Markov Microsimulation Model Research Articles

Screening for Asymptomatic Coronary Artery Disease in Waitlisted Kidney Transplant Candidates: A Cost-Utility Analysis

On account of the high prevalence of cardiovascular disease in patients with kidney failure, clinical practice guidelines recommend regular screening for asymptomatic coronary artery disease (CAD) in patients on the kidney transplant waitlist. To date, the cost-effectiveness of such screening has not been evaluated. A Canadian-Australasian randomized controlled trial of screening kidney transplant candidates for CAD (CARSK) is currently is being conducted to answer this question. We conducted a cost-utility analysis to determine, before completion of the trial, the cost-effectiveness of no further screening versus regular screening for asymptomatic CAD and to evaluate potential influential variables that may affect results of the economic evaluation. A modeled cost-utility analysis. A theoretical cohort of adult Australian and New Zealand kidney transplant candidates on the waitlist. No further screening for asymptomaticCAD versus regular protocolized screening (annual or second yearly)for CADafter kidney transplant waitlisting. Incremental cost-effectiveness ratio, reported as cost per quality-adjusted life-year (QALY). Markov microsimulation model, health system perspective and over a lifetime horizon. In the base case, the incremental cost-effectiveness ratio of no further screening was $11,122 per QALY gained when compared with regular screening. No further screening increased survival by 0.49 life-year or 0.35 QALY. One-way sensitivity analyses identified the costs of transplantation in the first year and CAD prevalence as the mostinfluential variables. Probabilistic sensitivity analyses showed that 94% of the simulations were cost-effective below a willingness-to-paythreshold of $50,000 per QALY gained. Rates of cardiovascular events in waitlisted candidates and transplant recipients are limited in the contemporary era. The results may not be generalizable to populations outside Australia and New Zealand. No further screening for CAD after waitlisting is likely to be cost-effective and may improve survival. Precision around CAD prevalence estimates and health careresource use will reduce existing uncertainty.

Predicting the intervention threshold for initiating osteoporosis treatment among postmenopausal women in China: a cost-effectiveness analysis based on real-world data

SummaryThis study built a micro-simulation Markov model to determine the treatment threshold of osteoporosis in postmenopausal women in Mainland China. Treatment with zoledronate is cost-effective when FRAX-based (Fracture risk assessment tool) fracture probability is over 7%.IntroductionThe purpose of this study is to estimate FRAX-based fracture probabilities in Mainland China using real-world data, at which intervention could be cost-effective.MethodsWe developed a micro-simulation Markov model to capture osteoporosis states and relevant morbidities including hip fracture, vertebral fracture, and wrist fracture. Baseline characteristics including incidences of osteoporosis and distribution of risk factors were derived from the Peking Vertebral Fracture study, the largest prospective cohort study of postmenopausal women in Mainland China. We projected incidences of fractures and deaths by age groups under two treatment scenarios: 1) no treatment, and 2) zoledronate. We also projected total quality-adjusted life-years (QALY) and total costs including fracture management and osteoporosis drugs for cost-effectiveness analysis. Cost-effective intervention thresholds were calculated based on the Chinese FRAX model.ResultsTreatment with zoledronate was cost-effective when the 10-year probability of major osteoporotic fracture based on FRAX was above 7%. The FRAX threshold increased by age from 51 to 65 years old, and decreased in elder age groups, ranging from 4% to 9%.ConclusionsUsing real-world data, our model indicated that widespread use of zoledronate was of both clinical and economic benefit among Chinese postmenopausal women. Using a FRAX-based intervention threshold of 7% with zoledronate should permit cost-effective access to therapy to patients and contribute to reducing the disease burden of osteoporosis in Mainland China.

THE IMPACT OF FUNCTIONAL DISABILITY ON HOSPITALIZATION SPENDING IN SINGAPORE

Singapore is one of the fastest-aging populations due to increased life expectancy and lowered fertility. Lifestyle changes increase the burden of chronic diseases and disability. These have important implications for social protection systems. The goal of this paper is to model future functional disability and healthcare expenditures based on current trends. To project the health, disability and hospitalization spending of future elders, we adapted the Future Elderly Model (FEM) to Singapore. The FEM is a dynamic Markov microsimulation model developed in the US. Our main source of population data was the Singapore Chinese Health Study (SCHS) consisting of 63,000 respondents followed up over three waves from 1993 to 2010. The FEM model enables us to investigate the effects of disability compounded over the lifecycle and hospitalization spending, while adjusting for competing risk of multi-comorbidities. Results indicate that by 2050, 1 in 6 older adults will have at least one ADL disability and 1 in 3 older adults will have at least one IADL disability, an increase from 1 in 12 elders and 1 in 5 elders respectively in 2014. The highest prevalence of functional disability will be in those aged 85 years and above. Lifetime hospitalization spending of elders aged 55 and above is US$24,400 (30.2%) higher among people with functional disability compared to those without disability. Policies that successfully tackle diabetes and promote healthy living may reduce or delay the onset of disability, leading to potential saving. In addition, further technological improvements may reduce the financial burden of disability.

Abstract 3352: Cost-effectiveness of current and potential serum based colorectal screening strategies: Can a serum based test do better

Abstract Background: Despite efficacy of colorectal cancer (CRC) screening, recent trends in screening rates have not improved. Furthermore, national society recommendations have not prioritized a single screening modality. Both flexible sigmoidoscopy (Flex-Sig) and guaiac fecal occult blood test (gFOBT)) have been recommended. Studies suggest that noninvasive tests may improve screening rates, however, compliance remains modest for such tests. A recent study found that health system transition from gFOBT to a fecal immunochemical test (FIT) moderately improved test compliance rates. However, FIT is an expensive substitute for gFOBT and sensitivity of fecal based tests for precursor lesions in the colon remain inferior to structural examinations. Serum-based blood tests (SBT) may provide higher compliance rates, but necessary accuracy for such a test to be a dominant or cost-effective screening strategy over current recommendations have not been determined. This study analyzed the cost-effectiveness of multiple CRC screening strategies and estimated minimum test characteristics of a hypothetical SBT to be a preferred screening strategy over current modalities. Methods: A Markov microsimulation model was developed to analyze the costs and effects, (quality-adjusted life-years, QALYs) of CRC screening following a hypothetical cohort of 10,000 individuals at age 50 until death. Our model considered three strategies: 1) initial colonoscopy followed by Flex-Sig every 5 years, 2) initial colonoscopy with yearly gFOBT, and 3) initial colonoscopy with yearly FIT. An initial colonoscopy with a hypothetical yearly SBT was also examined at a range of test sensitivities. A long-term payer perspective was assumed for professional and facility costs and lifetime costs of cancer treatment. Model probabilities and utility values were obtained from the literature or calculated from National Vital Statistics Reports. Results: Annual gFOBT was the least costly strategy ($3,242) while annual FIT was eliminated through extended dominance. Flex-Sig was the costliest strategy at $4,667 but had the highest expected QALYs at 19.68. The incremental cost-effectiveness ratio (ICER) of Flex-Sig relative to gFOBT was $35,615. Our secondary analysis demonstrated that a minimum joint sensitivity of 70% and 60% is required for an SBT at 80% and 100% compliance rates, respectively, to achieve extended dominance of both Flex-Sig and FIT by SBT and gFOBT. ICER’s of SBT ranged from $12,984 to $4,779 in these sensitivity ranges compared to gFOBT with expected QALYs as high as 19.96. Total individual costs in the model varied from $365 to $111,535. Conclusion: With improved sensitivity and high compliance rates, annual screening for CRC via a non-invasive SBT is a cost-effective approach compared to structural examinations and currently recommended gFOBT and FIT. Citation Format: Ali Jalali, Richard Nelson, Raminder Nirula. Cost-effectiveness of current and potential serum based colorectal screening strategies: Can a serum based test do better [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3352.

Is risk-stratified breast cancer screening economically efficient in Germany?

ObjectivesRisk stratification has so far been evaluated under the assumption that women fully adhere to screening recommendations. However, the participation in German cancer screening programs remains low at 54%. The question arises whether risk-stratified screening is economically efficient under the assumption that adherence is not perfect.MethodWe have adapted a micro-simulation Markov model to the German context. Annual, biennial, and triennial routine screening are compared with five risk-adapted strategies using thresholds of relative risk to stratify screening frequencies. We used three outcome variables (mortality reduction, quality-adjusted life years, and false-positive results) under the assumption of full adherence vs. an adherence rate of 54%. Strategies are evaluated using efficiency frontiers and probabilistic sensitivity analysis (PSA).ResultsThe reduced adherence rate affects both performance and cost; incremental cost-effectiveness ratios remain constant. The results of PSA show that risk-stratified screening strategies are more efficient than biennial routine screening under certain conditions. At any willingness-to-pay (WTP), there is a risk-stratified alternative with a higher likelihood of being the best choice. However, without explicit decision criteria and WTP, risk-stratified screening is not more efficient than biennial routine screening. Potential improvements in the adherence rates have significant health gains and budgetary implications.ConclusionIf the participation rate for mammographic screening is as low as in Germany, stratified screening is not clearly more efficient than routine screening but dependent on the WTP. A more promising design for future stratified strategies is the combination of risk stratification mechanisms with interventions to improve the low adherence in selected high-risk groups.

PMS26 COST-EFFECTIVENESS OF SEQUENTIAL TREATMENT WITH ABALOPARATIDE FOLLOWED BY ALENDRONATE VS ALENDRONATE MONOTHERAPY FOR THE PREVENTION OF FRACTURES IN POSTMENOPAUSAL US WOMEN AT INCREASED RISK OF FRACTURE

Emerging evidence supports sequential therapy with osteoanabolic followed by antiresorptive in patients at high-risk of fragility fractures. Further cost-effectiveness evaluation of sequential abaloparatide (ABL) followed by alendronate (ALN) vs ALN monotherapy is needed to inform prescribers about the economic value of anabolic first for those at high risk of fracture. This study aims to assess the cost-effectiveness of sequential ABL followed by ALN (ABL/ALN) vs ALN monotherapy for postmenopausal osteoporosis, from the US payer perspective. A Markov microsimulation model was developed to estimate the cost-effectiveness of sequential ABL/ALN vs ALN with a lifetime horizon from the US payer perspective. Patients were assumed to receive 18 months ABL followed by 5 years ALN. The effects of ABL on fracture risk were derived from the ACTIVExtend trial and were assumed to be maintained during subsequent ALN treatment, consistent with ACTIVExtend. Evaluation was completed for high-risk patients 50-80 years old with a BMD T-score ≤-3.5 or BMD T-score between -2.5 and -3.5 and a history of ≥1 osteoporotic fracture. Sensitivity analyses were performed to test the robustness of the model results. In simulated populations, sequential ABL/ALN was cost-effective (threshold of $150,000/QALYs) vs generic ALN monotherapy, in women ≥60 years with a BMD T-score ≤-3.5 without a history of prior fracture and in women with BMD T-score between -2.5 and -3.5 and history of osteoporotic fracture. In patients aged 70 years with BMD T-score ≤-3.5, sequential ABL/ALN reduced the expected number of fractures per patient by 0.340 and increased lifetime QALY gained by 0.163 over a patient’s lifetime. Probabilistic sensitivity analyses suggested ABL/ALN was cost-effective in 65.5%, 96% and 92.5% of simulations at the ages of 60, 70 and 80 years, respectively. Sequential ABL/ALN therapy is cost-effective vs ALN monotherapy for US postmenopausal women at increased risk of fractures.

The Burden of Chronic Hepatitis C in China From 2004 to 2050: An Individual-Based Modeling Study.

The launch of new direct-acting antivirals (DAAs) is expected to substantially reduce the burden of hepatitis C virus (HCV) in China. However, the effect of these changes has not yet been modeled in China. Therefore, we aim to predict the burden of HCV-related diseases in China by simulating different scenarios that incorporate recent therapeutic advances of HCV and China's current screening strategy. We developed an individual-based microsimulation Markov model that simulated disease progression of HCV-infected patients in China from 2004 to 2050. We simulated four scenarios with different assumptions about treatment, including a natural history scenario, a pre-DAAs scenario, a DAA treatment for all patients with a METAVIR fibrosis score ≥F3 (DAAs [≥F3]) scenario, and a DAAs (≥F0) scenario. The introduction of DAAs is predicted to have great impacts on the burden of HCV in China, particularly under the DAAs (≥F0) scenario in which we rapidly expand DAAs to all HCV-infected patients (≥F0) in 2021. Under this scenario, prevalence of chronic HCV is expected to peak at 10.75 million (95% confidence interval [CI], 8.30-12.85) around 2020 and then decrease to 7.92 million (95% CI, 5.41-10.08) in 2050. Conclusion: If the future increasing burden of HCV-related diseases is to be averted, China needs to start launching the new DAA treatment and rapidly increase the number of patients treated. However, to maximize the benefits of new DAAs, expanded screening is necessary to identify more cases that require treatment in the short term. Without these changes, the HCV burden in China will remain high in the future.

Cost-effectiveness of gastro-resistant risedronate tablets for the treatment of postmenopausal women with osteoporosis in France

SummaryThe use of gastro-resistant risedronate, a convenient dosing regimen for oral bisphosphonate therapy, seems a cost-effective strategy compared with weekly alendronate, generic risedronate, and no treatment for the treatment of postmenopausal women with osteoporosis in France.IntroductionGastro-resistant (GR) risedronate tablets are associated with improved persistence compared to common oral bisphosphonates but are slightly more expensive. This study assessed its cost-effectiveness compared to weekly alendronate and generic risedronate for the treatment of postmenopausal women with osteoporosis in France.MethodsA previously validated Markov microsimulation model was used to estimate the lifetime costs (expressed in €2017) per quality-adjusted life-years (QALY) of GR risedronate compared with weekly alendronate, generic risedronate, and no treatment. Pooled efficacy data for bisphosphonates derived from a previous meta-analysis were used for all treatment options, and persistence data (up to 3 years) were obtained from a large Australian longitudinal study. Evaluation was done for high-risk women 60–80 years of age, with a bone mineral density (BMD) T-score ≤ − 2.5 and/or prevalent vertebral fractures.ResultsIn all of the simulated populations, GR risedronate was cost-effective compared to alendronate, generic risedronate, and no treatment at a threshold of €60,000 per QALY gained. In women with a BMD T-score ≤ − 2.5 and prevalent vertebral fractures, the cost per QALY gained of GR risedronate compared to alendronate, generic risedronate, and no treatment falls below €20,000 per QALY gained. In women aged 75 years and older, GR risedronate was even shown to be dominant (more QALYs, less costs) compared to alendronate, generic risedronate, and no treatment.ConclusionThis study provides the first economic results about GR risedronate, suggesting that it represents a cost-effective strategy compared with weekly alendronate and generic risedronate for the treatment of postmenopausal women with osteoporosis in France.

Cost-effectiveness of sequential treatment with abaloparatide vs. teriparatide for United States women at increased risk of fracture

ObjectivesThere is emerging evidence supporting sequential therapy with an osteoanabolic followed by an antiresorptive in patients at high-risk of fragility fractures. This study assessed the cost-effectiveness of sequential treatment with abaloparatide (ABL) followed by alendronate (ALN) [(ABL/ALN)] compared with teriparatide (TPTD) followed by ALN (TPTD/ALN). MethodsA previously validated Markov microsimulation model was adapted to estimate the cost-effectiveness of sequential ABL/ALN compared with sequential TPTD/ALN and no treatment with a lifetime horizon from the US payer perspective. Patients were assumed to receive ABL or TPTD for 18 months followed by 5 years of ALN in line with clinical recommendations. The effects of ABL on fracture risk were derived from the ACTIVExtend trial. The effects of TPTD were assumed to be maintained during subsequent ALN treatment, consistent with ACTIVExtend findings for ABL. Evaluation was completed for patients, aged 50–80 years with a BMD T-score ≤ −3.5 or with a T-score between −2.5 and −3.5 and a history of ≥ one osteoporotic fracture. ResultsIn all simulated populations, sequential ABL/ALN therapy was dominant (lower costs, higher QALYs) compared with sequential TPTD/ALN therapy, resulting from the improved efficacy and lower drug price of ABL. Probabilistic sensitivity analyses suggested that ABL/ALN was dominant in at least 99% of the simulations. Compared to no treatment, the cost per QALY gained of ABL/ALN was always below $130,000. ConclusionsSequential ABL/ALN therapy is a cost-effective (dominant) strategy compared with sequential TPTD/ALN therapy for the treatment of US women at increased risk of fractures.

Cost-effectiveness of physical activity in the management of COPD patients in the UK.

BackgroundWhile the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines advise exercise to reduce disease progression, little investment in promoting physical activity (PA) is made by health care authorities. The purpose of this study was to estimate the cost-effectiveness of regular PA vs sedentary lifestyle in people with COPD in the UK.MethodsEfficacy, quality of life, and economic evidence on the PA effects in COPD patients were retrieved from literature to serve as input for a Markov microsimulation model comparing a COPD population performing PA vs a COPD population with sedentary lifestyle. The GOLD classification defined the model health states. For the base case, the cost of PA was estimated at zero, a lifetime horizon was used, and costs and effects were discounted at 3.5%. Analyses were performed from the UK National Health Service (NHS) perspective. Uncertainty around inputs and assumptions were explored via scenario and sensitivity analyses, including a cost threshold analysis. Outcomes were cost/quality-adjusted life year (QALY) gained and cost/year gained.ResultsBased on our model, the effects of PA in the UK COPD population would be lower mortality (−6%), fewer hospitalizations (−2%), gains in years (+0.82) and QALYs (+0.66), and total cost savings of £2,568. The cost/QALY and cost/year gained were dominant. PA was cost-saving at costs <£35/month and cost-effective at cost <£202/month. The main model drivers were age and PA impact on death and hospital-treated exacerbations.ConclusionIncluding PA in the management of COPD leads to long-term clinical benefits. If the NHS promotes only exercise via medical advice, this would lead to health care cost savings. If the NHS chose to fund PA, it would still likely be cost-effective.

The Long-Term Impact of Functional Disability on Hospitalization Spending in Singapore.

Singapore is one of the fastest-aging populations due to increased life expectancy and lowered fertility. Lifestyle changes increase the burden of chronic diseases and disability. These have important implications for social protection systems. The goal of this paper is to model future functional disability and healthcare expenditures based on current trends. To project the health, disability and hospitalization spending of future elders, we adapted the Future Elderly Model (FEM) to Singapore. The FEM is a dynamic Markov microsimulation model developed in the US. Our main source of population data was the Singapore Chinese Health Study (SCHS) consisting of 63,000 respondents followed up over three waves from 1993 to 2010. The FEM model enables us to investigate the effects of disability compounded over the lifecycle and hospitalization spending, while adjusting for competing risk of multi-comorbidities. Results indicate that by 2050, 1 in 6 elders in Singapore will have at least one ADL disability and 1 in 3 elders will have at least one IADL disability, an increase from 1 in 12 elders and 1 in 5 elders respectively in 2014. The highest prevalence of functional disability will be in those aged 85 years and above. Lifetime hospitalization spending of elders aged 55 and above is US$24,400 (30.2%) higher among people with functional disability compared to those without disability. Policies that successfully tackle diabetes and promote healthy living may reduce or delay the onset of disability, leading to potential saving. In addition, further technological improvements may reduce the financial burden of disability.

The Ross procedure versus mechanical aortic valve replacement in young patients: a decision analysis.

Our goal was to determine the range of perioperative mortality rates associated with the Ross procedure that results in a life expectancy similar to that seen with mechanical aortic valve replacement (mAVR) in young patients with aortic valve disease. A fully probabilistic Markov microsimulation model with 1000 outer loops and 10000 inner loops was constructed to compare gain in life expectancy and quality-adjusted life years between the index treatment with the Ross procedure versus mAVR for a theoretical cohort of young patients with aortic valve disease. Inputs for early deaths and late complications (death, stroke, bleeding, reoperation) were obtained from a single-centre study of 208 propensity score matched patients. In the primary analysis, the perioperative mortality rate for the Ross procedure was varied by increments of 0.5% to determine its impact on life expectancy and quality-adjusted life years. A 2-way sensitivity analysis was conducted to determine simultaneously the impact of the Ross reoperation rate and Ross reoperative mortality rate on life expectancy. Life expectancy was improved with the Ross procedure when the perioperative mortality rate with the Ross procedure was <2.5% and was equivalent to mAVR when the mortality rate was 2.5% to 5%. Similarly, when the perioperative mortality rate of the Ross procedure was between 4% and 5.5%, the quality-adjusted life years gained were similar between the Ross procedure and mAVR. Life expectancy was improved when the Ross procedure reoperative mortality rate was <7% at an incidence of Ross reoperations of 18% at 20 years. Improved life expectancy can be expected with the Ross procedure when the operative mortality rate is less than 2.5%.

PMS63 - COST-EFFECTIVENESS OF ACTONEL® 35 MG (RISEDRONATE) GASTRO-RESISTANT TABLETS FOR THE TREATMENT OF POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS IN FRANCE

Actonel ® 35 mg (risedronate) gastro-resistant (GR risedronate) tablets are associated with improved persistence compared to common oral bisphosphonates, but are also slightly more expensive. This study assessed its cost-effectiveness compared to weekly alendronate and generic risedronate for the treatment of postmenopausal women with osteoporosis in France. A previously validated Markov microsimulation model was used to estimate the lifetime cost (expressed in €2017) per quality-adjusted life-years (QALY) of GR risedronate compared with generic risedronate and alendronate. The model was populated with cost and epidemiological data from a French healthcare perspective. Pooled efficacy results for bisphosphonates derived from a previous NICE meta-analysis was used for all treatment options and persistence data (up to 3 years) were obtained from a large longitudinal study. Evaluation was done for high-risk women 60-80 years of age, with a bone mineral density (BMD) T-score ≤-2.5 and/or prevalent vertebral fractures. One-way and probabilistic sensitivity analyses were performed to test the robustness and uncertainty of the model results. In all of the simulated populations, GR risedronate was cost-effective compared to generic risedronate and alendronate at a threshold of €60,000 per QALY gained. In women with a BMD T-score ≤-2.5 and prevalent vertebral fractures, the cost per QALY gained of GR risedronate compared to both generic risedronate and alendronate fall below €20,000 per QALY gained. In women aged 75 years and older, GR risedronate was even shown to be dominant (more QALYs, less costs) compared to generic risedronate and alendronate. This study provides the first economic results about Actonel ® 35 mg (risedronate) gastro-resistant, suggesting that it represents a cost-effective strategy compared with generic risedronate and alendronate for the treatment of postmenopausal women with osteoporosis in France.

PMS43 - AN ECONOMIC VALUE FRAMEWORK TO ASSESS THE COST EFFECTIVENESS OF FRACTURE PREVENTION TREATMENTS IN PATIENTS WITH OSTEOPOROSIS AT IMMINENT RISK OF FRACTURE

Osteoporotic fractures increase the risk of subsequent fracture. This risk is distinctly elevated immediately after the fragility fracture (‘imminent risk’) and can remain elevated for 10 years, highlighting the importance of early identification and treatment. Treatment sequences for new bone-forming agents are being assessed for use in patients at imminent risk of fracture. Here, we describe a new cost-effectiveness model framework relevant to the use of bone-forming agents. We developed a Markov-microsimulation model to simulate the projected treatment pathway, quality adjusted life years (QALYs) and lifetime costs of a patient with a fragility fracture, with treatment sequencing and time since fracture as factors. The patient could switch treatment when a lack of response was confirmed, or at any time point, dependent on clinical practice. In each 6-month cycle, we assessed risk of subsequent hip, vertebral and non-hip/non-vertebral fracture, remaining without subsequent fracture, or death. Fracture risk was derived from FRAX® and imminent fracture risk algorithms, and was updated for each patient in the event of subsequent fracture. Hypothetical examples were used for illustrative purposes. Treatment with a bone-forming agent immediately after fragility fracture was compared with treatment given 2 years after fracture. In an illustrative 75-year old woman with an initial vertebral fracture, the 10-year cumulative risk of a subsequent fracture was 11% lower for immediate treatment versus treatment after 2 years, fracture-related costs were 6% lower, QALY gain was 0.0172 and total costs were £1,758 higher. Similar values were derived with a lifetime perspective. This new economic modelling framework allows an estimation of the consequences of recurring fragility fractures over time and of the utility of flexible treatment sequencing. Our model will enable future evaluation of the cost effectiveness of individual treatment strategies.

Comparison of the flexible parametric survival model and Cox model in estimating Markov transition probabilities using real-world data.

Background and objectiveMarkov micro-simulation models are being increasingly used in health economic evaluations. An important feature of the Markov micro-simulation model is its ability to consider transition probabilities of heterogeneous subgroups with different risk profiles. A survival analysis is generally performed to accurately estimate the transition probabilities associated with the risk profiles. This study aimed to apply a flexible parametric survival model (FPSM) to estimate individual transition probabilities.Materials and methodsThe data were obtained from a cohort study investigating ischemic stroke outcomes in Western China. In total, 585 subjects were included in the analysis. To explore the goodness of fit of the FPSM, we compared the estimated hazard ratios and baseline cumulative hazards, both of which are necessary to the calculate individual transition probabilities, and the Markov micro-simulation models constructed using the FPSM and Cox model to determine the validity of the two Markov micro-simulation models and cost-effectiveness results.ResultsThe flexible parametric proportional hazards model produced hazard ratio and baseline cumulative hazard estimates that were similar to those obtained using the Cox proportional hazards model. The simulated cumulative incidence of recurrent ischemic stroke and 5-years cost-effectiveness of Incremental cost-effectiveness Ratios (ICERs) were also similar using the two approaches. A discrepancy in the results was evident between the 5-years cost-effectiveness and the 10-years cost-effectiveness of ICERs, which were approximately 0.9 million (China Yuan) and 0.5 million (China Yuan), respectively.ConclusionsThe flexible parametric survival model represents a good approach for estimating individual transition probabilities for a Markov micro-simulation model.

Treatment for Symptomatic SLAP Tears in Middle-Aged Patients Comparing Repair, Biceps Tenodesis, and Nonoperative Approaches: A Cost-Effectiveness Analysis

To evaluate the cost-effectiveness of nonoperative management, primary SLAP repair, and primary biceps tenodesis for the treatment of symptomatic isolated type II SLAP tear. A microsimulation Markov model was constructed to compare 3 strategies for middle-aged patients with symptomatic type II SLAP tears: SLAP repair, biceps tenodesis, or nonoperative management. A failed 6-month trial of nonoperative treatment was assumed. The principal outcome measure was the incremental cost-effectiveness ratio in 2017 U.S. dollars using a societal perspective over a 10-year time horizon. Treatment effectiveness was expressed in quality-adjusted life-years (QALY). Model results were compared with estimates from the published literature and were subjected to sensitivity analyses to evaluate robustness. Primary biceps tenodesis compared with SLAP repair conferred an increased effectiveness of 0.06 QALY with cost savings of $1,766. Compared with nonoperative treatment, both biceps tenodesis and SLAP repair were cost-effective (incremental cost-effectiveness ratio values of $3,344/QALY gained and $4,289/QALY gained, respectively). Sensitivity analysis showed that biceps tenodesis was the preferred strategy in most simulations (52%); however, for SLAP repair to become cost-effective over biceps tenodesis, its probability of failure would have to be lower than 2.7% or the cost of biceps tenodesis would have to be higher than $14,644. When compared with primary SLAP repair and nonoperative treatment, primary biceps tenodesis is the most cost-effective treatment strategy for type II SLAP tears in middle-aged patients. Primary biceps tenodesis offers increased effectiveness when compared with both primary SLAP repair and nonoperative treatment and lower costs than primary SLAP repair. Level III, economic decision analysis.

Personalized Mammography Screening and Screening Adherence—A Simulation and Economic Evaluation

ObjectivePersonalized breast cancer screening has so far been economically evaluated under the assumption of full screening adherence. This is the first study to evaluate the effects of nonadherence on the evaluation and selection of personalized screening strategies. MethodsDifferent adherence scenarios were established on the basis of findings from the literature. A Markov microsimulation model was adapted to evaluate the effects of these adherence scenarios on three different personalized strategies. ResultsFirst, three adherence scenarios describing the relationship between risk and adherence were identified: 1) a positive association between risk and screening adherence, 2) a negative association, or 3) a curvilinear relationship. Second, these three adherence scenarios were evaluated in three personalized strategies. Our results show that it is more the absolute adherence rate than the nature of the risk-adherence relationship that is important to determine which strategy is the most cost-effective. Furthermore, probabilistic sensitivity analyses showed that there are risk-stratified screening strategies that are more cost-effective than routine screening if the willingness-to-pay threshold for screening is below US $60,000. ConclusionsOur results show that “nonadherence” affects the relative performance of screening strategies. Thus, it is necessary to include the true adherence level to evaluate personalized screening strategies and to select the best strategy.

A cost-effectiveness analysis of E/C/F/TAF vs three boosted regimens in the Italian context

BACKGROUND: Highly Active Antiretroviral Therapy (HAART) has transformed HIV into a lifelong condition. Following the chronicity of the disease, and significant increase in lifespan – the prevalence of comorbidities increased in HIV+ subjects that are exposed both to a higher risk of developing cardiovascular disease, renal disease, osteopenia/osteoporosis and diabetes, and to the risk of developing them early. Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Fumarate (E/C/F/TAF), a complete, Single-Tablet antiretroviral Regimen (STR) that combines the effectiveness and tolerability of integrase inhibitors with an innovative backbone was recently introduced in Italy. Compared to Tenofovir Disoproxil Fumarate (TDF), TAF reaches the sites of action more efficiently, reducing tenofovir plasma concentration to more than 90% and the risk of off-target effects.OBJECTIVE: A patient-level micro-simulation model was adapted to the Italian context to evaluate E/C/F/TAF cost-effectiveness vs three boosted regimens for HIV+ patients treatment.METHODS: A Markov micro-simulation model was adapted to the Italian context for the evaluation of the cost-effectiveness in patients with HIV. The total cost per patient accounts for drug therapies and the management of adverse events and comorbidities. The quality-adjusted life expectancy (in QALYs) is calculated by weighing the years of life lived by the utility weights. A 70-year time horizon was adopted to simulate a lifetime analysis; shorter time horizons were considered in the sensitivity analyses. 3.5% discount rate was applied both for costs and future benefits. The rate of virologic suppression at 48 weeks with E/C/F/TAF is 92.3%; for the other treatments such proportion is calculated by applying to the reference rate the relative risks, as calculated in a recent network meta-analysis (NMA). Alternative treatments considered in this analysis are three boosted regimens commonly used in Italy: tenofovir disoproxil fumarate/emtricitabine/elvitegravir/cobicistat in STR; tenofovir disoproxil fumarate/emtricitabine + darunavir/ritonavir; tenofovir disoproxil fumarate/emtricitabine + atazanavir/ritonavir.RESULTS: E/C/F/TAF improves survival and quality of life (20.17 LY and 14.89 QALY), with the lowest total cost (€ 280,528), thus resulting dominant over three comparators considered as starting therapy. The sensitivity analysis confirms the results of the base case: at a willingness-to-pay threshold of € 30,000 per QALY, the E/C/F/TAF strategy is the most cost-effective, with a 90% probability and it is the most cost-effective even with a threshold of € 10,000 per QALY, with a 50% probability.CONCLUSION: E/C/F/TAF can be a sustainable alternative to currently available treatments, combining the advantage of the STR to lower risks of kidney and bone damage than observed in regimens based on TDF.

School-Based Influenza Vaccination: Health and Economic Impact of Maine's 2009 Influenza Vaccination Program.

To estimate the societal economic and health impacts of Maine's school-based influenza vaccination (SIV) program during the 2009 A(H1N1) influenza pandemic. Primary and secondary data covering the 2008-09 and 2009-10 influenza seasons. We estimated weekly monovalent influenza vaccine uptake in Maine and 15 other states, using difference-in-difference-in-differences analysis to assess the program's impact on immunization among six age groups. We also developed a health and economic Markov microsimulation model and conducted Monte Carlo sensitivity analysis. We used national survey data to estimate the impact of the SIV program on vaccine coverage. We used primary data and published studies to develop the microsimulation model. The program was associated with higher immunization among children and lower immunization among adults aged 18-49years and 65 and older. The program prevented 4,600 influenza infections and generated $4.9million in net economic benefits. Cost savings from lower adult vaccination accounted for 54 percent of the economic gain. Economic benefits were positive in 98 percent of Monte Carlo simulations. SIV may be a cost-beneficial approach to increase immunization during pandemics, but programs should be designed to prevent lower immunization among nontargeted groups.

Cost-Effectiveness of Different Durations of Dual-Antiplatelet Use After Percutaneous Coronary Intervention

BackgroundThere is uncertainty regarding the optimal duration of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). Our goal was to evaluate the cost-effectiveness of different durations of DAPT. MethodsWe created a probabilistic patient-level Markov microsimulation model to assess the discounted lifetime costs and quality-adjusted life years (QALYs) of short duration (3-6 months: short-duration group) vs standard therapy (12 months: standard-duration group) vs prolonged therapy (30-36 months: long-duration group) in patients undergoing PCI. ResultsThe majority of patients in the model underwent PCI for stable angina (47.1%) with second-generation drug-eluting stents (62%) and were receiving clopidogrel (83.6%). Short-duration DAPT was the most effective strategy (7.163 ± 1.098 QALYs) compared with standard-duration DAPT (7.161 ± 1.097 QALYs) and long-duration DAPT (7.156 ± 1.097 QALYs). However, the magnitude of these differences was very small. Similarly, the average discounted lifetime cost was CAN$24,859 ± $6533 for short duration, $25,045 ± $6533 for standard duration, and $25,046 ± $6548 for long duration. Thus, in the base-case analysis, short duration was dominant, being more effective and less expensive. However, there was a moderate degree of uncertainty, because short duration was the preferred option in only ∼ 55% of simulations at a willingness to pay threshold of $50,000. ConclusionsBased on a stable angina cohort receiving clopidogrel with second-generation stents, a short duration of DAPT was marginally better. However, the differences are minimal, and decisions about duration of therapy should be driven by clinical data, patient risk of adverse events, including bleeding, and cardiovascular events.