Conventional Cost-effectiveness Research Articles

Lifetime Health and Economic Outcomes of Biparametric Magnetic Resonance Imaging as First-Line Screening for Prostate Cancer : A Decision Model Analysis.

Contemporary prostate cancer (PCa) screening uses first-line prostate-specific antigen (PSA) testing, possibly followed by multiparametric magnetic resonance imaging (mpMRI) for men with elevated PSA levels. First-line biparametric MRI (bpMRI) screening has been proposed as an alternative. To evaluate the comparative effectiveness and cost-effectiveness of first-line bpMRI versus PSA-based screening. Decision analysis using a microsimulation model. Surveillance, Epidemiology, and End Results database; randomized trials. U.S. men aged 55 years with no prior screening or PCa diagnosis. Lifetime. U.S. health care system. Biennial screening to age 69 years using first-line PSA testing (test-positive threshold, 4 µg/L) with or without second-line mpMRI or first-line bpMRI (test-positive threshold, PI-RADS [Prostate Imaging Reporting and Data System] 3 to 5 or 4 to 5), followed by biopsy guided by MRI or MRI plus transrectal ultrasonography. Screening tests, biopsies, diagnoses, overdiagnoses, treatments, PCa deaths, quality-adjusted and unadjusted life-years saved, and costs. For 1000 men, first-line bpMRI versus first-line PSA testing prevented 2 to 3 PCa deaths and added 10 to 30 life-years (4 to 11 days per person) but increased the number of biopsies by 1506 to 4174 and the number of overdiagnoses by 38 to 124 depending on the biopsy imaging scheme. At conventional cost-effectiveness thresholds, first-line PSA testing with mpMRI followed by either biopsy approach for PI-RADS 4 to 5 produced the greatest net monetary benefits. First-line PSA testing remained more cost-effective even if bpMRI was free, all men with low-risk PCa underwent surveillance, or screening was quadrennial. Performance of first-line bpMRI was based on second-line mpMRI data. Decision analysis suggests that comparative effectiveness and cost-effectiveness of PCa screening are driven by false-positive results and overdiagnoses, favoring first-line PSA testing with mpMRI over first-line bpMRI. National Cancer Institute.

An electromechanically driven dielectric elastomer based tunable reflector

Deformable optics offer numerous advantages over conventional optical assemblies, including compactness, cost-effectiveness, efficiency, and flexibility. This study focuses on a reflector based on dielectric elastomer actuators (DEAs) with an internal fluid (air) coupling. DEAs are a class of electroactive materials adept at accommodating substantial actuation strains and rapid responses. Fluid distributed between the active and passive parts remains entirely enclosed by the device and transmits actuation pneumatically. Dynamic maneuvers conducted through a series of controlled electrical signals demonstrate proper control over optical characteristics. However, DEs exhibit inherent flaws in dynamic actuation, referred to as instabilities, which are mitigated by applying an initial pre-stretch. The study identifies optimal parameters that confer stability to the reflector: minimum to no creep, zero residual vibrations, and low viscous losses. An analytical framework is developed to assess device performance, focusing on the spherical curvature assumption that closely resembles the behavior of tunable spherical reflectors. Additionally, an optical bench setup is employed to demonstrate the relationship between focal length and applied pressure. Notably, this paper underscores the potential of a DE-based variable focal length reflector to function effectively within a dynamic environment.

Green Synthesis and Antibiofilm Activity of Silver Nanoparticles by Camellia sinensis L. (White Tea Leaf)

Biosynthesis of nanoparticles refers to the production or synthesis of nanoparticles using organisms, such as bacteria, fungi, plants or their byproducts. This approach offers several advantages over conventional chemical methods, including eco-friendliness, cost-effectiveness, and potential for large-scale production. The silver nanoparticles (AgNPs) synthesized using aqueous Camellia sinensis L. (white tea leaf) extracts as reducing and stabilizing agents were reported and evaluated for antibiofilm activity against test microorganisms (Acinetobacter baumanii ATCC 19606 NRRLB 3704, Pseudomonas aeruginosa ATCC 27853 (Gram –), and Bacillus subtilis ATCC 6633, Staphylococcus haemolyticus ATCC 43252 (Gram +), and Candida albicans ATCC 10231) in the study. The synthesized AgNPs were observed and characterized using Uv-Vis spectroscopic analysis, scanning electron and transmission electron microscopy energy-dispersive spectra and Fourier transform infrared spectroscopy. The synthesized AgNP was also screened for antibiofilm activity against test microorganisms. Our results show that the synthesized AgNPs have the potential to be used for antibiofilm materials and different biomedical applications.

RNA-Based Vaccines and Therapeutics Against Intracellular Pathogens.

RNA-based vaccines have sparked a paradigm shift in the treatment and prevention of diseases by nucleic acid medicines. There has been a notable surge in the development of nucleic acid therapeutics and vaccines following the global approval of the two messenger RNA-based COVID-19 vaccines. This growth is fueled by the exploration of numerous RNA products in preclinical stages, offering several advantages over conventional methods, i.e., safety, efficacy, scalability, and cost-effectiveness. In this chapter, we provide an overview of various types of RNA and their mechanisms of action for stimulating immune responses and inducing therapeutic effects. Furthermore, this chapter delves into the varying delivery systems, particularly emphasizing the use of nanoparticles to deliver RNA. The choice of delivery system is an intricate process involved in developing nucleic acid medicines that significantly enhances their stability, biocompatibility, and site-specificity. Additionally, this chapter sheds light on the current landscape of clinical trials of RNA therapeutics and vaccines against intracellular pathogens.

Generalized cost-effectiveness analysis to assess treatment value in hepatitis C.

To estimate the comprehensive value of direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) compared with peginterferon alfa and ribavirin (PEG/riba) employing a generalized cost-effectiveness analysis (GCEA). To assess the societal-level cost-effectiveness of DAA treatment for HCV, we extended a previously published discrete-time Markov simulation model of HCV transmission and progression to include market dynamics and broader elements of value. We followed a stepwise process to add novel value elements to a traditional CEA model for HCV treatments. For each additional element of value, we estimated incremental cost-effectiveness ratios (ICERs) of DAAs compared with PEG/riba. The health technology assessment (HTA)-style model yielded an ICER value of $64,512 per quality-adjusted life-year (QALY). Adding transmission dynamics resulted in an ICER value of $52,971 per QALY, whereas accounting for transmission dynamics and dynamic price and efficacy further decreased ICER values by 90% to $6406 per QALY. Incorporating genericization, productivity loss, caregiver spillover, and differential valuations of LYs vs quality of life, disease severity, and insurance value further decreased the ICER value to $4487 per QALY, a 93% reduction from the baseline HTA-style CEA to the fully realized GCEA. Our GCEA study results confirm that DAAs are a cost-effective treatment for HCV compared with PEG/riba even when using conventional cost-effectiveness approaches. Incorporating broader elements of value resulted in more than a 10-fold improvement in cost-effectiveness, emphasizing the substantive impact of a generalized approach and the importance of incorporating GCEAs into decision-making.

Equitable Care for Severe Hemophilia_A: Distributional Cost-Effectiveness of Prophylactic Weekly Efanesoctocog Alfa Versus Standard-Care Factor VIII in Patients with Severe Hemophilia_A in the United States

Introduction: Prophylactic coagulation factor replacement is crucial to decrease bleeding episodes and improve quality-adjusted life expectancy (QALE) for patients with severe hemophilia A. Even with prophylactic treatment (i.e., at three to four times weekly) patients remain at risk of bleeding events and still develop chronic arthropathy across their lifetimes. The additional economic burden associated with lifelong prophylactic treatment is a major equity concern for patients with hemophilia A and their families. Efanesoctocog alfa is a recently developed extended half-life agent for hemophilia A prophylaxis and management, supporting the possibility of once-weekly prophylaxis. An open-label multicenter study (XTEND-1) showed that once-weekly dosing of efanesoctocog alfa improves the annualized bleeding rate (ABR) by 77% versus prophylaxis with standard-care factor VIII in patients with severe hemophilia A. We sought to evaluate, both for the first time, the conventional and distributional cost-effectiveness of prophylaxis with efanesoctocog alfa versus with standard-care factor VIII for patients with severe hemophilia A in the United States. Methods: For this independent analysis free of industry influence, we built a Markov model to examine the conventional cost-effectiveness of prophylaxis with efanesoctocog alfa versus standard-care factor VIII for patients with severe hemophilia A. Transition probabilities for ABRs and product utilization were informed by phase 3 study data and supplemented with FDA package insert information. Within ABRs, we accounted for treated bleeding severity and bleeding event types, inclusive of hemarthrosis, intracranial hemorrhage, in addition to assuming the prevalence of chronic arthropathy with SHL (i.e., due to silent bleed burden) is eliminated by efanesoctocog alfa. Costs for the base-case were sourced from the Centers for Medicare & Medicaid Services with negotiated (i.e., lower) cost of efanesoctocog alfa supplied from the Veterans Affairs Federal Supply Schedule Service (VA-FSS). Age-, sex- and disease-specific background mortality were employed. Utilities for severe hemophilia A and disutilities for bleed events and hospitalizations were informed by extensive literature specific to severe hemophilia A. The primary outcome was the incremental cost-effectiveness ratio (ICER) in USD/QALY, at a willingness-to-pay threshold of $150,000/quality-adjusted life-year (QALY). The secondary outcome was a threshold analysis for the maximum efanesoctocog alfa price that renders efanesoctocog alfa prophylaxis cost-effective. To account for health inequities in the care of patients with hemophilia A we then conducted a distributional cost-effectiveness analysis (DCEA) to derive an equity weight threshold (i.e., inequality aversion parameter) for the decision of prophylaxis with efanesoctocog alfa versus with standard-care factor VIII. This threshold was then compared to prior estimates for commonly used equity weights in the United States (range 0.5-3.0). Results: In the base-case, prophylaxis with efanesoctocog alfa versus with standard-care factor VIII accrued 19.4 and 15.4 QALYs at mean costs of $17.3 and $9.7 million. The ICER for efanesoctocog alfa was $1,890,000/QALY (95% credible interval 1,190,000-3,330,000). Threshold analysis showed that prophylaxis with efanesoctocog alfa became cost-effective when the price of efanesoctocog alfa decreased by at least 59%. In deterministic sensitivity analysis, the model was most sensitive to the costs of efanesoctocog alfa and factor VIII. In probabilistic sensitivity analysis, standard-care factor VIII was favored over efanesoctocog alfa in 100% of 10,000 Monte Carlo simulations. The equity weight threshold for the treatment decision of prophylaxis with efanesoctocotog alfa versus with standard-care factor VIII was 7.4, higher than commonly used equity weights in the US. This implies a threshold that is higher than what has previously been used in the United States, per DCEA standards. Conclusion: As compared to standard-care factor VIII and at VA-FSS pricing, efanesoctocog alfa prophylaxis is conventionally cost-ineffective for patients with severe hemophilia A. Prophylaxis with efanesoctocog alfa does not meet commonly used distributive equity standards in the United States at this time.

Allotransplantation and Gene Therapy Equity for Children with Sickle Cell Disease: Distributional Cost-Effectiveness of Allotransplantation Vs Gene Therapy Vs Standard-of-Care in Pediatric Patients with Sickle Cell Disease in the United States

Introduction: Patients with sickle cell disease (SCD) have reduced quality-adjusted life expectancy due to substantial mortality risks and decreased quality-of-life for every year lived with the disease. Allotransplantation was the first treatment with curative potential, but it carries concomitant risks of transplant-related mortality and graft-versus-host disease (GVHD). Once approved, gene therapy would be the second treatment with the possibility of lifelong cure but unlike allotransplantation, it may do so without the concomitant risks. Prior research has shown that even if gene therapy is conventionally cost-ineffective versus the standard-of-care (SOC), it can be a justifiable treatment option for a historically marginalized patient population in the United States, as demonstrated by equity-weighted cost-effectiveness. For allotransplantation and gene therapy, neither conventional nor distributional (i.e., equity-weighted) cost-effectiveness is known. Accordingly, we conducted the first conventional and distributional cost-effectiveness analyses of allotransplantation therapy for pediatric patients with SCD in the United States. Methods: We built a Markov model of pediatric patients with sickle cell disease to examine the cost-effectiveness of allotransplantation vs gene therapy vs SOC and determine equity weight thresholds. Sex-, age-, and disease-severity-specific annual costs and transition probabilities across disease severities for SOC were informed by 11 years of data from US commercially insured patients with SCD (2007-2017; Optum). Disease severity was defined based on annual number of hospitalizations for vaso-occlusive crises, as defined in clinical trials. SOC included hydroxyurea, opioid therapy, antibiotics, vaccinations, and blood transfusions. Allotransplantation- and GVHD-specific transition probabilities and costs were informed by prior literature and health resource utilization data, originally reported from the Center for International Blood and Marrow Transplant Research and the Pediatric Health Information System. Quality-adjusted life-years (QALYs) were informed by published lifetime simulations of patients living with SCD and matched controls, derived initially from a polynomial fit linking Euroqual-5 Dimensions to the visual analog scale for pain in patients with SCD in several studies. Age-, sex- and disease-specific background mortality probabilities were employed. Conventional cost-effectiveness was quantified using an incremental cost-effectiveness ratio (ICER), at a willingness-to-pay threshold of $100,000/QALY. Given expert clinical experience with optimizing allotransplantation outcomes in SCD, we employed a maximum patient starting age of 12 and assumed that gene therapy cost $2.45 million and was 100% effective. To account for health inequities in SCD, we then conducted a distributional cost-effectiveness analysis (DCEA), which applies an inequality aversion parameter (i.e., how much weight one puts on reducing disparities), to the distribution of outcomes across relevant sub-groups for allotransplantation to be favored over SOC and justify funding per DCEA standards. These were compared to prior estimates for commonly used equity weights in the United States (range 0.5-3.0). Results: In the base-case, allotransplantation, gene therapy, and SOC accrued 22.1, 25.5, 15.7 discounted lifetime QALYs at costs of $1.9, $2.8, $1.0 million, respectively, with all therapies on the cost-effectiveness frontier (Table 1). The ICERs and equity weight thresholds were $138,000/QALY and 0.5, and $253,000/QALY and 4.5, for allotransplantation (vs SOC) and gene therapy (vs allotransplantation), respectively. Conclusion: Similar to findings for gene therapy versus SOC in the first published DCEA in sickle cell disease, allotransplantation also appears to be an equitable therapeutic option for pediatric patients with sickle cell disease, regardless of conventional cost-ineffectiveness and as compared to SOC. The consideration of patient-population-specific equity offers an important opportunity to derive transparent benchmarks for intertwined equity- and value-informed decision making. Quantitative consideration of equity in the context of conventional cost-ineffectiveness can be an important tipping point in justification of funding.

Multistakeholder Perceptions of Additional Value Elements for United States Value Assessment of Health Interventions

ObjectivesLimitations in conventional cost-effectiveness methods have led to calls for incorporation of additional value elements in assessments of health technologies. However, gaps remain in how additional value elements may inform decision making. This study aimed to prioritize additional value elements from the perspective of healthy individuals without a specific condition or indicated for a specific treatment in the United States among a multistakeholder panel and compare the importance of perspective-specific value elements. MethodsAdditional value elements were prioritized in 2 phases: (1) we identified and categorized additional value elements in a targeted literature review, and (2) we convened a multistakeholder group-based preference elicitation study (N = 28) to evaluate the description of each value element and rank and generate normalized weights of each value element for its significance in value assessment. The importance of additional value elements was also weighted relative to patient-centric value elements. ResultsThe rank and weight of contextual value elements among 28 stakeholders were “severity of the disease” (26.2%), “disadvantaged and vulnerable target populations highly represented” (21.8%), “broader economic impact” (17.3%), “risk protection” (13.8%), “rarity of the disease” (11.3%), and “novel mechanism of action” (9.7%). Relative weight of the additional value elements versus patient-centric value elements was 52% and 48%, respectively. ConclusionsStudy findings may inform priority setting for value frameworks and emerging US government assessments. The group-based elicitation method is repeatable and useful for structured deliberative processes in value assessment and may help improve the consistency and predictability of what is important to stakeholders.

Role of White Rot Fungi in Industrial Wastewater Treatment: A Review

White Rot Fungi (WRF) are a class of microorganisms widely understood for their ability to breakdown an extensive range of pollutants generally found in industrial wastewater. This specific literature review centers on the abilities of the White Rot Fungi to treat industrial wastewater, analysis of the biodegradation mechanism, future applications, and scaling up for practical implementation. WRF usually carry out the degradation process with ligninolytic enzyme by targeting complex industrial pollutants, such as aromatic hydrocarbons, dyes, pharmaceuticals, and products of personal care. The unique enzymatic system of WRF converts the complex and harmful industrial pollutants into harmless end and byproducts, thus minimizing the impact on the environment and ecosystem. This review paper also discusses the potential applications of WRF, such as bioremediation, biosorption, and co-culturing with bacteria to enhance the pollutants removal efficiency of already functional wastewater treatment plants. However, there are still challenges in scaling up WRF-based treatment facilities due to factors such as the optimization of conditions and processes of already functional conventional wastewater treatment plants, cost effectiveness, and design modifications of treatment facilities. Conclusively, WRF fungi can play an important role in degrading complex organic and inorganic pollutants specifically, which are not usually treated by conventional wastewater treatment plants.

Distributional Cost-Effectiveness of Equity-Enhancing Gene Therapy in Sickle Cell Disease in the United States.

Gene therapy is a potential cure for sickle cell disease (SCD). Conventional cost-effectiveness analysis (CEA) does not capture the effects of treatments on disparities in SCD, but distributional CEA (DCEA) uses equity weights to incorporate these considerations. To compare gene therapy versus standard of care (SOC) in patients with SCD by using conventional CEA and DCEA. Markov model. Claims data and other published sources. Birth cohort of patients with SCD. Lifetime. U.S. health system. Gene therapy at age 12 years versus SOC. Incremental cost-effectiveness ratio (ICER) (in dollars per quality-adjusted life-years [QALYs] gained) and threshold inequality aversion parameter (equity weight). Gene therapy versus SOC for females yielded 25.5 versus 15.7 (males: 24.4 vs. 15.5) discounted lifetime QALYs at costs of $2.8 million and $1.0 million (males: $2.8 million and $1.2 million), respectively, with an ICER of $176 000 per QALY (full SCD population). The inequality aversion parameter would need to be 0.90 for the full SCD population for gene therapy to be preferred per DCEA standards. SOC was favored in 100.0% (females) and 87.1% (males) of 10 000 probabilistic iterations at a willingness-to-pay threshold of $100 000 per QALY. Gene therapy would need to cost less than $1.79 million to meet conventional CEA standards. Benchmark equity weights (as opposed to SCD-specific weights) were used to interpret DCEA results. Gene therapy is cost-ineffective per conventional CEA standards but can be an equitable therapeutic strategy for persons living with SCD in the United States per DCEA standards. Yale Bernard G. Forget Scholars Program and Bunker Endowment.

EE449 Use of Novel and Social Elements of Value in Cost-Effectiveness Analyses

In 2018, an ISPOR Special Task Force argued that conventional cost-effectiveness analyses (CEAs) often fail to account for a full range of considerations pertinent to an intervention’s benefits and costs. The panel published a “value flower”, with each petal representing either a conventional or so-called “novel” value element. We sought to characterize the inclusion of novel and social value elements in CEAs.

PD27-04 AURORA A 3D MODEL GUIDED NERVE SPARING TECHNIQUE IN ROBOTIC RADICAL PROSTATECTOMY

You have accessJournal of UrologyCME1 Apr 2023PD27-04 AURORA A 3D MODEL GUIDED NERVE SPARING TECHNIQUE IN ROBOTIC RADICAL PROSTATECTOMY Christian Engesser, Brantner Philip, Julian Gehweiler, Matthias Walter, Christian Wetterauer, Helge Seifert, Svetozar Subotic, Cyrill Rentsch, Lukas Bubendorf, Tatjana Vlajnic, Abolfazl Hosseini, and Jan Ebbing Christian EngesserChristian Engesser More articles by this author , Brantner PhilipBrantner Philip More articles by this author , Julian GehweilerJulian Gehweiler More articles by this author , Matthias WalterMatthias Walter More articles by this author , Christian WetterauerChristian Wetterauer More articles by this author , Helge SeifertHelge Seifert More articles by this author , Svetozar SuboticSvetozar Subotic More articles by this author , Cyrill RentschCyrill Rentsch More articles by this author , Lukas BubendorfLukas Bubendorf More articles by this author , Tatjana VlajnicTatjana Vlajnic More articles by this author , Abolfazl HosseiniAbolfazl Hosseini More articles by this author , and Jan EbbingJan Ebbing More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003305.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Nerve-sparing (NS) procedures in radical prostatectomy have gained importance as they show better functional outcomes in terms of erectile function. It is recommended that the neurovascular bundle (NVB) should be removed if residual tumor is suspected. Alternatively, intraoperative fresh frozen section (FFS) may help in this decision. However, standard FFS techniques do not provide a direct visual impression of the positive surgical margin (PSM) for guidance regarding secondary resection (SR) at the GNB. We therefore intend to optimize precision for SR using a personalized 3D printed prostate model in robotic-assisted radical prostatectomy (RARP). METHODS: We prospectively included 100 patients in which NS-RARP was performed between September 2018 and August 2021 at the University Hospital Basel and Cantonal Hospital Basel-Land. Image data of the preoperative pelvic MRI scan were used to render and print a personalized 3D prostate model. PIRADS lesions (>grade 3) and potential capsular involvement were color-characterized in the model. The model was used during surgery to allow the pathologist to mark a positive surgical margin (PSM) on the model and to help guide the surgeon for selective SR (SSR). Functional outcome was assessed using IIEF-5 prior and one year after surgery. RESULTS: 17.0% (17/100) of all patients had PSM in final histology with a rate of 15.4% in pT2 and 25% in pT3 tumors, respectively. PSM was identified during FFS in 23.0% (23/100) of patients, and SSR achieved a tumor-free surgical margin on final histology in 19 of these 23 patients (82.6%), with SSR containing tumor tissue in 9 of 23 patients (39.1%). Intraoperative PSM was associated with a PIRADS lesion in 11 patients (48%). PSA was undetectable 6 weeks postoperatively in 18/19 (94.7%) patients with successful SSR but only in 76.5 % of patients with PSM in final pathology. False negative rate of FFS was 16.9% (13/77). Despite 6/8 (75%) patients with biochemical recurrence (BCR) having a PSM successfully converted, only 1 had imageproven local recurrence in PSMA PET CT. CONCLUSIONS: 3D printed prostate models are a promising approach to precision SSR and improve communication between surgeons and pathologists. Successful conversion rates (82.6%) were similar to procedures using NEUROSafe (86%). The sensitivity of MRI, the false-negative rate of conventional FFS and cost effectiveness remain critical limitations. Source of Funding: Intuitive Surgical © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e742 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christian Engesser More articles by this author Brantner Philip More articles by this author Julian Gehweiler More articles by this author Matthias Walter More articles by this author Christian Wetterauer More articles by this author Helge Seifert More articles by this author Svetozar Subotic More articles by this author Cyrill Rentsch More articles by this author Lukas Bubendorf More articles by this author Tatjana Vlajnic More articles by this author Abolfazl Hosseini More articles by this author Jan Ebbing More articles by this author Expand All Advertisement PDF downloadLoading ...

Estimating the value of sodium-glucose cotransporter-2 inhibitors within the context of contemporary guidelines and the totality of evidence.

To comprehensively estimate the cost-effectiveness of sodium glucose cotransporter-2 (SGLT2) inhibitor usage in the management of type 2 diabetes mellitus (T2DM) at established clinical review points, incorporating the totality of proven health benefits. This study considered the cardio- and reno-protective effects of SGLT2 inhibitors using the Cardiff type 2 diabetes model. Conventional cost-effectiveness evaluations were undertaken for eligible populations at relevant intensification points reflecting the 2022 guidelines versus the 2015 National Institute of Health and Care Excellence (NICE) guidelines; incremental cost-effectiveness ratio lifetime trajectories and timepoints for complete cost-offset were estimated for each pathway. Treatment effects, utility decrements and costs (applied additively and discounted at 3.5%) were sourced from the published literature. For all subpopulations on treatment pathways reflecting the NG28-2022 guidelines, SGLT2 inhibitor introduction was cost-effective, becoming cost-saving between 2 and 16 years post-initiation. Despite increases in pharmacy costs, predicted lifetime costs were lower than for pathways reflecting the NG28-2015 guidelines, driven by a reduction in heart failure hospitalization and chronic kidney disease costs. Incremental gains in quality-adjusted life years (ranging from 0.58-1.12) resulted in dominance for the updated NG28-2022 guidance in all scenarios. Our results show that SGLT2 inhibitors have the potential to lower healthcare costs while improving health outcomes in eligible patient subpopulations.

The impact of conventional cost-effectiveness analysis on pricing dynamics in the market of new medicines: a proposed countervailing approach

ABSTRACT Background Countries using cost effectiveness ratio as a decision tool for price and reimbursement decisions still witness accelerating price increases. The objective of this paper is to propose a change in the application of the incremental cost effectiveness ratio as a criterion for price policy. Research design We develop a model that sets a price for marginal effectiveness equal to the marginal willingness to pay, but it reimburses average effectiveness according to the size of increased QALY gain. Results This new formula also allows to split the economic value of drug between patients and the industry and creates a reward to invest into QALY gains. We show some empirical data of the new prices derived from the application of the new formula, as well as the implications in terms of the consumer and manufacturer´s surplus based on two potential scenarios of the incentives generated by this new formulation. Discussion We propose that small increases in life expectancy be priced differently from substantial as a way of containing the price dynamics. Conclusions A change in the application of the ICER threshold will help to reduce the price pressure on public budgets.

Does in vitro fertilization (IVF) treatment provide good value for money? A cost-benefit analysis.

Using traditional health technology assessment (HTA) outcome metrics, such as quality-adjusted life-years, to assess fertility treatments raises considerable methodological challenges because the objective of fertility treatments is to create new life rather than extend, save, or improve health-related quality of life. The aim of this study was to develop a novel cost-benefit framework to assess value for money of publicly funded IVF treatment; to determine the number of cost-beneficial treatment cycles for women of different ages; and to perform an incremental cost-benefit analysis from a taxpayer perspective. We developed a Markov model to determine the net monetary benefit (NMB) of IVF treatment by female age and number of cycles performed. IVF treatment outcomes were monetized using taxpayers' willingness-to-pay values derived from a discrete choice experiment (DCE). Using the current funding environment as the comparator, we performed an incremental analysis of only funding cost-beneficial cycles. Similar outputs to cost-effectiveness analyses were generated, including net-benefit acceptability curves and cost-benefit planes. We created an interactive online app to provide a detailed and transparent presentation of the results. The results suggest that at least five publicly funded IVF cycles are cost-beneficial in women aged <42 years. Cost-benefit planes suggest a strong taxpayer preference for restricting funding to cost-beneficial cycles over current funding arrangements in Australia from an economic perspective. The provision of fertility treatment is valued highly by taxpayers. This novel cost-benefit method overcomes several challenges of conventional cost-effectiveness methods and provides an exemplar for incorporating DCE results into HTA. The results offer new evidence to inform discussions about treatment funding arrangements.

Cost effectiveness analyses of pharmacological treatments in heart failure.

In a rapidly growing and aging population, heart failure (HF) has become recognised as a public health concern that imposes high economic and societal costs worldwide. HF management stems from the use of highly cost-effective angiotensin converting enzyme inhibitors (ACEi) and β-blockers to the use of newer drugs such as sodium-glucose cotransporter-2 inhibitors (SGLT2i), ivabradine, and vericiguat. Modelling studies of pharmacological treatments that report on cost effectiveness in HF is important in order to guide clinical decision making. Multiple cost-effectiveness analysis of dapagliflozin for heart failure with reduced ejection fraction (HFrEF) suggests that it is not only cost-effective and has the potential to improve long-term clinical outcomes, but is also likely to meet conventional cost-effectiveness thresholds in many countries. Similar promising results have also been shown for vericiguat while a cost effectiveness analysis (CEA) of empagliflozin has shown cost effectiveness in HF patients with Type 2 diabetes. Despite the recent FDA approval of dapagliflozin and empagliflozin in HF, it might take time for these SGLT2i to be widely used in real-world practice. A recent economic evaluation of vericiguat found it to be cost effective at a higher cost per QALY threshold than SGLT2i. However, there is a lack of clinical or real-world data regarding whether vericiguat would be prescribed on top of newer treatments or in lieu of them. Sacubitril/valsartan has been commonly compared to enalapril in cost effectiveness analysis and has been found to be similar to that of SGLT2i but was not considered a cost-effective treatment for heart failure with reduced ejection fraction in Thailand and Singapore with the current economic evaluation evidences. In order for more precise analysis on cost effectiveness analysis, it is necessary to take into account the income level of various countries as it is certainly easier to allocate more financial resources for the intervention, with greater effectiveness, in high- and middle-income countries than in low-income countries. This review aims to evaluate evidence and cost effectiveness studies in more recent HF drugs i.e., SGLT2i, ARNi, ivabradine, vericiguat and omecamtiv, and gaps in current literature on pharmacoeconomic studies in HF.

EE462 Value-Based Pricing for Patent-Protected Medicines: Pricing Anomalies in the "Age of Cures” and Their Implications for Dynamic Efficiency

The application of a conventional cost-effectiveness analysis (C-CEA) for the value-based pricing of new medicines has largely ignored the implications of a fixed patent life or data exclusivity period. We believe that this creates several anomalies: 1) C-CEA will produce a different result than an actual CEA that considers generic or biosimilar entry; 2) the pricing of long-term treatments for chronic conditions and “repeated-dose cures” in a free and flexible pricing environment is likely to result in predictable price increases at the end of the exclusivity period that will upset patients and the public; and 3) “one-time administration cures” have the potential to capture a greater share of the consumer surplus over the product lifetime, which may be efficient per se, but also may inadvertently disadvantage the development of valuable long-term therapies for chronic conditions or repeated-dose cures. Emergence of the Institute for Clinical and Economic Review, which is arguably a form of “privately supplied regulation” of US drug prices and relies on C-CEA, may be producing inadvertent anomalies that distort prices and research and development (R&D) incentives. A demand exists for long-term solutions to these issues that would promote dynamically efficient global R&D. More work is needed on 1) the relationship between surplus reward and the amount and composition of global R&D, because we may be as likely to be encouraging excessive R&D in some areas and undersupplying it in others, and 2) the size of the surplus reward to R&D cost and to return on investment.

Evaluating Discrete Choice Experiment Willingness to Pay [DCE-WTP] analysis, and Relative Social Willingness to Pay [RS-WTP] analysis in a Health Technology Assessment of a treatment for an ultra-rare childhood disease [CLN2

Background : Conventional cost-effectiveness analysis [CEA] using cost per QALY thresholds may counteract other incentives introduced to foster development of treatments for rare and ultra-rare diseases. Therefore, alternative economic evaluation methods were explored, namely Discrete Choice Experiment Willingness to Pay (DCE-WTP) and Relative Social Willingness to Pay (RS-WTP), to value interventions for an ultra-rare childhood disease, Neuronal Ceroid Lipofuscinosis type 2 (CLN2). Research Design and Methods Treatment for CLN2 was valued from a citizen’s (“social”) perspective using DCE-WTP and RS-WTP in a survey of 4,009 United Kingdom [UK] adults. Three attributes (initial quality of life, treatment effect, and life expectancy) were used in both analyses. For DCE-WTP a cost attribute (marginal income tax increase) was also included. Optimal econometric models were identified. Results DCE-WTP indicated that UK adults are willing to pay incremental increases through taxation for improvements in CLN2 attributes. RS-WTP identified a willingness to allocate >40% of a pre-assigned healthcare budget to prevent child mortality and approximately 15% for improved health status. Conclusions Both techniques illustrated substantive social WTP for CLN2 interventions, despite the small number of children benefitting. This highlights a gap between UK citizens’ willingness to spend on rare disease interventions and current funding policies.

The History and Future of the “ISPOR Value Flower”: Addressing Limitations of Conventional Cost-Effectiveness Analysis

ObjectivesSince its publication as part of the 2018 ISPOR Special Task Force (STF) on US Value Assessments, the “ISPOR value flower,” with its petals highlighting elements that may be overlooked or underappreciated in conventional drug value assessments, has been discussed and debated. We review the history of the value flower, describe recent developments, and consider implications for future value assessments. MethodsWe discuss various antecedents to the value flower, as well as conceptual and empirical articles published in the past 4 years. ResultsSince the publication of the ISPOR STF report, researchers have provided more rigorous theoretical and mathematical foundations for certain novel value elements (eg, severity of illness, value of insurance, value of hope) through “generalized risk-adjusted cost-effectiveness analysis,” which incorporates risk aversion in people’s preferences and uncertainty in treatment outcomes. Empirical estimates are also emerging to support key elements, such as insurance value, real option value, value of hope, and value of knowing. Although health technology assessment bodies have applied or are considering certain elements (eg, severity modifiers to cost-effectiveness thresholds), other elements have yet to gain traction. ConclusionsFive years after the STF began its work, the development of novel value measures continues to evolve. Although it is encouraging to see supporting empirical studies emerging, more are needed. Additional efforts are also needed to illustrate how the estimates can be used in the deliberative processes that are integral to health technology assessments.

Confocal laser endomicroscopy in gastro-intestinal endoscopy: technical aspects and clinical applications.

Confocal laser endomicroscopy (CLE) is an advanced endoscopic imaging technology that provides a magnified, cellular level view of gastrointestinal epithelia. In conjunction with topical or intravenous fluorescent dyes, CLE allows for an "optical biopsy" for real-time diagnosis. Two different CLE system have been used in clinical endoscopy, probe-based CLE (pCLE) and endoscope-based CLE (eCLE). Using pCLE, the device can be delivered: (I) into the luminal gastrointestinal tract through the working channel of standard endoscopes; (II) into extraluminal cystic and solid parenchymal lesions through an endoscopic ultrasound (EUS) needle; or (III) into the biliary system through an endoscopic retrograde cholangiopancreatography (ERCP) accessory channel. With eCLE, the probe is directly integrated into the tip of a conventional endoscope, however, these endoscopes are no longer commercially available. CLE has moderate to high diagnostic accuracy for neoplastic and inflammatory conditions through the gastrointestinal tract including: oesophageal, gastric and colonic neoplasia, pancreatic cysts and solid lesions, malignant pancreatobiliary strictures and inflammatory bowel disease. Some studies have demonstrated the diagnostic benefit of CLE imaging when combined with either conventional white light endoscopy or advanced imaging technologies. Therefore, optical biopsies using CLE can resolve diagnostic dilemmas in some cases where conventional imaging fails to achieve conclusive results. CLE could also reduce the requirement for extensive tissue sampling during surveillance procedures. In the future, CLE in combination with molecular probes, could allow for the molecular characterization of diseases and assess response to targeted therapy. However, the narrow field of view, high capital costs and specialized operator training requirements remain the main limitations. Future multi-center, randomized trials with a focus on conventional diagnostic applications, cost-effectiveness and standardized training will be required for definitive evidence. The objective of this review is to evaluate the technical aspects and current applications of CLE in patients with gastrointestinal and pancreatobiliary diseases and discuss future directions for this technique.