Discrete Health States Research Articles

Cost-effectiveness of Sacituzumab Govitecan versus Single-agent Chemotherapy for Patients with Metastatic Triple-Negative Breast Cancer in China

IntroductionPatients with metastatic triple-negative breast cancer (mTNBC) have poor prognosis and survival outcomes. Sacituzumab govitecan was newly approved into Chinese market for mTNBC. However, whether its price matches the survival benefit still needs exploring. Here, this study aimed to evaluate the cost-effectiveness of sacituzumab govitecan versus chemotherapy in patients with mTNBC from the perspective of Chinese healthcare system. MethodsA partitioned survival model consisting of three discrete health states was constructed to assess the cost-effectiveness of sacituzumab govitecan versus single-agent chemotherapy. The key clinical data in the model were from the ASCENT trial. Costs and utility inputs were collected from published literatures. Life-years gained, quality adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefits, and incremental net monetary benefits were calculated between 2 treatment strategies. One-way and probabilistic sensitivity analyses were conducted to account for uncertainty and verify model robustness. Subgroup and cost-threshold analysis were also performed. ResultsSacituzumab govitecan provided an additional 0.25 QALYs and an incremental cost of $ 81,778.61 compared with chemotherapy, which was associated with an ICER of $ 323,603.84/QALY. One-way sensitivity analysis revealed that the model was most sensitive to the cost of sacituzumab govitecan, weight, and utility of progression-free survival. The probabilistic sensitivity analysis indicated that the probability of sacituzumab govitecan being cost-effective was 0%. Considering a willingness-to-pay (WTP) of 3 times GDP, the maximum cost of sacituzumab govitecan that would make it cost-effective was $155.65 per unit (180 mg). ConclusionsSacituzumab govitecan was not cost-effective for patients with mTNBC compared with chemotherapy at the commonly adopted WTP threshold of 3 times GDP per capita per QALY in China.

OP11 Cost-Effectiveness Of Atezolizumab Plus Chemotherapy As A First-Line Treatment For Metastatic Non-Squamous Non-Small Cell Lung Cancer

IntroductionTreatment with atezolizumab plus standard chemotherapy can prolong the overall survival of patients with metastatic non-squamous non-small cell lung cancer (NSCLC). However, the economic value of this treatment regimen is unknown. This study aimed to estimate the cost effectiveness of atezolizumab plus chemotherapy in the first-line treatment of metastatic non-squamous NSCLC from a healthcare system perspective in China.MethodsA partitioned survival model consisting of three discrete health states was developed to estimate the cost and effectiveness of atezolizumab plus carboplatin or cisplatin plus pemetrexed (APP) versus carboplatin or cisplatin plus pemetrexed (PP) in the first-line treatment of metastatic non-squamous NSCLC over a 12-year lifetime horizon. Key clinical data were generated from the IMpower132 trial. Local direct medical and non-medical costs were used and health preference data were collected from patients with NSCLC in 13 tertiary hospitals across five provinces in China. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were measured. One-way and probabilistic sensitivity analyses were performed to assess the robustness of the model.ResultsCompared with the PP regimen, APP therapy yielded a gain of 0.21 QALYs at an increased cost of CNY145,602 (USD22,574), resulting in an ICER of CNY684,894 (USD106,185) per QALY gained. The ICER was significantly higher than three times the gross domestic product per capita for China in 2021 (USD37,663). One-way sensitivity analyses revealed that one of the most influential factors in this model was the cost of atezolizumab. Probabilistic sensitivity analysis showed that there was 14.7% probability that atezolizumab plus chemotherapy was cost effective at a willingness-to-pay value of CNY242,928 (USD37,663) per QALY gained.ConclusionsThe APP regimen could prolong survival and improve health benefits over standard chemotherapy in the first-line treatment of patients with metastatic non-squamous NSCLC, but it is unlikely to be a cost-effective treatment option in China.

Cost-effectiveness analysis of tislelizumab in combination with chemotherapy for the first-line treatment of patients with metastatic or recurrent nasopharyngeal carcinoma in China.

The combination of tislelizumab and gemcitabine plus cisplatin (GP) in the first-line treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) has yielded significant results. However, it is not clear whether this treatment option is cost-effective in China. The purpose of this study is to evaluate the cost-effectiveness of tislelizumab plus GP for the first-line treatment of R/M NPC from the perspective of the Chinese healthcare system. A partitioned survival model with three discrete health states was constructed to evaluate the cost-effectiveness of tislelizumab plus GP versus GP in patients with R/M NPC. The target population enrolled in the RATIONALE-309 trial had previously not treated for R/M NPC. Drug costs were obtained from relevant databases, and the remaining cost and health utility data were collected from the literature. The main outcomes include the expected life years, quality-adjusted life years (QALYs), total cost, and incremental cost-benefit ratio (ICER). The tislelizumab plus GP regimen produced an additional cost ($18392.76) and additional 1.57 QALYs compared with GP used alone. The ICER was $18392.75/QALYs. Sensitivity analysis showed that the analysis was robust and the utility of PD status was most sensitive to the model results. The possibility of tislelizumab plus GP being cost-effective at the willingness-to-pay (WTP) threshold of $37 653/QALY was 99.8%. Subgroup analysis showed that high PD-L1 expression had little impact on the ICER of this regimen. In patients with R/M NPC, the regimen of tislelizumab plus GP, as the first-line treatment, is more cost-effective than the GP regimen in China.

Multinational cost-effectiveness analysis of empagliflozin for heart failure patients with ejection fraction >40.

Heart failure is a chronic progressive condition, with considerable burden on patients' quality of life and economic burden for the healthcare systems. Before the approval of empagliflozin, there were no proven effective treatments for patients with heart failure with left ventricular ejection fraction (HF LVEF)>40%. The aim of this study was to evaluate the cost-effectiveness of empagliflozin+standard of care (SoC) compared with SoC alone for patients with HF LVEF>40%, from the perspective of the healthcare systems of the United Kingdom (UK), Spain, and France, and to quantify the healthcare costs for these patients. A lifetime Markov cohort state-transition model was developed based on discrete health states defined by Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score quartiles to track disease severity. Model inputs relied primarily on the EMPEROR-Preserved trial data or obtained from published literature or country-specific databases, as well as local guidelines for the requirements for the conduct of the economic evaluation of healthcare technologies. The total lifetime cost of receiving SoC per patient was £10092, €15765, and €14958 in the UK, Spain, and France, respectively, which increased by £1407, €1148, and €1485, respectively, with the addition of empagliflozin to the SoC. Empagliflozin+SoC was associated with significantly reduced number of hospitalization for HF or cardiovascular death compared with SoC alone, which was a key driver offsetting its drug acquisition costs. The incremental cost-effectiveness ratio per quality-adjusted life year (QALY) gained was consistently favourable at £14851, €11706, and €15447 in the UK, Spain, and France, respectively. Scenario analysis using the New York Heart Association functional class showed similar results. Probabilistic sensitivity analyses showed more than 50% probability for cost-effectiveness for a willingness-to-pay (WTP) threshold of £/€20000/QALY for the three countries. Empagliflozin was found to be the first targeted treatment option that is clinically effective and cost-effective for patients with HF LVEF>40%. Prescribing empagliflozin with SoC to patients with HF LVEF>40% is expected to improve clinical outcomes and patients' quality of life and substantially below accepted WTP threshold for the healthcare systems in the UK, Spain, and France.

Economic evaluation of 27,540 patients with mood and anxiety disorders and the importance of waiting time and clinical effectiveness in mental healthcare

Understanding the drivers of health and economic cost for the treatment of mental health conditions is critical to meet the accelerating demands for care. We conducted an economic evaluation of real-world healthcare-systems data from 27,540 patients receiving care for a mood or an anxiety disorder within the UK National Healthcare Service. Using Markov models built on discrete health states to compare the cost-effectiveness of different interventions, we show that the principal drivers of healthcare cost relate to waiting times and treatment effectiveness. We find that internet-delivered cognitive behavioral therapy has a ‘dominant’ incremental cost-effectiveness ratio relative to standard care, offering similar clinical effectiveness but with shorter treatment times. In most healthcare systems, the clinical effectiveness of mental healthcare remains unquantified, and long treatment times are common. The potential for these findings to inform mental healthcare policy is substantial, particularly around immediacy of access and the importance of outcomes-focused quality management.

Cost-effectiveness of sintilimab plus chemotherapy versus chemotherapy alone as first-line treatment of locally advanced or metastatic oesophageal squamous cell carcinoma.

Sintilimab plus chemotherapy significantly prolongs overall survival (OS) for patients with advanced or metastatic oesophageal squamous cell carcinoma (OSCC). However, the cost-effectiveness of this high-priced therapy is currently unknown. We evaluated the cost-effectiveness of sintilimab plus chemotherapy vs chemotherapy alone as fist-line therapy in patients with advanced or metastatic OSCC from the perspective of Chinese healthcare system. A partitioned survival model consisting of 3 discrete health states was constructed to assess the cost and effectiveness of sintilimab plus chemotherapy vs chemotherapy as first-line treatment of OSCC. Key clinical data in the model came from the ORIENT-15 trial. Costs and utilities were collected from published sources. Life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were calculated for the two treatment strategies. One-way and probabilistic sensitivity analyses were conducted to account for uncertainty and model stability. Additional subgroup and scenario analyses were performed. Treatment with sintilimab plus chemotherapy provided an additional 0.37 QALYs and an incremental cost of $8,046.58 compared with chemotherapy, which resulted in an ICER of $21,782.24 per QALY gained. One-way sensitivity analysis revealed that the model was most sensitive to utility of progression-free survival (PFS) and the cost of sintilimab. The probabilistic sensitivity analysis indicated that the probability of sintilimab plus chemotherapy being cost-effective was 0.01%, 76.80% and 98.60% at the threshold of 1, 2 or 3 times GDP per capita per QALY, respectively. Subgroup analysis found that all subgroups other than PD-L1 expression combined positive scores < 1 subgroup favored sintilimab plus chemotherapy treatment due to its association with positive INHBs by varying the hazard ratios for OS and PFS. The scenario analyses showed altering the time horizon of the model or fitting survival curves separately did not reverse results of the model. Sintilimab plus chemotherapy was associated with improved QALYs and an additional cost but was estimated to be cost-effective compared with chemotherapy alone as a first-line treatment for patients with advanced or metastatic OSCC at the commonly adopted willingness-to-pay threshold of 3 times GDP per capita per QALY in China.

Self-reported health status and latent health dynamics

Many dynamic structural models that include health as a state variable use categorical self-reported health status (SRHS) as their sole empirical measure of health. Commonly, transition probabilities among discrete health states are calculated directly from one-wave-ahead transitions observed in panel data. The predicted dynamics of SRHS generated from these calculations rapidly deviate from empirical transitions more than one wave ahead, as the assumption of a Markovian process is not satisfied. Consequently, models that treat SRHS as a true representation of health are not well calibrated to accurately match the long term dynamics of individual health. This paper specifies a model in which SRHS is a noisy measure of a continuous latent health state. I estimate the model by maximum likelihood on several panel datasets, exploiting long sequences of SRHS rather than simple wave-to-wave transitions. By accounting for transitory reporting error, the latent health model is able to match both short-run and long-run SRHS transitions up to twenty years in the future, as well as other features of empirical SRHS dynamics. Moreover, the measure of latent health is at least as good at predicting other outcomes (including mortality, labor supply, and medical expenses) as SRHS itself. To aid structural modelers in replacing their representation of health, I provide simple software tools for generating a discretized latent health process, and for filtering observed sequences of SRHS into (a distribution of) latent health.

Multistate Diagnosis and Prognosis of Lubricating Oil Degradation Using Sticky Hierarchical Dirichlet Process–Hidden Markov Model Framework

In this study, we present a state-based diagnostic and prognostic methodology for lubricating oil degradation based on a nonparametric Bayesian approach, i.e., sticky hierarchical Dirichlet process–hidden Markov model (HDP-HMM). An accurate health state-space assessment for diagnostics and prognostics has always been unobservable and hypothetical in the past. The lubrication condition monitoring (LCM) data is generally segregated as “healthy or unhealthy”, representing a binary state-based perspective to the problem. This two-state performance-based formulation poses limitations to the precision and accuracy of the diagnosis and prognosis for real data wherein there may be multiple states of discrete performance that are characteristic of the system functionality. In particular, the reversible and nonlinear time-series trends of degradation data increase the complexity of state-based modeling. We propose a multistate diagnostic and prognostic framework for LCM data in the wear-out phase (i.e., the unhealthy portion of degradation data), accounting for irregular oil replenishment and oil change effects (i.e., nonlinearity in the degradation signal). The LCM data is simulated for an elementary mechanical system with four components. The sticky HDP sets the prior for the HMM parameters. The unsupervised learning over infinite observations and emission reveals four discrete health states and helps estimate the associated state transition probabilities. The inferred state sequence provides information relating to the state dynamics, which provides further guidance to maintenance decision making. The decision making is further backed by prognostics based on the conditional reliability function and mean residual life estimation.

Cost-Effectiveness of Nivolumab Plus Ipilimumab as First-Line Therapy in Advanced Non-small-cell Lung Cancer.

Purpose: The effectiveness of nivolumab plus ipilimumab for advanced non-small cell lung cancer (NSCLC) has been demonstrated. Decisions have to be made about allocating healthcare resources. Economic evidence could support policy decisions to fund expensive interventions. The current analysis evaluated the cost-effectiveness of nivolumab plus ipilimumab in advanced NSCLC harboring no EGFR or ALK mutations. It is set in the context of the US and China, representing developed and resource-constrained settings, respectively. Patients and Methods: A Markov model consisting of three discrete health states was used to assess the cost-effectiveness of nivolumab plus ipilimumab vs. chemotherapy. The key clinical data were derived from the CheckMate-227 trial, and the cost and health preference data were derived from the literature. Costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs) and incremental net health benefits (INHBs) were calculated for the two strategies. Subgroup, one-way and probabilistic sensitivity analyses were performed. Results: In the United States, nivolumab plus ipilimumab increased by 1.260 QALYs with an additional cost of $95,617 compared with the features of chemotherapy, which led to an ICER of $75,871 per QALY gained. INHB indicated that nivolumab plus ipilimumab treatment had a 99% probability of being cost-effective at the ICER threshold of $100,000/QALY in all subgroups. The results of sensitivity analyses revealed that the model outcomes were robust. In China, the ICER of nivolumab plus ipilimumab vs. chemotherapy was $59,773/QALY, and the INHB was -1.972 QALY at the threshold of $27,351/QALY. Conclusion: Nivolumab plus ipilimumab treatment is a cost-effective option compared with chemotherapy for patients with advanced NSCLC harboring no EGFR or ALK mutations in the United States. However, nivolumab plus ipilimumab is not a preferred option in China.

Cost-effectiveness analysis of treatment for Koos 2 and 3 vestibular schwannomas: Wait & scan or radiosurgery

ObjectiveVestibular schwannomas are benign slowly growing tumors, with 3 treatment options: wait and scan, radiosurgery, and microsurgery with specific advantages and disadvantages. Contemporary debate has focused on medium size tumor. The present study used a Markov model to try to identify the cost-effectiveness in a lifelong perspective of the “wait & scan” or “radiosurgery” strategies for Koos 2 and 3 tumors. MethodsThe present model was defined by 5 discrete health states. All decision and chance nodes were assigned a probability of occurrence derived from a thorough review of the related literature. We calculated the expected effects and costs associated with the two strategies, then evaluated the incremental cost-effectiveness ratio. Sensitivity analysis was performed by altering the input values within a clinically reasonable range to assess the effects of uncertainties. ResultsRadiosurgery always requires more costs than wait & scan, and seems to generate small effects. However, the incremental cost-effectiveness ratio was significantly influenced by the hazard ratio of risk generated by deferred radiosurgery. One-way and two-way sensitivity analysis indicated that radiosurgery always yields negative effectiveness, compared with wait & scan at hazard ratio of less than 3.0, regardless of any other assumptions. ConclusionsTreatment strategy for medium size vestibular schwannoma should primarily be based on the future increased risk of radiosurgery after failure of conservative management. Wait & scan strategy may be the optimum approach for most Koos 2 and 3 tumors, but relatively large Koos 3 tumors are candidates for immediate radiosurgery.

Cost-effectiveness of Atezolizumab Plus Bevacizumab vs Sorafenib as First-Line Treatment of Unresectable Hepatocellular Carcinoma

Treatment with atezolizumab plus bevacizumab may prolong overall survival among patients with unresectable hepatocellular carcinoma. However, to our knowledge, the cost-effectiveness of using this high-priced therapy for this indication is currently unknown. To evaluate the cost-effectiveness of atezolizumab plus bevacizumab to treat unresectable hepatocellular carcinoma from the US payer perspective. This economic evaluation used a partitioned survival model consisting of 3 discrete health states to assess the cost-effectiveness of treatment of hepatocellular carcinoma with atezolizumab plus bevacizumab vs sorafenib. The characteristics of patients in the model were similar to patients in a phase 3, open-label randomized clinical trial (IMbrave150) who had unresectable hepatocellular carcinoma and had not previously received systemic treatment. Key clinical data were generated from the IMbrave150 trial conducted between March 15, 2018, and January 30, 2019, and cost and health preference data were collected from the literature. Costs, quality-adjusted life-years (QALYs), incremental cost-utility ratios, incremental net health benefits, and incremental net monetary benefits were calculated for the 2 treatment strategies. Subgroup, 1-way sensitivity, and probabilistic sensitivity analyses were performed. Treatment of hepatocellular carcinoma with atezolizumab plus bevacizumab added 0.530 QALYs and resulted in an incremental cost of $89 807 compared with sorafenib therapy, which had an incremental cost-utility ratio of $169 223 per QALY gained. The incremental net health benefit was -0.068 QALYs, and the incremental net monetary benefit was -$10 202 at a willingness-to-pay threshold of $150 000/QALY. The probabilistic sensitivity analysis indicated that treatment with atezolizumab plus bevacizumab achieved a 35% probability of cost-effectiveness at a threshold of $150 000/QALY. One-way sensitivity analysis revealed that the results were most sensitive to the hazard ratio of overall survival. The subgroup analysis found that treatment with atezolizumab plus bevacizumab was associated with preferred incremental net health benefits in several subgroups, including patients with hepatitis B and C. Atezolizumab plus bevacizumab treatment is unlikely to be a cost-effective option compared with sorafenib for patients with unresectable hepatocellular carcinoma. Reducing the prices of atezolizumab and bevacizumab may improve cost-effectiveness. The economic outcomes also may be improved by tailoring treatments based on individual patient factors.

Power and sample size for multistate model analysis of longitudinal discrete outcomes in disease prevention trials.

For clinical trials where participants pass through a number of discrete health states resulting in longitudinal measures over time, there are several potential primary estimands for the treatment effect. Incidence or time to a particular health state are commonly used outcomes but the choice of health state may not be obvious and these estimands do not make full use of the longitudinal assessments. Multistate models have been developed for some diseases and conditions with the purpose of understanding their natural history and have been used for secondary analysis to understand mechanisms of action of treatments. There is little published on the use of multistate models as the primary analysis method and potential implications on design features, such as assessment schedules. We illustrate methods via analysis of data from a motivating example; a Phase III clinical trial of pressure ulcer prevention strategies. We clarify some of the possible estimands that might be considered and we show, via a simulation study, that under some circumstances the sample size could be reduced by half using a multistate model based analysis, without adversely affecting the power of the trial.

Lenalidomide plus rituximab Vs rituximab alone in relapsed or refractory indolent lymphoma: A cost-effectiveness analysis.

BackgroundThe aim of the study was to evaluate the cost‐effectiveness of lenalidomide plus rituximab vs rituximab alone in patients with relapsed or refractory indolent lymphoma.MethodsA Markov decision model was established to carry out the cost‐effectiveness analysis. Three discrete health states, progression‐free survival (PFS), progressive disease (PD), and death, were included. Cycle length was set at 1 month, and utility scores were derived from previously published literature. The incremental cost‐effectiveness ratio (ICER) was defined as the primary endpoint, and the willingness‐to‐pay (WTP) threshold was set at $29,306.43 per quality‐adjusted life year (QALY). Both cost and effectiveness were determined using a 3% annual discount rate. Furthermore, one‐way and probabilistic sensitivity analyses were performed to check the robustness of the model.ResultsLenalidomide plus rituximab gained 6.08 QALYs at a cost of $120,979.62 while rituximab alone gained 4.84 QALYs at a cost of $48,052.11. The ICER of lenalidomide plus rituximab vs rituximab alone was $58,812.51/QALY. The parameters most significantly influenced the model were the utility values for the PFS state, the duration of the PFS state in the lenalidomide plus rituximab group, and the cost of lenalidomide. The probability of lenalidomide plus rituximab or rituximab alone being the most cost‐effective option was 0% and 100%, respectively, at a WTP threshold of $29,306.43/QALY.ConclusionsLenalidomide plus rituximab is not a cost‐effective strategy compared with rituximab monotherapy for relapsed or refractory indolent lymphoma from a Chinese societal perspective.

PNS337 IMPROVING ON CYCLE CORRECTIONS FOR TIME-HOMOGENEOUS MARKOV MODELS

Markov models, which specify transition probabilities between discrete health states at each time step, are widely used within health economic modelling. Decision problems are usually assessed by attaching utilities and costs to states and summing the total utility and cost of decision options over some time-frame. Frequently, a correction method (e.g. half-cycle correction (HCC)) is applied to naïve discrete-time outputs to yield a closer approximation to an underlying continuous-time Markov chain. In this study, we note that an underlying continuous-time Markov chain that corresponds to the proposed discrete time analogue may not exist, question the rationale for corrections in this case, and introduce a novel approximation method based on Gaussian Quadrature (GQ). We considered a simple model with three health states – well, unwell and dead. We exploited analytical results for time-homogeneous Markov chains in terms of matrix exponentials and inverses to compactly express calculations, and to introduce a new n-order GQ-based numerical integration method, which is applied to naïve discrete-time output. An n-order GQ method approximates the continuous-time Markov chain result by a weighted sum of function values at specified points within the range of integration and yields exact values for polynomials of degree up to 2n – 1. We conducted a simulation study to compare the GQ methodology and other existing cycle correction methods (HCC, trapezoidal, and Simpson 1/3 and 3/8 methods), to the exact continuous-time process outcomes (gold standard). At first order, we found that the GQ method replicated HCC. In our simulation study, the third-order GQ method outperformed other existing methods (HCC, trapezoidal and Simpson 1/3 and 3/8) in approximating the gold standard results. Simpson 1/3 turned out to be the second-best method. The third-order GQ method, applied to naïve discrete-time output, can outperform other cycle correction methods for homogeneous models. Defining models in continuous-time avoids potential inconsistencies.

754P - Effect of second-line cabozantinib on health states for patients with advanced hepatocellular carcinoma (aHCC) after sorafenib: QTWiST analysis from the CELESTIAL study

754P - Effect of second-line cabozantinib on health states for patients with advanced hepatocellular carcinoma (aHCC) after sorafenib: QTWiST analysis from the CELESTIAL study

The effect of model selection on cost-effectiveness research: a comparison of kidney function-based microsimulation and disease grade-based microsimulation in chronic kidney disease modeling

BackgroundCost effectiveness research is emerging in the chronic kidney disease (CKD) research field. Especially, an individual-level state transition model (microsimulation) is widely used for these researches. Some researchers set CKD grades as discrete health states, and the transition probabilities between these states were dependent on the CKD grades (disease grade-based microsimulation, MSM-dg), while others set estimated glomerular filtration rate value which determines the severity of CKD as a main variable describing patients’ continuous status (kidney function-based microsimulation, MSM-kf). MSM-kf seems to reflect the real world more precisely but is more difficult to implement. We compared the calculation results of these two microsimulation models to evaluate the effect of model selection on CKD cost-effectiveness analysis.MethodsWe implemented simplified MSM-dg and MSM-kf emulating natural course of CKD in general, and compared models using parameters derived from an IgA nephropathy cohort. After checking these models’ overall behavior, life-years, utilities, and thresholds regarding intervention costs below which the intervention is thought as dominant (V0) or cost-effective (V1) were calculated. In addition, one-way and probabilistic sensitivity analyses were performed.ResultsWith base-case parameters, the calculated life-years was shorter in MSM-dg (73.89 vs. 75.80 years) while the thresholds were almost equal (86.87 vs. 90.43 (V0), 132.29 vs. 146.25 [V1 in 1000 USD]) compared to MSM-kf. Sensitivity analyses showed a tendency of the MSM-dg to show shorter results in life-years. V0 and V1 were distributed by approximately ±100,000 USD (V0) and ± 150,000 USD (V1) between models.ConclusionsEstimated cost-effectiveness thresholds by both models were not the same and its difference distributed too wide to be ignored. This result indicated that model selection in CKD cost-effectiveness research has large effect on their conclusions.

QTWiST analysis of the RECOURSE trial of trifluridine/tipiracil in metastatic colorectal cancer

PurposeA Quality-adjusted Time WIthout Symptoms of disease or Toxicity (QTWiST) analysis was carried out to assess quality-adjusted survival time in the RECOURSE trial of trifluridine/tipiracil versus placebo in pretreated metastatic colorectal cancer (mCRC).MethodsDuration of overall survival in the RECOURSE trial (n=798 patients) was partitioned into three discrete health states: toxicity (TOX), time without symptoms or toxicity (TWIST) and relapse (REL). TOX was defined as time spent with grade 3 or 4 treatment-related adverse events (AEs) after randomisation and before progression or censoring. AEs were limited to those related to trifluridine/tipiracil and known to affect quality of life (QoL) (ie, nausea, vomiting, diarrhoea, fatigue/asthaenia, anorexia and febrile neutropaenia). The estimated mean duration of each state, weighted by a utility coefficient representing QoL, was combined into a global QTWiST score.ResultsIn the RECOURSE trial, overall survival was 7.1 months with trifluridine/tipiracil versus 5.3 months with placebo. Patients receiving trifluridine/tipiracil spent longer in each health state than placebo recipients. Using assumed utility coefficients of 1 for TWIST and 0.5 for TOX and REL, the QTWiST was 5.48 months for the trifluridine/tipiracil group and 3.98 months for the placebo group, a difference of 1.5 (95% CI 1.49 to 1.52) months in favour of trifluridine/tipiracil. A sensitivity analysis using large variations in utility coefficients for TOX and REL produced a range of only approximately 0.5 months from minimum to maximum QTWiST.ConclusionsQuality-adjusted survival, as measured by QTWiST, shows clinically meaningful improvements in patients treated with trifluridine/tipiracil versus placebo in pretreated mCRC.

The Use of Health State Utility Values in Decision Models.

Methodological issues of how to use health state utility values (HSUVs) in decision models arise frequently, including the most appropriate evidence to use as the baseline (e.g. the baseline HSUVs associated with avoiding a particular health condition or event), how to capture changes due to adverse events and how to appropriately capture uncertainty in progressive conditions where the expected change in quality of life is likely to be monotonically decreasing over time. As preference-based measures provide different values when collected from the same patient, it is important to ensure that all HSUVs used within a single model are obtained from the same instrument where ever possible. When people enter the model without the condition of interest (e.g. primary prevention of cardiovascular disease, screening or vaccination programmes), appropriate age- and gender-adjusted HSUVs from people without the particular condition should be used as the baseline. General population norms may be used as a proxy if the exact condition-specific evidence is not available. Individual discrete health states should be used for serious adverse reactions to treatment and the corresponding HSUVs sourced as normal. Care should be taken to avoid double counting when capturing the effects for both less severe adverse reactions (e.g. itchy skin rash or dry cough) and more severe adverse events (e.g. fatigue in oncology). Transparency in reporting standards for both the justification of the evidence used and any 'adjustments' is important to increase readers' confidence that the evidence used is the most appropriate available.

Latin American Clinical Epidemiology Network Series – Paper 4: Economic evaluation of Kangaroo Mother Care: cost utility analysis of results from a randomized controlled trial conducted in Bogotá

Background and ObjectiveAlthough kangaroo mother care (KMC) has been shown to be safe and effective in randomized controlled trials (RCTs), there are no published complete economic evaluations including the three components of the full intervention. MethodsA cost utility analysis performed on the results of an RCT conducted in Bogotá, Colombia between 1993 and 1996. Hospital and ambulatory costs were estimated by microcosting in a sample of preterm infants from a University Hospital in Bogotá in 2011 and at a KMC clinic in the same period. Utility scores were assigned by experts by means of (1) direct ordering and scoring discrete health states and (2) constructing a multi-attribute utility function. Ninety-five percent confidence intervals (CIs) for the incremental cost–utility ratios (ICURs) were computed by the Fiellers theorem method. One-way sensitivity analysis on price estimates for valuing costs was performed. ResultsICUR at 1 year of corrected age was $ −1,546 per extra quality-adjusted life year gained using the KMC method (95% CI $ −7,963 to $ 4,910). ConclusionIn Bogotá, the use of KMC is dominant: more effective and cost-saving. Although results from an economic analysis should not be extrapolated to different systems and communities, this dominant result suggests that KMC could be cost-effective in similar low and middle income countries settings.

Lifetime Effects of Small Unruptured Intracranial Aneurysms

Recent prospective multicenter studies have shown that the probability of rupture of unruptured aneurysms with maximal diameter <7 mm is rather low. However, the overall risks and long-term impact of unruptured aneurysms on lifetime quality of life are still unknown. A mathematical model of the natural history of intracranial aneurysms was constructed, in which the hypothetical individuals with or without unruptured aneurysm transit between discrete health states. The annual rupture rate of small aneurysms was assumed to be 0.5% in the baseline analysis, followed by the subsequent sensitivity analysis. The analyses were continued until cumulative death rate from subarachnoid hemorrhage or other causes reached 1.0. Age-specific ratios of death of subarachnoid hemorrhage in the individuals harboring unruptured aneurysm, if dying at 60 years old, were 25% in men and 43% in women. These ratios decreased rapidly with higher age. Most (more than 90%) patients with small aneurysms were expected to die of diseases other than subarachnoid hemorrhage. In the baseline analysis (60-year-old individuals), lifetime lost to small aneurysms could be estimated as 3.8% for men and 4.2% for women, but a somewhat larger impact could be identified in the young and/or female individuals compared with in the elderly and/or male individuals. Lifetime effects of small unruptured aneurysms without risk factors increasing the probability of rupture are relatively small, and most patients were expected to die of diseases other than subarachnoid hemorrhage.