Health State Transition Research Articles

An Adaptive Modeling Framework for Bearing Failure Prediction

Rolling element bearings are a common component in rotating equipment, a class of machines that is essential in a wide range of industries. Detecting and predicting bearing failures is then vital for reducing maintenance and production costs due to unplanned downtime. In previous literature, significant efforts have been devoted to building data-driven health models from historical bearing data. However, a common limitation is that these methods are typically tailored to specific failure instances and have limited ability to model bearing failures between repairs in the same system. In this paper, we propose a multi-state health model to predict bearing failures before they occur. The model employs a regression-based method to detect health state transition points and applies an exponential random coefficient model with a Bayesian updating process to estimate time-to-failure distributions. A model training framework is also introduced to make our proposed model applicable to more bearing instances in the same system setting. The proposed method has been tested on a publicly available bearing prognostics dataset. Case study results show that the proposed method provides accurate failure predictions across several system failures, and that the training approach can significantly reduce the time necessary to generate an effective, generalized model.

Quality of life and cost consequence of delays in endovascular treatment for acute ischemic stroke in China

BackgroundAlthough endovascular therapy (EVT) improves clinical outcomes in patients with acute ischemic stroke, the time of EVT initiation significantly influences clinical outcomes and healthcare costs. This study evaluated the impact of EVT treatment delay on cost-effectiveness in China.MethodsA model combining a short-term decision tree and long-term Markov health state transition matrix was constructed. For each time window of symptom onset to EVT, the probability of receiving EVT or non-EVT treatment was varied, thereby varying clinical outcomes and healthcare costs. Clinical outcomes and cost data were derived from clinical trials and literature. Incremental cost-effectiveness ratio and incremental net monetary benefits were simulated. Deterministic and probabilistic sensitivity analyses were performed to assess the robustness of the model. The willingness-to-pay threshold per quality-adjusted life-year (QALY) was set to ¥71,000 ($10,281).ResultsEVT performed between 61 and 120 min after the stroke onset was most cost-effective comparing to other time windows to perform EVT among AIS patients in China, with an ICER of ¥16,409/QALY ($2376) for performing EVT at 61–120 min versus the time window of 301–360 min. Each hour delay in EVT resulted in an average loss of 0.45 QALYs and 165.02 healthy days, with an average net monetary loss of ¥15,105 ($2187).ConclusionsEarlier treatment of acute ischemic stroke patients with EVT in China increases lifetime QALYs and the economic value of care without any net increase in lifetime costs. Thus, healthcare policies should aim to improve efficiency of pre-hospital and in-hospital workflow processes to reduce the onset-to-puncture duration in China.

A Novel Health Prognosis Method for a Power System Based on a High-Order Hidden Semi-Markov Model

Power system health prognosis is a key process of condition-based maintenance. For the problem of large error in the residual lifetime prognosis of a power system, a novel residual lifetime prognosis model based on a high-order hidden semi-Markov model (HOHSMM) is proposed. First, HOHSMM is developed based on the hidden semi-Markov model (HSMM). An order reduction method and a composite node mechanism of HOHSMM based on permutation are proposed. The health state transition matrix and observation matrix are improved accordingly. The high-order model is transformed into the corresponding first-order model, and more node dependency information is stored in the parameter group to be estimated. Secondly, in order to estimate the parameters and optimize the structure of the proposed model, an intelligent optimization algorithm group is used instead of the expectation–maximization (EM) algorithm. Thus, the simplification of the topology of the high-order model by the intelligent optimization algorithm can be realized. Then, the state duration variables in the high-order model are defined and deduced. The prognosis method based on polynomial fitting is used to predict the residual lifetime of the power system when the prior distribution is unknown. Finally, the intelligent optimization algorithm is used to solve the proposed model, and experiments are performed based on a set of power system data sets to evaluate the performance of the proposed model. Compared with HSMM, the proposed model has better performance on the power system health prognosis problem and can get a relatively good solution in a short computation time.

Microsimulation Model for Evaluating the Cost-Effectiveness of Surveillance in BAP1 Pathogenic Variant Carriers.

Pathogenic BAP1 germline variants cause a tumor-predisposition syndrome (BAP1-TPDS) linked to uveal melanoma, mesothelioma, cutaneous melanoma, and renal cell carcinoma. Surveillance of carriers of pathogenic BAP1 variants provides an opportunity for early tumor detection; however, there are no evidence-based guidelines for management of BAP1-TPDS, nor health economic evaluation; this study aims to provide this evidence. We created a Markov microsimulation health state transition model of BAP1 germline carriers to predict if active surveillance for the four main tumors influences survival and improves associated economic costs with a time horizon of 100 years from the perspective of the healthcare system (N = 10,000). Model inputs were derived from data published by the BAP1 Interest Group Consortium and other studies. Management and healthcare costs were extracted from Australian costing schedules (final figures converted to US dollars [USD]), and outcomes compared for individuals receiving surveillance with those in a nonsurveillance arm. Robustness was evaluated on 10,000 iterations of a 100-sample random sampling of the model output. On average, surveillance of BAP1 carriers increased survival by 4.9 years at an additional cost of $6,197 USD for the healthcare system including surveillance costs ($1,265 USD per life year gained). The nonsurveillance arm had more diagnosed late tumors (62.8% v 10.7%) and a higher rate of BAP1-related deaths (50.2% v 35.4%; a 29.5% increase). The model was cost-effective under all sensitivity analyses. Our secondary robustness analysis estimated that 99.86% of 100-sample iterations were cost-effective and 19.67% of these were cost-saving. It is recommended that carriers of BAP1 germline variants are identified and undertake active surveillance, as this model suggests that this could improve survival and be cost-effective for the healthcare system.

OP130 Economic Evaluation Of High-Cost Drugs For Relapsing-Remitting Multiple Sclerosis In Thailand

IntroductionDrugs for relapsing-remitting multiple sclerosis (RRMS) are costly and not included in the National List of Essential Medicines of Thailand yet. This study aims to conduct an economic evaluation of high-cost drugs for RRMS.MethodsThe Markov model was used to estimate lifetime costs and quality-adjusted life years (QALYs) gained. The treatment options include Interferon beta-1a (IFN) and Teriflunomide (TERI) (first-line), Fingolimod (FIN) and Natalizumab (NATA) (second-line), and Alemtuzumab (ALEM) (third-line) compared with usual care. The effectiveness of drugs was retrieved by network meta-analysis. The probability of health state transition was obtained from primary data. Treatment-related costs were derived from the national database. Other costs and utilities were obtained from the study in Thai RRMS patients.ResultsThe lowest lifetime costs option was usual care (THB2 million) (USD65,808), while the highest QALY gained option was IFN-NATA-ALEM (8.6 QALY gained). All treatment options were not cost-effective compared with usual care at the threshold of THB160,000 (USD5,300) per QALY gained. However, the option of IFN-NATA-ALEM yielded the lowest incremental cost-effectiveness ratio (ICER), which was THB4.4 million (USD144,778) per QALY gained.ConclusionsHigh-cost drugs were not cost-effective; nonetheless, the IFN-NATA-ALEM option could increase QALY gained with the lowest additional budget. The government should negotiate the price of IFN to decrease by eighty percent.

Improving Outcomes for Patients with Multiple Myeloma through the Optimization of Treatment Sequences

Introduction: Multiple myeloma (MM) is an incurable disease characterized by the proliferation of malignant plasma cells within the bone marrow, causing a wide range of burdensome symptoms. Patients initiating treatment typically receive a combination of drugs across various classes with or without autologous stem cell transplantation (ASCT). However, patients will invariably relapse following initial treatment, and often require many lines of drug treatment over the course of their disease. Real-word data showed that a significant proportion of newly diagnosed MM patients that receive frontline (FL) treatment did not receive subsequent treatment. These high attrition rates suggest that using the best treatment upfront is crucial in delaying disease progression.The CASSIOPEIA (transplant-eligible [TE] setting), MAIA and ALCYONE (transplant-ineligible [TIE] setting) trials demonstrate that the addition of daratumumab (DARA) to standard of care treatments in FL significantly improves patient outcomes. Based on data from these trials, the European marketing authorization for DARA has been extended to the FL setting. To ensure the best possible long-term patient outcomes in clinical practice, the availability of new FL treatment options requires a redefinition of treatment patterns. Thus, we aim to investigate whether the adoption of DARA as a FL, as opposed to later-line, treatment of MM leads to better outcomes and improved clinical practice.Methods: In the absence of real-world sequencing data, we developed a clinical sequencing simulation using individual patient data from the DARA trials and indirect comparative evidence, across all indications in MM. We used progression-free survival curves to simulate health state transition probabilities across four lines of active treatment, to capture the efficacy of treatment sequences in MM. Patients start with initiation of FL treatment, and ASCT eligibility determines the sequences patients receive. Clinical expert opinion was sought to determine 1) the full range of meaningful treatment sequences and 2) which of these are used most in Italian clinical practice. Based on the clinical simulation outcomes, we calculated average time spent in each line of treatment, percentage of patients alive at different timepoints, and the total survival for patients initiating a sequence. This analysis included conservative attrition rates from trial data, 14% for TE (CASSIOPEIA) and 24% for TIE (MAIA/ALCYONE), assumed as similar across regimens in each setting.Results: In the TE setting, the best outcomes were achieved when using the DARA-based regimen (DVTd) as FL treatment, followed by either a LEN-based regimen (KRd) or a BOR-based regimen (PVd), resulting in a total survival of 14.2 and 14.1 years, respectively. In the TIE setting, the best outcomes were achieved when DRd or DVMP were used as FL treatment, followed by either a BOR-based regimen (PVd, for DRd) or a LEN-based regimen (KRd, for DVMP), resulting in a total survival of 11.7 and 10.9 years, respectively.In both the FL and second line (2L) settings, there was a clear survival benefit of using DARA. When comparing the DARA-based sequence with the current FL TE benchmark sequence (DVTd + KRd + Pd + Vd versus VTd + DRd + Kd + Pd), an additional survival of 1.5 years was observed in TE patients. When DARA was added to the current FL TIE benchmark sequence (DRd + PVd + Kd + Vd versus VMP + DRd + Kd + Pd), TIE patients lived on average 2.8 years longer. For TE patients, time spent progression-free ranged from an average of 4.83 to 7.99 years at FL, 1.42 to 5.40 years in 2L, 0.23 to 2.24 years in 3L and 0.17 to 1.53 years on 4L. For TIE patients, the variation was higher, leaving more room for optimization: 1.97 to 7.31 years at FL, 0.68 to 4.76 years in 2L, 0.17 to 3.25 years in 3L and 0.19 to 0.51 years in 4L.Conclusion: To our knowledge, this is the first sequencing simulation to consider optimal patient outcomes across several lines of MM treatment. The results show that the longest time in remission is achieved with the use of DARA-based regimens as FL treatment, significantly improving patient outcomes.Time spent progression free decreases with each subsequent line of treatment and the magnitude of the effect seen in the third and fourth treatment lines is not as significant as that of the effect seen in earlier treatment lines. Therefore, patients should be treated with the most effective treatment upfront. DisclosuresPetrucci: Celgene: Honoraria, Other: Advisory Board; Janssen-Cilag: Honoraria, Other: Advisory Board; BMS: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; GSK: Honoraria, Other: Advisory Board; Karyopharm: Honoraria, Other: Advisory Board. Mendes: Janssen-Cilag Farmacêutica: Current Employment. Boer: Janssen: Consultancy. Casamassima: Janssen: Current Employment. Willis: Janssen: Consultancy. Wadlund: Janssen: Current Employment. Matthijsse: Janssen: Consultancy. Armeni: Astrazeneca: Consultancy; Boehringer Ingelheim: Consultancy; Novartis: Consultancy; Sanofi: Consultancy; Johnson & Johnson: Consultancy; Amgen: Consultancy; Janssen: Consultancy.

Heterogeneity in Radiotherapeutic Parameter Assumptions in Cost-Effectiveness Analyses in Prostate Cancer: A Call for Uniformity

ObjectivesCost-effectiveness analyses (CEAs) may provide useful data to inform management decisions depending on the robustness of a model’s input parameters. We sought to determine the level of heterogeneity in health state utility values, transition probabilities, and cost estimates across published CEAs assessing primarily radiotherapeutic management strategies in prostate cancer. MethodsWe conducted a systematic review of prostate cancer CEAs indexed in MEDLINE between 2000 and 2018 comparing accepted treatment modalities across all cancer stages. Search terms included “cost effectiveness prostate,” “prostate cancer cost model,” “cost utility prostate,” and “Markov AND prostate AND (cancer OR adenocarcinoma).” Included studies were agreed upon. A Markov model was designed using the parameter estimates from the systematic review to evaluate the effect of estimate heterogeneity on strategy cost acceptability. ResultsOf 199 abstracts identified, 47 publications were reviewed and 37 were included; 508 model estimates were compared. Estimates varied widely across variables, including gastrointestinal toxicity risk (0%-49.5%), utility of metastatic disease (0.25-0.855), intensity-modulated radiotherapy cost ($21 193-$61 996), and recurrence after external-beam radiotherapy (1.5%-59%). Multiple studies assumed that different radiotherapy modalities delivering the same dose yielded varying cancer control rates. When using base estimates for similar parameters from included studies, the designed model resulted in 3 separate acceptability determinations. ConclusionsSignificant heterogeneity exists across parameter estimates used to perform CEAs evaluating treatment for prostate cancer. Heterogeneity across model inputs yields variable conclusions with respect to the favorability and cost-effectiveness of treatment options. Decision makers are cautioned to review estimates in CEAs to ensure they are up to date and relevant to setting and population.

Imputing missing patient-level data and propensity score matching in cost-effectiveness analysis in Crohn's disease

ABSTRACT Objectives The effect of imputing missing data followed by propensity score analysis on the incremental cost-effectiveness ratio (ICER) in a cost-effectiveness analysis is unknown. The objective was to compare alternative approaches in grouping data following imputation and prior to calculating propensity scores for use in economic evaluation. Methods Patient-level data from an observational study of 573 children with Crohn’s disease were used in a microsimulation model to determine the incremental cost of early anti-tumor necrosis factor-α treatment compared to standard care per remission week gained. Multiple imputation of a missing covariate followed by propensity score matching to create comparator groups was approached in two ways. The Within approach calculated propensity scores on each imputed dataset separately, while the Across method averaged propensity scores to create one matched population resulting in multiple sets of health state transition probabilities. Results The incremental cost per remission week gained ranged from CAD$2,236 to CAD$12,464 (mean CAD$4,266) with Within datasets and was CAD$4,679 per remission week gained with the Across dataset. Conclusion Imputation of missing patient-level data and propensity score analysis increases methodological uncertainty in cost-effectiveness analysis. The present study indicated that the Across approach may be less cumbersome, and slightly reduce bias and variance.

PCV15 Cost-Effectiveness of Screening for and Treating Masked Hypertension with out-of-Office Blood Pressure Monitoring

Masked hypertension (office blood pressure [BP] <130/80 mmHg, out-of-office BP ≥130/80 mmHg) increases cardiovascular disease (CVD) event risk nearly two-fold compared to sustained normotension (office BP <130/80 mmHg, out-of-office BP <130/80 mmHg) . We compared the lifetime health and economic outcomes of screening for and treating masked hypertension by adding ambulatory or home BP monitoring (i.e., ABPM or HBPM) to standard care (no screening) from a US healthcare sector perspective. The CVD Policy Model, a microsimulation health state transition model, simulates the annual risk of fatal and non-fatal CVD events, treatment-related adverse events, and non-CVD deaths. We simulated screening of 500,000 US adults aged ≥20 years at risk for masked hypertension (office BP 120-129/<80 mmHg, on no antihypertensive medications, without CVD history). Based on published literature, we assumed ABPM had 100% sensitivity and 100% specificity (gold standard), and HBPM had 91.8% sensitivity and 41.4% specificity. We projected total direct health care costs (2020 USD), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Future costs and QALYs were discounted 3% annually. A threshold of <$150,000/QALY gained defined intermediate cost-effectiveness. Primary analyses were performed using 100 probabilistic simulations. Parameter uncertainty was assessed using one-way sensitivity analyses. Relative to standard care, mean (95%CI) time to first CVD event increased with ABPM 0.232 (0.152-0.326) years and 0.233 (0.149-0.328) years with HBPM masked hypertension screening, but the percent experiencing treatment-related serious adverse events increased 10.9% (9.8%-11.7%) with ABPM and 11.4% (11.1%-11.7%) with HBPM. Compared to standard care, lifetime QALYs increased 0.018 (0.005-0.034) with ABPM and 0.017 (0.003-0.032) with HBPM screening, but neither strategy was cost-effective (ICER: ABPM $433,000/QALY gained, HBPM $428,000/QALY gained). No sensitivity analyses resulted in either ABPM or HBPM becoming cost-effective. Screening for masked hypertension with ABPM or HBPM leads to modest health gains but is not cost-effective compared to standard care.

Cost-effectiveness of a hypothetical cell or gene therapy cure for sickle cell disease

Sickle cell disease (SCD) is a group of inherited genetic conditions associated with lifelong complications and increased healthcare resource utilization. Standard treatment for SCD in the US varies based on stage of the disease and observed clinical severity. In this study, we aim to evaluate the potential cost-effectiveness of a durable cell or gene therapy cure for sickle cell disease from the US healthcare sector perspective. We developed a lifetime Markov model to evaluate the cost-effectiveness of a hypothetical single-administration durable treatment (DT) for SCD provided at birth, relative to standard of care (SOC). We informed model inputs including direct healthcare costs, health state utility weights, transition probabilities, and mortality rates using a retrospective database analysis of commercially insured individuals and the medical literature. Our primary outcome of interest was the incremental cost-effectiveness ratio (ICER) of DT versus SOC evaluated at a base case willingness-to-pay (WTP) threshold of $150,000 per quality-adjusted life year (QALY). We tested the robustness of our base case findings through scenario, deterministic sensitivity (DSA), and probabilistic sensitivity analyses (PSA). In the base case analysis, treatment with DT was cost-effective with an ICER of $140,877/QALY relative to SOC for a hypothetical cohort involving 47% females. Both males (ICER of $135,574/QALY) and females (ICER of $146,511/QALY) were similarly cost-effective to treat. In univariate DSA the base case ICER was most sensitive to the costs of treating males, DT treatment cost, and the discount rate. In PSA, DT was cost-effective in 32.7%, 66.0%, and 92.6% of 10,000 simulations at WTP values of $100,000, $150,000, and $200,000 per QALY, respectively. A scenario analysis showed cost-effectiveness of DT is highly contingent on assumed lifetime durability of the cure. A hypothetical cell or gene therapy cure for SCD is likely to be cost-effective from the US healthcare sector perspective. Large upfront costs of a single administration cure are offset by significant downstream gains in health for patients treated early in life. We find cost-effectiveness outcomes do not vary substantially by gender; however, several model parameters including assumed durability and upfront cost of DT are likely to influence cost-effectiveness findings.

Cost-effectiveness of catheter ablation versus medical therapy for the treatment of atrial fibrillation in the United Kingdom

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): This research study was funded by Biosense Webster, Inc. Dr Leung has received research support from Attune Medical (Chicago, IL) towards a research fellowship at St. George"s University of London. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Background Randomised data on patient-related outcomes comparing catheter ablation to medical therapy for the treatment of atrial fibrillation (AF) have shown the effectiveness of catheter ablation. Ablation versus medical therapy should also be analysed from a health economics perspective to achieve optimal healthcare resource allocation. Purpose To determine the cost effectiveness of catheter ablation compared to medical therapy for the treatment of atrial fibrillation, from the perspective of the UK National Health Service. Methods A patient-level Markov health-state transition model was used to conduct a cost utility analysis comparing catheter ablation and medical therapy for the treatment of AF. A systematic review and meta-analysis of catheter ablation treatment versus medical therapy (rhythm and/or rate control drugs) was conducted to enable comparison of AF recurrence between treatment groups utilising the model. Additional model parameters were established based upon a best-evidence review of the literature. The model simulated care delivered from a secondary care perspective. Total patients simulated in this model over a lifetime were 250,000, with patients entering the model at age 64. Only previously treated AF patients were included, including those with concomitant heart failure. A separate scenario analysis was conducted to determine the cost effectiveness specifically in the cohort of patients with AF and heart failure. Main outcomes measures Incremental cost-effectiveness ratio (ICER) and average total expected costs and quality-of-life years (QALYs) incurred over the lifetime of a patient. AF recurrence, complications and cardiovascular adverse events were compared over the total duration inside the model. Results In the base case analysis, catheter ablation resulted in a favourable ICER of £8,614 per additional QALY gained when compared to medical therapy, well below the national Willingness-to-Pay threshold of £20,000. Catheter ablation was associated with an expected increase of 1.01 QALYs, while adding an additional cost £8,742 over a patient’s lifetime. The cost-effectiveness of catheter ablation was improved in the heart failure sub-group analysis, with an ICER of £6,438. A significantly greater proportion of patients in the medical therapy group failed rhythm control at any stage compared to catheter ablation (72% vs 24%) and at a faster rate (median time to treatment failure: 3.8 vs 10 years). Conclusion Catheter ablation appears to be a highly cost-effective treatment for atrial fibrillation, compared to medical therapy, from the perspective of the UK National Health Service. With low rates of adverse events and superiority in achieving rhythm control, AF ablation services should be prioritised with appropriate allocation of healthcare resources.

Modeling the cost-effectiveness of adjuvant osimertinib in resected EGFR-mutant non-small cell lung cancer patients.

8527 Background: Adjuvant Osimertinib (Osi) was recently approved for resected EGFR-mutant non-small cell lung cancer (NSCLC) based on disease free survival (DFS) benefits from the ADAURA trial. Prior studies of adjuvant EGFR inhibitors yielding DFS benefits have lacked an overall survival (OS) benefit, leading to debate over early clinical implementation given the associated drug costs. This study aims to evaluate the cost-effectiveness (CE) of Osi in this setting. Methods: We constructed Markov models using post-resection health state transitions with digitized DFS data from the ADAURA trial to compare cost and quality-adjusted life years (QALYs) of the use of 3 years of adjuvant Osi versus placebo in the ADAURA patient population of stage IB to IIIA NSCLC patients over a 10-year time horizon. All patients entering the progressive disease (PD) state were assigned for re-treatment with Osi. Cost and utility values were derived from Medicare reimbursement data and literature (Table). A CE threshold of 3 times the GDP per capita was used. Deterministic sensitivity analyses were performed to assess the impact of a range of OS benefit, as the impact of adjuvant Osi on OS has not yet been reported. Results: The incremental cost-effectiveness ratio (ICER) for adjuvant Osi was $317,119.90 per QALY gained. Initial costs of Osi are higher in the first 3 years, but become lower than the placebo group in year 4 onward, with similar costs after year 7. Costs due to PD are higher in the placebo group through the first 6.5 years. Average pre-PD, post-PD, and total costs were $2,388, $379,047, and $502,937, respectively in the placebo group, compared to $505,775, $255,638, and $800,697, respectively in the Osi group. QALYs were higher in the Osi arm throughout. Sensitivity analysis using incremental OS gains reaches the CE threshold of $195,000 between 25-30% OS benefit of Osi over placebo. A 50% discount to the Osi annual cost yielded an ICER of $115,419. Conclusions: 3 years of adjuvant Osi is more cost-effective than placebo if one is willing to pay $317,119 more per QALY gained, with most costs accruing in the first 3 years as drug cost. This strategy became cost-effective with an OS benefit between 25-30% over placebo. Discount to Osi annual costs improves the ICER significantly. True cost-effectiveness of adjuvant Osi will require further study due to immaturity of ADAURA OS data and model limitations.[Table: see text]

Cost-utility analysis of stereotactic body radiotherapy plus cetuximab in previously irradiated recurrent squamous cell carcinoma of the head and neck

ABSTRACT Background This study aimed to estimate the cost-utility of stereotactic body radiotherapy (SBRT) plus cetuximab for patients with previously irradiated recurrent squamous cell carcinoma of the head and neck. Methods We constructed a Markov health-state transition model to simulate costs and clinical outcomes of recurrent squamous cell carcinoma of the head and neck. Model parameters were derived from the published literature and the National Health Insurance Administration reimbursement price list. Incremental cost-effectiveness ratio and the net monetary benefit were calculated from a health payer perspective. The impact of uncertainty was modeled with one-way and probabilistic sensitivity analyses. Results In the base-case, SBRT plus cetuximab compared to SBRT alone resulted in an ICER of NT$ 840,455 per QALY gained. In the one-way sensitivity analysis, the utility of progression-free state for patients treated with SBRT plus cetuximab or SBRT alone and the cost of progression-free survival for SBRT+Cet were the most sensitive parameters in the model. Probabilistic sensitivity analysis showed that the probability of cost-effectiveness at a willingness-to-pay threshold of NT$ 2,252,340 per QALY was 100% for SBRT plus cetuximab but 0% for SBRT alone. Conclusions This study showed that SBRT+Cet was cost-effective and benefited patients with previously irradiated rSCCHN.

Stability of person-specific blood-based infrared molecular fingerprints opens up prospects for health monitoring

Health state transitions are reflected in characteristic changes in the molecular composition of biofluids. Detecting these changes in parallel, across a broad spectrum of molecular species, could contribute to the detection of abnormal physiologies. Fingerprinting of biofluids by infrared vibrational spectroscopy offers that capacity. Whether its potential for health monitoring can indeed be exploited critically depends on how stable infrared molecular fingerprints (IMFs) of individuals prove to be over time. Here we report a proof-of-concept study that addresses this question. Using Fourier-transform infrared spectroscopy, we have fingerprinted blood serum and plasma samples from 31 healthy, non-symptomatic individuals, who were sampled up to 13 times over a period of 7 weeks and again after 6 months. The measurements were performed directly on liquid serum and plasma samples, yielding a time- and cost-effective workflow and a high degree of reproducibility. The resulting IMFs were found to be highly stable over clinically relevant time scales. Single measurements yielded a multiplicity of person-specific spectral markers, allowing individual molecular phenotypes to be detected and followed over time. This previously unknown temporal stability of individual biochemical fingerprints forms the basis for future applications of blood-based infrared spectral fingerprinting as a multiomics-based mode of health monitoring.

Treatment strategies for reflux esophagitis including a potassium-competitive acid blocker: A cost-effectiveness analysis in Japan.

IntroductionGastroesophageal reflux disease is a common condition, and proton pump inhibitors (PPIs) are the mainstays of treatment. However, concerns have been raised about the safety of PPIs. A potassium‐competitive acid blocker (P‐CAB), vonoprazan (VPZ), was recently introduced, which may provide clinical benefits. This study was performed to investigate the cost‐effectiveness of alternative long‐term strategies including continuous and discontinuous treatment with VPZ for the management of reflux esophagitis in Japan.MethodsA health state transition model was developed to capture the long‐term management of reflux esophagitis. Four different strategies were compared: (a) intermittent PPI using lansoprazole (LPZ); (b) intermittent P‐CAB; (c) maintenance PPI using LPZ; and (d) maintenance P‐CAB.ResultsIntermittent P‐CAB was the most cost‐effective, and the number of days for which medication was required with this strategy was fewest. Maintenance PPI was more efficacious, but more costly than intermittent P‐CAB. Maintenance P‐CAB was more efficacious, but more costly than maintenance PPI. Co‐payments were higher for maintenance PPI than for intermittent P‐CAB, and for maintenance P‐CAB than for maintenance PPI, which were considered reasonable for the majority of patients to improve symptoms.ConclusionsIntermittent P‐CAB appears to be the strategy of choice for the majority of reflux esophagitis patients in clinical practice. If a patient is not satisfied with the symptom control of the current strategy, switching to a more effective strategy appears to be a reasonable option for the majority of patients.

A Data-Driven Aero-Engine Degradation Prognostic Strategy.

Degradation prognostics of aero-engine are a well-recognized challenging issue. Data-driven prognostic techniques have been receiving attention because they rely on neither expert knowledge nor mathematic model of the system. But they are highly dependent on the quantity and quality of degradation data. To solve the problems caused by unlabeled, unbalanced condition monitoring (CM) data and uncertainties of the prognostics process, a novel data-driven aero-engine degradation prognostic strategy is proposed in this article. First, two indicators are defined to remove redundant degradation features. Then, the number of discrete states of health is determined by a fuzzy c -means algorithm, and the health state labels can be automatically assigned for health state estimation, where the uncertain initial condition and the uncertainty of health state's transition are fully considered. Finally, a multivariate health estimation model and a multivariate multistep-ahead long-term degradation prediction model are proposed for remaining useful life estimation for aero-engines. Verification results using the aero-engine data from NASA can show that the proposed data-driven degradation prognostic strategy is effective and feasible.

Cost-Effectiveness of Dual Bronchodilator Indacaterol/Glycopyrronium for COPD Treatment in China.

BackgroundIndacaterol/glycopyrronium (IND/GLY) is a once-daily dual bronchodilator for long-term treatment of patients with chronic obstructive pulmonary disease (COPD). The efficacy and safety of IND/GLY have been proved before, but the cost-effectiveness is unknown in China.PurposeThis study assessed cost-effectiveness of IND/GLY comparing with salmeterol/fluticasone (SAL/FLU) and tiotropium.MethodsA patient-level simulation model was established from Chinese payer perspective. Patient parameters were randomly simulated through resampling from parameter distributions based on clinical trials and China-specific cost data to represent individual level health state and health state transitions in the model. We simulated patient-level health state, costs, life years (LYs) and quality-adjusted life years (QALYs) of whole life horizon to evaluate the cost-effectiveness of IND/GLY comparing with SAL/FLU and tiotropium respectively.ResultsComparing with SAL/FLU, IND/GLY resulted in 0.384 LYs and 0.255 QALYs gained. The incremental cost-effectiveness ratio (ICER) is −35,822 CNY/LY and the incremental cost-utility ratio (ICUR) is −53,834 CNY/QALY for IND/GLY versus SAL/FLU. Comparing with tiotropium, IND/GLY resulted in 0.232 LYs and 0.146 QALYs gained. The ICER is 39,729 CNY/LY and the ICUR is 63,246 CNY/QALY for IND/GLY versus tiotropium.ConclusionThis study found that dual bronchodilator IND/GLY is cost-effective for stable COPD treatment in China from Chinese payer's perspective.

Revisiting the Cost-Effectiveness of HPV Co-Testing Versus Primary HPV Testing for Cervical Cancer Screening

Objectives: Consensus U.S. cervical cancer screening guidelines recommend women aged 30–65 years should be screened: (1) every 5 years with high-risk HPV testing alone; or (2) every 5 years with Pap and high-risk HPV co-testing; or (3) every 3 years with Pap alone. However, nearly 1-in-5 cancers (18.6%) are missed by HPV testing alone and 12.2% of cancers are missed by Pap testing alone. Hence, co-testing is the preferred screening method, but the cost implications are not fully known. For deeper understanding, we performed updated clinical-economic comparisons of cervical cancer screening with co-testing versus primary HPV from a U.S. perspective. Methods: A health state transition (Markov) model with one-year cycling was previously developed using epidemiologic, clinical, and economic data from healthcare databases and published literature. After updating the model, it was used to perform simulations of women receiving either 3-year or 5-year interval cervical cancer screening with either co-testing or HPV primary, starting from age 30 years and running up through age 64 years. Outcomes included total and incremental differences in costs, number of referral colposcopies (true and false positive), invasive cervical cancer (ICC) cases, ICC deaths, and quality-adjusted life years (QALYs) for cost-effectiveness calculations. Results: In the 3-year and 5-year screening interval scenarios, per-patient cumulative costs of screening and management over 35 years with co-testing versus HPV primary led to cost savings of $15 and $217, respectively. These cost saving resulted from fewer referral colposcopies, fewer ICC cases, and fewer ICC deaths. Co-testing also conferred more QALYs. Cost-effectiveness calculations showed co-testing as the economically dominant screening strategy by simultan-eously confers greater effectiveness (i.e., more QALYs) at lower cost compared with HPV primary. National average annual cost savings of $154 to $655 million could be realized if every woman in the U.S. was routinely screened with co-testing instead of HPV primary. Conclusions: Model results demonstrate that cervical cancer screening with co-testing provides valuable clinical and economic outcomes when compared to primary HPV testing alone. These findings are relevant to healthcare payers and women’s health policy advocates seeking cost-effective cervical cancer screening options.

Health State Transition Model by Binary Expression and Cubic Lattice Representation Corresponding to the Specific Health Checkup

Health State Transition Model by Binary Expression and Cubic Lattice Representation Corresponding to the Specific Health Checkup

Maximizing Probability of Staying in Objective States in Healthcare Software with Unknown Health State Transition Probabilities

Maximizing Probability of Staying in Objective States in Healthcare Software with Unknown Health State Transition Probabilities