Preferences for Monitoring Comprehensive Heart Failure Care: A Latent Class Analysis.

OBJECTIVE: To measure preference heterogeneity for monitoring systems among patients with a chronic heart failure. METHODS: A best-worst scaling experiment (BWS case 3) was conducted among patients with chronic heart failure to assess preferences for hypothetical monitoring care scenarios. These were characterized by the attributes mobility, risk of death, risk of hospitalization, type and frequency of monitoring, risk of medical device, and system-relevant complications. A latent class analysis (LCA) was used to analyze and interpret the data. In addition, a market simulator was used to examine which treatment configurations participants in the latent classes preferred. RESULTS: Data from 278 respondents were analyzed. The LCA identified four heterogeneous classes. For class 1, the most decisive factor was mobility with a longer distance covered being most important. Class 2 respondents directed their attention toward attribute "monitoring," with a preferred monitoring frequency of nine times per year. The attribute risk of hospitalization was most important for respondents of class 3, closely followed by risk of death. For class 4, however, risk of death was most important. A market simulation showed that, even with high frequency of monitoring, most classes preferred therapy with high improvement in mobility, mortality, and hospitalization. CONCLUSION: Using LCA, variations in preferences among different groups of patients with chronic heart failure were examined. This allows treatment alternatives to be adapted to individual needs of patients and patient groups. The findings of the study enhance clinical and allocative decision-making while elevating the quality of clinical data interpretation.

Patient Preferences in Pulmonary Arterial Hypertension, a Latent Class Analysis to Identify Preference Heterogeneity.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a chronic, progressive disease of the pulmonary circulation characterized by vascular remodeling that, if untreated, can lead to right heart dysfunction and death. This analysis measured heterogeneity in patient preferences for PAH-specific treatment regimens. METHOD: Adult patients with PAH with slight to marked limitations during physical activity were recruited through a patient organization in Germany. Participants completed an online best-worst scaling case 3 survey. Patients chose among 3 hypothetical treatment profiles defined by 6 benefits and risks at varying levels. Participants completed 12 choice tasks. Preference heterogeneity was assessed using latent class analysis. RESULTS: A total of 83 participants (76% female) completed the survey. Best-fit model revealed 4 classes. Class 1 (19% of participants) assigned importance to multiple attributes particularly side effects, class 2 (34%) to physical activity limitations, class 3 (30%) to survival and physical activity limitations, and class 4 (17%) to survival. No differences in sociodemographic characteristics were observed across classes. Compared with other classes, class 4 was most likely to report having marked physical activity limitations (79%) and needing daily help (100%), while considering higher daily activity levels to be ordinary (walking >1 km [71%] or climbing several flights of stairs [50%]). CONCLUSION: This first patient preference study in a PAH population suggests that physical activity limitations in addition to survival matter most to patients; however, preference heterogeneity between groups of patients was observed. Patient preferences should be considered in treatment decision making to better balance patient's expectations regarding the known risk-benefit ratio of treatment.

A stronger acceptor decreases the rates of charge transfer: ultrafast dynamics and on/off switching of charge separation in organometallic donor-bridge-acceptor systems.

To unravel the role of driving force and structural changes in directing the photoinduced pathways in donor-bridge-acceptor (DBA) systems, we compared the ultrafast dynamics in novel DBAs which share a phenothiazine (PTZ) electron donor and a Pt(ii) trans-acetylide bridge (-C[triple bond, length as m-dash]C-Pt-C[triple bond, length as m-dash]C-), but bear different acceptors conjugated into the bridge (naphthalene-diimide, NDI; or naphthalene-monoimide, NAP). The excited state dynamics were elucidated by transient absorption, time-resolved infrared (TRIR, directly following electron density changes on the bridge/acceptor), and broadband fluorescence-upconversion (FLUP, directly following sub-picosecond intersystem crossing) spectroscopies, supported by TDDFT calculations. Direct conjugation of a strong acceptor into the bridge leads to switching of the lowest excited state from the intraligand 3IL state to the desired charge-separated 3CSS state. We observe two surprising effects of an increased strength of the acceptor in NDI vs. NAP: a ca. 70-fold slow-down of the 3CSS formation-(971 ps)-1vs. (14 ps)-1, and a longer lifetime of the 3CSS (5.9 vs. 1 ns); these are attributed to differences in the driving force ΔGet, and to distance dependence. The 100-fold increase in the rate of intersystem crossing-to sub-500 fs-by the stronger acceptor highlights the role of delocalisation across the heavy-atom containing bridge in this process. The close proximity of several excited states allows one to control the yield of 3CSS from ∼100% to 0% by solvent polarity. The new DBAs offer a versatile platform for investigating the role of bridge vibrations as a tool to control excited state dynamics.

Population preferences for non-pharmaceutical interventions to control the SARS-CoV-2 pandemic: trade-offs among public health, individual rights, and economics.

PROBLEM: Policymakers must decide on interventions to control the pandemic. These decisions are driven by weighing the risks and benefits of various non-pharmaceutical intervention alternatives. Due to the nature of the pandemic, these decisions are not based on sufficient evidence regarding the effects, nor are decision-makers informed about the willingness of populations to accept the economic and health risks associated with different policy options. This empirical study seeks to reduce uncertainty by measuring population preferences for non-pharmaceutical interventions. METHODS: An online-based discrete choice experiment (DCE) was conducted to elicit population preferences. Respondents were asked to choose between three pandemic scenarios with different interventions and impacts of the Corona pandemic. In addition, Best-worst scaling (BWS) was used to analyze the impact of the duration of individual interventions on people's acceptance. The marginal rate of substitution was applied to estimate willingness-to-accept (WTA) for each intervention and effect by risk of infection. RESULTS: Data from 3006 respondents were included in the analysis. The DCE showed, economic effect of non-pharmaceutical measures had a large impact on choice decisions for or against specific lockdown scenarios. Individual income decreases had the most impact. Excess mortality and individual risk of infection were also important factors influencing choice decisions. Curfews, contact restrictions, facility closures, personal data transmissions, and mandatory masking in public had a lesser impact. However, significant standard deviations in the random parameter logit model (RPL) indicated heterogeneities in the study population. The BWS results showed that short-term restrictions were more likely to be accepted than long-term restrictions. According to WTA estimates, people would be willing to accept a greater risk of infection to avoid loss of income. DISCUSSION: The results can be used to determine which consequences of pandemic measures would be more severe for the population. For example, the results show that citizens want to limit the decline in individual income during pandemic measures. Participation in preference studies can also inform citizens about potential tradeoffs that decision-makers face in current and future decisions during a pandemic. Knowledge of the population's preferences will help inform decisions that consider people's perspectives and expectations for the future. Survey results can inform decision-makers about the extent to which the population is willing to accept certain lockdown measures, such as curfews, contact restrictions, lockdowns, or mandatory masks.

Patient preferences in the treatment of hemophilia A: A latent class analysis.

OBJECTIVE: To examine subgroup-specific treatment preferences and characteristics of patients with hemophilia A. METHODS: Best-Worst Scaling (BWS) Case 3 (four attributes: application type; bleeding frequencies/year; inhibitor development risk; thromboembolic events of hemophilia A treatment risk) conducted via online survey. Respondents chose the best and the worst option of three treatment alternatives. Data were analyzed via latent class model (LCM), allowing capture of heterogeneity in the sample. Respondents were grouped into a predefined number of classes with distinct preferences. RESULTS: The final dataset contained 57 respondents. LCM analysis segmented the sample into two classes with heterogeneous preferences. Preferences within each were homogeneous. For class 1, the most decisive factor was bleeding frequency/year. Respondents seemed to focus mainly on this in their choice decisions. With some distance, inhibitor development was the second most important. The remaining attributes were of far less importance for respondents in this class. Respondents in class 2 based their choice decisions primarily on inhibitor development, also followed, by some distance, the second most important attribute bleeding frequency/year. There was statistical significance (P < 0.05) between the number of annual bleedings and the probability of class membership. CONCLUSIONS: The LCM analysis addresses heterogeneity in respondents' choice decisions, which helps to tailor treatment alternatives to individual needs. Study results support clinical and allocative decision-making and improve the quality of interpretation of clinical data.

Personalized diabetes management: what do patients with diabetes mellitus prefer? A discrete choice experiment.

BACKGROUND: There are unresolved procedural and medical problems in the care of diabetes, which cause high costs for health systems. These include the inadequate glycemic adjustment, care gaps, therapeutic inertia, and a lack of motivation. Personalized diabetes management can be seen as a kind of "standard process" that provides both physicians and patients with a framework. The aim of this empirical survey is the evaluation of patient preferences regarding personalized diabetes management. The purpose of this experiment is to demonstrate the properties of the programs that are relevant for the choice of insulin-based therapy regimens for patients with type II diabetes mellitus. METHODS: A discrete choice experiment (DCE) was applied to identify preferences for a personalized diabetes management in patients with type II diabetes mellitus. Six attributes were included. The DCE was conducted in June 2017 using a fractional factorial design, and the statistical data analysis used random effect logit models. RESULTS: N = 227 patients (66.1% male) were included. The preference analysis showed dominance for the attribute "occurrence of severe hypoglycemias per year" [level difference (LD) 2765]. Preference analysis also showed that participants weight the "risk of myocardial infarction (over 10 years)" (LD 1.854) highest among the side effects. Within the effectiveness criterion of "change in the long-term blood glucose level (HbA1c)" a change at an initial value of 9.5% (LD 1.146) is weighted slightly higher than changes at 7.5% (LD 1.141). Within the random parameter logit estimation, all coefficients proved to be significantly different from zero at the level p ≤ 0.01. The latent class analysis shows three heterogeneous classes, each showing clearly different weights of the therapeutic properties. This results in a clear three-folding: for 1/3 of the respondents the change of the long-term blood sugar (HbA1c value) is the top objective. Another third is solely interested in the short-term effectiveness of the therapy in the sense of the occurrence of severe hypoglycemias per year. The last third of the interviewees finally focuses on the follow-up regarding cardiovascular events. Overall, there were five structural and personality traits which have an influence on the respective probability of the class membership. DISCUSSION/CONCLUSION: This study identifies and weights the key decision-making criteria for optimal management of diabetes from the perspective of patients. It was shown that the effectiveness of a care program is the most important from the perspective of the patient and avoiding severe a hypoglycemia has the greatest influence on the choice. The risk of myocardial infarction as a follow-up disease and the long-term adjustment of the blood glucose follow the importance. In the analysis of possible subgroup differences by means of latent class analysis, it was found that three preference patterns exist within the sample. The generated preference data can be used for the design of personalized management approaches. It remains open to the extent to which expert opinions and patient preferences diverge.

Patient Preferences in the Treatment of Hemophilia A: A Best-Worst Scaling Case 3 Analysis.

OBJECTIVE: To assess patient preferences for benefits and risks in hemophilia A treatment. METHODS: A systematic literature search and pretest interviews were conducted to determine the most patient-relevant endpoints in terms of effects, risks, and administration of hemophilia A treatments. A Best-Worst Scaling (BWS; Case 3 or multiprofile case) approach was applied in a structured questionnaire. Patients were surveyed by interviewers in a computer-assisted personal interview. Treatments in the choice scenarios comprised bleeding frequency per year, application type, risk of thromboembolic event risk, and inhibitor development. Each respondent answered 13 choice tasks, including 1 dominant task, comparing 3 treatment profiles. Data were analyzed using a mixed logit model (random-parameters logit). RESULTS: Data from 57 patients were used. The attributes "bleeding frequency per year" and "inhibitor development" had the greatest impact on respondents' choice decisions. Patients disliked being at risk of inhibitor development more than being at risk of thromboembolic events. The type of application, whether intravenous or subcutaneous, was of less importance for patients. There was a significant preference variation for all attributes. CONCLUSIONS: Patients value low frequency of bleeding per year and low risk of development of inhibitors the most. An increase of risk and frequency would significantly decrease the impact on choice decisions. The type of application does not seem to influence the choice decision very much compared with the other attributes. Regarding preference heterogeneity, further analysis is needed to identify subgroups among patients and their characteristics. This may help to adapt individually patient-tailored treatment alternatives for hemophilia A patients.

[The Probabilistic Efficiency Frontier: A Value Assessment of Treatment Options in Hepatitis C]. / Die probabilistische Effizienzgrenze: eine Wirtschaftlichkeitsanalyse von Therapieoptionen im Indikationsgebiet Hepatitis C.

BACKGROUND: The German Institute for Quality and Efficiency in Health Care (IQWiG) recommends the concept of the efficiency frontier to assess health care interventions. The efficiency frontier supports regulatory decisions on reimbursement prices for the appropriate allocation of health care resources. Until today this cost-benefit assessment framework has only been applied on the basis of individual patient-relevant endpoints. This contradicts the reality of a multi-dimensional patient benefit. OBJECTIVE: The objective of this study was to illustrate the operationalization of multi-dimensional benefit considering the uncertainty in clinical effects and preference data in order to calculate the efficiency of different treatment options for hepatitis C (HCV). This case study shows how methodological challenges could be overcome in order to use the efficiency frontier for economic analysis and health care decision-making. METHOD: The operationalization of patient benefit was carried out on several patient-relevant endpoints. Preference data from a discrete choice experiment (DCE) study and clinical data based on clinical trials, which reflected the patient and the clinical perspective, respectively, were used for the aggregation of an overall benefit score. A probabilistic efficiency frontier was constructed in a Monte Carlo simulation with 10000 random draws. Patient-relevant endpoints were modeled with a beta distribution and preference data with a normal distribution. The assessment of overall benefit and costs provided information about the adequacy of the treatment prices. The parameter uncertainty was illustrated by the price-acceptability-curve and the net monetary benefit. RESULTS: Based on the clinical and preference data in Germany, the interferon-free treatment options proved to be efficient for the current price level. The interferon-free therapies of the latest generation achieved a positive net cost-benefit. Within the decision model, these therapies showed a maximum overall benefit. Due to their high additional benefit and approved prices, the therapies lie above of the extrapolated efficiency frontier, which suggests that these options have efficient reimbursement prices. Considering uncertainty, even a higher price would have resulted in a positive cost-benefit ratio. CONCLUSION: IQWiG's efficiency frontier was used to assess the value of different treatment options in HCV. This study demonstrates that the probabilistic efficiency frontier, price-acceptability-curve and the net monetary benefit can contribute essential information to reimbursement decisions and price negotiations.

Incentives for Blood Donation: A Discrete Choice Experiment to Analyze Extrinsic Motivation.

Background: Demographic trends affect size and age structure of populations. One of the consequences will be an increasing need for blood products to treat age-related diseases. Donation services rely on voluntariness and charitable motivation. It might be questioned whether there will be sufficient blood supply with voluntary donation. The present study focused on elicitation of preferences for incentives and aimed to contribute to the discussion on how to increase donation rates. Methods: A self-administered discrete choice experiment (DCE) was applied. Respondents were repeatedly asked to choose between hypothetical blood donation centers. In case of reluctance to receiving incentives a none-option was included. Random parameter logit (RPL) and latent class models (LCM) were used for analysis. Results: The study sample included 416 college students from the US and Germany. Choice decisions were significantly influenced by the characteristics of the donation center in the DCE. Incentives most preferred were monetary compensation, paid leave, and blood screening test. LCM identified subgroups with preference heterogeneity. Small subgroups indicated moderate to strong aversion to incentives. Conclusion: The majority of the sample positively responded to incentives and indicated a willingness to accept incentives. In face of future challenges, the judicious use and appropriate utilization of incentives might be an option to motivate potential donors and should be open to discussion.

Treatment Preferences in Germany Differ Among Apheresis Patients with Severe Hypercholesterolemia.

BACKGROUND: Severe hypercholesterolemia is a major risk factor of death in patients with coronary heart disease. New adjunctive drug therapies (proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors) have gained approval in Europe and the USA. OBJECTIVE: In this empirical study, we documented preferences regarding adjuvant drug therapy in apheresis-treated patients with severe familial hypercholesterolemia. METHODS: We conducted a systematic literature search to identify patient-relevant outcomes in patients with severe hypercholesterolemia currently undergoing apheresis. Data were used to generate a semi-structured qualitative interview that enabled seven patient-relevant characteristics with three levels each to be identified. For the discrete choice experiment, an experimental design (7 × 3) was generated using NGene Software that consisted of 96 choices divided into eight blocks. The survey was conducted between November 2015 and April 2016 using computer-assisted personal interviews. RESULTS: The survey was completed by 348 patients (64.9% male). The random parameter logit estimation showed predominance for the attribute 'reduction of LDL-C (low-density lipoprotein cholesterol) level'. 'Risk of myopathy' and 'frequency of apheresis' dominated next. Within the random parameter logit estimation, all coefficients were significant (P ≤ 0.01). The latent class analysis identified three patient groups. The first group (126 patients) found 'reduction of LDL-C level in blood' to be most important. This group focused solely on this treatment outcome independently of apheresis frequency or additional injections. The second group (106 patients) focused on three attributes: 'frequency of apheresis', 'risk of myopathy', and 'reduction of LDL-C level in blood'. Respondents clearly considered a high frequency of apheresis to have a negative impact. The third group (116 patients) demonstrated the highest preference for apheresis. These patients have adjusted to apheresis for > 10 years. CONCLUSION: Regarding patient preference, clinical efficacy seems to dominate. Hence, 'reduction of LDC-C in blood' was ranked highest above patient-relevant modes of administration and adverse effects. In the patient groups identified, reduction of apheresis was important for only a subsegment (30%) of patients. Another 30% wanted effective LDL-C reduction by whatever means necessary. Most strikingly, another 30% preferred higher frequencies of apheresis.

The Probabilistic Efficiency Frontier: A Framework for Cost-Effectiveness Analysis in Germany Put into Practice for Hepatitis C Treatment Options.

BACKGROUND: The German Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen) adapted the efficiency frontier (EF) approach to conform to statutory provisions on cost-effectiveness analysis of health technologies. EF serves as a framework for evaluating cost-effectiveness and indirectly for pricing and reimbursement decisions. OBJECTIVES: To calculate an EF on the basis of single multidimensional benefit by taking patient preferences and uncertainty into account; to evaluate whether EF is useful to inform decision makers about cost-effectiveness of new therapies; and to find whether a treatment is efficient at given prices demonstrated through a case study on chronic hepatitis C. METHODS: A single multidimensional benefit was calculated by linear additive aggregation of multiple patient-relevant end points. End points were identified and weighted by patients in a previous discrete-choice experiment (DCE). Aggregation of overall benefit was ascertained using preferences and clinical data. Monte-Carlo simulation was applied. Uncertainty was addressed by price acceptability curve (PAC) and net monetary benefit (NMB). RESULTS: The case study illustrates that progress in benefit and efficiency of hepatitis C virus treatments could be depicted very well with the EF. On the basis of cost, effect, and preference data, the latest generations of interferon-free treatments are shown to yield a positive NMB and be efficient at current prices. CONCLUSIONS: EF was implemented taking uncertainty into account. For the first time, a DCE was used with the EF. The study shows how DCEs in combination with EF, PAC, and NMB can contribute important information in the course of reimbursement and pricing decisions.

Tuning the excited state of water-soluble Ir(III)-based DNA intercalators that are isostructural with [Ru(II)(NN)2(dppz)] light-switch complexes.

The synthesis of two new Ir(III)  complexes which are effectively isostructural with well-established [Ru(NN)2(dppz)](2+) systems is reported (dppz=dipyridophenazine; NN=2,2'-bipyridyl, or 1,10-phenanthroline). One of these Ir(III) complexes is tricationic and has a conventional N6 coordination sphere. The second dicationic complex has a N5C coordination sphere, incorporating a cyclometalated analogue of the dppz ligand. Both complexes show good water solubility. Experimental and computational studies show that the photoexcited states of the two complexes are very different from each other and also differ from their Ru(II) analogues. Both of the complexes bind to duplex DNA with affinities that are two orders of magnitude higher than previously reported Ir(dppz)-based systems and are comparable with Ru(II)(dppz) analogues.

Blood donor management in china.

Despite a steady increase in total blood collections and voluntary non-remunerated blood donors, China continues to have many challenges with its blood donation system. The country's donation rate remains low at 9%o, with over 60% of donors being first-time donors. Generally there is a lack of adequate public awareness about blood donation. The conservative donor selection criteria, the relatively long donation interval, and the small donation volume have further limited blood supply. To ensure a sufficient and safe blood supply that meets the increasing clinical need for blood products, there is an urgent need to strengthen the country's blood donor management. This comprehensive effort should include educating and motivating more individuals especially from the rural areas to be involved in blood donation, developing rational and evidence-based selection criteria for donor eligibility, designing a donor follow-up mechanism to encourage more future donations, assessing the current donor testing strategy, improving donor service and care, building regional and national shared donor deferral database, and enhancing the transparency of the blood donation system to gain more trust from the general public. The purpose of the review is to provide an overview of the key process of and challenges with the blood donor management system in China.