Favorable Incremental Cost-effectiveness Ratio Research Articles

Cost-effectiveness analysis of alternative screening strategies for the detection of cervical cancer among women in rural areas of Western Kenya.

While the incidence of cervical cancer has dropped in high-income countries due to organized cytology-based screening programs, it remains the leading cause of cancer death among women in Eastern Africa. Therefore, the World Health Organization (WHO) now urges providers to transition from widely prevalent but low-performance visual inspection with acetic acid (VIA) screening to primary human papillomavirus (HPV) DNA testing. Due to high HPV prevalence, effective triage tests are needed to identify those lesions likely to progress and so avoid over-treatment. To identify the optimal cost-effective strategy, we compared the VIA screen-and-treat approach to primary HPV DNA testing with p16/Ki67 dual-stain cytology or VIA as triage. We used a Markov model to calculate the budget impact of each strategy with incremental quality-adjusted life years and incremental cost-effectiveness ratios (ICER) as the main outcome. Deterministic cost-effectiveness analyses show that the screen-and-treat approach is highly cost-effective (ICER 2469 Int$), while screen, triage, and treat with dual staining is the most effective with favorable ICER than triage with VIA (ICER 9943 Int$ compared with 13,177 Int$). One-way sensitivity analyses show that the results are most sensitive to discounting, VIA performance, and test prices. In the probabilistic sensitivity analyses, the triage option using dual stain is the optimal choice above a willingness to pay threshold of 7115 Int$ being cost-effective as per WHO standards. The result of our analysis favors the use of dual staining over VIA as triage in HPV-positive women and portends future opportunities and necessary research to improve the coverage and acceptability of cervical cancer screening programs.

Cost-Effectiveness of 9-Valent HPV Vaccination for Patients Treated for High-Grade Cervical Intraepithelial Neoplasia in the UK

Patients who have been treated for high-grade cervical intraepithelial neoplasia (CIN grade ≥2) are at a high risk for subsequent CIN and other cancers and diseases related to human papillomavirus (HPV). HPV vaccination can reduce the risk of subsequent disease in patients surgically treated for grade 2 or greater CIN; however, there is no formal recommendation for prophylactic HPV vaccination in this high-risk population, and the cost-effectiveness is unknown. To assess the incremental lifetime outcomes, costs, and cost-effectiveness of integrating peritreatment 9-valent HPV (9vHPV) vaccination in combination with posttreatment surveillance for the prevention of cervical cancer and other HPV-attributable diseases in patients surgically treated for grade 2 or greater CIN vs posttreatment surveillance alone from a UK payer perspective. This economic evaluation used 3 independent Markov model structures. Model inputs for vaccine efficacy, utilities, and costs were obtained from published sources, and cervical cancer screening data were obtained from the National Health Service Cervical Screening Program. Costs were adjusted to 2022 to 2023 reference years. Data were analyzed from October 2022 to September 2023. Peritreatment vaccination with 9vHPV in combination with posttreatment surveillance compared with posttreatment surveillance alone. Clinical outcomes included grade 1, 2, or 3 CIN; cervical cancer; vaginal cancer; vulvar cancer; anal cancer; head and neck cancer; genital warts; and recurrent respiratory papillomatosis. Incremental cost-effectiveness ratios (ICERs) using a willingness-to-pay threshold (WTP) of £20 000 (US $26 200) per quality-adjusted life-year (QALY) were estimated. Deterministic sensitivity analysis and probabilistic sensitivity analysis were performed. Vaccination with 9vHPV in conjunction with posttreatment surveillance was cost-effective, with a favorable ICER of £13 789.07 (US $18 064.68) per QALY gained (ie, below the WTP of £20 000 per QALY) vs posttreatment surveillance alone. The resulting ICER was £52 358.01 (US $68 588.99) per HPV-related cancer averted and £64 090 (US $83 958.18) per HPV-related cancer death averted. The ICER was most sensitive to discount rate, incidence of HPV infection, vaccine price, and age at initial treatment for grade 2 or greater CIN. Results of the probabilistic sensitivity analysis showed peritreatment 9vHPV vaccination was cost-effective at the WTP recommended by the UK's Joint Committee on Vaccination and Immunisation (90% of iterations <£30 000 [US $39 300] per QALY) in 100% of iterations. These findings suggest that peritreatment prophylactic 9vHPV vaccination is a cost-effective option for preventing subsequent HPV-attributable diseases in patients surgically treated for grade 2 or greater CIN.

Cost-Effectiveness of Rivaroxaban Compared with Other Direct Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation in Public Sector of Malaysia

Despite the amount of research performed, the cost-effectiveness of direct oral anticoagulants (DOACs) in subpopulations with different risk factors for stroke has been very little studied. This study aims to explore the cost-effectiveness of the DOACs available in Malaysia in preventing stroke in different subpopulations from a government perspective. An existing Markov model was adapted to assess the cost-effectiveness of the DOACs that are available in Malaysia namely, apixaban (AP), dabigatran (DA) and rivaroxaban (RV). Each was compared with vitamin K antagonists (VKA) in stroke prevention in different patient subpopulations including chronic kidney disease (CKD), high-age, diabetes (DM), and prolonged hospital stay. Cost-effectiveness was assessed by the incremental cost-effectiveness ratio (ICER) benchmarked against the local threshold for cost-effectiveness. The total cost of VKA, AP, DA and RV was Malaysian Ringit (RM) RM9,811 (1USD=RM4.76), RM16,858, RM18,318 and RM20,161 respectively. The quality adjusted life-years (QALYs) gained compared with VKA were 6.11, 6.09 and 6.15 respectively. The ICER when compared with VKA at base case was 57,539, -90,682 and 68,156 respectively. AP had the most favourable ICER at base case. RV had the best ICER compared to AP and DA in patients with CKD and DM at a willingness-to-pay threshold of 1-GDP. Probabilistic sensitivity analysis showed that RV was consistently the most favourable DOAC under a threshold of 2-GDP for all subpopulations. These findings suggested that rivaroxaban has the most favourable ICER in the CKD and DM patient subgroups for stroke prevention among the DOACs available in Malaysia at a threshold of 2-GDP.

Reducing overdose deaths among persons with opioid use disorder in connecticut

BackgroundPeople in Connecticut are now more likely to die of a drug-related overdose than a traffic accident. While Connecticut has had some success in slowing the rise in overdose death rates, substantial additional progress is necessary.MethodsWe developed, verified, and calibrated a mechanistic simulation of alternative overdose prevention policy options, including scaling up naloxone (NLX) distribution in the community and medications for opioid use disorder (OUD) among people who are incarcerated (MOUD-INC) and in the community (MOUD-COM) in a simulated cohort of people with OUD in Connecticut. We estimated how maximally scaling up each option individually and in combinations would impact 5-year overdose deaths, life-years, and quality-adjusted life-years. All costs were assessed in 2021 USD, employing a health sector perspective in base-case analyses and a societal perspective in sensitivity analyses, using a 3% discount rate and 5-year and lifetime time horizons.ResultsMaximally scaling NLX alone reduces overdose deaths 20% in the next 5 years at a favorable incremental cost-effectiveness ratio (ICER); if injectable rather than intranasal NLX was distributed, 240 additional overdose deaths could be prevented. Maximally scaling MOUD-COM and MOUD-INC alone reduce overdose deaths by 14% and 6% respectively at favorable ICERS. Considering all permutations of scaling up policies, scaling NLX and MOUD-COM together is the cost-effective choice, reducing overdose deaths 32% at ICER $19,000/QALY. In sensitivity analyses using a societal perspective, all policy options were cost saving and overdose deaths reduced 33% over 5 years while saving society $338,000 per capita over the simulated cohort lifetime.ConclusionsMaximally scaling access to naloxone and MOUD in the community can reduce 5-year overdose deaths by 32% among people with OUD in Connecticut under realistic budget scenarios. If societal cost savings due to increased productivity and reduced crime costs are considered, one-third of overdose deaths can be reduced by maximally scaling all three policy options, while saving money.

Rituximab or cyclosporine a for the treatment of membranous nephropathy: Economic evaluation of the MENTOR trial.

The MENTOR trial (MEmbranous Nephropathy Trial Of Rituximab) showed that rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria and was superior in maintaining proteinuria remission. However, the cost of rituximab may prohibit first-line use for some patients and health care payers. A Markov model was used to determine the incremental cost-effectiveness ratio (ICER) of rituximab compared with cyclosporine for the treatment membranous nephropathy from the perspective of a health care payer with a life-time time horizon. The model was informed by data from the MENTOR trial where possible; additional parameters including cost and utility inputs were obtained from the literature. Sensitivity analyses were performed to evaluate the impact of reduced cost biosimilar rituximab. Rituximab for the treatment of membranous nephropathy was cost-effective (assuming a willingness-to-pay threshold of ${\$}$50000 per quality adjusted life year (QALY) gained; ${\$}$US 2021) compared with cyclosporine, with an ICER of ${\$}$8373/QALY over a lifetime time horizon. The incremental cost of rituximab therapy was ${\$}$28007 with an additional 3.34 QALYs compared with cyclosporine. Lower cost of rituximab biosimilars resulted in a more favourable ICER, and in some cases resulted in rituximab being dominant (lower cost and great benefit) compared to cyclosporine. Despite the greater cost of rituximab, it may be a cost-effective option for the treatment of membranous nephropathy when compared with cyclosporine. The cost-effectiveness of rituximab is further improved with the use of less expensive biosimilars.

Cost-effectiveness and budget impact of pembrolizumab+axitinib versus sunitinib in patients with advanced clear-cell renal cell carcinoma in the Netherlands.

The phase 3 clinical trial KEYNOTE-426 suggested a higher efficacy regarding overall survival (OS) and progression-free survival (PFS) of pembrolizumab+axitinib compared to sunitinib as a first-line treatment for patients with advanced renal cell carcinoma. In this analysis, the potential cost-effectiveness of this combination treatment versus sunitinib for patients with advanced clear-cell renal cell carcinoma (accRCC) was examined from the societal perspective in the Netherlands. For this analysis, a partitioned survival model was constructed. Clinical data were obtained from the published KEYNOTE-426 trial reports; data on costs and (dis-)utilities were derived from published literature. Costs outside of the healthcare sector included treatment-related travel, informal care and productivity loss. Next to a probabilistic scenario analysis, various scenario analyses were performed that aimed at survival extrapolation, different utility values, treatment duration and drug pricing, as well as restricting the cohort to patients with an intermediate or poor prognosis. Further, a budget impact analysis over three years was conducted, in which a sensitivity analysis concerning ranges in costs and the number of patients was applied. Moreover, a scenario concerning increasing market penetration of pembrolizumab+axitinib up to a market share of 80% in the third year was analyzed. The incremental cost-effectiveness ratio (ICER) of pembrolizumab+axitinib was estimated at €368,396/quality-adjusted life year (QALY) gained, with an incremental QALY gain of 0.55 over sunitinib. The probability of cost-effectiveness at a willingness-to-pay threshold of €80,000/QALY was estimated at 0%, a 50% probability was estimated at €340,000/QALY. Cost-effectiveness was not achieved in any of the applied scenarios. The budget impact over three years amounted to €417.3 million upon instantaneous and full replacement of sunitinib, and to €214.9 million with increasing market penetration. Pembrolizumab+axitinib was not estimated to be cost-effective compared to sunitinib as a first-line treatment for patients with accRCC in the Netherlands from a societal perspective. In none of the analyzed scenarios, cost-effectiveness was achieved. However, price reductions and shorter treatment durations might lead to a more favorable ICER.

Estimation of Value-Based Price for 48 High-Technology Medical Devices.

Value-based price is estimated quite frequently for medicines, but its application to medical devices is scarce. While some reports have been published in which this parameter has occasionally been determined for devices, no large-scale application has yet been reported. Our objective was to pursue a systematic analysis of the literature published on value-based pricesof medical devices. Pertinent papers were selected upon the criterion that the value-based pricewas reported for the device examined. The real prices of the devices were compared with their values of value-based priceand the ratios between real priceversus value-based pricewere calculated. A total of 239economic articles focused on high-technology medical devices were selected from a standard PubMed search. Among these, the proportion of analyses unsuitable for value-based price estimation was high (191/239; 80%), whereas adequate clinical and economic information for estimatingthis parameter was available in 48 cases (20%). Standard equations of cost-effectiveness were applied. The value-based price was determined according to a willingness-to-pay threshold of 60,000 € per quality-adjusted life year. Real prices of devices were compared with the corresponding estimates of value-based prices. From each analysis, we extracted also the value of incremental cost-effectiveness ratio (ICER). Our final dataset included 47 analyses because one was published twice. There were five analyses in which the ICER could be estimated for the treatment, but not for the device. In the dataset of 42 analyses with complete information, 36 out of 42 devices (86%) were found to have an ICER lower than the pre-specified threshold (favorable ICER). Three ICERs were borderline. A separate analysis was conducted on the other three devices that showed an ICER substantially greater than the threshold (unfavorable ICER). Regarding value-based prices, the values of real price were appreciably lower than the corresponding value-based price in 36 cases (86%). For three devices, the real price was substantially higher than the value-based price. In the remaining three cases, real prices and value-based priceswere very similar.To our knowledge, this is the first experience in which a systematic analysis of the literature has been focused on the application of value-based pricing in the field of high-technology devices. Our results are encouraging and suggest a wider application of cost-effectiveness in this field.

Cost-effectiveness of folic acid therapy for primary prevention of stroke in patients with hypertension

BackgroundFor hypertensive patients without a history of stroke or myocardial infarction (MI), the China Stroke Primary Prevention Trial (CSPPT) demonstrated that treatment with enalapril-folic acid reduced the risk of primary stroke compared with enalapril alone. Whether folic acid therapy is an affordable and beneficial treatment strategy for the primary prevention of stroke in hypertensive patients from the Chinese healthcare sector perspective has not been thoroughly explored.MethodsWe performed a cost-effectiveness analysis alongside the CSPPT, which randomized 20,702 hypertensive patients. A patient-level microsimulation model based on the 4.5-year period of in-trial data was used to estimate costs, life years, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) for enalapril-folic acid vs. enalapril over a lifetime horizon from the payer perspective.ResultsDuring the in-trial follow-up period, patients receiving enalapril-folic acid gained an average of 0.016 QALYs related primarily to reductions in stroke, and the incremental cost was $706.03 (4553.92 RMB). Over a lifetime horizon, enalapril-folic acid treatment was projected to increase quality-adjusted life years by 0.06 QALYs or 0.03 life-year relative to enalapril alone at an incremental cost of $1633.84 (10,538.27 RMB), resulting in an ICER for enalapril-folic acid compared with enalapril alone of $26,066.13 (168,126.54 RMB) per QALY gained and $61,770.73 (398,421.21 RMB) per life-year gained, respectively. A probabilistic sensitivity analysis demonstrated that enalapril-folic acid compared with enalapril would be economically attractive in 74.5% of simulations at a threshold of $37,663 (242,9281 RMB) per QALY (3x current Chinese per capita GDP). Several high-risk subgroups had highly favorable ICERs < $12,554 (80,976 RMB) per QALY (1x GDP).ConclusionsFor both in-trial and over a lifetime, it appears that enalapril-folic acid is a clinically and economically attractive medication compared with enalapril alone. Adding folic acid to enalapril may be a cost-effective strategy for the prevention of primary stroke in hypertensive patients from the Chinese health system perspective.

Cost Effectiveness Analysis of Venetoclax Plus Azacitidine Versus Azacitidine in Newly Diagnosed Adult Patients with Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy from a United States Payer Perspective

Background: The phase 3 VIALE-A trial (NCT02993523) demonstrated that venetoclax plus azacitidine (VEN+AZA) improved overall survival (OS) and led to higher remission rates compared with AZA monotherapy, in patients with newly diagnosed (ND) acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. Based on the results from VIALE-A, VEN+AZA received full United States (US) Food and Drug Administration approval in October 2020 for patients with ND AML aged ≥75 years, or who were ineligible for intensive induction chemotherapy due to comorbidities. This study aims to assess the long-term cost-effectiveness value of the VEN+AZA regimen from the VIALE-A trial from a US third-party payer perspective.Methods: A partitioned survival model with a 28-day cycle was developed to estimate costs and outcomes of treatment with VEN+AZA vs. AZA among patients with ND AML, who are ineligible for intensive chemotherapy, over a lifetime time horizon. The model included three health states: event-free survival (EFS), progressive/relapsed disease, and death. Within the EFS state, patients were further partitioned into time spent in complete remission (CR) or CR with incomplete marrow recovery (CRi), and time spent in non-CR/CRi. Efficacy inputs (OS, EFS, and CR/CRi rate) for both treatment arms were estimated using VIALE-A data. Best-fit parametric models per Akaike information criterion (AIC) were used to extrapolate OS until it reached EFS, and extrapolate EFS for each treatment until Year 5. Patients who remained in EFS after Year 5 were considered cured, and were assumed to have the same mortality as the US general population. Mean time on treatment (ToT) for both regimens was based on the time observed in VIALE-A. The costs for drug acquisition, drug administration for initial and subsequent treatments, subsequent stem cell transplant procedures, adverse events (AEs), and healthcare resource utilization (HRU) associated with each health state were obtained from the literature or publicly available data. All costs were inflated to 2021 US dollars. Utilities for each health state were estimated using EuroQol-5 dimension-5 level (EQ-5D-5L) data from VIALE-A, based on the US crosswalk value set. Information on disutilities due to Grade 3/4 AEs were obtained from the literature. Incremental cost-effectiveness ratios (ICERs) per life year (LY) and quality-adjusted life year (QALY) gained were estimated. Deterministic sensitivity analyses (DSA), scenario analyses and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of the results.Results: Over a lifetime time horizon, compared with AZA, VEN+AZA was associated with an increase of 1.89 LYs (1.10 vs. 2.99, respectively) and 1.45 QALYs (0.84 vs. 2.30, respectively). Patients in the VEN+AZA arm incurred higher total costs ($250,486 vs. $110,034 for patients in the AZA arm). The ICER for VEN+AZA vs. AZA was estimated to be $74,141 per LY gained, and $96,579 per QALY gained. Results from the DSA and scenario analyses supported the base-case findings, with ICERs ranging from $60,922 to $138,554 per QALY gained. The results were most sensitive to alternative approaches for ToT estimation, subsequent treatment HRU costs, cure time point, and the extrapolation approach for EFS. Results from PSA showed that compared with AZA, VEN+AZA was cost-effective in 99.9% of cases at a willingness-to-pay (WTP) threshold of $150,000.Conclusions: Compared with AZA monotherapy, VEN+AZA results in a favorable ICER of $96,579 per QALY gained over a lifetime time horizon. The base-case results suggest that, compared with AZA, VEN+AZA is a cost-effective strategy based on a WTP threshold of $150,000 per QALY gained. Sensitivity analyses support the base-case results. Thus, VEN+AZA offers a cost-effective strategy in the treatment of patients with ND AML who are ineligible for intensive chemotherapy from a US third-party payer perspective. DisclosuresPratz: Agios: Consultancy; Abbvie: Consultancy, Honoraria, Research Funding; University of Pennsylvania: Current Employment; BMS: Consultancy, Honoraria; Novartis: Consultancy; Astellas: Consultancy, Honoraria, Research Funding; Cellgene: Consultancy, Honoraria; Millenium: Research Funding. Chai: Analysis Group, Inc.: Consultancy, Current Employment; Genentech, Inc.: Consultancy. Yin: Analysis Group, Inc.: Consultancy, Current Employment; Genentech, Inc.: Consultancy. Nie: Analysis Group, Inc.: Consultancy, Current Employment; Genentech, Inc.: Consultancy. Montez: Genentech, Inc: Current Employment, Other: May hold equity. Iantuono: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Downs: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Ma: Genentech, Inc.: Current Employment, Other: May hold equity.

Cost-effectiveness of a Province-wide Quality Improvement Initiative for Reducing Potentially Inappropriate Use of Antipsychotics in Long-Term Care in British Columbia, Canada.

BackgroundPotentially inappropriate use of antipsychotics (PIUA) raises serious concerns about safety, quality, and cost of care for residents in long-term care (LTC).ObjectiveThis study aimed to estimate the cost-effectiveness of the Call for Less Antipsychotics in Long-Term Care (Clear) initiative compared with the status quo (pre-Clear, baseline).MethodsA model-based cost-utility analysis, from a public-payer perspective in British Columbia, was conducted using secondary data of residents in LTC homes from 2013 to 2019. Residents’ health resource utilization and quality-adjusted life-year (QALY) measures were extracted from multiple administrative databases. Six Markov states were modelled for post-antipsychotic progression representing PIUA, appropriate use of antipsychotic, complete withdrawal, and death. The primary outcome was the incremental cost per QALY gained.ResultsA cohort of 35,669 residents was included in the primary analysis. The Clear initiative, over 10 years, was estimated to have an incremental cost-effectiveness ratio (ICER) of CA$26,055 (2020 Canadian dollars) per QALY gained at an incremental cost of CA$5211 per resident and a QALY gain of 0.20. In the subgroup analyses, our findings were even more favourable for Clear wave 2 (ICER of CA$24,447 per QALY gained) and Clear wave 3 (ICER of CA$25,933 per QALY gained). At a willingness-to-pay of CA$50,000 per QALY gained, the probabilities of Clear waves 2 and 3 were 82% cost-effective.ConclusionThis study demonstrated incremental costs and yielded favourable ICERs for Clear compared with the baseline. More research is needed to understand the level of support for individual care homes to sustain the Clear initiative in the long run.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41669-021-00267-6.

For which diseases do broader value elements matter most? An evaluation across 20 ICER evidence reports.

BACKGROUND: U.S. value framework developers such as the Institute for Clinical and Economic Review (ICER) use cost-effectiveness analysis to value new health care technologies. Often, these value assessment frameworks use a health system perspective without fully accounting for societal and broader benefits and costs of an intervention. Although there is ongoing debate about the most appropriate methods for including broader value elements in value assessment, it remains unclear whether the inclusion of these value elements is likely to affect the quantitative estimates of treatment value. OBJECTIVE: To assess variations in the relevance of broader value elements to cost-effectiveness analysis across diseases. METHODS: Thirty-two broader value elements (e.g., caregiver burden, health equity, real option value, productivity) not traditionally included in health technology assessments were identified through a targeted literature review. Evidence reports published by ICER between July 2017 and January 2020 were evaluated to identify which broader value elements were discussed as relevant to each disease in the report text. The study examined whether there were associations among ICER's discussion of broader value elements, rare disease status, treatment cost, estimated treatment cost-effectiveness, and ICER committee voting results for contextual considerations and additional benefits/disadvantages. RESULTS: The most commonly cited broader value element category in the ICER evidence reports was household and leisure (e.g., absenteeism from normal activities and caregiver burden). More value elements were cited for inherited retinal disease (19 elements) and sickle cell disease (18 elements) than for other diseases. Cardiovascular disease and diabetes had the fewest number of value elements cited (7 elements). Rare diseases were more likely to have broader value elements cited compared with nonrare diseases (15.9 vs. 11.5, P < 0.001). Treatments with higher (i.e., less favorable) incremental cost-effectiveness ratios were more likely to have a greater number of broader value elements cited (ρ = 0.625, P < 0.001). CONCLUSIONS: The presence of broader value elements varied across diseases, with less cost-effective treatments more likely to have a higher number of relevant broader value elements. Inclusion of all relevant value elements in value assessments will more appropriately incentivize innovation and improve allocation of research funding. DISCLOSURES: This study was sponsored by Novartis Pharmaceutical Corporation. At the time of this study, Shafrin was employed by PRECISIONheor, a consultancy to the life sciences industry that received financial support from Novartis to conduct this study. Dennen, Pednekar, and Birch are employed by PRECISIONheor. Bhor was an employee of Novartis Pharmaceutical Corporation at the time this research was conducted and manuscript was developed and reports grants from Novartis, unrelated to this work. Kanter has served on scientific advisory boards and steering committees for and reports receiving consulting fees from Novartis Pharmaceutical Corporation and is a site principal investigator on studies funded by Novartis Pharmaceutical Corporation. Kantar also reports support from Sickle Cell Disease Association of America Inc. and National Heart, Lung, and Blood Institute, unrelated to this work. Neumann reports advisory boards or consulting fees from Novartis Pharmaceutical Corporation and PRECISIONheor, as well as advisory boards or consulting fees unrelated to this study from AbbVie, Amgen, Avexis, Bayer, Congressional Budget Office, Janssen, Merck, Novartis, Novo Nordisk, Precision Health Economics, Veritech, Vertex; funding from The CEA Registry Sponsors by various pharmaceutical and medical device companies; and grants from Amgen, Lundbeck, Bill and Melinda Gates Foundation, National Pharmaceutical Council, Alzheimer's Association, and the National Institutes for Health.

A preliminary cost-effectiveness analysis of lung protective ventilation with extra corporeal carbon dioxide removal (ECCO2R) in the management of acute respiratory distress syndrome (ARDS).

BackgroundMechanical ventilation (MV) is the cornerstone in the management of the acute respiratory distress syndrome (ARDS). Recent research suggests that decreasing the intensity of MV using lung protective ventilation (LPV) with lower tidal volume (Vt) and driving pressure (∆P) could improve survival. Extra-corporal CO2 removal (ECCO2R) precisely enables LPV by allowing lower Vt, ∆P and mechanical power while maintaining PaCO2 within a physiologic range. This study evaluates the potential cost-effectiveness of ECCO2R-enabled LPV in France.MethodsWe modelled the distribution over time of ventilated ARDS patients across 3 health-states (alive & ventilated, alive & weaned from ventilation, dead). We compared the outcomes of 3 strategies: MV (no ECCO2R), LPV (ECCO2R when PaCO2 > 55 mmHg) and Ultra-LPV (ECCO2R for all). Patients characteristics, ventilation settings, survival and lengths of stay were derived from a large ARDS epidemiology study. Survival benefits associated with lower ∆P were taken from the analysis of more than 3000 patients enrolled in 9 randomized trials. Health outcomes were expressed in quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios (ICERs) were computed with both Day 60 cost and Lifetime cost.ResultsBoth LPV and ULPV as enabled by ECCO2R provided favorable results at Day 60 as compared to MV. Survival rates were increased with the protective strategies, notably with ULPV that provided even more manifest benefits as compared to MV. LPV and ULPV produced +0.162 and + 0.627 incremental QALYs as compared to MV, respectively. LPV and ULPV costs were augmented because of their survival benefits. Nonetheless, ICERs of LPV and ULPV vs. MV were all well below the €50,000 threshold. ULPV also presented with favorable ICERs as compared to LPV (i.e. less than €25,000/QALY).ConclusionsECCO2R-enabled LPV strategies might provide cost-effective survival benefit. Additional data from interventional and observational studies are needed to support this preliminary model-based analysis.

Cost-effectiveness of nivolumab in squamous and non-squamous non-small cell lung cancer in Canada and Sweden: an update with 5-year data

Aims Nivolumab has been approved for advanced squamous and non-squamous non-small cell lung cancer (NSCLC) following platinum-based chemotherapy in both Canada and Sweden. We aimed to determine the value-for-money of nivolumab versus docetaxel in a Canadian and Swedish setting based on 5-year data. Methods These cost effectiveness analyses used partitioned survival models with three mutually exclusive health states: progression-free, progressed disease, and death. All clinical parameters were derived from two registration phase 3 randomized trials, CheckMate 017 and CheckMate 057, with a minimum follow-up of 5 years. Treatment duration was based on time-on-treatment data from the clinical trials. Costs were derived from published sources. The primary outcomes of the analyses were quality-adjusted life-years (QALYs), life-years gained, and incremental cost-effectiveness ratios (ICERs). The model input parameters for each analysis were chosen in line with guidance from the respective HTA authorities. Results From a Canadian payer perspective, the ICERs were CAN$140,753 per QALY in the squamous population, and CAN$173,804 per QALY in the non-squamous population, assuming a 10-year time horizon and a 5% discount rate for both costs and outcomes. Sensitivity analyses demonstrated that changes to the discount rates for outcomes had the highest impact on the ICERs. In the Swedish analysis, the ICERs were SEK568,895 per QALY in the squamous population and SEK662,991 per QALY in the non-squamous population, assuming a 15-year time horizon, a 3% discount rate, and a 2-year maximum treatment duration for nivolumab. Sensitivity analyses demonstrated that the ICERs were most sensitive to changes in the discount rate for outcomes. Conclusion These updated analyses, based on more mature trial data with a minimum follow-up of 5 years, generate more favorable ICERs versus the previously submitted HTA assessments that resulted in approval of nivolumab for patients with previously treated NSCLC in Canada and Sweden.

Cost-Effectiveness of Earlier Transition to Angiotensin Receptor Neprilysin Inhibitor in Patients With Heart Failure and Reduced Ejection Fraction

BackgroundAngiotensin receptor neprilysin inhibitor (ARNi) therapy improves clinical outcomes in patients with heart failure and reduced left ventricular ejection fraction. However, ARNi therapy uptake remains modest, potentially in part due to perceived cost considerations of early transition from angiotensin converting enzyme inhibitor or angiotensin receptor blocker therapy. MethodsWe constructed a decision-analytic Markov model to assess cost-effectiveness of 3 different ARNi initiation strategies according to timing of initiation: (1) de novo, or immediate initiation at baseline, (2) Early or after 3 months, or (3) Late, or after 9 months. Initiation strategies were compared with (4) current care, with utilization of ARNi derived from a large observational database. Total costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) were estimated over a 5-year time horizon in the base case analysis. ResultsCurrent care was associated with the lowest total cost (CAD$26,664) and accrued benefit (3.28 QALYs). The de novo strategy yielded an ICER of $34,727 per QALY gained, whereas Early and Late initiation strategies yielded a less favourable ICER per QALY gained of $35,871 and $40,234, respectively. The model was most sensitive to the cost of ARNi therapy. ConclusionA strategy of de novo ARNi initiation is economically attractive and becomes less favourable as the delay of initiation increases. Our results suggest that ARNi therapy should be initiated as soon as possible for patients with heart failure and reduced left ventricular ejection fraction.

Favorable incremental cost-effectiveness ratio for lung cancer screening in Italy

ObjectivesLung cancer detection by low-dose computed tomographic screening reduces mortality. However, it is essential to assess cost-effectiveness. We present a cost-effectiveness analysis of screening in Italians at high risk of lung cancer, from the point of view of the Italian tax-payer. Materials and methodsWe used a decision model to estimate the cost-effectiveness of annual screening for 5 years in smokers (≥30 pack-years) of 55–79 years. Patients diagnosed in the COSMOS study were the screening arm; patients diagnosed and treated for lung cancer in the Lombardy Region, Italy, constituted the usual care arm. Treatment costs were extracted from our hospital database. Lung cancer survival in screened patients was adjusted for 2-year lead-time bias. Life-years and quality-adjusted life-years were estimated by stage at diagnosis, from which incremental cost-effectiveness ratios per life-year and quality-adjusted life-year gained were estimated. ResultsBase-case incremental cost-effectiveness ratios were 3297 and 2944 euro per quality-adjusted life-year and life-year gained, respectively. Deterministic sensitivity analysis indicated that these values were particularly sensitive to lung cancer prevalence, screening sensitivity and specificity, screening cost, and treatment costs for stage I and IV disease. From the probabilistic sensitivity analysis incremental cost-effectiveness ratios had a 98 % probability of being <25,000 euro (widely-accepted threshold) and a 55 % probability of being <5000 euro. ConclusionsLow-dose computed tomographic screening is associated with an incremental cost of 2944 euro per life-year gained in high risk population, implying that screening can be introduced in Italy at contained cost, saving the lives of many lung cancer patients.

Impact of preventive screening and lifestyle interventions in women with a history of preeclampsia: A micro-simulation study.

Preeclampsia is a female-specific risk factor for the development of future cardiovascular disease. Whether early preventive cardiovascular disease risk screenings combined with risk-based lifestyle interventions in women with previous preeclampsia are beneficial and cost-effective is unknown. A micro-simulation model was developed to assess the life-long impact of preventive cardiovascular screening strategies initiated after women experienced preeclampsia during pregnancy. Screening was started at the age of 30 or 40 years and repeated every five years. Data (initial and follow-up) from women with a history of preeclampsia was used to calculate 10-year cardiovascular disease risk estimates according to Framingham Risk Score. An absolute risk threshold of 2% was evaluated for treatment selection, i.e. lifestyle interventions (e.g. increasing physical activity). Screening benefits were assessed in terms of costs and quality-adjusted-life-years, and incremental cost-effectiveness ratios compared with no screening. Expected health outcomes for no screening are 27.35 quality-adjusted-life-years and increase to 27.43 quality-adjusted-life-years (screening at 30 years with 2% threshold). The expected costs for no screening are €9426 and around €13,881 for screening at 30 years (for a 2% threshold). Preventive screening at 40 years with a 2% threshold has the most favourable incremental cost-effectiveness ratio, i.e. €34,996/quality-adjusted-life-year, compared with other screening scenarios and no screening. Early cardiovascular disease risk screening followed by risk-based lifestyle interventions may lead to small long-term health benefits in women with a history of preeclampsia. However, the cost-effectiveness of a lifelong cardiovascular prevention programme starting early after preeclampsia with risk-based lifestyle advice alone is relatively unfavourable. A combination of risk-based lifestyle advice plus medical therapy may be more beneficial.

Estimating the cost-effectiveness of screening for hepatitisC virus infection in Japan.

The management of hepatitisC virus (HCV) has changed with the advent of interferon (IFN)-free treatment and the declining prevalence of HCV infection, which may impact the cost-effectiveness of the screening. We aimed to compare the cost-effectiveness and clinical outcomes of three screening strategies in the Japanese general population: no screening, screening plus IFN-based therapy, and screening plus IFN-free therapy. We developed a decision analytic Markov model for screening intervention and natural history of HCV. Model parameters were derived from published literature. A lifetime horizon and the healthcare payer perspective were taken. Subanalyses included high screening scenario with improved rates of screening and attending referral, in addition to heterogeneity analysis by age subgroup. In the base case, the incremental cost-effectiveness ratio in the Japanese general population aged 40-89years was ¥1 124 482 and ¥1 085 183 per quality-adjusted life year gained for screening plus IFN-free therapy compared with no screening and screening plus IFN-based therapy, respectively. Screening plus IFN-free therapy remained cost-effective below ¥5 000 000 per quality-adjusted life year gained in sensitivity analyses. Incremental cost-effectiveness ratios were lower in the younger population. Nearly 0.2% of HCV-related deaths were avoided by 1.5% of the general population screened followed by IFN-free therapy relative to no screening; the impact was greater with improved rates of screening and attending referral. Screening and subsequent IFN-free therapy for HCV appears to be cost-effective. Early diagnosis and treatment would produce a favorable incremental cost-effectiveness ratio. Improved rates of screening and attending referral would result in further reduction of disease progression.

Infliximab, adalimumab, golimumab, vedolizumab and tofacitinib in moderate to severe ulcerative colitis: comparative cost-effectiveness study in Poland.

Background:Current management of ulcerative colitis (UC) is aimed to treat active disease and to maintain remission. For patients in whom conventional treatment is no longer effective, biological or small molecule therapy may be an option. The aim was to assess the cost-effectiveness of induction and maintenance treatment up to 1 year of UC with infliximab (IFX), adalimumab (ADA), golimumab, vedolizumab (VDZ) and tofacitinib (TFB) compared with standard of care (SoC) in Poland.Methods:A hybrid decision tree/Markov model was used to estimate the expected costs and effects of four biologics, TFB and placebo in patients with the diagnosis of moderate to severe UC who had an inadequate response, lost response, or were intolerant to a conventional therapy. Prior exposure to anti-TNF was considered. At the beginning of the maintenance phase, the decision to continue biological therapy was determined by the achievement of response at the end of induction. Efficacy data were obtained from a network meta-analysis using placebo as the common comparator. Costs were presented in 2018 Polish zloty (PLN) and outcomes included quality-adjusted life-years (QALYs). The analysis was performed from the Polish public payer’s perspective and lifetime horizon was set.Results:In anti-TNF naïve, IFX and VDZ were characterized by the most favourable incremental cost-effectiveness ratios (ICURs) compared with SoC, PLN211,250.78 and PLN361,694.61/QALY (€49,589.38 and €84,904.84/QALY), respectively. In anti-TNF-exposed population the most effective treatment was TFB. Both ADA and VDZ were more effective than SoC; however, ICUR values were much above the cost-effectiveness threshold. The incorporation of biosimilars reversed the ranking of treatments in relation to the growing ICUR.Conclusion:Although ICUR values for all biological therapies exceeded the acceptability threshold in Poland, for anti-TNF-naïve UC patients IFX and for anti-TNF-exposed UC patients VDZ are currently the most cost-effective alternatives.

Projected Cost-Effectiveness for 2 Gene-Drug Pairs Using a Multigene Panel for Patients Undergoing Percutaneous Coronary Intervention

BackgroundFor patients undergoing percutaneous coronary intervention, gene-drug associations exist relevant to first-line treatment options–antiplatelet agent, clopidogrel, and pain medication, tramadol. Knowledge of genotype information may allow for avoidance of adverse drug events during critical clinical windows. ObjectiveThis evaluation estimated cost-effectiveness associated with a multi-gene panel pre-emptively testing two genes providing CYP2C19 genotype-guided strategy for antiplatelet therapy, with CYP2D6 genotype-guided pain management, compared to single gene test for CYP2C19 with random assignment for pain treatment, and to no testing (empiric clopidogrel with random assignment for pain treatment). MethodsDecision analysis modeling was used to project costs from a payer perspective and patient quality-adjusted life years (QALYs) from the three strategies. The model captured composite risks of major adverse cardiovascular events and pain therapy-related adverse drug events and associated utility estimates. We conducted sensitivity analyses to assess influential input parameters. ResultsOver 15 months, multi-gene testing was least costly and yielded more QALYs compared to both single gene and no testing; total incremental costs were $1646 lower with incremental gains of 0.04 QALYs for multi-gene compared with single gene and $11 368 lower with 0.17 QALY gains compared to no test. Base case analyses revealed multi gene was dominant compared to both single gene and no test, as it demonstrated cost savings with increased QALYs. ConclusionsFor these patients, a multi-gene-guided strategy yields a favorable incremental cost-effectiveness ratio compared to the other two treatment strategies. Pre-emptively ascertaining additional gene-drug pair information can inform clinical and economic decision-making at the point of care.

A Cost-Effectiveness Model for Adjunctive Smoked Cannabis in the Treatment of Chronic Neuropathic Pain.

Background: A recent meta-analysis affirmed the benefit of medicinal cannabis for chronic neuropathic pain, a disabling and difficult-to-treat condition. As medicinal cannabis use is becoming increasingly prevalent among Americans, an exploration of its economic feasibility is warranted. We present this cost-effectiveness analysis of adjunctive cannabis pharmacotherapy for chronic peripheral neuropathy.Materials and Methods: A published Markov model comparing conventional therapies for painful diabetic neuropathy was modified to include arms for augmenting first-line, second-line (if first-line failed), or third-line (if first- and second-line failed) therapies with smoked cannabis. Microsimulation of 1,000,000 patients compared the cost (2017 U.S. dollars) and effectiveness (quality-adjusted life years [QALYs]) of usual care with and without adjunctive cannabis using a composite of third-party and out-of-pocket costs. Model efficacy inputs for cannabis were adapted from clinical trial data. Adverse event rates were derived from a prospective study of cannabis for chronic noncancer pain and applied to probability inputs for conventional therapies. Cannabis cost was derived from retail market pricing. Parameter uncertainty was addressed with one-way and probabilistic sensitivity analysis.Results: Adding cannabis to first-line therapy was incrementally less effective and costlier than adding cannabis to second-line and third-line therapies. Third-line adjunctive cannabis was subject to extended dominance, that is, the second-line strategy was more effective with a more favorable incremental cost-effectiveness ratio of $48,594 per QALY gained, and therefore, third-line adjunctive cannabis was not as cost-effective. At a modest willingness-to-pay threshold of $100,000/QALY gained, second-line adjunctive cannabis was the strategy most likely to be cost-effective.Conclusion: As recently proposed willingness-to-pay thresholds for the United States health marketplace range from $110,000 to $300,000 per QALY, cannabis appears cost-effective when augmenting second-line treatment for painful neuropathy. Further research is warranted to explore the long-term benefit of smoked cannabis and standardization of its dosing for chronic neuropathic pain.