Three-state Markov Model Research Articles

Cost-effectiveness of bevacizumab plus paclitaxel versus paclitaxel for the first-line treatment of HER2-negative metastatic breast cancer in specialist oncology centers in France

BackgroundEvidence from clinical trials suggests that the addition of bevacizumab to chemotherapy in the first-line treatment of patients with HER2-negative metastatic breast cancer improves progression-free survival (PFS) but not overall survival (OS). However, a retrospective analysis of real-world data from the French Comprehensive Cancer Centers (FCCC) through the Epidemiological Strategy and Medical Economics (ESME) Research Program, suggested that in this setting, the addition of bevacizumab may confer a significant benefit in terms of both PFS and OS. A cost-effectiveness analysis was performed to determine the cost-effectiveness of bevacizumab plus paclitaxel versus paclitaxel alone in the first-line treatment of HER2-negative metastatic breast cancer at specialist oncology centers in France.MethodsThe analysis was performed using a three-state Markov model and clinical input data from N = 3426 HER2-negative metastatic breast cancer patients treated with bevacizumab plus paclitaxel or paclitaxel alone. The analysis was performed from a third party payer perspective over a 10-year time horizon; future costs and clinical outcomes were discounted at 4% per annum.ResultsIn the overall population, the addition of bevacizumab to paclitaxel led to incremental gain of 0.72 life years and 0.48 quality-adjusted life years (QALYs) relative to paclitaxel alone. The incremental lifetime cost of the addition of bevacizumab was EUR 27,390, resulting in an incremental cost-effectiveness ratio (ICER) of EUR 56,721 per QALY gained for bevacizumab plus paclitaxel versus paclitaxel alone. In a subgroup of triple negative patients the ICER was EUR 66,874 per QALY gained.ConclusionsThe analysis indicated that the combination of bevacizumab plus paclitaxel is likely to be cost-effective compared with paclitaxel alone for the first-line treatment of HER2-negative metastatic breast cancer in specialized oncology centers in France.

Multistate Markov model for predicting the natural disease progression of type 2 diabetes based on hemoglobin A1c

Introduction: Type 2 diabetes is a common non-communicable disease, especially in developing countries like India, posing a huge economic burden on the family and nation as a whole. It is a chronic metabolic disorder in which prevalence has been increasing steadily all over the world. In studies of many chronic medical conditions, the health status of a patient may be characterized using a finite number of disease states. The multi-state Markov model is a useful way to describe states of a disease over time. In this research article, we have illustrated the usefulness of multistate Markov models in the analysis of follow-up of diabetes. The valuable information provided by the hemoglobin A1c (HbA1c) test has rendered it as a reliable biomarker for the diagnosis and prognosis of diabetes. Objectives: The main purpose of this study is to assess the importance and significance of HbA1c as a useful disease marker for type 2 diabetes by using a three-state Markov model. Patients and Methods: A total of 246 type 2 diabetic patients were included in this study. These patients are classified in different states on the basis of their available baseline value of HbA1c. HbA1c repeated after every 1 year for consecutive four years. Based on ranges of HbA1c, three transient states (4 ≤ HbA1C ≤ 5.6, 5.7 ≤ HbA1C ≤ 6.4 and HbA1C ≥ 6.5%) have been defined. Additionally, transition intensities, transition probabilities, mean sojourn time in each state and also expected state specific survival time have been assessed. All the statistical analysis has been performed using the msm package in R software. Results: The mean age of patients at diagnosis was 26.12 years (SD=7.60), ranging from 10 to 49 years. The estimates of transition intensities reveal that a patient in state 1 is 16.4 (0.82/0.05) times more likely to move to state 2 than to move to diabetic state. Similarly, a patient in pre-diabetic is 7.5 (2.34/0.31) times more likely to move to diabetic state as compared to normal state. Additionally, once a patient is in a diabetic state there is 79% chances of remaining in a diabetic state as compared to 4% and 17% of moving to normal or pre-diabetic state, this implies that a patient who once in the diabetic state is difficult to move to a normal or pre-diabetic state. Conclusion: The estimated total length of time spent in each state is forecasted to be four months in normal state, five months in pre-diabetic state and 39 months in diabetic state. Hence, it has been concluded that, once the patient enters the diabetic state (HbA1c>6.4), the chances of getting back to normal or pre-diabetic state are very small.

Worklife by Occupation Physical Requirements: A Three-State Model

Abstract Do workers in more physically demanding jobs have different worklives than those in more sedentary occupations? To answer this question, we link individual data from the Current Population Survey with occupation characteristics from the Occupational Information Network to categorize individuals into three mutually exclusive initial labor market states: inactive, or active in either a more or less physically demanding occupation. A three-state Markov model estimates worklives given transitions across states over time. There is not a significant difference in worklives between the two occupation groups, even when controlling for sex, age and education. Men and women initially in more physically demanding occupations can be expected to work just as long as their counterparts initially in less physically demanding occupations.

Cost-effectiveness of pembrolizumab versus brentuximab vedotin for patients with relapsed or refractory classical Hodgkin’s lymphoma: a United States payer perspective

Aims: Patients with classical Hodgkin’s lymphoma (cHL) who have relapsed after or are ineligible for autologous stem cell transplantation (ASCT) have limited treatment options and generally a poor prognosis. Pembrolizumab was recently approved in the US for the treatment of such patients having demonstrated clinical benefit and tolerability in relapsed/refractory cHL; however, the cost-effectiveness of pembrolizumab in this population is currently unknown.Materials and methods: A three-state Markov model (progression-free [PF], progressed disease, and death) was developed to assess the cost-effectiveness of pembrolizumab (200 mg) vs brentuximab vedotin (BV; 1.8 mg/kg) in patients with relapsed/refractory cHL after ASCT who have not received BV post-ASCT over a 20-year time horizon from a US payer perspective. PF survival was modeled using a naïve indirect treatment comparison of data from KEYNOTE-087 and the SG035-003 trial. Post-progression survival was modeled using data from published literature. Costs (drug acquisition and administration, disease management, subsequent treatment, and adverse events) and outcomes were discounted at an annual rate of 3.0%. Uncertainty surrounding cost-effectiveness was assessed via probabilistic, deterministic, and scenario analyses.Results: In the base case, pembrolizumab was predicted to yield an additional 0.574 life-years (LYs) and 0.500 quality-adjusted life-years (QALYs) vs BV and cost savings of $63,278. Drug acquisition costs were the biggest driver of incremental costs between strategies. Pembrolizumab had a 99.6% probability of being cost-effective compared with BV at a willingness-to-pay threshold of $20,000/QALY and dominated BV in all scenarios tested.Limitations: The analysis was subject to potential bias due to the use of a naïve indirect treatment comparison and, given the current immaturity of OS in KEYNOTE-087, PPS was assumed equivalent across both treatments.Conclusion: Pembrolizumab is a cost-effective alternative to BV for patients with relapsed/refractory cHL after ASCT.

(P14) Cost Effectiveness of Radiation and Chemotherapy for High-Risk Low Grade Glioma

The standard of care treatment for maximally resected, high risk (≥ 40 years old or sub-totally resected) low grade glioma (LGG) patients was established by RTOG 9802, which showed an overall survival (OS) of 13.3 years for patients treated with radiotherapy (RT) + PCV (procarbazine, lomustine [CCNU], vincristine) chemotherapy compared to 7.8 years for RT alone. In the era of value-based health care, cost-effectiveness analyses (CEA) have the potential to inform coverage decisions and patient care. To our knowledge, there has been no study assessing the value of RT+PCV as adjuvant therapy for high risk LGG. We sought to analyze the cost-effectiveness of this strategy. The base case comprised patients with high risk LGG after maximal safe resection with indications for adjuvant therapy. A decision tree with an integrated three-state Markov model was created to follow patients treated with RT and RT + PCV. Patients existed in one of 3 health states: stable, progressive, and dead. All patients were assumed to be free of progression at baseline. Survival and freedom from progression were modeled to reflect the results of RTOG 9802 using time-dependent transition probabilities. Health utility values and costs of care were derived from the literature and national registry databases. Starting at initial age of 40 years (median age on RTOG 9802), patients were followed monthly over a maximum time horizon of 60 years after diagnosis (effectively over their remaining lifetimes). Analysis was conducted from the healthcare perspective. Probabilistic sensitivity analysis of modeled parameter distributions was conducted with Monte Carlo simulation of 10,000 samples. Modeled outcomes demonstrated agreement with clinical data in OS, progression free survival (PFS), and expected benefit of addition of PCV to adjuvant RT. In our model, 5-year and 10-year OS rates for RT+PCV vs RT alone were 71.5% vs. 64.8%, and 62.1% vs. 39.2%, respectively; 5-year and 10-year PFS rates for RT+PCV vs RT alone were 61.7% vs. 45.2%, and 50.5% vs. 20.1%, respectively. Patients treated with RT alone accrued 5.17 quality-adjusted life-years (QALYs) (9.63 life-years) at a cost of $139,598. Patients treated with RT+PCV accrued 9.94 QALYs (21.45 life-years) at a cost of $188,234. The addition of PCV to RT yielded an incremental benefit of 4.77 QALYs at an incremental monetary cost of $48,637, leading to an incremental cost-effectiveness ratio of $10,188 per QALY gained. Probabilistic sensitivity analysis demonstrates that cost-effectiveness of RT+PCV was insensitive to variations in modeled distributions of input parameters, with 99.96% probability of cost-effectiveness at a willingness-to-pay threshold of $100,000 per QALY. Based on the impressive benefits in outcomes observed in RTOG 9802, the addition of PCV chemotherapy to RT provides high value for cost in the treatment of patients with high-risk low grade glioma.

Spatiotemporal relationships defining the adaptive gating of the bacterial mechanosensitive channel MscS.

Adaptive desensitization and inactivation are common properties of most ion channels and receptors. The mechanosensitive channel of small conductance MscS, which serves as a low-threshold osmolyte release valve in most bacteria, inactivates not from the open, but from the resting state under moderate tensions. This mechanism enables the channel to respond differently to slow tension ramps versus abruptly applied stimuli. In this work, we present a reconstruction of the energy landscape for MscS transitions based on patch current kinetics recorded under special pressure protocols. The data are analyzed with a three-state continuous time Markov model, where the tension-dependent transition rates are governed by Arrhenius-type relations. The analysis provides assignments to the intrinsic opening, closing, inactivation, and recovery rates as well as their tension dependencies. These parameters, which define the spatial (areal) distances between the energy wells and the positions of barriers, describe the tension-dependent distribution of the channel population between the three states and predict the experimentally observed dynamic pulse and ramp responses. Our solution also provides an analytic expression for the area of the inactivated state in terms of two experimentally accessible parameters: the tension at which inactivation probability is maximized, γ*, and the midpoint tension for activation, γ0.5. The analysis initially performed on Escherichia coli MscS shows its applicability to the recently characterized MscS homolog from Pseudomonas aeruginosa. Inactivation appears to be a common property of low-threshold MscS channels, which mediate proper termination of the osmotic permeability response and contribute to the environmental fitness of bacteria.

记忆信道中基于三状态Markov链模型的多跳ARQ协议吞吐量的分析

记忆信道中基于三状态Markov链模型的多跳ARQ协议吞吐量的分析

Cost-Effectiveness of Radiation and Chemotherapy for High-Risk Low Grade Glioma

The standard of care treatment for maximally resected, high risk (≥ 40 years old or sub-totally resected) low grade glioma (LGG) patients was established by RTOG 9802, which showed an overall survival (OS) of 13.3 years for patients treated with radiotherapy (RT) + PCV (procarbazine, lomustine [CCNU], vincristine) chemotherapy compared to 7.8 years for RT alone. In the era of value-based health care, cost-effectiveness analyses (CEA) have the potential to inform coverage decisions and patient care. To our knowledge, there has been no study assessing the value of RT + PCV as adjuvant therapy for high risk LGG. We sought to analyze the cost-effectiveness of this strategy. The base case comprised patients with high risk LGG after maximal safe resection with indications for adjuvant therapy. A decision tree with an integrated three-state Markov model was created to follow patients treated with RT and RT + PCV. Patients existed in one of three health states: stable, progressive, and dead. All patients were assumed to be free of progression at baseline. Survival and freedom from progression were modeled to reflect the results of RTOG 9802 using time-dependent transition probabilities. Health utility values and costs of care were derived from the literature and national registry databases. Starting at initial age of 40 years (median age on RTOG 9802), patients were followed monthly over a maximum time horizon of 60 years after diagnosis (effectively over their remaining lifetimes). Analysis was conducted from the healthcare perspective. Probabilistic sensitivity analysis of modeled parameter distributions was conducted with Monte Carlo simulation of 10,000 samples. Modeled outcomes demonstrated agreement with clinical data in OS, progression free survival (PFS), and expected benefit of addition of PCV to adjuvant RT. In our model, 5-year and 10-year OS rates for RT + PCV vs RT alone were 71.5% vs. 64.8%, and 62.1% vs. 39.2%, respectively; 5-year and 10-year PFS rates for RT + PCV vs RT alone were 61.7% vs. 45.2%, and 50.5% vs. 20.1%, respectively. Patients treated with RT alone accrued 5.17 quality-adjusted life-years (QALYs) (9.63 life-years) at a cost of $139,598. Patients treated with RT+PCV accrued 9.94 QALYs (21.45 life-years) at a cost of $188,234. The addition of PCV to RT yielded an incremental benefit of 4.77 QALYs at an incremental monetary cost of $48,637, leading to an incremental cost-effectiveness ratio of $10,188 per QALY gained. Probabilistic sensitivity analysis demonstrates that cost-effectiveness of RT + PCV was insensitive to variations in modeled distributions of input parameters, with 99.96% probability of cost-effectiveness at a willingness-to-pay threshold of $100,000 per QALY. Based on the impressive benefits in outcomes observed in RTOG 9802, the addition of PCV chemotherapy to RT provides high value for cost in the treatment of patients with high-risk low grade glioma.

Disparities in the Clinical Evolution of Anal Neoplasia in an HIV-Infected Cohort.

A recent meta-analysis suggested that anal intraepithelial neoplasia and invasive anal cancer are more prevalent among black men having sex with men (MSM). We conducted a retrospective cohort of HIV-infected adult patients under care between 2001 and 2012. Disparities in clinical evolution of anal intraepithelial neoplasia to high-grade squamous intraepithelial lesion (HSIL) and invasive anal cancer were evaluated in a three-state Markov model adjusted for cytology misclassification. We studied sociodemographic covariate effects for each state transition using multivariable models controlling for antiretroviral therapy and infrared coagulation treatment of HSIL. Among 2804 patients with a median age of 40years, 78% were MSM and 38% non-white. There were no disparities in HSIL prevalence (14%) by age, sex, race, or risk group. After 4.0years of follow-up, 23 patients developed invasive anal cancer. Females and black patients had lower transition rates from <HSIL→HSIL (HR=0.35 and HR=0.55, respectively); those with age >40 had lower rates of both <HSIL→HSIL progression (HR=0.64) and HSIL→<HSIL regression (HR=0.56); and MSM had higher rates of progression from <HSIL→HSIL (HR=3.30). Controlling for antiretroviral therapy and infrared coagulation (IRC) treatment as time-updated covariates, the univariable effects of sex, black race, and HIV risk factor remained significant. Black race was not associated with prevalent anal intraepithelial neoplasia nor with post-baseline progression of anal intraepithelial neoplasia.

The Cost-Effectiveness of Entresto™ (Sacubitril and Valsartan) Compared with Enalapril in Managing Chronic Heart Failure in Ghana: Decision Analytic Modelling

Background: Over the years, Angiotensin-converting enzyme inhibitors (ACEis) and Angiotensin Receptor Blockers (ARBs) have been the groups of medications of choice for managing Chronic Heart Failure (CHF). However, Entresto™, a formulation of Sacubitril and Valsartan has shown to be of superior effectiveness and thus, approved for use in many countries. Nonetheless, there is a limited economic evaluation of Entresto™ in Low-and-Middle Income Countries (LMICs), leaving significant gaps in the body of evidence supporting its cost-effectiveness. Objective: To model the lifetime cost-effectiveness of Entresto™ as compared to Enalapril in the treatment of a cohort of 42-year old patients with stage II-IV CHF with reduced ejection fraction, from the health system perspective. Methods: A three-state Markov model was developed to simulate the long-term outcomes and costs of care for a hypothetical cohort of 42-year-old patients with CHF who were assumed to receive either Entresto™ plus recommended therapy or Enalapril plus recommended therapy (standard care). One-way sensitivity analysis was conducted using a best and worst case scenario analysis while probabilistic sensitivity analysis was done using beta distribution around the input parameters. Results: The results show that after 30 years, more patients taking Enalapril died as compared with those taking Entresto™ (85.3% vs. 96.5%) but the lifetime cost of Entresto™ treatment was higher than Enalapril [US$44,656.13 (GH¢192,021.35) vs. US$922.99 (GH¢3,968.86)]. Also, Entresto™ as compared with Enalapril, yielded higher QALYs (7.59 vs. 5.33) culminating in an Incremental Cost Effectiveness Ratio (ICER) of US$19,343 (GH¢83,175.08) per QALY which may be deemed not cost-effective based on an assumed Willingness to Pay (WTP) threshold of US$5,121 (three times Gross Domestic Product Per Capita). Conclusion: In the context of Ghana, with maximum WTP threshold of US$5,121 per QALY (threefold per capita GDP), Entresto™ is not deemed a cost-effective alternative to Enalapril unless its US market price of US$380 per monthly pack is reduced by at least 73% or the WTP threshold is raised above US$10,000 per QALY. The National Health Insurance Authority (NHIA) and the Ghana National Drugs Programme (GNDP) should consider engaging the manufacturers of Entresto™ for a possible price reduction or secure a subsidy from the government or both to make the drug available for Ghanaian CHF patients.

A Multistate Model for Correlated Interval-Censored Life History Data in Caries Research

SummaryWe propose a three-state frailty Markov model coupled with likelihood-based inference to analyse tooth level life course data in caries research. This analysis is challenging because of intraoral clustering, interval censoring, multiplicity of caries states and computational complexities. We also develop a Bayesian approach to predict future caries transition probabilities given observed life history data. Numerical experiments demonstrate that the methods proposed perform very well in finite samples with moderate sizes. The practical utility of the model is illustrated by using life course data from a unique longitudinal study of dental caries in young low income urban African-American children. In this analysis, we evaluate for any spatial symmetry in the mouth with respect to the life course of dental caries, and whether the same type of tooth has a similar decay process in boys and girls.

Cost-effectiveness of drug-eluting stents versus bare-metal stents in patients undergoing percutaneous coronary intervention

ObjectiveTo determine the cost-effectiveness of drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients requiring a percutaneous coronary intervention in France, using a recent meta-analysis including second-generation DES.MethodsA cost-effectiveness...

A framework for the reliability evaluation of grid-connected photovoltaic systems in the presence of intermittent faults

A framework for the reliability evaluation of grid-connected PV (photovoltaic) systems with intermittent faults is proposed using DBNs (dynamic Bayesian networks). A three-state Markov model is constructed to represent the state transition relationship of no faults, intermittent faults, and permanent faults for PV components. The model is subsequently fused into the DBNs. The reliability and availability of three simple PV systems with centralized, string, and multistring configurations, as well as a complex PV system, are analyzed through the proposed framework. The sequence of the degree of importance of PV components is investigated using mutual information. The effects of intermittent fault parameters, including the coefficients of intermittent fault, permanent fault, and intermittent repair, on the reliability and availability are explored. Results show that the reliability and availability of the PV system with centralized configuration rapidly decrease, compared with those of the PV systems with string and multistring configurations. The sequence of the degree of importance of PV components is DC/AC inverter, DC/DC converter, DC combiner, and PV module arranged from the largest to the smallest. The finding indicates that the DC/AC inverter should be given considerable attention to improve the reliability and availability and to prevent their possible failures.

Cost-effectiveness analysis of EGFR mutation testing and gefitinib as first-line therapy for non-small cell lung cancer

The combination use of gefitinib and epidermal growth factor receptor (EGFR) testing is a standard first-line therapy for patients with non-small cell lung cancer (NSCLC). Here, we examined the cost-effectiveness of this approach in Japan. Our analysis compared the 'EGFR testing strategy', in which EGFR mutation testing was performed before treatment and patients with EGFR mutations received gefitinib while those without mutations received standard chemotherapy, to the 'no-testing strategy,' in which genetic testing was not conducted and all patients were treated with standard chemotherapy. A three-state Markov model was constructed to predict expected costs and outcomes for each strategy. We included only direct medical costs from the healthcare payer's perspective. Outcomes in the model were based on those reported in the Iressa Pan-Asia Study (IPASS). The incremental cost-effectiveness ratio (ICER) was calculated using quality-adjusted life-years (QALYs) gained. Sensitivity and scenario analyses were conducted. The incremental cost and effectiveness per patient of the 'EGFR testing strategy' compared to the 'no-testing strategy' was estimated to be approximately JP¥122,000 (US$1180; US$1=JP¥104 as of February 2014) and 0.036 QALYs. The ICER was then calculated to be around JP¥3.38 million (US$32,500) per QALY gained. These results suggest that the 'EGFR testing strategy' is cost-effective compared with the 'no-testing strategy' when JP¥5.0 million to 6.0 million per QALY gained is considered an acceptable threshold. These results were supported by the sensitivity and scenario analyses. The combination use of gefitinib and EGFR testing can be considered a cost-effective first-line therapy compared to chemotherapy such as carboplatin-paclitaxel for the treatment for NSCLC in Japan.

Accident risk assessment in marine transportation via Markov modelling and Markov Chain Monte Carlo simulation

There are many technological and environmental safety factors involved in marine accidents. This paper deals with an analytic approach to accident risk modelling when data for analyzing safety factors is limited or unavailable. The purpose of this paper is to propose a simulated accident model for assessing accident risk in marine transportation. The proposed approach is based on Markov modelling and Markov Chain Monte Carlo (MCMC) simulation and it is illustrated using an example from marine transportation. A three-state continuous time Markov model is used to record and estimate marine occurrence rates and probabilities. The MCMC simulation requires the occurrence data of the Markov model to estimate the accident risk. However, it can be used when only a limited amount of information is available. Compared with other models, the approach in this paper is applicable to any type of marine accident or marine transportation system. A numerical example is also given to illustrate the procedure.

Cost-Effectiveness of Three Adjunct Cellular/Tissue-Derived Products Used in the Management of Chronic Venous Leg Ulcers

ObjectivesDetermine the cost-effectiveness of three topically applied cellular/tissue-derived products (CTPs) used as adjunct therapies to standard care in the management of venous leg ulcers (VLUs). MethodsA three-state Markov model derived from the medical literature was developed to estimate the comparative cost-effectiveness of three CTPs in relation to VLU standard care. CTPs evaluated in the study included extracellular matrix (ECM), human skin equivalent (HSE), and living skin equivalent (LSE). The three Markov states included unhealed, healed, and death. A 1-year time horizon was used to determine the number of ulcer-free weeks and the expected costs of therapies. The payer perspective was taken in the analysis and only the direct costs of care were considered. Sensitivity analyses were performed to gauge model parameter uncertainty. ResultsThe expected costs for standard care, ECM, HSE, and LSE VLU therapy were $6,132, $6,732, $10,638, and $11,237, while the expected outcomes were 24, 31, 29, and 27 ulcer-free weeks, respectively. ECM was economically dominant among the three CTPs. In the base case of ECM versus standard care, the incremental cost-effectiveness ratio for ECM therapy was $86 per ulcer-free week. Sensitivity analysis did not alter ECM dominance. Clinic visits and home health utilization exhibited the greatest influence on cost. ConclusionsECM is the most cost-effective CTP when used in the management of VLUs as an adjunct to standard care. These findings suggest that VLU standard care therapy with ECM can yield potential cost savings and produce better outcomes than do other CTPs.

Cost-effectiveness analysis of aflibercept in combination with FOLFIRI in the treatment of patients with metastatic colorectal cancer

To estimate the incremental cost per life-year gained (LYG) of aflibercept in combination with FOLFIRI as second-line treatment in metastatic colorectal cancer (mCRC) patients previously treated with oxaliplatin. Based on clinical trial VELOUR results, a three-state Markov model (stable disease, progression and death) with 2-week cycle duration was designed. Transition to health state «progression» implied the interruption of second-line treatment and administration of a third-line treatment (post-second line chemotherapy). Cost estimation included disease management cost (pharmaceutical, adverse event management, administration costs, etc.). Both cost and outcomes were discounted (3% annually). Sensitivity analyses (SA) were performed to test model robustness. Administration of aflibercept + FOLFIRI as second-line treatment provided 1.78 LYG (21 life-months gained). With FOLFIRI 1.43 LYG (17 months) were obtained. The cost of the clinical management of aflibercept + FOLFIRI implied an additional investment of Euros 13,564 compared with FOLFIRI for a lifetime horizon, being total costs for aflibercept + FOLFIRI of Euros 38,346, compared to Euros 24,782 with FOLFIRI. In the cost-effectiveness analysis Euros 38,931/LYG was obtained with aflibercept in combination with FOLFIRI versus FOLFIRI. Aflibercept in combination with FOLFIRI increased overall survival versus FOLFIRI, so it is an effective strategy in the treatment of patients with mCRC. Aflibercept in combination with FOLFIRI is an efficient strategy for second-line mCRC treatment from the National Health System perspective.

An epidemiologic model to project the impact of changes in glomerular filtration rate on quality of life and survival among persons with chronic kidney disease.

PurposePredicting the timing and number of end-stage renal disease (ESRD) cases from a population of individuals with pre-ESRD chronic kidney disease (CKD) has not previously been reported. The objective is to predict the timing and number of cases of ESRD occurring over the lifetime of a cohort of hypothetical CKD patients in the US based on a range of baseline estimated glomerular filtration rate (eGFR) values and varying rates of eGFR decline.MethodsA three-state Markov model – functioning kidney, ESRD, and death – with an annual cycle length is used to project changes in baseline eGFR on long-term health outcomes in a hypothetical cohort of CKD patients. Using published eGFR-specific risk equations and adjusting for predictive characteristics, the probability of ESRD (eGFR <10), time to death, and incremental cost-effectiveness ratios for hypothetical treatments (costing US$10, $5, and $2/day), are projected over the cohort’s lifetime under two scenarios: an acute drop in eGFR (mimicking acute kidney injury) and a reduced hazard ratio for ESRD (mimicking an effective intervention).ResultsAmong CKD patients aged 50 years, an acute eGFR decrement from 45 mL/minute to 35 mL/minute yields decreases of 1.6 life-years, 1.5 quality-adjusted life-years (QALYs), 0.8 years until ESRD, and an increase of 183 per 1,000 progressing to ESRD. Among CKD patients aged 60 years, lowering the hazard ratio of ESRD to 0.8 yields values of 0.2, 0.2, 0.2, and 46 per 1,000, respectively. Incremental cost-effectiveness ratios are higher (ie, less favorable) for higher baseline eGFR, indicating that interventions occurring later in the course of disease are more likely to be economically attractive.ConclusionBoth acute kidney injury and slowing the rate of eGFR decline produce substantial shifts in expected numbers and timing of ESRD among CKD patients. This model is a useful tool for planning management of CKD patients.

Cost-effectiveness of adding bevacizumab to first line therapy for patients with advanced ovarian cancer

ObjectiveTo evaluate, from a societal perspective, the cost-effectiveness of adding bevacizumab to first-line therapy based on outcomes from the GOG-218 and ICON-7 trials. MethodsA three-state Markov model was used. The time horizon was until the death of 99% of the initial cohort of 1000 individuals. Costs and quality-adjusted life-years (QALYs) were discounted at an annual rate of 3%. All costs were adjusted to 2013 USD. The incremental cost-effectiveness ratio (ICER) was reported as incremental cost per QALY gained. The robustness of the result was checked with one-way sensitivity analyses and for relevant clinical situations (i.e. varying the drug of choice to treat cancer recurrence). Subgroup analysis was conducted to identify subgroup of population for whom the strategy could be cost-effective. The potential impact of biosimilar bevacizumab was considered, using a 30% price reduction. ResultsFor the GOG-218 study protocol, widely followed in US, the addition of bevacizumab results in an ICER of $2,420,691/QALY. For the ICON-7 study protocol, the ICER is $225,515/QALY. The results of the model were sensitive to the quality of life (QoL) and the median progression free survival (PFS). Biosimilar bevacizumab didn't reduce cost sufficiently to change conclusions. First-line augmentation is cost-effective, with biosimilar bevacizumab, for stage IV patients ($126,169/QALY), ECOG PS1 patients ($116,575/QALY) and for patients with suboptimal residual disease ($122,822/QALY) as per the ICON-7 protocol. ConclusionAddition of bevacizumab, by in large, is cost-ineffective. It can become cost-effective with the ICON-7 protocol, in patients at high risk of progression using biosimilar bevacizumab.

Towards Realtime Spatiotemporal Prediction of District Level Meningitis Incidence in Sub-Saharan Africa

Summary Within an area of sub-Saharan Africa termed ‘the meningitis belt’, meningococcal meningitis epidemics are a major public health concern. The epidemic control strategy that is currently utilized is reactive, such that a vaccination programme is initiated in a district once a predefined weekly incidence threshold has been exceeded. We report progress towards the development of an early warning system based on statistical modelling of district level weekly incidence data. Four modelling approaches are considered and their forecasting performances are compared by using weekly epidemiological data from Niger for the period 1986–2007. We conclude that the models under consideration are advantageous in different situations. The three-state Markov model described in which observed incidence is categorized according to policy-defined thresholds gives the most reliable short-term forecasts, whereas the dynamic linear model proposed, using log-transformed weekly incidence as the response variable, gives more reliable predictions of annual epidemics.