This Dead or That Dead: Framing Effects in the Evaluation of Health States.

OBJECTIVES: Current approaches to health state valuation rely on credible classification of states as either "better than dead" or "worse than dead" (WTD). We investigate how such evaluations of health states are affected by the framing in pairwise comparison tasks. METHODS: We conducted an online survey with 361 participants to compare the propensity to evaluate a state as WTD under 6 frames: (A) using a regular time trade-off (TTO) choice task, (B) using a lead-time TTO choice task, (C) excluding the immediacy of death, (D) avoiding reference to the process of dying, (E) focusing on longevity, and (F) focusing on improvements in quality of life. Each participant evaluated 9 EQ-5D-5L health states using 3 frames. The frames were compared using several statistical approaches to confirm robustness to indirect comparisons or respondent heterogeneity and inattentiveness. RESULTS: The odds of a state being evaluated as WTD, compared with frame A, increase 2.7-fold and 1.5-fold in frame B and E, respectively, and decrease >5-fold in frame F. Frames C and D do not differ significantly from frame A. CONCLUSIONS: Different framings for questions about whether a state is WTD or better than dead, even if theoretically equivalent, yield substantially different results. Notably, whether a state is evaluated as WTD differs greatly between the regular TTO and lead-time TTO choice tasks and when either final outcomes or improvements over time are considered.

Re-revisiting the Utilities of Health States Worse than Dead: The Problem Remains.

BACKGROUND: In valuation studies of the EQ-5D-5L instrument, the composite time tradeoff method (cTTO) is often used to elicit preferences. In cTTO, some health states are considered worse than dead (WTD) and are assigned negative utility values. However, these negative values correlate poorly with state severity, which suggests that cTTO is insufficiently sensitive. A recent threshold explanation has been offered to account for the lack of correlation: because the severity threshold beyond which a state is considered WTD differs between respondents, the correlation should be studied for individual respondents clustered by the number of WTD states. The results obtained in such a threshold approach were interpreted to disprove the insensitivity of the cTTO method. AIM: To scrutinize the threshold explanation and test whether it indeed refutes the insensitivity of cTTO. METHODS: The study uses data from the EQ-5D-5L Polish valuation study, which includes cTTO responses from 1,510 participants, each of whom evaluated 10 EQ-5D-5L states. The correlation analysis and threshold approach are repeated to confirm the results from previous studies. The data are then modified in 2 contrasting ways. First, negative utilities are randomly reshuffled to test whether the threshold approach can capture cTTO insensitivity. Second, individual-level regressions are used to simulate negative values to ensure they correlate with severity at the individual respondent level, verifying whether the overall severity-utility correlation should be observed. RESULTS: First, reshuffling negative utilities does not change the results of the threshold approach. Hence, the threshold explanation fails to prove cTTO sensitivity. Second, when sensitivity was introduced on an individual level, a significant overall correlation between severity and negative utility arose. CONCLUSION: cTTO is insensitive to severity for WTD states. HIGHLIGHTS: For the composite time tradeoff method, the utility values of health states worse than dead correlate poorly with state severity, which suggests that cTTO has insufficient sensitivity.Recently, a so-called threshold explanation was offered for the lack of correlation.I show why the threshold explanation fails and why the composite time tradeoff is indeed insensitive for worse-than-dead states.

Child health valuation protocol for a discrete choice experiment comparing paired comparison and kaizen tasks and estimating US EQ-5D-Y-3L values on an experience scale.

INTRODUCTION: A decade ago, the first national valuation study of the EQ-5D-Y-3L (Y-3L) involved a discrete choice experiment (DCE) that asked 4155 US adult respondents to complete 40 paired comparisons, choosing between two dying children. Instead of choosing between dying children, the respondents in this novel protocol are asked whether 'being in a coma' is better or worse than experiencing 'health problems' (ie, experience scale) and how they would relieve health problems (ie, kaizen tasks). Our aims are to compare the preference evidence of the paired comparison and kaizen tasks and to conduct a DCE for the valuation of Y-3L profiles on an experience scale. METHODS AND ANALYSIS: Under this protocol, we will conduct an online survey that collects preference evidence from 600 US adult respondents on the health of a 10-year-old child for a week. Across all scenarios, each child will be described as either being 'in a coma' or having 'health problems', namely five three-level attributes (Y-3L). In this DCE, each respondent will be randomly assigned to one of four D-efficient blocks, including five coma comparisons (ie, Y-3L vs coma), 10 paired comparisons (Y-3L vs Y-3L) and 10 kaizen tasks (preference paths). In addition to comparing evidence by task (aim 2), the analysis plan includes the estimation of main-effects conditional logit models to create a Y-3L value set on an 'experience scale' where positive (negative) experiences have positive (negative) values (0 is 'being in a coma' and 1 is full health). ETHICS AND DISSEMINATION: The institutional review board (IRB) (Advarra) determined that this project (Pro00072276) is exempt from IRB oversight based on DHHS 45 CFR 46.104(d)(2) and is not subject to requirements for continuing review. The results will be prepared for publication in peer-reviewed journals and presented at scientific meetings. The data and code will be made available on reasonable request.

Simple yet (more?) effective. Venous thromboembolism risk assessment model for germ cell tumour patients receiving first-line chemotherapy.

BACKGROUND: Germ cell tumours (GCT) are highly curable malignancies. Venous thromboembolism (VTE) is a serious complication, needing better risk assessment models (RAM). AIM: Identification of VTE incidence and risk factors in metastatic GCT patients starting first-line chemotherapy. Developing a RAM and comparing it to Khorana risk score (KRS) and Padua Prediction Score (PPS). MATERIAL AND METHODS: We retrospectively analysed GCT patients staged IS-IIIC. VTE risk factors were identified with logistic regression. Area under curve of receiver operating characteristic (AUC-ROC), Akaike and Bayesian Information Criteria (AIC, BIC) were calculated for the developed RAM, KRS and PPS. RESULTS: Among 495 eligible patients, VTE occurred in 69 (13.9%), including 40 prior to chemotherapy. Vein compression (OR: 8.96; 95% CI: 2.85-28.13; p < 0.001), clinical stage IIIB-IIIC (OR: 5.68; 95% CI: 1.82-17.70; p = 0.003) and haemoglobin concentration (OR for 1 g/dL decrease: 1.32; 95% CI: 1.03-1.67; p = 0.026) were significant in our RAM. KRS ≥ 3 (OR: 3.31; 95% CI: 1.77-6.20; p < 0.001), PPS 4-5 (OR: 3.06; 95% CI: 1.49-6.29; p = 0.002) and PPS > 5 (OR 8.05; 95% CI 3.79-17.13; p < 0.001) correlated with VTE risk. Diagnostic criteria (AUC-ROC, AIC, BIC) for the developed RAM, KRS and PPS were (0.885; 0.567; -1641), (0.588; 0.839; -1576) and (0.700; 0.799; -1585), respectively. In the numerical score, the optimal cut-off point for high-risk was ≥9, with sensitivity, specificity, positive and negative predictive value of 0.78, 0.77, 0.35 and 0.96, respectively. CONCLUSIONS: Our RAM, based on vein compression, clinical stage and haemoglobin concentration proved superior to both KRS and PPS. VTE is frequent in GCT patients.

Measuring the Indirect Cost of Illness Using EQ-5D-5L While Accounting for Job Characteristics.

BACKGROUND: The EQ-5D-5L questionnaire is used to measure treatment effects on the quality of life. For cost-utility analyses, EQ-5D-5L profiles are assigned numbers representing societal preferences (index weights). On the cost side, the indirect costs are frequently included: the value of product lost due to illness-related absences (absenteeism) or diminished productivity (presenteeism). The possibility to use EQ-5D data to estimate absenteeism and presenteeism (A&P) would be useful, if real-world data on A&P are lacking. However, beyond-health factors may also matter for A&P. OBJECTIVE: We aimed to assess how A&P depend on the EQ-5D-5L profile, while accounting for job characteristics (e.g. remote or in-office). METHODS: We surveyed 756 employed Poles. Respondents reported their job characteristics and evaluated the impact of eight hypothetical EQ-5D-5L profiles on A&P (two blocks of states used). Econometric modelling was used to establish the determinants of A&P. RESULTS: Both A&P increase with health problems as indicated across EQ-5D-5L dimensions (especially mobility and self-care), and this impact differs from the impact on index weight (e.g. pain/discomfort barely impact the A&P). The job characteristics mattered: absenteeism decreases in sedentary occupations and increases in those occupations performed remotely or requiring cooperation, while presenteeism increases in jobs performed remotely and decreases for those requiring creative thinking. CONCLUSIONS: The entire EQ-5D-5L profile, not just index weights, should be used to estimate A&P. That job characteristics matter may be relevant in applications, as some diseases concentrate in specific subgroups.

Modifying the Composite Time Trade-Off Method to Improve Its Discriminatory Power.

OBJECTIVES: In cost-effectiveness analysis of health technologies, health state utilities are needed. They are often elicited with a composite time trade-off (cTTO) method, particularly for the widely used EQ-5D-5L. Unfortunately, cTTO discriminatory power is hindered by (1) respondents' nontrading (NT) of time for quality, (2) censoring of utilities at -1, and (3) poor correlation of negative utilities with state severity. We investigated whether modifying cTTO can mitigate these effects. METHODS: We interviewed online 478 students (February to April, 2021) who each valued the same 10 EQ-5D-5L health states in 1 of 3 arms. Arm A used a standard cTTO, expanded with 2 questions to explore reasons for NT and censoring. Arms B and C used a time trade-off with modified alternatives offered to overcome loss aversion, to unify the tasks for positive and negative utilities, and to enable eliciting utilities < -1. RESULTS: In arms B and C, we observed less NT than in A (respectively, 4% and 4% vs 10%), more strictly negative utilities (38% and 40% vs 25%), and more utilities ≤ -1 (18% and 30% vs 10%). The average utility of state 55555 dropped to -2.15 and -2.52 from -0.53. Enabling finer trades in arm A reduced NT by 70%. Arms B and C yielded an intuitive association between negative utilities and state severity. These arms were considered more difficult and resulted in more inconsistencies. CONCLUSIONS: The discriminatory power of cTTO can be improved, but it may require increasing the difficulty of the task. The standard cTTO may overestimate the utilities, especially of severe states.

What if 0 is not equal to 0? Inter-personal health utilities anchoring using the largest health gains.

Prioritizing health technologies requires comparisons of improvements in longevity or quality of life (QoL), or both. For this purpose, value sets are constructed that contain weights assigned to health states based on societal preferences. I show that how this is typically done may distort the results by giving unjustifiably larger impact to individuals who prioritize improvements in QoL over longevity. The problem results from equating the utility differences between being dead and full health across people, ignoring the fact that interpersonal utility comparisons are forbidden (or at least problematic) in economics. I propose another approach: the numerical value of maximal health gain (either in longevity or QoL) is assumed to be equal across individuals, to remove the impact of the range of utilities differing between people. I test this approach using EQ-5D-5L and EQ-5D-3L utilities elicited in Poland for two modeling techniques: a simple econometric model and a Bayesian one that accounts for censoring. The proposed approach increases the utilities of the worst health state: from [Formula: see text] to [Formula: see text] in EQ-5D-5L and from about [Formula: see text] to [Formula: see text] in EQ-5D-3L. In the Bayesian approach, the impact is greater: from [Formula: see text] to [Formula: see text] for EQ-5D-5L and from [Formula: see text] to [Formula: see text] for EQ-5D-3L. I discuss some normative arguments why the proposed approach may be more justifiable for aggregating individual preferences for health outcomes.

Mechanochemical Conversion of Aromatic Amines to Aryl Trifluoromethyl Ethers.

Increased interest in the trifluoromethoxy group in organic synthesis and medicinal chemistry has induced a demand for new, selective, general, and faster methods applicable to natural products and highly functionalized compounds at a later stage of hit-to-lead campaigns. Applying pyrylium tetrafluoroborate, we have developed a mechanochemical protocol to selectively substitute the aromatic amino group with the OCF3 functionality. The scope of our method includes 31 examples of ring-substituted anilines, including amides and sulfonamides. Expected SNAr products were obtained in excellent yields. The presented concise method opens a pathway to new chemical spaces for the pharmaceutical industry.

Innovative medical technologies in the percutaneous treatment of tricuspid regurgitation in Poland.

Tricuspid regurgitation (TR) usually develops secondarily to left-sided heart diseases, whereas primary lesions to the valve apparatus is less common. Untreated severe TR has a poor prognosis and surgical treatment, i.e., valve repair or replacement, is the only treatment option with class I recommendation. However, cardiac surgical procedures may be associated with a high risk of complications. Recent advances in percutaneous approaches to managing structural heart diseases, especially mitral valve diseases, have enabled the implementation of this therapeutic strategy in the population of patients with TR. This paper presents data on the clinical efficacy, cost-effectiveness and expected population size for one of these procedures, namely the TriClip TTVr System procedure. Its efficacy was assessed in the TRILUMINATE study involving 85 patients with co-morbidities and at high surgical risk. After 1 year of follow-up, the reduction in the TR grade was reported in 71% of patients. Clinical improvement in New York Heart Association functional class, a 6-minute walk test, and the quality of life were also observed. A published analysis comparing percutaneous treatment modalities with a drug therapy based on data from medical registers was utilized, and propensity score matching was also employed. Percutaneous treatment reduced 1-year mortality and rehospitalization risk. The economic analysis showed the use of TriClip TTVr System is cost-effective: the cost of an additional quality-adjusted life year ranged from approximately PLN 85,000 to PLN 100,000, which is below the official threshold in Poland. The potential annual number of candidates for this treatment modality in Poland is estimated at 265.

Cu-Catalyzed Arylation of Bromo-Difluoro-Acetamides by Aryl Boronic Acids, Aryl Trialkoxysilanes and Dimethyl-Aryl-Sulfonium Salts: New Entries to Aromatic Amides.

We describe a mechanism-guided discovery of a synthetic methodology that enables the preparation of aromatic amides from 2-bromo-2,2-difluoroacetamides utilizing a copper-catalyzed direct arylation. Readily available and structurally simple aryl precursors such as aryl boronic acids, aryl trialkoxysilanes and dimethyl-aryl-sulfonium salts were used as the source for the aryl substituents. The scope of the reactions was tested, and the reactions were insensitive to the electronic nature of the aryl groups, as both electron-rich and electron-deficient aryls were successfully introduced. A wide range of 2-bromo-2,2-difluoroacetamides as either aliphatic or aromatic secondary or tertiary amides were also reactive under the developed conditions. The described synthetic protocols displayed excellent efficiency and were successfully utilized for the expeditious preparation of diverse aromatic amides in good-to-excellent yields. The reactions were scaled up to gram quantities.

Cost-effectiveness of telerehabilitation in patients with heart failure in Poland: an analysis based on the results of Telerehabilitation in the Heart Failure Patients (TELEREH-HF) randomized clinical trial.

BACKGROUND: Telerehabilitation in the Heart Failure Patients (TELEREH-HF) study showed a statistically significant improvement in the tertiary outcomes i.e. the New York Heart Association (NYHA) class after a 9-week follow-up, consistent with telerehabilitation-related benefits to quality of life (QoL) measured with the 36-item Short Form questionnaire (SF-36). AIMS: The study analyzed the cost-effectiveness of hybrid telerehabilitation compared to standard care in heart failure patients in the Polish setting using findings from the TELEREH-HF trial. METHODS: Cost-utility analysis was conducted from the perspective of a public payer (the Polish National Health Fund). The quality-adjusted life-year (QALY) measure was based on QoL, as survival benefit was not confirmed in the TELEREH-HF. Utility values were estimated based on NYHA improvement and a systematic review of NYHA-specific utility values. Alternatively, SF-36 results were translated into utility values. Telerehabilitation costs covered 8 weeks, 5 days/week, at a daily cost of 74 Polish zloty (PLN). Standard care costs resulted from extra in-patient and out-patient rehabilitation costs incurred for selected patients. A lifetime horizon was adopted, with an estimated average survival time of 3.9 years based on 2 years TELEREH-HF follow-up and subsequent literature-derived prognosis. RESULTS: Base case analysis yielded a 0.044 and 0.027 gain in QALY for the NYHA and SF-36-based approaches, corresponding to a cost per QALY of 58.7 and 96 thousand PLN, respectively. Sensitivity analysis confirmed that the cost per QALY value was likely below the official cost-effectiveness threshold in Poland. CONCLUSIONS: The use of telerehabilitation was found cost-effective in Poland, i.e., the clinical benefits justify the additional costs.

EQ-5D-Derived Health State Utility Values in Hematologic Malignancies: A Catalog of 796 Utilities Based on a Systematic Review.

OBJECTIVES: We performed a systematic review of health state utility values (HSUVs) obtained using the EQ-5D questionnaire for patients with hematologic malignancies. METHODS: The following databases were searched up to September 2018: MEDLINE, EMBASE, The Cochrane Library, and the EQ-5D publications database on the EuroQol website. Additional references were extracted from reviewed articles. Only studies presenting EQ-Index results were incorporated. In view of the heterogeneity across the included publications, we limited ourselves to a narrative synthesis of original HSUVs found. RESULTS: Fifty-nine studies (described in 63 articles) met the inclusion criteria. Data from 21 635 respondents provided 796 HSUV estimates for hematologic malignancy patients. EQ-Index scores ranged from -0.025 to 0.980. The most represented area was multiple myeloma (4 studies, 11 112 patients, and 249 HSUVs). In clinical areas such as chronic myeloid leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and mantle cell lymphoma, we described over 50 health utilities in each. In contrast, we identified only 13 HSUVs (based on 4 studies and the data of 166 patients) for Hodgkin lymphoma. Areas without EQ-5D-based health utilities comprised: polycythemia vera, primary myelofibrosis, essential thrombocythemia, mastocytosis, myeloid sarcoma, chronic myelomonocytic, eosinophilic leukemia, and neutrophilic leukemia. CONCLUSIONS: There is a wide range of HSUVs available for hematologic cancer patients with different indications. The review provides a catalog of utility values for use in cost-effectiveness models for hematologic malignancies.

Outcomes of ex vivo liver resection and autotransplantation: A systematic review and meta-analysis.

BACKGROUND: Many patients with hepatic tumors cannot benefit from resection owing to the difficult anatomic sites of their lesions. Some of these patients might be eligible for ex vivo liver resection and autotransplantation. This procedure consists of complete hepatectomy, extracorporeal liver resection, and autotransplantation of the remnant liver. METHODS: Four databases were searched for studies reporting cases of ex vivo liver resection and autotransplantation. Outcomes of this procedure were evaluated by meta-analysis of proportions with random effects model and individual participant data analysis. RESULTS: Fifty-three studies were assessed. Meta-analysis revealed an R0 resection rate of 93.4% (95% confidence interval: 81.0-97.9%, I2 = 0%), a frequency of major surgical complications of 24.5% (95% confidence interval, 16.9-34.3%, I2 = 26%), a 30-day mortality of 9.5% (95% confidence interval: 5.9-14.9%, I2 = 0%), and a 1-year survival of 78.4% (95% confidence interval: 62.2-88.8%, I2 = 64%). We were able to obtain the individual participant data in 244 patients; R0 resection was achieved in 98.6%, with no obvious difference between analyzed subgroups. The 30-day mortality and 1-year survivals were 7.9% and 82.1%, respectively. For groups with malignant and nonmalignant tumors, the 30-day mortalities were 11.3% vs. 6.3% (P = .181), and 1-year survivals were 65.0% vs. 89.7% (P < .001). When comparing those with malignant versus those with nonmalignant lesions, major surgical complications occurred in 50.0% vs. 21.0%; P < .001). Regression analysis revealed that outcomes of patients with benign tumors were better compared with those with malignant tumors (1-year survival, odds ratio: 4.629; 95% confidence interval: 2.181-10.097, P < .001). CONCLUSION: Ex vivo liver resection and autotransplantation facilitates radical treatment in selected patients with conventionally unresectable hepatic tumors and normal liver function. The outcomes of treatment of malignant lesions appear to be less satisfactory.

The cost-effectiveness of food consistency modification with xanthan gum-based Nutilis Clear® in patients with post-stroke dysphagia in Poland.

BACKGROUND: Dysphagia is a well-known stroke complication characterised by difficulty in swallowing. It may affect the majority of stroke patients and increases mortality and morbidity, due to aspiration pneumonia and malnutrition. Food thickening may help patients to feed themselves, and its effectiveness was demonstrated. However, the cost-effectiveness studies are lacking. We evaluate the cost-utility of xanthan gum-based consistency modification therapy (Nutilis Clear®) in adult post-stroke patients from the public payer perspective in Poland. METHODS: Routine clinical practice was used as a comparator, as no alternative specific treatment for dysphagia is available. To verify the robustness of the results against the modelling approach, we built two models: a static (a fixed simple-equations model, 8-week time horizon of dysphagia) and a dynamic one (Markov model, with a possible dysphagia resolution over a 1-year horizon). In both models, the treatment costs, health state utilities, and clinical events (i.e. aspiration, aspiration pneumonia, death) were included. Parameters were estimated jointly for both models, except for the duration of dysphagia and the risk of aspiration pneumonia (specific to the time horizon). We only assumed Nutilis Clear® to prevent aspirations, without affecting dysphagia duration. RESULTS: The average cost of one quality-adjusted life year (i.e. the incremental cost-utility ratios, ICURs) amounted to 21,387 PLN (€1 ≈ 4.5 PLN), and 20,977 PLN in static and dynamic model, respectively; far below the cost-effectiveness threshold in Poland (147,024 PLN). The one-way, scenario, and probabilistic sensitivity analysis confirmed these findings. CONCLUSIONS: Nutilis Clear® is highly cost-effective in Poland from the public payer perspective. Our approach can be used in other countries to study the cost-effectiveness of food thickening in stroke patients.

Ranking the Criteria Used in the Appraisal of Drugs for Reimbursement: A Stated Preferences Elicitation With Health Technology Assessment Stakeholders Across Jurisdictional Contexts.

OBJECTIVES: Our goal was to estimate the relative importance assigned to health technology assessment (HTA) criteria by stakeholders involved in the HTA process. HTA is an increasingly common framework used in the appraisal of drugs for public reimbursement. It identifies clinical, economic, social, and organizational criteria to be considered. The criteria can vary across jurisdictions and are typically appraised by multidisciplinary expert committees. Guidance on the relative weighing of criteria is often absent. METHODS: We elicited stakeholders' preferences using a single-scenario discrete choice experiment and a best-worst scaling model with conviction scores to assess the weights assigned to selected criteria by HTA stakeholders. We recruited 111 HTA stakeholders across multiple jurisdictions, including members of expert committees, clinical and economic experts, patients, and public payer representatives. Each judged twelve hypothetical cancer drug profiles for suitability for public funding and identified which characteristics were best and worst. In addition to standard discrete choice experiment and best-worst scaling models, we estimated a hybrid model to obtain a ranking of criteria by importance they played in the appraisal. RESULTS: A strong clinical benefit proved the most important criterion, followed by cost considerations, presence of adverse events, and availability of other treatments. The importance of clinical benefit was moderated by unmet need, adverse events, and number of patients. CONCLUSION: Policymakers might want to consider providing an explicit weighing scheme, or moving to a 2-stage selection process with an assessment of the quality of clinical evidence as a gatekeeping step for a full HTA review.

Valuation of EQ-5D-5L Health States in Poland: the First EQ-VT-Based Study in Central and Eastern Europe.

OBJECTIVE: Cost-utility analyses are becoming increasingly important in Central and Eastern Europe. We aimed to develop a Polish utility tariff for EQ-5D-5L health states. METHODS: Face-to-face, computer-assisted interviews were collected in a representative sample. Each respondent followed a standardised protocol to collect ten composite time trade-off and seven discrete choice experiment observations. In the Bayesian approach, several model specifications were compared based on model fit, the usability of the final value set and how they reflect the elicitation procedure (e.g. censoring). A hybrid approach (using composite time trade-off and discrete choice experiment data) was employed in the final set, which was compared with the existing ones: EQ-5D-3L and EQ-5D-5L cross-walk. RESULTS: Data from 1252 respondents (11,480 composite time trade-off valuations and 8764 discrete choice experiment pairs) were collected over the period June to October 2016. The final model accounted for random parameters, error scaling with fat tails, censoring at - 1, unwillingness to trade in time trade-off by the religious people and Cauchy distribution in discrete choice experiments. Pain/discomfort impacts the utility most: the disutility equals 0.575 when at level 5. In the value set, 4.4% of EQ-5D-5L states are worse than dead. The new value set has a comparable range (minimum of - 0.590 compared to - 0.523) and the same ordering of the first three dimensions (pain/discomfort, mobility, self-care) as the EQ-5D-3L value set and the EQ-5D-5L cross-walk value set. Moreover, it is more sensitive to a moderate decline in health. CONCLUSIONS: The new value set supports consistency with past decisions in cost-utility studies, while offering a better assessment of even moderate improvements in health. It could represent an option for Central and Eastern Europe countries lacking their own value sets.

Copper-catalyzed direct C-H arylselenation of 4-nitro-pyrazoles and other heterocycles with selenium powder and aryl iodides. Access to unsymmetrical heteroaryl selenides.

A one-pot, Cu-catalyzed direct C-H arylselenation protocol using elemental Se and aryl iodides was developed for nitro-substituted, N-alkylated pyrazoles, imidazoles and other heterocycles including 4H-chromen-4-one. This general and concise method allows one to obtain a large number of unsymmetrical heteroaryl selenides bearing a variety of substituents. The presence of the nitro group was confirmed to be essential for the C-H activation and can also be used for further functionalisation and manipulation. Several examples of heteroannulated benzoselenazines were also synthesized using the developed synthetic protocol.

Choice Defines Value: A Predictive Modeling Competition in Health Preference Research.

OBJECTIVE: To identify which specifications and approaches to model selection better predict health preferences, the International Academy of Health Preference Research (IAHPR) hosted a predictive modeling competition including 18 teams from around the world. METHODS: In April 2016, an exploratory survey was fielded: 4074 US respondents completed 20 out of 1560 paired comparisons by choosing between two health descriptions (e.g., longer life span vs. better health). The exploratory data were distributed to all teams. By July, eight teams had submitted their predictions for 1600 additional pairs and described their analytical approach. After these predictions had been posted online, a confirmatory survey was fielded (4148 additional respondents). RESULTS: The victorious team, "Discreetly Charming Econometricians," led by Michal Jakubczyk, achieved the smallest χ2, 4391.54 (a predefined criterion). Its primary scientific findings were that different models performed better with different pairs, that the value of life span is not constant proportional, and that logit models have poor predictive validity in health valuation. CONCLUSIONS: The results demonstrated the diversity and potential of new analytical approaches in health preference research and highlighted the importance of predictive validity in health valuation.

The cost-effectiveness of screening strategies for familial hypercholesterolaemia in Poland.

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) elevates the cholesterol level and increases the risk of coronary events and death. Early detection and treatment reduce this risk. We aimed to determine the cost-effectiveness of FH screening in Poland in children, first job takers, and after an acute coronary syndrome (ACS) event, each followed by a cascade screening in the relatives of the positively-diagnosed subjects. METHODS: A decision tree was constructed to model the diagnosis process. We considered scenarios with and without genetic testing. A life-time Markov was built to investigate the effectiveness (life years gained, LYG; and quality-adjusted life years, QALY) and cost (public payer perspective) of treatment in FH-affected subjects. The clinical benefits result from early treatment reducing the risk of coronary heart disease (and death, in result). Model parameters were based on published data and experts' opinions. The costs (patients visits, tests, drugs) were estimated from the National Health Fund data and other publicly-available sources. RESULTS: Screening ACS patients below 55/65 years of age in men/women is the most cost-effective strategy: the cost of one LYG (QALY) amounts to 100 EUR (110 EUR). Removing the age limit or using genetic tests reduced cost-effectiveness; nonetheless, all strategies remained cost effective: the cost of one LYG or QALY was <5040 EUR, much lower than the official threshold of ca. 29,800 EUR/QALY. CONCLUSIONS: Screening for FH is highly cost-effective in Poland. The strategies are complementary, and using a combination thereof is recommended.

A framework for sensitivity analysis of decision trees.

In the paper, we consider sequential decision problems with uncertainty, represented as decision trees. Sensitivity analysis is always a crucial element of decision making and in decision trees it often focuses on probabilities. In the stochastic model considered, the user often has only limited information about the true values of probabilities. We develop a framework for performing sensitivity analysis of optimal strategies accounting for this distributional uncertainty. We design this robust optimization approach in an intuitive and not overly technical way, to make it simple to apply in daily managerial practice. The proposed framework allows for (1) analysis of the stability of the expected-value-maximizing strategy and (2) identification of strategies which are robust with respect to pessimistic/optimistic/mode-favoring perturbations of probabilities. We verify the properties of our approach in two cases: (a) probabilities in a tree are the primitives of the model and can be modified independently; (b) probabilities in a tree reflect some underlying, structural probabilities, and are interrelated. We provide a free software tool implementing the methods described.