. Results: 103 incremental QALY and 108 cost/QALY measures met our inclusion criteria. The figures show incremental QALYs and cost/QALY, respectively, by approval year. The regression analysis shows that -- for innovations as a whole -- incremental QALYs gained have declined with approval year by 0.079 per year (95% CI -0.128 to -0.030). Cost effectiveness has worsened somewhat over time although that trend is not statistically significant (cost/QALY increase of $36,147 per year, 95%CI -$29,575 to $101,868). CAR-T is substantially more effective than both pharmaceutical cancer innovations outside of hematology (5.17 more incremental QALYs, 95%CI 4.09 to 6.25) and other innovations within hematology (4.67 more incremental QALYs, 95%CI 3.44 to 5.90). Innovations in hematology other than CAR-T are somewhat more effective than innovations outside of hematology (0.5 more incremental QALYs, 95%CI -0.09 to 1.09), although the difference is not statistically significant. Differences in cost/QALY between CAR-T and other pharmaceutical interventions are not statistically significant. Conclusions: CAR-T therapy improved health outcomes (measured in QALYs) to a greater extent than both treatments for non-hematologic cancers and non-CAR-T treatments for hematologic cancers, with no significant differences in cost/QALY. Those improvements represent a break from a trend previously reported in the literature of negligible incremental effectiveness and rising costs per life-year gained. Disclosures Baumgardner: Precision Health Economics: Employment. Everson:Precision Health Economics: Employment. Brauer:Precision Health Economics: Employment. Zhang:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Hao:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Liu:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Lakdawalla:Precision Health Economics: Consultancy; Novartis Pharmaceuticals Corporation: Other: PHE conducted the research underlying this study with funding from Novartis.; Precision Medicine Group: Equity Ownership.

PP11 Would A Highly Specialized Technology Be Approved In England Under The New NICE Guidance?

Introduction:In April 2017, the National Institute for Health and Care Excellence (NICE) updated its guidance for highly specialized technology (HST) appraisals, whereby it would automatically fund technologies for very rare diseases that fall below a threshold of an incremental cost-effectiveness ratio (ICER) of GBP 100,000 (USD 133,000) per quality-adjusted life year (QALY). In addition, NICE proposed to introduce a ‘QALY modifier’, weighting QALYs gained by the size of gain, which will advantage treatments that offer greater QALY gains.Methods:We reviewed all technologies reviewed through the NICE HST process until November 2017 and assessed whether additional QALYs may be awarded, and subsequently result in ICERs below the new NICE threshold.Results:Six products (eculizumab, elosulfase alfa, ataluren, migalistat, eliglustat, and asfotase alfa) have been through HST process. Within the appraisal documents, most analyses were cost consequence analyses with no ICERs reported. The estimated cost per patient per year ranged from approximately GBP 100,000 (USD 133,000) to GBP 400,000 (USD 532,000; listed prices). Of the six technologies, three resulted in at least ten incremental QALYs (eclizumab, elosulfase alfa and asfotase alfa). From the information in the public domain, it is unclear whether this would result in ICERs below GBP 100,000 (USD 133,000) per QALY.Conclusions:It may become more difficult for HSTs to get recommended by NICE under the new guidance, which requires cost-effectiveness analyses, whereas previously there was no official ICER threshold. The additional weighting of QALYs may be insufficient to meet an ICER threshold of GBP 100,000 (USD 133,000) per QALY.