The assessment of quality of care of patients with type 2 diabetes mellitus in a population-based cohort in the District of Landeck in Austria.

INTRODUCTION: Structured diabetes care based on evidence-based guidelines is one of the main strategies to improve glycemic control and to reduce long-term complications in diabetes mellitus. METHODS: This study is based on the "Diabetes-Landeck Cohort", a population-based cohort of patients with diabetes mellitus type 2 (T2DM). We assessed the quality of diabetes care and compared it between three groups of care units, that is, general practitioners (GP), diabetes specialists in private practice (DSPP), and hospitals (HOSP). RESULTS: The total study population comprised 1616 patients with T2DM, including 378 patients of GP, 281 of DSPP, and 957 from HOSP. We identified statistically significant differences: DSPP showed the highest percentage of structured training, sufficient training, eye examinations and foot examinations. The group HOSP showed the highest proportion for increased HbA1c≥ 7.5 and almost all long-term complications surveyed, that is, nephropathy (23.2%), neuropathy (14.4%), diabetic foot (5.1%), and cerebrovascular diseases (10.9%). CONCLUSION: This population-based cohort study on patients with T2DM in Austria showed significant differences in important quality-of-care process and outcome parameters across different groups of care units. Future research should also include prediction modeling for early warning and monitoring systems as well as adjustment for patient characteristics and duration and severity of disease.

Nature-based social interventions to address loneliness among vulnerable populations: a common study protocol for three related randomized controlled trials in Barcelona, Helsinki, and Prague within the RECETAS European project.

BACKGROUND: The negative effects of loneliness on population health and wellbeing requires interventions that transcend the medical system and leverage social, cultural, and public health system resources. Group-based social interventions are a potential method to alleviate loneliness. Moreover, nature, as part of our social and health infrastructure, may be an important part of the solutions that are needed to address loneliness. The RECETAS European project H2020 (Re-imagining Environments for Connection and Engagement: Testing Actions for Social Prescribing in Natural Spaces) is an international research project aiming to develop and test the effectiveness of nature-based social interventions to reduce loneliness and increase health-related quality of life. METHODS: This article describes the three related randomized controlled trials (RCTs) that will be implemented: the RECETAS-BCN Trial in Barcelona (Spain) is targeting people 18+ from low socio-economic urban areas; the RECETAS-PRG Trial in Prague (Czech Republic) is addressing community-dwelling older adults over 60 years of age, and the RECETAS-HLSNK trial is reaching older people in assisted living facilities. Each trial will recruit 316 adults suffering from loneliness at least sometimes and randomize them to nature-based social interventions called "Friends in Nature" or to the control group. "Friends in Nature" uses modifications of the "Circle of Friends" methodology based on group processes of peer support and empowerment but including activities in nature. Participants will be assessed at baseline, at post-intervention (3 months), and at 6- and 12-month follow-up after baseline. Primary outcomes are the health-related quality-of-life according to 15D measure and The De Jong Gierveld 11-item loneliness scale. Secondary outcomes are health and psychosocial variables tailored to the specific target population. Nature exposure will be collected throughout the intervention period. Process evaluation will explore context, implementation, and mechanism of impact. Additionally, health economic evaluations will be performed. DISCUSSION: The three RECETAS trials will explore the effectiveness of nature-based social interventions among lonely people from various ages, social, economic, and cultural backgrounds. RECETAS meets the growing need of solid evidence for programs addressing loneliness by harnessing the beneficial impact of nature on enhancing wellbeing and social connections. TRIAL REGISTRATION: Barcelona (Spain) trial: ClinicalTrials.gov, ID: NCT05488496. Registered 29 July 2022. Prague (Czech Republic) trial: ClinicalTrials.gov, ID: NCT05522140. Registered August 25, 2022. Helsinki (Finland) trial: ClinicalTrials.gov, ID: NCT05507684. Registered August 12, 2022.

Determinants of low health-related quality of life in patients with myelodysplastic syndromes: EUMDS Registry study.

Patients with myelodysplastic syndromes (MDS) frequently experience a significant symptom burden, which reduces health-related quality of life (HRQoL). We aimed to identify determinants of low HRQoL in patients recently diagnosed with MDS, for guiding early intervention strategies. We evaluated longitudinal data in 2205 patients with MDS during their first year after diagnosis. Median values of EQ-5D 3-level (EQ-5D-3L) index (0.78) and visual analog scale (VAS) score (0.70) were used as thresholds for low HRQoL. In addition, the 5 dimensions of EQ-5D-3L were analyzed for impairments (any level vs "no problem" category). After multiple imputation of missing values, we used generalized estimating equations (GEE) to estimate odds ratios (OR) for univariable determinant screening (P < .15), and to subsequently derive multivariable models for low HRQoL with 95% confidence intervals (CI). Multivariable GEE analysis showed the following independent determinants (OR, 95% CI) for low EQ-5D index: increased age (60-75 years: 1.33, 1.01-1.75; >75: 1.84, 1.39-2.45), female sex (1.70, 1.43-2.03), high serum ferritin level (≥1000 vs ≤300 µg/L: 1.41, 1.06-1.87), comorbidity burden (per unit: 1.11, 1.02-1.20), and reduced Karnofsky performance status (KPS, per 10 units: 0.62, 0.58-0.67). For low VAS score, additional determinants were transfusion dependence (1.53, 1.03-2.29), low hemoglobin <10 g/dL (1.34, 1.12-1.61), and high body mass index (≥30 vs 23-29.9 kg/m2: 1.26, 1.02-1.57). Sex, KPS, comorbidity burden, hemoglobin count, and transfusion burden were determinants for all EQ-5D dimensions. Low HRQoL is determined by multiple factors, which should be considered in the management and shared decision making of patients with MDS. This trial was registered at www.clinicaltrials.gov as #NCT00600860.

A population-based cohort of adult patients with diabetes mellitus in a Western District of Austria: The Diabetes Landeck cohort.

INTRODUCTION: Diabetes mellitus (DM) has become an important and exacerbating health epidemic, with severe consequences for both patients and health systems. The National Diabetes Strategy of Austria addresses the lack of high-quality data on DM in Austria and the need for developing a national data network. The aims of our study are to establish a cohort including all adult diabetes patients in a district in western Austria, describe the demographic and clinical characteristics of this cohort, and provide an estimation of diabetes prevalence. METHODS: We recruited a population-based cohort of adult patients with a diagnosis of DM in cooperation with a network of all caregivers. Data collection was based on a case report form, including patient characteristics, clinical parameters and long-term complications. RESULTS: In total, 1845 patients with DM were recruited and analysed. We observed an overall prevalence of 5.3% [95% CI: 5.0%-5.5%]. For the subsequent main analysis, we included 1755 patients with DM after excluding 90 patients with gestational DM. There were significant differences between genders in the distribution of specific clinical parameters, patient characteristics, and the long-term complications diabetic foot, amputation and cardiovascular disease. CONCLUSION: To the best of our knowledge, we established the first diabetes cohort study in Austria. Prevalence and the proportion of specific long-term complications were lower when compared to the international context. We assume that the Diabetes Landeck Cohort has reached a high degree of completeness; however, we were not able to identify independent data sources for a valid check of completeness.

Familial hypercholesterolemia: A systematic review of modeling studies on screening interventions.

BACKGROUND AND AIMS: FH is still underdiagnosed. Cost-effectiveness results of preventive screening strategies vary. We aimed at systematically assessing the benefits, harms and cost effectiveness of screening for familial hypercholesterolemia (FH) and at providing an overview of the main characteristics and methodological approaches of applied decision-analytic models. METHODS: A systematic literature search was conducted in MEDLINE, EconLit, CRD-databases and the CEA-registry for FH screening starting 2012. Earlier studies were included from a published systematic review. Results were reported in standardized semi-quantitative evidence tables. Costs were converted to current euros. Incremental cost-effectiveness ratios (ICERs) were recalculated according to economic guidelines. RESULTS: Out of our 211 retrieved studies, eight were included in the review in addition to six studies from an earlier review. Studies were conducted in Europe (UK, The Netherlands, Spain, Poland), USA and Australia evaluating cascade (CS), opportunistic (OS), universal screening (UniS), or combinations using genetic testing, clinical criteria or combinations. Studies evaluating only CS identified strategies with an ICER of up to 37,100 EUR/quality-adjusted life-year (QALY) but some strategies were dominated depending on test combinations. UniS of newborns in combination with CS had an ICER≤15,000 EUR/QALY for sequential cholesterol-genetic screening. In other studies, UniS was dominated by OS/CS. CONCLUSIONS: Our systematic review demonstrates the values of FH screening and provides an overview of potentially relevant screening strategies to be tested using a decision-analytic model for the respective country or region. Future research is needed on the transferability of results to other countries and modeling spillover effects to newborns.

Estimating Treatment-Switching Bias in a Randomized Clinical Trial of Ovarian Cancer Treatment: Combining Causal Inference with Decision-Analytic Modeling.

BACKGROUND: Bevacizumab is efficacious in delaying ovarian cancer progression and controlling ascites. The ICON7 trial showed a significant benefit in overall survival for bevacizumab, whereas the GOG-218 trial did not. GOG-218 allowed control group patients to switch to bevacizumab upon progression, which may have biased the results. Lack of data on switching behavior prevented the application of g-methods to adjust for switching. The objective of this study was to apply decision-analytic modeling to estimate the impact of switching bias on causal treatment-effect estimates. METHODS: We developed a causal decision-analytic Markov model (CDAMM) to emulate the GOG-218 trial and estimate overall survival. CDAMM input parameters were based on data from randomized clinical trials and the published literature. Overall switching proportion was based on GOG-218 trial information, whereas the proportion switching with and without ascites was estimated using calibration. We estimated the counterfactual treatment effect that would have been observed had no switching occurred by denying switching in the CDAMM. RESULTS: The survival curves generated by the CDAMM matched well with the ones reported in the GOG-218 trial. The survival curve correcting for switching showed an estimated bias such that 79% of the true treatment effect could not be observed in the GOG-218 trial. Results were most sensitive to changes in the proportion progressing with severe ascites and mortality. LIMITATIONS: We used a simplified model structure and based model parameters on published data and assumptions. Robustness of the CDAMM was tested and model assumptions transparently reported. CONCLUSIONS: Medical-decision science methods may be merged with empirical methods of causal inference to integrate data from other sources where empirical data are not sufficient. We recommend collecting sufficient information on switching behavior when switching cannot be avoided.

Core set of patient-reported outcomes for myelodysplastic syndromes: an EUMDS Delphi study involving patients and hematologists.

Patient-reported outcomes (PROs) are relevant and valuable end points in the care of patients with myelodysplastic syndromes (MDS). However, a consensus-based selection of PROs for MDS, derived by both patients and hematologists, is lacking. We aimed to develop a core set of PROs for patients with MDS as part of the prospective European LeukemiaNet MDS (EUMDS) Registry. According to international guidelines, candidate PROs were identified from a comprehensive literature search of MDS studies. Overall, 40 PROs were selected and evaluated in a two-round Delphi survey by 40 patients with MDS and 38 hematologists in the first round and 38 patients and 32 hematologists in the second round. Based on an agreement scale and predefined inclusion criteria, both patients and hematologists selected "general quality of life" as a core PRO. Hematologists also selected "transfusion-dependency burden" and "ability to work/activities of daily living" as core PROs. The second Delphi round increased PRO rating agreements. Statistically significant rating differences between patients and hematologists were observed for 28 PROs (Mann-Whitney U test; P < .05) in the first round and for 19 PROs in the second round, with "disease knowledge" and "confidence in health care services" rated notably higher by patients. The overall mean PRO ratings correlation between the 2 groups was moderate (Spearman's rank correlation coefficient = 0.5; P < .05). This first consensus on a core set of PROs jointly developed by patients and hematologists forms the basis for patient-centered care in daily practice and clinical research.

Benefits and Harms of a Prevention Program for Iodine Deficiency Disorders: Predictions of the Decision-Analytic EUthyroid Model.

Background: Iodine deficiency is one of the most prevalent causes of intellectual disability and can lead to impaired thyroid function and other iodine deficiency disorders (IDDs). Despite progress made on eradicating iodine deficiency in the last decades in Europe, IDDs are still prevalent. Currently, evidence-based information on the benefit/harm balance of IDD prevention in Europe is lacking. We developed a decision-analytic model and conducted a public health decision analysis for the long-term net benefit of a mandatory IDD prevention program for the German population with moderate iodine deficiency, as a case example for a European country. Methods: We developed a decision-analytic Markov model simulating the incidence and consequences of IDDs in the absence or presence of a mandatory IDD prevention program (iodine fortification of salt) in an open population with current demographic characteristics in Germany and with moderate ID. We collected data on the prevalence, incidence, mortality, and quality of life from European studies for all health states of the model. Our primary net-benefit outcome was quality-adjusted life years (QALYs) predicted over a period of 120 years. In addition, we calculated incremental life years and disease events over time. We performed a systematic and comprehensive uncertainty assessment using multiple deterministic one-way sensitivity analyses. Results: In the base-case analysis, the IDD prevention program is more beneficial than no prevention, both in terms of QALYs and life years. Health gains predicted for the open cohort over a time horizon of 120 years for the German population (82.2 million inhabitants) were 33 million QALYs and 5 million life years. Nevertheless, prevention is not beneficial for all individuals since it causes additional hyperthyroidism (2.7 million additional cases). Results for QALY gains were stable in sensitivity analyses. Conclusions: IDD prevention via mandatory iodine fortification of salt increases quality-adjusted life expectancy in a European population with moderate ID, and is therefore beneficial on a population level. However, further ethical aspects should be considered before implementing a mandatory IDD prevention program. Costs for IDD prevention and treatment should be determined to evaluate the cost effectiveness of IDD prevention.

Barriers Against Prevention Programs for Iodine Deficiency Disorders in Europe: A Delphi Study.

Background: Although substantial progress has been made in recent decades in eliminating iodine deficiency, iodine deficiency disorders (IDDs) are still prevalent in European countries. Challenges include ineffective public health programs and discontinuation of IDD prevention. However, the barriers against the implementation and continuation of prevention and monitoring of IDD remain unclear. Therefore, the objective of our study was to identify potential barriers against pan-European IDD prevention and monitoring programs and to find solutions for the different challenges. Methods: We conducted a Delphi study consisting of three rounds. We identified potential participants with expertise and experience in relevant fields from all European countries, including policy makers, health care professionals, health scientists, and patient representatives. The Delphi method was conducted with open-ended questions and item ranking to achieve group consensus on potential barriers against national and pan-European IDD prevention and monitoring programs and related solutions to overcome those barriers. The answers of the Delphi rounds were analyzed using qualitative content analysis and descriptive analysis methods. In addition, we conducted two expert interviews to analyze and discuss the study results. Results: Eighty experts from 36 countries and different fields of work participated in the first Delphi round, 52 in the second, and 46 in the third. Potential barriers include challenges in the fields of knowledge and information, implementation and management, communication and cooperation, political support, and differences between the European countries. Ranked solutions addressing these barriers include cooperation with different stakeholders, gaining knowledge, sharing information, the development of a European program with national specification, European guidelines/recommendations, and European monitoring. The ranking gives a first overview as to which of these barriers would need to be solved most urgently and which solutions may be most helpful. Conclusion: In our study, we derived key information and first insights with regard to barriers against IDD prevention programs from a broad range of stakeholders. Most barriers were found in the category of implementation and management. Also a lack of political support seems to play an important role. The findings of our study may help decision makers in health policy to develop more effective IDD prevention and monitoring strategies.

The economic impact of prevention, monitoring and treatment strategies for iodine deficiency disorders in Germany.

OBJECTIVE: More than 30% of the German population suffers from mild to moderate iodine deficiency causing goiter and other iodine deficiency disorders (IDDs). The economic burden of iodine deficiency is still unclear. We aimed to assess costs for prevention, monitoring and treatment of IDDs in Germany. DESIGN: We performed a comprehensive cost analysis. METHODS: We assessed direct medical costs and direct non-medical costs for inpatient and outpatient care of IDDs and costs for productivity loss due to the absence of work in 2018. Additionally, we calculated total costs for an IDD prevention program comprising universal salt iodization (USI). We performed threshold analyses projecting how many cases of IDDs or related treatments would need to be avoided for USI to be cost-saving. RESULTS: Annual average costs per case in the year of diagnosis were € 211 for goiter/thyroid nodules; € 308 for hyperthyroidism; and € 274 for hypothyroidism. Average one-time costs for thyroidectomy were € 4184 and € 3118 for radioiodine therapy. Average costs for one case of spontaneous abortion were € 916. Annual costs of intellectual disability were € 14,202. In the German population, total annual costs for USI would amount to 8 million Euro. To be cost-saving, USI would need to prevent, for example, 37,900 cases of goiter/thyroid nodules. CONCLUSION: USI potentially saves costs, if a minimum amount of IDDs per year could be avoided. In order to recommend the implementation of USI, a full health-economic evaluation including a comprehensive benefit-harm assessment is needed.

Long-Term Effectiveness and Cost Effectiveness of Multiple Myeloma Treatment Strategies for Elderly Transplant-Ineligible Patients in Serbia.

INTRODUCTION: Evidence on long-term effectiveness and cost effectiveness of treatment sequences for multiple myeloma (MM) is sparse. We used published data and country-specific data to assess the cost effectiveness of four-line treatment sequences for elderly transplant-ineligible patients with MM in Serbia. METHOD: We developed a Markov cohort model to compare long-term effectiveness and cost effectiveness of five sequential MM treatment alternatives from the perspective of the national healthcare provider. Effectiveness parameters on progression, mortality and adverse events were extracted from published clinical trials. Costs were based on price lists of the National Health Insurance Fund. We compared life expectancy, costs, and incremental cost-effectiveness ratios among alternative courses of action. The model was analyzed over a lifelong time horizon applying a 3% annual discount rate for effectiveness outcomes and costs. Robustness of the model was tested in multiple deterministic sensitivity analyses. RESULTS: The sequences were defined by the frontline treatment: MPT (melphalan-prednisone-thalidomide), MPV (melphalanprednisone-bortezomib), CTD (cyclophosphamide-thalidomide-dexamethasone), VCD (bortezomib-cyclophosphamidedexamethasone) and BP (bendamustine-prednisone). MPV sequence resulted in the highest remaining life expectancy (4.76 life years). Cost-effectiveness analysis resulted in three non-dominated strategies: MPT, VCD, and MPV sequences, with an incremental cost-effectiveness ratio of EUR 35,300 per life-year gained (LYG) for VCD and EUR 47,200/LYG for MPV relative to MPT. CONCLUSION: MPV sequence was the most effective in terms of life expectancy for elderly transplant-ineligible MM patients in Serbia. Bortezomib-based strategies would be recommended for the frontline treatment of patients with MM in Serbia if the willingness-to-pay threshold is around EUR 35,000-60,000/LYG.

Development of a core outcome set for myelodysplastic syndromes - a Delphi study from the EUMDS Registry Group.

Treatment options for myelodysplastic syndromes (MDS) vary widely, depending on the natural disease course and patient-related factors. Comparison of treatment effectiveness is challenging as different endpoints have been included in clinical trials and outcome reporting. Our goal was to develop the first MDS core outcome set (MDS-COS) defining a minimum set of outcomes that should be reported in future clinical studies. We performed a comprehensive systematic literature review among MDS studies to extract patient- and/or clinically relevant outcomes. Clinical experts from the European LeukemiaNet MDS (EUMDS) identified 26 potential MDS core outcomes and participated in a three-round Delphi survey. After the first survey (56 experts), 15 outcomes met the inclusion criteria and one additional outcome was included. The second round (38 experts) resulted in six included outcomes. In the third round, a final check on plausibility and practicality of the six included outcomes and their definitions was performed. The final MDS-COS includes: health-related quality of life, treatment-related mortality, overall survival, performance status, safety, and haematological improvement. This newly developed MDS-COS represents the first minimum set of outcomes aiming to enhance comparability across future MDS studies and facilitate a better understanding of treatment effectiveness.

Decision-Analytic Modeling Studies in Prevention and Treatment of Iodine Deficiency and Thyroid Disorders: A Systematic Overview.

Background: Prevention and treatment of iodine deficiency-related diseases remain an important public health challenge. Iodine deficiency can have severe health consequences, such as cretinism, goiter, or other thyroid disorders, and it has economic implications. Our aim was to give an overview of studies applying decision-analytic modeling to evaluate the effectiveness and/or cost-effectiveness of iodine deficiency-related prevention strategies or treatments related to thyroid disorders. Methods: We performed a systematic literature search in PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), EMBASE (Excerpta Medica Database), Tuft's Cost-Effectiveness Analysis Registry, and National Health System Economic Evaluation Database (NHS EED) to identify studies published between 1985 and 2018 comparing different prevention or treatment strategies for iodine deficiency and thyroid disorders by applying a mathematical decision-analytic model. Studies were required to evaluate patient-relevant health outcomes (e.g., remaining life years, quality-adjusted life years [QALYs]). Results: Overall, we found 3950 studies. After removal of duplicates, abstract/title, and full-text screening, 17 studies were included. Eleven studies evaluated screening programs (mainly newborns and pregnant women), five studies focused on treatment approaches (Graves' disease, toxic thyroid adenoma), and one study was about primary prevention (consequences of iodine supplementation on offspring). Most of the studies were conducted within the U.S. health care context (n = 7). Seven studies were based on a Markov state-transition model, nine studies on a decision tree model, and in one study, an initial decision tree and a long-term Markov state-transition model were combined. The analytic time horizon ranged from 1 year to lifetime. QALYs were evaluated as health outcome measure in 15 of the included studies. In all studies, a cost-effectiveness analysis was performed. None of the models reported a formal model validation. In most cases, the authors of the modeling studies concluded that screening is potentially cost-effective or even cost-saving. The recommendations for treatment approaches were rather heterogeneous and depending on the specific research question, population, and setting. Conclusions: Overall, we predominantly identified decision-analytic modeling studies evaluating specific screening programs or treatment approaches; however, there was no model evaluating primary prevention programs on a population basis. Conclusions deriving from these studies, for example, that prevention is cost-saving, need to be carefully interpreted as they rely on many assumptions.

Effectiveness, benefit harm and cost effectiveness of colorectal cancer screening in Austria.

BACKGROUND: Clear evidence on the benefit-harm balance and cost effectiveness of population-based screening for colorectal cancer (CRC) is missing. We aim to systematically evaluate the long-term effectiveness, harms and cost effectiveness of different organized CRC screening strategies in Austria. METHODS: A decision-analytic cohort simulation model for colorectal adenoma and cancer with a lifelong time horizon was developed, calibrated to the Austrian epidemiological setting and validated against observed data. We compared four strategies: 1) No Screening, 2) FIT: annual immunochemical fecal occult blood test age 40-75 years, 3) gFOBT: annual guaiac-based fecal occult blood test age 40-75 years, and 4) COL: 10-yearly colonoscopy age 50-70 years. Predicted outcomes included: benefits expressed as life-years gained [LYG], CRC-related deaths avoided and CRC cases avoided; harms as additional complications due to colonoscopy (physical harm) and positive test results (psychological harm); and lifetime costs. Tradeoffs were expressed as incremental harm-benefit ratios (IHBR, incremental positive test results per LYG) and incremental cost-effectiveness ratios [ICER]. The perspective of the Austrian public health care system was adopted. Comprehensive sensitivity analyses were performed to assess uncertainty. RESULTS: The most effective strategies were FIT and COL. gFOBT was less effective and more costly than FIT. Moving from COL to FIT results in an incremental unintended psychological harm of 16 additional positive test results to gain one life-year. COL was cost saving compared to No Screening. Moving from COL to FIT has an ICER of 15,000 EUR per LYG. CONCLUSIONS: Organized CRC-screening with annual FIT or 10-yearly colonoscopy is most effective. The choice between these two options depends on the individual preferences and benefit-harm tradeoffs of screening candidates.

Alternative Conversion Methods for Transition Probabilities in State-Transition Models: Validity and Impact on Comparative Effectiveness and Cost-Effectiveness.

Background. In state-transition models (STMs), decision problems are conceptualized using health states and transitions among those health states after predefined time cycles. The naive, commonly applied method (C) for cycle length conversion transforms all transition probabilities separately. In STMs with more than 2 health states, this method is not accurate. Therefore, we aim to describe and compare the performance of method C with that of alternative matrix transformation methods. Design. We compare 2 alternative matrix transformation methods (Eigenvalue method [E], Schure-Padé method [SP]) to method C applied in an STM of 3 different treatment strategies for women with breast cancer. We convert the given annual transition matrix into a monthly-cycle matrix and evaluate induced transformation errors for the transition matrices and the long-term outcomes: life years, quality-adjusted life-years, costs and incremental cost-effectiveness ratios, and the performance related to the decisions. In addition, we applied these transformation methods to randomly generated annual transition matrices with 4, 7, 10, and 20 health states. Results. In theory, there is no generally applicable correct transformation method. Based on our simulations, SP resulted in the smallest transformation-induced discrepancies for generated annual transition matrices for 2 treatment strategies. E showed slightly smaller discrepancies than SP in the strategy, where one of the direct transitions between health states was excluded. For long-term outcomes, the largest discrepancy occurred for estimated costs applying method C. For higher dimensional models, E performs best. Conclusions. In our modeling examples, matrix transformations (E, SP) perform better than transforming all transition probabilities separately (C). Transition probabilities based on alternative conversion methods should therefore be applied in sensitivity analyses.

Effectiveness and Cost-Effectiveness of Triple Therapy With Telaprevir and Boceprevir for Chronic Hepatitis C: A Decision Analysis From the Brazilian Public Health System Perspective.

OBJECTIVES: Because of the lack of evidence regarding long-term effectiveness and cost-effectiveness of first-generation direct-acting antivirals for chronic hepatitis C (CHC) treatment in Brazil, we performed a cost-utility analysis comparing standard dual therapy (peginterferon plus ribavirin [pegIFN/RBV]), boceprevir, and telaprevir for CHC patients. METHODS: We developed a state-transition Markov model simulating the progression of CHC. Long-term outcomes included remaining life expectancy in life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Short-term outcomes included sustained virological response rates (SVR). Direct medical costs were obtained from Brazilian databases. A lifelong time horizon was considered and a 5% annual discount rate was applied for costs and clinical outcomes. A willingness-to-pay threshold of approximately $20 000 per QALY was used. We performed multiple sensitivity analyses. RESULTS: For short- and long-term scenarios, therapy with boceprevir was dominated by telaprevir, which was more effective than standard dual therapy (75.0% vs 40.4% SVR rate, 13.47 vs 12.59 LYs, and 9.74 vs 8.49 QALYs, respectively) and was also more expensive ($15 742 vs $5413). The corresponding ICERs were $29 854/SVR, $11 803/LY, and $8277/QALY. Based on our model, triple therapy with telaprevir was the most cost-effective treatment for the Brazilian health system. Despite a lack of data regarding the Brazilian population, we incorporated as many applicable parameters as possible. CONCLUSIONS: Telaprevir is more effective and cost-effective than boceprevir. Our model may be applied for other settings with a few adjustments in the input parameters.

Budget Impact Analysis of Cancer Screening: A Methodological Review.

BACKGROUND: Budget impact analyses (BIAs) describe changes in intervention- and disease-related costs of new technologies. Evidence on the quality of BIAs for cancer screening is lacking. OBJECTIVES: We systematically reviewed the literature and methods to assess how closely BIA guidelines are followed when BIAs are performed for cancer-screening programs. DATA SOURCES: Systematic searches were conducted in MEDLINE, EMBASE, EconLit, CRD (Centre for Reviews and Dissemination, University of York), and CEA registry of the Tufts Medical Center. STUDY ELIGIBILITY CRITERIA: Eligible studies were BIAs evaluating cancer-screening programs published in English, 2010-2018. SYNTHESIS METHODS: Standardized evidence tables were generated to extract and compare study characteristics outlined by the ISPOR BIA Task Force. RESULTS: Nineteen studies were identified evaluating screening for breast (5), colorectal (6), cervical (3), lung (1), prostate (3), and skin (1) cancers. Model designs included decision-analytic models (13) and simple cost calculators (6). From all studies, only 53% reported costs for a minimum of 3 years, 58% compared to a mix of screening options, 42% reported model validation, and 37% reported uncertainty analysis for participation rates. The quality of studies appeared to be independent of cancer site. LIMITATIONS: "Gray" literature was not searched, misinterpretation is possible due to limited information in publications, and focus was on international methodological guidelines rather than regional guidelines. CONCLUSIONS: Our review highlights considerable variability in the extent to which BIAs evaluating cancer-screening programs followed recommended guidelines. The annual budget impact at least over the next 3-5 years should be estimated. Validation and uncertainty analysis should always be conducted. Continued dissemination efforts of existing best-practice guidelines are necessary to ensure high-quality analyses.

Systematic assessment of decision-analytic models evaluating diagnostic tests for acute myocardial infarction based on cardiac troponin assays.

INTRODUCTION: Despite the emphasis on the clinical importance of cardiac troponin assays (cTn), there are insufficient cost-effectiveness comparisons of various troponin test protocols for the diagnosis of myocardial infarction (MI). Therefore, the purpose of the review was to identify and systematically assess published economic evaluations using decision-analytic models for diagnostic testing strategies based on cTn and to make recommendations for the development of future models. AREAS COVERED: MEDLINE, Science Direct, Cochrane Database, CRD Database, and gray literature were screened for full economic evaluation studies with relevant clinical outcomes over a defined time horizon addressing a population with suspected MI and comparison of different diagnostic test strategies. Standardized forms for data extraction and evidence tables were used for the summary of study design, methodological framework and data sources. Studies were assessed for quality using the CHEERS and the BMJ checklists. EXPERT COMMENTARY: Although there are 11 identified studies and several well-designed models, there remains a need for decision-analytic models including differential diagnosis for acute MI, different health facility configurations, clinician preferences, and behavioral components, and in the top of the subgroup analyses additional important personalized medicine aspects.

Development of a novel prognostic score for breast cancer patients using mRNA expression of CHAC1.

AIM: To develop a prognostic score for primary breast cancer patients integrating conventional predictors and the novel biomarker CHAC1 to aid adjuvant chemotherapy decisions. PATIENTS & METHODS: A prognostic score for overall survival was developed using: conventional predictors from a dataset of 1777 patients and the weight of CHAC1 mRNA expression from an independent dataset of 106 patients using multivariate Cox regression. RESULTS: The new score includes: CHAC1 mRNA expression, age, tumor size, HER2 neu status, lymph node status and degree of malignancy. Using a cut-off value of 11 score points, 10-year survival was 82% in low-risk (n = 34) and 43% in high-risk patients (n = 72). The addition of CHAC1 resulted in 16% reclassification. CONCLUSION: Including CHAC1 in prognostic prediction may aid (and change) personalized treatment selection.

Personalized treatment of women with early breast cancer: a risk-group specific cost-effectiveness analysis of adjuvant chemotherapy accounting for companion prognostic tests OncotypeDX and Adjuvant!Online.

BACKGROUND: Due to high survival rates and the relatively small benefit of adjuvant therapy, the application of personalized medicine (PM) through risk stratification is particularly beneficial in early breast cancer (BC) to avoid unnecessary harms from treatment. The new 21-gene assay (OncotypeDX, ODX) is a promising prognostic score for risk stratification that can be applied in conjunction with Adjuvant!Online (AO) to guide personalized chemotherapy decisions for early BC patients. Our goal was to evaluate risk-group specific cost effectiveness of adjuvant chemotherapy for women with early stage BC in Austria based on AO and ODX risk stratification. METHODS: A previously validated discrete event simulation model was applied to a hypothetical cohort of 50-year-old women over a lifetime horizon. We simulated twelve risk groups derived from the joint application of ODX and AO and included respective additional costs. The primary outcomes of interest were life-years gained, quality-adjusted life-years (QALYs), costs and incremental cost-effectiveness (ICER). The robustness of results and decisions derived were tested in sensitivity analyses. A cross-country comparison of results was performed. RESULTS: Chemotherapy is dominated (i.e., less effective and more costly) for patients with 1) low ODX risk independent of AO classification; and 2) low AO risk and intermediate ODX risk. For patients with an intermediate or high AO risk and an intermediate or high ODX risk, the ICER is below 15,000 EUR/QALY (potentially cost effective depending on the willingness-to-pay). Applying the AO risk classification alone would miss risk groups where chemotherapy is dominated and thus should not be considered. These results are sensitive to changes in the probabilities of distant recurrence but not to changes in the costs of chemotherapy or the ODX test. CONCLUSIONS: Based on our modeling study, chemotherapy is effective and cost effective for Austrian patients with an intermediate or high AO risk and an intermediate or high ODX risk. In other words, low ODX risk suggests chemotherapy should not be considered but low AO risk may benefit from chemotherapy if ODX risk is high. Our analysis suggests that risk-group specific cost-effectiveness analysis, which includes companion prognostic tests are essential in PM.