Model-based Health Economic Evaluation Research Articles

Evaluating the Cost-Utility of Continuous Glucose Monitoring in Individuals with Type 1 Diabetes: A Systematic Review of the Methods and Quality of Studies Using Decision Models or Empirical Data.

This review presents a critical appraisal of differences in the methodologies and quality of model-based and empirical data-based cost-utility studies on continuous glucose monitoring (CGM) in type 1 diabetes (T1D) populations. It identifies key limitations and challenges in health economic evaluations on CGM and opportunities for their improvement. The review and its documentation adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. Searches for articles published between January 2000 and January 2023 were conducted using the MEDLINE, Embase, Web of Science, Cochrane Library, and Econlit databases. Published studies using models and empirical data to evaluate the cost utility of all CGM devices used by T1D patients were included in the search. Two authors independently extracted data on interventions, populations, model settings (e.g., perspectives and time horizons), model types and structures, clinical outcomes used to populate the model, validation, and uncertainty analyses. They subsequently met to confirm consensus. Quality was assessed using the Philips checklist for model-based studies and the Consensus Health Economic Criteria(CHEC) checklist for empirical studies. Model validation was assessed using the Assessment of the Validation Status of Health-Economicdecision models (AdViSHE) checklist. The extracted data were used to generate summary tables and figures. The study protocol is registered with PROSPERO (CRD42023391284). In total, 34 studies satisfied the selection criteria, two of which only used empirical data. The remaining 32 studies applied 10 different models, with a substantial majority adopting the CORE Diabetes Model. Model-based studies often lacked transparency, as their assumptions regarding the extrapolation of treatment effects beyond available evidence from clinical studies and the selection and processing of the input data were not explicitly stated. Initial scores for disagreements concerning checklists were relatively high, especially for the Philips checklist. Following their resolution, overall quality scores were moderate at 56%, whereas model validation scores were mixed. Strikingly, costing approaches differed widely across studies, resulting in little consistency in the elements included in intervention costs. The overall quality of studies evaluating CGM was moderate. Potential areas of improvement include developing systematic approaches for data selection, improving uncertainty analyses, clearer reporting, and explaining choices for particular modeling approaches. Few studies provided the assurance that all relevant and feasible options had been compared, which is required by decision makers, especially for rapidly evolving technologies such as CGM and insulin administration. High scores for disagreements indicated that several checklists contained questions that were difficult to interpret consistently for quality assessment. Therefore, simpler but comprehensive quality checklists may be needed for model-based health economic evaluation studies.

Quantifying societal burden of radiation-induced small bowel toxicity in patients with rectal cancer.

Advancements in rectal cancer (RC) treatment not only led to an increase in lives saved but also improved quality of life (QoL). Notwithstanding these benefits, RC treatment comes at the price of gastrointestinal morbidity in many patients. Health economic modelling poses an opportunity to explore the societal burden of such side-effects. This study aims to quantify radiation-induced late small bowel (SB) toxicity in survivors of RC for Three-Dimensional Conformal Radiation Therapy (3D-CRT), Intensity Modulated Radiation Therapy (IMRT) and Intensity Modulated Radiation Therapy - Image Guided Radiation Therapy (IMRT/IGRT). Materials and A model-based health economic evaluation was performed. The theoretical cohort consists of a case-mix of survivors of RC aged 25-99 years according to Belgian age-specific incidence rates. A societal perspective was adopted. The base case analysis was complemented with one-way deterministic analyses, deterministic scenario analyses and probabilistic sensitivity analysis (1,000 iterations). Results were presented as mean lifetime incremental cost (€) and utility (QALYs) per patient. The analyses showed that the use of innovative radiotherapy (RT) improves lifetime QoL in survivors of RC by 0.11 QALYs and 0.05 QALYs by preferring IMRT/IGRT and IMRT over 3D-CRT, respectively. The use of IMRT/IGRT and IMRT results in an incremental cost-saving of €3,820 and €1,863 per patient, solely by radiation-induced SB toxicity, compared to 3D-CRT. It is important to consider late toxicity effects in decisions regarding investments and reimbursement as our analysis highlighted the potential long-term cost-savings and improved QoL of novel RT techniques in patients with rectal cancer.

Cost and Utility Estimates per Modified Rankin Scale Score up to 2 Years Post Stroke: Data to Inform Economic Evaluations From a Societal Perspective

ObjectivesModel-based health economic evaluations of ischemic stroke are in need of cost- and utility estimates related to relevant outcome measures. This study aims to describe societal cost- and utility estimates per modified Rankin Scale (mRS)-score at different time points within 2 years post stroke. MethodsIncluded patients had a stroke between 3 months and 2.5 years ago. mRS and EQ-5D-5L were scored during a telephone interview. Based on the interview date, records were categorized into a time point: 3 months (3M; 3-6 months), 1 year (Y1; 6-18 months), or 2 years (Y2; 18-30 months). Patients completed a questionnaire on healthcare utilization and productivity losses in the previous 3 months. Initial stroke hospitalization costs were assessed. Mean costs and utilities per mRS and time point were derived with multiple imputation nested in bootstrapping. Cost at 3 months post stroke were estimated separately for endovascular treatment (EVT)-/non-EVT-patients. Results1106 patients were included from 18 Dutch centers. At each time point, higher mRS-scores were associated with increasing average costs and decreasing average utility. Mean societal costs at 3M ranged from €11 943 (mRS 1, no EVT) to €55 957 (mRS 5, no EVT). For Y1, mean costs in the previous 3 months ranged from €885 (mRS 0) to €23 215 (mRS 5), and from €1655 (mRS 0) to €22 904 (mRS 5) for Y2. Mean utilities ranged from 0.07 to 0.96, depending on mRS and time point. ConclusionsThe mRS-score is a major determinant of costs and utilities at different post-stroke time points. Our estimates may be used to inform future model-based health economic evaluations.

Costs and health effects of CT perfusion-based selection for endovascular thrombectomy within 6 hours of stroke onset: a model-based health economic evaluation

BackgroundAlthough CT perfusion (CTP) is often incorporated in acute stroke workflows, it remains largely unclear what the associated costs and health implications are in the long run of CTP-based patient...

Cost-effectiveness analysis of artificial intelligence-based diabetic retinopathy screening in rural China based on the Markov model.

This study assessed the cost-effectiveness of different diabetic retinopathy (DR) screening strategies in rural regions in China by using a Markov model to make health economic evaluations. In this study, we determined the structure of a Markov model according to the research objectives, which required parameters collected through field investigation and literature retrieval. After perfecting the model with parameters and assumptions, we developed a Markov decision analytic model according to the natural history of DR in TreeAge Pro 2011. For this model, we performed Markov cohort and cost-effectiveness analyses to simulate the probabilistic distributions of different developments in DR and the cumulative cost-effectiveness of artificial intelligence (AI)-based screening and ophthalmologist screening for DR in the rural population with diabetes mellitus (DM) in China. Additionally, a model-based health economic evaluation was performed by using quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios. Last, one-way and probabilistic sensitivity analyses were performed to assess the stability of the results. From the perspective of the health system, compared with no screening, AI-based screening cost more (the incremental cost was 37,257.76 RMB (approximately 5,211.31 US dollars)), but the effect was better (the incremental utility was 0.33). Compared with AI-based screening, the cost of ophthalmologist screening was higher (the incremental cost was 14,886.76 RMB (approximately 2,070.19 US dollars)), and the effect was worse (the incremental utility was -0.31). Compared with no screening, the incremental cost-effectiveness ratio (ICER) of AI-based DR screening was 112,146.99 RMB (15,595.47 US dollars)/QALY, which was less than the threshold for the ICER (< 3 times the per capita gross domestic product (GDP), 217,341.00 RMB (30,224.03 US dollars)). Therefore, AI-based screening was cost-effective, which meant that the increased cost for each additional quality-adjusted life year was merited. Compared with no screening and ophthalmologist screening for DR, AI-based screening was the most cost-effective, which not only saved costs but also improved the quality of life of diabetes patients. Popularizing AI-based DR screening strategies in rural areas would be economically effective and feasible and can provide a scientific basis for the further formulation of early screening programs for diabetic retinopathy.

Comparative analysis of disease modelling for health economic evaluations of systemic therapies in advanced hepatocellular carcinoma.

The objective of this study was to systematically analyse methodological and structural assumptions utilised in model-based health economic evaluations of systemic advanced hepatocellular carcinoma (HCC) therapies, discuss the existing challenges, and develop methodological recommendations for future models in advanced HCC. We performed literature searches using five databases (Embase, PubMed, Web of Science, Econlit, and CNKI) up to December 4, 2022. Technology appraisals from Canada, England, Australia, and the United States were also considered. Model-based full economic evaluations of systemic advanced HCC therapies in English or Chinese met the eligibility criteria. The reporting quality was assessed by using the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. Of 12,863 records retrieved, 55 were eligible for inclusion. Markov model (n = 29, 53%) and partitioned survival model (n = 27, 49%) were the most commonly used modelling techniques. Most studies were based on health-state-driven structure (n = 51, 93%), followed by treatment-line-driven structure (n = 2, 4%) and combination structure (n = 1, 2%). Only three studies (5%) adopted external real-world data to extrapolate the overall survival or calibrate the extrapolation. Few studies reported the assumptions of transition probabilities. Utility modelling approaches were state-based (n = 51, 93%) and time-to-death (n = 1, 2%). Only 13 studies (24%) reported five types of model validation. Economic evaluation results of specific treatment strategies varied among studies. Disease modelling for health economic evaluations of systemic therapies in advanced HCC has adopted various modelling approaches and assumptions, leading to marked uncertainties in results. By proposing methodological recommendations, we suggest that future model-based studies for health economic evaluation of HCC therapies should follow good modelling practice guidelines and improve modelling methods to generate reliable health and economic evidence.

Cost-effectiveness of CT perfusion for the detection of large vessel occlusion acute ischemic stroke followed by endovascular treatment: a model-based health economic evaluation study

ObjectivesCT perfusion (CTP) has been suggested to increase the rate of large vessel occlusion (LVO) detection in patients suspected of acute ischemic stroke (AIS) if used in addition to a standard diagnostic imaging regime of CT angiography (CTA) and non-contrast CT (NCCT). The aim of this study was to estimate the costs and health effects of additional CTP for endovascular treatment (EVT)–eligible occlusion detection using model-based analyses.MethodsIn this Dutch, nationwide retrospective cohort study with model-based health economic evaluation, data from 701 EVT-treated patients with available CTP results were included (January 2018–March 2022; trialregister.nl:NL7974). We compared a cohort undergoing NCCT, CTA, and CTP (NCCT + CTA + CTP) with a generated counterfactual where NCCT and CTA (NCCT + CTA) was used for LVO detection. The NCCT + CTA strategy was simulated using diagnostic accuracy values and EVT effects from the literature. A Markov model was used to simulate 10-year follow-up. We adopted a healthcare payer perspective for costs in euros and health gains in quality-adjusted life years (QALYs). The primary outcome was the net monetary benefit (NMB) at a willingness to pay of €80,000; secondary outcomes were the difference between LVO detection strategies in QALYs (ΔQALY) and costs (ΔCosts) per LVO patient.ResultsWe included 701 patients (median age: 72, IQR: [62–81]) years). Per LVO patient, CTP-based occlusion detection resulted in cost savings (ΔCosts median: € − 2671, IQR: [€ − 4721; € − 731]), a health gain (ΔQALY median: 0.073, IQR: [0.044; 0.104]), and a positive NMB (median: €8436, IQR: [5565; 11,876]) per LVO patient.ConclusionCTP-based screening of suspected stroke patients for an endovascular treatment eligible large vessel occlusion was cost-effective.Clinical relevance statement.Although CTP-based patient selection for endovascular treatment has been recently suggested to result in worse patient outcomes after ischemic stroke, an alternative CTP-based screening for endovascular treatable occlusions is cost-effective.Key Points• Using CT perfusion to detect an endovascular treatment-eligible occlusions resulted in a health gain and cost savings during 10 years of follow-up.• Depending on the screening costs related to the number of patients needed to image with CT perfusion, cost savings could be considerable (median: € − 3857, IQR: [€ − 5907; € − 1916] per patient).• As the gain in quality adjusted life years was most affected by the sensitivity of CT perfusion-based occlusion detection, additional studies for the diagnostic accuracy of CT perfusion for occlusion detection are required.

Optimising the current model of care for knee osteoarthritis with the implementation of guideline recommended non-surgical treatments: a model-based health economic evaluation

Structured exercise, education, weight management and painkiller prescription are guideline recommended non-surgical treatments for patients suffering from knee osteoarthritis. Despite its endorsement, uptake of guideline recommended non-surgical treatments remains low. It is unknown whether the implementation of these treatments into the current model of care for knee osteoarthritis would be cost-effective from a Swiss statutory healthcare perspective. We therefore aimed to (1) assess the incremental cost-effectiveness ratio of an optimised model of care incorporating guideline recommended non-surgical treatments in adults with knee osteoarthritis and (2) the effect of total knee replacement (TKR) delay with guideline recommended non-surgical treatments on the cost-effectiveness of the overall model of care. A Markov model from the Swiss statutory healthcare perspective was used to compare an optimised model of care incorporating guideline recommended non-surgical treatments versus the current model of care without standardised guideline recommended non-surgical treatments. Costs were derived from two Swiss health insurers, a national database, and a reimbursement catalogue. Utility values and transition probabilities were extracted from clinical trials and national population data. The main outcome was the incremental cost-effectiveness ratio for three scenarios: "base case" (current model of care vs optimised model of care with no delay of total knee replacement), "two-year delay" (current model of care vs optimised model of care + two-year delay of total knee replacement) and "five-year delay" (current model of care vs optimised model of care + five-year delay of total knee replacement). Costs and utilities were discounted at 3% per year and a time horizon of 70 years was chosen. Probabilistic sensitivity analyses were conducted. The "base case" scenario led to 0.155 additional quality-adjusted life years (QALYs) per person at an additional cost per person of CHF 341 (ICER = CHF 2,203 / QALY gained). The "two-year delay" scenario led to 0.134 additional QALYs and CHF -14 cost per person. The "five-year delay" scenario led to 0.118 additional QALYs and CHF -501 cost per person. Delay of total knee replacement by two and five years led to an 18% and 36% reduction of revision surgeries, respectively, and had a cost-saving effect. According to this Markov model, the optimisation of the current model of care by implementing guideline recommended non-surgical treatments would likely be cost-effective from a statutory healthcare perspective. If implementing guideline recommended non-surgical treatments delays total knee replacement by two or five years, the amount of revision surgeries may be reduced.

Comprehensive Review of Methods to Assess Uncertainty in Health Economic Evaluations

Uncertainty assessment is a cornerstone in model-based health economic evaluations (HEEs) that inform reimbursement decisions. No comprehensive overview of available uncertainty assessment methods currently exists. We aimed to review methods for uncertainty assessment for use in model-based HEEs, by conducting a snowballing review. We categorised all methods according to their stage of use relating to uncertainty assessment (identification, analysis, communication). Additionally, we classified identification methods according to sources of uncertainty, and subdivided analysis and communication methods according to their purpose. The review identified a total of 80 uncertainty methods: 30 identification, 28 analysis, and 22 communication methods. Uncertainty identification methods exist to address uncertainty from different sources. Most identification methods were developed with the objective to assess related concepts such as validity, model quality, and relevance. Almost all uncertainty analysis and communication methods required uncertainty to be quantified and inclusion of uncertainties in probabilistic analysis. Our review can help analysts and decision makers in selecting uncertainty assessment methods according to their aim and purpose of the assessment. We noted a need for further clarification of terminology and guidance on the use of (combinations of) methods to identify uncertainty and related concepts such as validity and quality. A key finding is that uncertainty assessment relies heavily on quantification, which may necessitate increased use of expert elicitation and/or the development of methods to assess unquantified uncertainty.

Understanding bias in probabilistic analysis in model-based health economic evaluation.

Guidelines of economic evaluations suggest that probabilistic analysis (using probability distributions as inputs) provides less biased estimates than deterministic analysis (using point estimates) owing to the non-linear relationship of model inputs and model outputs. However, other factors can also impact the magnitude of bias for model results. We evaluate bias in probabilistic analysis and deterministic analysis through three simulation studies. The simulation studies illustrate that in some cases, compared with deterministic analyses, probabilistic analyses may be associated with greater biases in model inputs (risk ratios and mean cost estimates using the smearing estimator), as well as model outputs (life-years in a Markov model). Point estimates often represent the most likely value of the parameter in the population, given the observed data. When model parameters have wide, asymmetric confidence intervals, model inputs with larger likelihoods (e.g., point estimates) may result in less bias in model outputs (e.g., costs and life-years) than inputs with lower likelihoods (e.g., probability distributions). Further, when the variance of a parameter is large, simulations from probabilistic analyses may yield extreme values that tend to bias the results of some non-linear models. Deterministic analysis can avoid extreme values that probabilistic analysis may encounter. We conclude that there is no definitive answer on which analytical approach (probabilistic or deterministic) is associated with a less-biased estimate in non-linear models. Health economists should consider the bias of probabilistic analysis and select the most suitable approach for their analyses.

Cost-Effectiveness of Mobile Health-Based Integrated Care for Atrial Fibrillation: Model Development and Data Analysis.

BackgroundMobile health (mHealth) technology is increasingly used in disease management. Using mHealth tools to integrate and streamline care has improved clinical outcomes of patients with atrial fibrillation (AF).ObjectiveThe aim of this study was to investigate the potential clinical and health economic outcomes of mHealth-based integrated care for AF from the perspective of a public health care provider in China.MethodsA Markov model was designed to compare outcomes of mHealth-based care and usual care in a hypothetical cohort of patients with AF in China. The time horizon was 30 years with monthly cycles. Model outcomes measured were direct medical cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed to examine the robustness of the base-case results.ResultsIn the base-case analysis, mHealth-based care gained higher QALYs of 0.0730 with an incurred cost of US $1090. Using US $33,438 per QALY (three times the gross domestic product) as the willingness-to-pay threshold, mHealth-based care was cost-effective, with an ICER of US $14,936 per QALY. In one-way sensitivity analysis, no influential factor with a threshold value was identified. In probabilistic sensitivity analysis, mHealth-based care was accepted as cost-effective in 92.33% of 10,000 iterations.ConclusionsThis study assessed the expected cost-effectiveness of applying mHealth-based integrated care for AF according to a model-based health economic evaluation. The exploration suggested the potential cost-effective use of mHealth apps in streamlining and integrating care via the Atrial fibrillation Better Care (ABC) pathway for AF in China. Future economic evaluation alongside randomized clinical trials is highly warranted to verify the suggestion and investigate affecting factors such as geographical variations in patient characteristics, identification of subgroups, and constraints on local implementation.

POSC55 Model-Based Health Economic Evaluations of Screening Using Chest Computed Tomography: A Systematic Review

Low-dose computed tomography (LDCT) is a promising technology for population-based screening programs because it is non-invasive, relatively inexpensive and has low radiation. Chest LDCT could be used to screen for different diseases of the lungs and heart. This review aimed to provide a detailed overview of the methodological decisions including organizational aspects (e.g. target screening population) reported in model-based health economic evaluations of screening programs using chest LDCT. Scopus and PubMed were searched for publications up to 25 June 2021. Eligible publications comprised prospective studies evaluating the long-term costs and health effects of screening with chest LDCT in a high-risk population, were written in English and published in the last ten years. Reporting quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. The search yielded 795 unique papers, of which 33 were included. Most papers focused on lung cancer screening (n=31, 94%), followed by coronary calcium scoring (n=2, 6%). There were no evaluations of screening for multiple diseases. Cohort models (e.g. decision trees) were the most common modelling technique (n=21, 64%), followed by microsimulation (n=12, 36%). Studies were in the healthcare context of the United States (n=10), Canada (n=3), the United Kingdom (n=3) and 11 other countries. Only 10 papers (24%) included the effect of an imperfect attendance rate. The reported incremental cost-effectiveness of lung cancer screening compared to no-screening was US$34,000/QALY (US$10,000/QALY-US$90,000/QALY) and US$21,700/QALY (US$10,500/QALY-US$32,900/QALY) for coronary calcium scoring compared to current practice. The incremental cost-effectiveness reported in model-based health economic evaluations of screening using chest LDCT differ substantially between studies as reported for lung cancer and calcium scoring. This variation could be caused by the healthcare contexts in different countries, modelling methods, inputs and assumptions. A gap still exists in literature to evaluate the combination of screening for multiple diseases.

PMS15 Assessing the Reporting Quality of Studies of Health Economic Evaluation Models in Osteoarthritis

Health economic evaluation models are increasingly used to compare alternative treatments and preventions for osteoarthritis (OA) to inform health care resource allocation decisions. Studies reporting economic evaluations are recommended to follow consistent and transparent reporting criteria to allow scrutiny of study findings, and ultimately, better health decisions. We aimed to assess the extent to which the existing reporting guidelines are adopted in model-based health economic evaluations (MHEEs) of OA interventions.

A Systematic Review of Models Used in Cost-Effectiveness of Treatments in Spondyloarthritis

This review was aimed to evaluate health economic models used in evaluations of different treatment strategies in spondyloarthritis (SpA). Model-based health economic evaluation studies are increasing and complex models with short-term and long-term horizon are applied to investigate the cost-effectiveness of SpA treatments. The objective of this study was to carry out a systematic review of the evolution of health economic models used in the treatment of SpA. Electronic searches within MEDLINE and EMBASE were carried out using a predefined search strategy. Inclusion and exclusion criteria were used to select relevant studies. Data on country, intervention, evaluation perspective, type of model, time horizon, types of costs and effectiveness measurement were extracted. Eighteen models were described in 22 publications, of which 81.8% were European. Study perspectives included the societal (n=6), healthcare system and payer (n=14), or patient and government (n=1). Time horizon ranged from 52 weeks to lifetime. Markov model was the most frequently used model, only one individual patient simulation models accounting for uncertainty in multiple parameters was reported. Most studies compared different biologics (including different TNFi/biosimilar and IL-17A antibody) with conventional care (NSAIDs) because of the high prize. Only half of studies took indirect costs into account. Modeling is of importance in health economic evaluations of SpA treatment. Long-term costs especially indirect costs should be considered when comparing different treatment alternatives in order to provide more information for policy makers and clinicians.

Supplementary data for a model-based health economic evaluation on lung cancer screening with low-dose computed tomography in a high-risk population.

This supplementary data is supportive to the research article entitled ‘Cost-effectiveness of lung cancer screening with low-dose computed tomography (LDCT) in heavy smokers: A micro-simulation modelling study’ (Yihui Du et al. 2020). This supplementary contains a description of the model input and the related model output data that were not included in the research article. The input data used for the tumour growth model and the self-detected tumour size model are provided. The output data of this article include the data used for cost-effectiveness analysis of lung cancer LDCT screening with the Dutch and international discount rates, the data of the sensitivity analysis, and the data of the model validation.

Clinical implications of assumptions in cost-effectiveness analyses of systemic therapies for metastatic colorectal cancer.

e16021 Background: Considerable variation is observed in model-based cost-effectiveness analyses of systemic therapies for metastatic colorectal cancer (mCRC). This review provides a comprehensive and detailed discussion of structural and methodological assumptions in such analyses, and how those might impact health and economic outcomes. Methods: Five databases (EMBASE, MEDLINE, Cochrane Library, Health Technology Assessment, and National Health Service Health Economic Evaluation Database) were searched for model-based health economic evaluations of systemic mCRC treatment. Study selection, appraisal using the Consolidated Health Economic Evaluation Reporting Standards checklist, and data extraction was performed by two reviewers independently. Data extraction included general study characteristics, economic methods and assumptions, model structures and modelling technique, evidence used, extrapolation methods, validation efforts, and analyses performed. Economic outcomes were indexed to 2019 US$. Results: The search yielded 1,418 publications of which 54 were included, representing 51 unique studies. Most studies focused on first-line treatment (n = 29, 57%), followed by third-line treatment (n = 13, 25%). Although most studies mentioned consideration of further treatments (n = 29, 57%), this was typically only done by means of a lumpsum treatment cost (n = 21). Studies used varied modelling techniques and model structures, and different control strategies were adopted by studies aiming to estimate the cost-effectiveness of the same treatment. Only 15 studies (29%) reported some sort of model validation. Health economic outcomes for specific strategies differed substantially between studies. For example, survival following first-line treatment with fluorouracil, leucovorin, and oxaliplatin ranged from 1.21 to 7.33 years, with treatment costs ranging from US$8,125 to US$126,606. Conclusions: Model-based cost-effectiveness analyses of systemic mCRC treatments have adopted varied modelling methods and structures, which has resulted in substantial different health economic outcome estimates between studies, for example in terms of overall survival and average treatment cost per patient. Models generally focus on first-line treatment without considering the use of downstream treatments, suggesting these studies likely present biased results. This may impact the uptake of new systemic therapies.

Probiotics in hospitalized adult patients: a systematic review of economic evaluations.

PurposeProbiotics may prevent healthcare-associated infections, such as ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea, and other adverse outcomes. Despite their potential benefits, there are no summative data examining the cost-effectiveness of probiotics in hospitalized patients. This systematic review summarized studies evaluating the economic impact of using probiotics in hospitalized adult patients.MethodsWe searched MEDLINE, EMBASE, CENTRAL, ACP Journal Club, and other EBM reviews (inception to January 31, 2019) for health economics evaluations examining the use of probiotics in hospitalized adults. Independently and in duplicate, we extracted data study characteristics, risk of bias, effectiveness and total costs (medications, diagnostics/procedures, devices, personnel, hospital) associated with healthcare-associated infections (ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea and antibiotic-associated diarrhea). We used Grading of Recommendations Assessment, Development and Evaluation methods to assess certainty in the overall cost-effectiveness evidence.ResultsOf 721 citations identified, we included seven studies. For the clinical outcomes of interest, there was one randomized-controlled trial (RCT)-based health economic evaluation, and six model-based health economic evaluations. Probiotics showed favourable cost-effectiveness in six of seven (86%) economic evaluations. Three of the seven studies were manufacturer-supported, all which suggested cost-effectiveness. Certainty of cost-effectiveness evidence was very low because of risk of bias, imprecision, and inconsistency.ConclusionProbiotics may be an economically attractive intervention for preventing ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea, and antibiotic-associated diarrhea in hospitalized adult patients. Nevertheless, certainty about their cost-effectiveness evidence is very low. Future RCTs examining probiotics should incorporate cost data to inform bedside practice, clinical guidelines, and healthcare policy.Trial registration: PROSPERO CRD42019129929; Registered 25 April, 2019.Electronic supplementary materialThe online version of this article (10.1007/s12630-019-01525-2) contains supplementary material, which is available to authorized users.

A New Method for Model-Based Health Economic Evaluation Utilizing and Extending Moment-Generating Functions.

Background. Health economic evaluations frequently include projections for lifetime costs and health effects using modeling frameworks such as Markov modeling or discrete event simulation (DES). Markov models typically cannot represent events whose risk is determined by the length of time spent in state (sojourn time) without the use of tunnel states. DES is very flexible but introduces Monte Carlo variation, which can significantly limit the complexity of model analyses. Methods. We present a new methodological framework for health economic modeling that is based on, and extends, the concept of moment-generating functions (MGFs) for time-to-event random variables. When future costs and health effects are discounted, MGFs can be used to very efficiently calculate the total discounted life-years spent in a series of health states. Competing risks are incorporated into the method. This method can also be used to calculate discounted costs and health effects when these payoffs are constant per unit time, one-off, or exponential with regard to time. MGFs are extended to additionally support costs and health effects which are polynomial with regard to time (as in a commonly used model of population norms for EQ-5D utility). Worked Example. A worked example is used to demonstrate the application of the new method in practice and to compare it with Markov modeling and DES. Results are compared in terms of convergence and accuracy, and computation times are compared. R code and an Excel workbook are provided. Conclusions. The MGF method can be applied to health economic evaluations in the place of Markov modeling or DES and has certain advantages over both.

From Design to Evaluation: Applications of Health Technology Assessment in Myanmar and Lessons for Low or Lower Middle-Income Countries.

ObjectivesHealth technology assessment (HTA) has been widely used to inform coverage decisions in high-income countries over the past few decades and has been getting increasing attention in middle-income countries as a tool for healthcare decision making in recent years. This study aims to use the case of the Maternal and Child Health Voucher Scheme ( MCHVS ) in Myanmar to understand how HTA can have a policy impact in a low or lower middleincome country.MethodsThe stages heuristic framework was used to describe the policy-making process. A document review was conducted and tacit knowledge of researchers involved was recorded. Results. The opportunity for a grant propelled maternal and child health to the policy agenda. An ex-ante HTA, which included a model-based health economic evaluation, informed the design of the scheme. The framework and key parameters from the ex-ante HTA were used for a midaterm review, which provided feedback to the policy implementation process. An ex-post HTA involved fielding a household survey to assess the impact of the scheme.ConclusionsHTA can be a useful method for informing resource allocation throughout the policy process in low and lower middle-income settings where no formal mechanism for making coverage decisions exists.

Toward Alignment in the Reporting of Economic Evaluations of Diagnostic Tests and Biomarkers: The AGREEDT Checklist

Objectives. General frameworks for conducting and reporting health economic evaluations are available but not specific enough to cover the intricacies of the evaluation of diagnostic tests and biomarkers. Such evaluations are typically complex and model-based because tests primarily affect health outcomes indirectly and real-world data on health outcomes are often lacking. Moreover, not all aspects relevant to the evaluation of a diagnostic test may be known and explicitly considered for inclusion in the evaluation, leading to a loss of transparency and replicability. To address this challenge, this study aims to develop a comprehensive reporting checklist. Methods. This study consisted of 3 main steps: 1) the development of an initial checklist based on a scoping review, 2) review and critical appraisal of the initial checklist by 4 independent experts, and 3) development of a final checklist. Each item from the checklist is illustrated using an example from previous research. Results. The scoping review followed by critical review by the 4 experts resulted in a checklist containing 44 items, which ideally should be considered for inclusion in a model-based health economic evaluation. The extent to which these items were included or discussed in the studies identified in the scoping review varied substantially, with 14 items not being mentioned in ≥47 (75%) of the included studies. Conclusions. The reporting checklist developed in this study may contribute to improved transparency and completeness of model-based health economic evaluations of diagnostic tests and biomarkers. Use of this checklist is therefore encouraged to enhance the interpretation, comparability, and—indirectly—the validity of the results of such evaluations.