Exploring health preference heterogeneity in the UK: Using the online elicitation of personal utility functions approach to construct EQ-5D-5L value functions on societal, group and individual level.

A new method has recently been developed for valuing health states, called 'Online elicitation of Personal Utility Functions' (OPUF). In contrast to established methods, such as time trade-off or discrete choice experiments, OPUF does not require hundreds of respondents, but allows estimating utility functions for small groups and even at the individual level. In this study, we used OPUF to elicit EQ-5D-5L health state preferences from a (not representative) sample of the UK general population, and then compared utility functions on the societal-, group-, and individual level. A demo version of the survey is available at: https://eq5d5l.me. Data from 874 respondents were included in the analysis. For each respondent, we constructed a personal EQ-5D-5L value set. These personal value sets predicted respondents' choices in three hold-out discrete choice tasks with an accuracy of 78%. Overall, preferences varied greatly between individuals. However, PERMANOVA analysis showed that demographic characteristics explained only a small proportion of the variability between subgroups. While OPUF is still under development, it has important strengths: it can be used to construct value sets for patient reported outcome instruments such as EQ-5D-5L, while also allowing examination of underlying preferences in an unprecedented level of detail. In the future, OPUF could be used to complement existing methods, allowing valuation studies in smaller samples, and providing more detailed insights into the heterogeneity of preferences across subgroups.

Using the Online Elicitation of Personal Utility Functions Approach to Derive a Patient-Based 5-Level Version of EQ-5D Value Set: A Study in 122 Patients With Rheumatic Diseases From Germany.

OBJECTIVES: Traditional preference elicitation methods, such as discrete choice experiments or time trade-off, usually require large sample sizes. This can limit their applicability in patient populations, where recruiting enough participants can be challenging. The objective of this study was to test a new method, called the Online elicitation of Personal Utility Functions (OPUF) approach, to derive an EQ-5D-5L value set from a relatively small sample of patients with rheumatic diseases. METHODS: OPUF is a new type of online survey that implements compositional preference elicitation techniques. Central to the method are 3 valuation steps: (1) dimension weighting, (2) level rating, and (3) anchoring. An English demo version of the OPUF survey can be accessed at https://valorem.health/eq5d5l. From the responses, a personal EQ-5D-5L utility function can be constructed for each participant, and a group-level value set can be derived by aggregating model coefficients across participants. RESULTS: A total of 122 patients with rheumatic disease from Germany completed the OPUF survey. The survey was generally well received; most participants completed the survey in less than 20 minutes and were able to derive a full EQ-5D-5L value set. The precision of mean coefficients was high, despite the small sample size. CONCLUSIONS: Our findings demonstrate that OPUF can be used to derive an EQ-5D-5L value set from a relatively small sample of patients. Although the method is still under development, we think that it has the potential to be a valuable preference elicitation tool and to complement traditional methods in several areas.

Hypothetical versus experienced health state valuation: a qualitative study of adult general public views and preferences.

OBJECTIVES: Responses from hypothetical and experienced valuation tasks of health-related quality of life differ, yet there is limited understanding of why these differences exist, what members of the public think about them, and acceptable resolutions. This study explores public understanding of, opinions on, and potential solutions to differences between hypothetical versus experienced responses, in the context of allocating health resources. METHODS: Six focus groups with 30 members of the UK adult public were conducted, transcribed verbatim, and analysed using framework analysis. Participants self-completed the EQ-5D-5L, before reporting the expected consequences of being in two hypothetical EQ-5D-5L health states for ten years. Second, participants were presented with prior results on the same task from a public (hypothetical) and patient (experienced) sample. Third, a semi-structured discussion explored participants': (1) understanding, (2) opinions, and (3) potential resolutions. RESULTS: Twenty themes emerged, clustered by the three discussion points. Most participants found imagining the health states difficult without experience, with those aligned to mental health harder to understand. Participants were surprised that health resource allocation was based on hypothetical responses. They viewed experienced responses as more accurate, but noted potential biases. Participants were in favour of better informing, but not influencing the public. Other solutions included incorporating other perspectives (e.g., carers) or combining/weighting responses. CONCLUSION: Members of the UK public appear intuitively not to support using potentially uninformed public values to hypothetical health states in the context of health resource allocation. Acceptable solutions involve recruiting people with greater experience, including other/combinations of views, or better informing respondents.

The Online Elicitation of Personal Utility Functions (OPUF) tool: a new method for valuing health states.

Introduction Standard valuation methods, such as TTO and DCE are inefficient. They require data from hundreds if not thousands of participants to generate value sets. Here, we present the Online elicitation of Personal Utility Functions (OPUF) tool; a new type of online survey for valuing EQ-5D-5L health states using more efficient, compositional elicitation methods, which even allow estimating value sets on the individual level. The aims of this study are to report on the development of the tool, and to test the feasibility of using it to obtain individual-level value sets for the EQ-5D-5L. Methods We applied an iterative design approach to adapt the PUF method, previously developed by Devlin et al., for use as a standalone online tool. Five rounds of qualitative interviews, and one quantitative pre-pilot were conducted to get feedback on the different tasks. After each round, the tool was refined and re-evaluated. The final version was piloted in a sample of 50 participants from the UK. A demo of the EQ-5D-5L OPUF survey is available at: https://eq5d5l.me Results On average, it took participants about seven minutes to complete the OPUF Tool. Based on the responses, we were able to construct a personal EQ-5D-5L value set for each of the 50 participants. These value sets predicted a participants' choices in a discrete choice experiment with an accuracy of 80%. Overall, the results revealed that health state preferences vary considerably on the individual-level. Nevertheless, we were able to estimate a group-level value set for all 50 participants with reasonable precision. Discussion We successfully piloted the OPUF Tool and showed that it can be used to derive a group-level as well as personal value sets for the EQ-5D-5L. Although the development of the online tool is still in an early stage, there are multiple potential avenues for further research.

Cost-effectiveness of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab in patients with a history of myocardial infarction in Sweden.

AIMS: To assess the cost-effectiveness of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab added to standard-of-care lipid-lowering treatment [maximum tolerated dose (MTD) of statin and ezetimibe] in Swedish patients with a history of myocardial infarction (MI). METHODS AND RESULTS: Cost-effectiveness was evaluated using a Markov model based on Swedish observational data on cardiovascular event rates and efficacy from the FOURIER trial. Three risk profiles were considered: recent MI in the previous year; history of MI with a risk factor; and history of MI with a second event within 2 years. For each population, three minimum baseline low-density lipoprotein cholesterol (LDL-C) levels were considered: 2.5 mmol/L (≈100 mg/dL), based on the current reimbursement recommendation in Sweden; 1.8 mmol/L (≈70 mg/dL), based on 2016 ESC/EAS guidelines; and 1.4 mmol/L (≈55 mg/dL), or 1.0 mmol/L (≈40 mg/dL) for MI with a second event, based on 2019 ESC/EAS guidelines. Proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab was associated with increased quality-adjusted life-years and costs vs. standard-of-care therapy. Incremental cost-effectiveness ratios (ICERs) were below SEK700 000 (∼€66 500), the generally accepted willingness-to-pay threshold in Sweden, for minimum LDL-C levels of 2.3 (recent MI), 1.7 (MI with a risk factor), and 1.7 mmol/L (MI with a second event). Sensitivity analyses demonstrated that base-case results were robust to changes in model parameters. CONCLUSION: Proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab added to MTD of statin and ezetimibe may be considered cost-effective at its list price for minimum LDL-C levels of 1.7-2.3 mmol/L, depending on risk profile, with ICERs below the accepted willingness-to-pay threshold in Sweden.

An Innovative Approach to Modelling the Optimal Treatment Sequence for Patients with Relapsing-Remitting Multiple Sclerosis: Implementation, Validation, and Impact of the Decision-Making Approach.

INTRODUCTION: An innovative computational model was developed to address challenges regarding the evaluation of treatment sequences in patients with relapsing-remitting multiple sclerosis (RRMS) through the concept of a 'virtual' physician who observes and assesses patients over time. We describe the implementation and validation of the model, then apply this framework as a case study to determine the impact of different decision-making approaches on the optimal sequence of disease-modifying therapies (DMTs) and associated outcomes. METHODS: A patient-level discrete event simulation (DES) was used to model heterogeneity in disease trajectories and outcomes. The evaluation of DMT options was implemented through a Markov model representing the patient's disease; outcomes included lifetime costs and quality of life. The DES and Markov models underwent internal and external validation. Analyses of the optimal treatment sequence for each patient were based on several decision-making criteria. These treatment sequences were compared to current treatment guidelines. RESULTS: Internal validation indicated that model outcomes for natural history were consistent with the input parameters used to inform the model. Costs and quality of life outcomes were successfully validated against published reference models. Whereas each decision-making criterion generated a different optimal treatment sequence, cladribine tablets were the only DMT common to all treatment sequences. By choosing treatments on the basis of minimising disease progression or number of relapses, it was possible to improve on current treatment guidelines; however, these treatment sequences were more costly. Maximising cost-effectiveness resulted in the lowest costs but was also associated with the worst outcomes. CONCLUSIONS: The model was robust in generating outcomes consistent with published models and studies. It was also able to identify optimal treatment sequences based on different decision criteria. This innovative modelling framework has the potential to simulate individual patient trajectories in the current treatment landscape and may be useful for treatment switching and treatment positioning decisions in RRMS.

Mapping EQ-5D-3L to EQ-5D-5L.

OBJECTIVES: The original 3-level EQ-5D (EQ-5D-3L) includes 5 dimensions with 3 levels of problems per dimension. Since 2010, a more sensitive version with 5 levels of problems per dimension (EQ-5D-5L) has become available. Population value sets have been developed for both versions of the questionnaire. The objective of this research was to develop a mapping function to link EQ-5D-3L responses to value sets for the EQ-5D-5L. METHODS: Various algorithms were developed to link EQ-5D-3L and EQ-5D-5L responses using data from an observational study including members of 10 subgroups (N = 3580) who completed both versions of the questionnaire. Nonparametric and ordinal logistic regression models were fit to the data and compared using Akaike's information criterion (AIC) as well as the mean absolute error and root mean squared error of predictions. Results were contrasted qualitatively and quantitatively with those of an alternative copula-based approach. RESULTS: Including indicants of problems for other EQ-5D-3L dimensions as regressors in the modeling yielded the greatest improvement in prediction accuracy. Adding age and gender lowered the AIC without improving predictions, while including a latent factor lowered the AIC further and slightly improved predictive accuracy. Models that conditioned on problems in other EQ-5D-3L dimensions yielded more accurate predictions than the alternative copula-based approach in subgroups defined by age and gender. CONCLUSION: We present novel algorithms to map EQ-5D-3L responses to EQ-5D-5L value sets. The recommended approach is based on an ordinal logistic regression that disregards age and gender and accounts for unobserved heterogeneity using a latent factor.

Critical appraisal and issues regarding generalisability of comparative effectiveness studies of NOACs in atrial fibrillation and their relation to clinical trial data: a systematic review.

OBJECTIVE: To critically appraise the published comparative effectiveness studies on non-vitamin K antagonist oral anticoagulants (NOACs) in non-valvular atrial fibrillation (NVAF). Results were compared with expectations formulated on the basis of trial results with specific attention to the patient years in each study. METHODS: All studies that compared the effectiveness or safety between at least two NOACs in patients with NVAF were eligible. We performed a systematic literature review in Medline and EMbase to investigate the way comparisons between NOACs were made, search date 23 April 2019. Critical appraisal of the studies was done using among others ISPOR Good Research Practices for comparative effectiveness research. RESULTS: We included 39 studies in which direct comparison between at least two NOACs were made. Almost all studies concerned patient registries, pharmacy or prescription databases and/or health insurance database studies using a cohort design. Corrections for differences in patient characteristics was applied in all but two studies. Eighteen studies matched using propensity scores (PS), 8 studies weighted patients based on the inverse probability of treatment, 1 study used PS stratification and 10 studies applied a proportional hazards model. These studies have some important limitations regarding unmeasured confounders and channelling bias, even though the larger part of the studies were well conducted technically. On the basis of trial results, expected differences are small and a naïve analysis suggests trials with between 7200 and 56 500 patients are needed to confirm the observed differences in bleedings and between 51 800 and 7 994 300 to confirm differences in efficacy. DISCUSSION: Comparisons regarding effectiveness and safety between NOACs on the basis of observational data, even after correction for baseline characteristics, may not be reliable due to unmeasured confounders, channelling bias and insufficient sample size. These limitations should be kept in mind when results of these studies are used to decide on ranking NOAC treatment options.

Mortality Prediction of the CHA2DS2-VASc Score, the HAS-BLED Score, and Their Combination in Anticoagulated Patients with Atrial Fibrillation.

BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) is associated with increased mortality, predictors of which are poorly characterized. We investigated the predictive power of the commonly used CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥ 75 years [doubled], diabetes, stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]), the HAS-BLED score (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio [INR], elderly [age ≥ 65 years], drugs/alcohol concomitantly), and their combination for mortality in AF patients. METHODS: The PREvention oF thromboembolic events-European Registry in Atrial Fibrillation (PREFER in AF) was a prospective registry including AF patients across seven European countries. We used logistic regression to analyze the relationship between the CHA2DS2-VASc and HAS-BLED scores and outcomes, including mortality, at one year. We evaluated the performance of logistic regression models by discrimination measures (C-index and DeLong test) and calibration measures (Hosmer and Lemeshow goodness-of-fit and integrated discrimination improvement (IDI), with bootstrap techniques for internal validation. RESULTS: In 5209 AF patients with complete information on both scores, average one-year mortality was 3.1%. We found strong gradients between stroke/systemic embolic events (SSE), major bleeding and-specifically-mortality for both CHA2DS2-VASc and HAS-BLED scores, with a similar C-statistic for event prediction. The predictive power of the models with both scores combined, removing overlapping components, was significantly enhanced (p < 0.01) compared to models including either CHA2DS2-VASc or HAS-BLED alone: for mortality, C-statistic: 0.740, compared to 0.707 for CHA2DS2-VASc or 0.646 for HAS-BLED alone. IDI analyses supported the significant improvement for the combined score model compared to separate score models for all outcomes. CONCLUSIONS: Both the CHA2DS2-VASc and the HAS-BLED scores predict mortality similarly in patients with AF, and a combination of their components increases prediction significantly. Such combination may be useful for investigational and-possibly-also clinical purposes.

Impact of Patient Characteristics on Treatment Outcomes in Symptomatic Venous Thromboembolism: Results of HOKUSAI-VTE Randomized Trial Analysis.

Introduction In patients with venous thromboembolism (VTE), direct oral anticoagulants (DOACs) such as edoxaban, apixaban, dabigatran, and rivaroxaban are more convenient, safer, and just as effective as vitamin K antagonists (VKAs). Limited information is known about the effects of patient characteristics on VTE efficacy and safety of DOACs compared with VKAs, without appropriate effect modifier adjustment comparisons of DOACs may be biased. This study considers the effect of variables that can modify the efficacy and safety of edoxaban and warfarin, using patient-level data. Materials and Methods The primary efficacy and safety outcomes in the HOKUSAI-VTE study were VTE recurrence and clinically relevant bleeding, respectively. Potential effect modifiers were age, creatinine clearance, and weight. The relationship between the percentage of time in international normalized ratio (INR) control and outcomes were considered for the warfarin arm. Univariate and multivariate regression were performed for each patient characteristic. Results The relationship between treatment and VTE recurrence differed by age (interaction p = 0.007) and by creatinine clearance ( p = 0.05). VTE recurrence differed by age for patients in the warfarin arm but not for those in the edoxaban arm and differed by INR control in the warfarin arm ( p < 0.005). A stronger relationship between creatinine clearance and clinically relevant bleeding was found in the warfarin arm than in the edoxaban arm ( p = 0.04). Clinically relevant bleeding differed by the percentage of time in INR control in the warfarin arm ( p < 0.005). Age appeared to be a more important effect modifier than creatinine clearance in patients with VTE. Discussion The finding that efficacy in older patients was greater for those taking edoxaban than for those taking warfarin in the HOKUSAI-VTE study needs further investigation. Modification of the treatment effect by age for those taking warfarin might bias estimates of comparative effectiveness among DOACs if VKAs are the reference treatment.

The EQ-5D-5L Value Set for England: Response to the "Quality Assurance".

OBJECTIVES: To respond to the 'quality assurance' of the EQ-5D-5L value set for England study. METHODS: We provide a point-by-point response to the issues raised by the authors of the quality assurance paper, drawing on theoretical arguments, empirical analyses and practical considerations. RESULTS: We provide evidence to show that many of the points made by the authors of the quality assurance are misleading, suggest misunderstandings, or are irrelevant. CONCLUSIONS: The modeling approaches which were used appropriately address the characteristics of the data and provide a reasonable representation of the average stated preferences of general public in England. We provide reflections on the conduct of stated preference studies, and suggestions for the way forward.

Updated Cost-effectiveness Analysis of Evolocumab in Patients With Very High-risk Atherosclerotic Cardiovascular Disease.

Importance: In October 2018, evolocumab was made available at a reduced annual list price of $5850 in the United States. This 60% reduction was aimed at improving patient access by lowering patient copays. Shortly thereafter, the 2018 American College of Cardiology/American Heart Association cholesterol management guideline was released. An updated cost-effectiveness analysis of evolocumab in the United States may be therefore of interest to payers and prescribers. Objective: To present an updated cost-effectiveness analysis of evolocumab added to standard background therapy compared with standard background therapy alone in patients with very high-risk atherosclerotic cardiovascular disease, reflecting the 2018 ACC/AHA guideline definition and using the new evolocumab list price. Design, Setting, and Participants: This study used the Markov model originally used in a previous study by Fonarow et al in 2017. A US societal perspective was considered, and a range of baseline cardiovascular event rates were modeled to reflect varying risk profiles in clinical practice within patients with very high-risk atherosclerotic cardiovascular disease. Exposures: Addition of evolocumab to standard background therapy, including maximally tolerated statin therapy (ie, the maximum intensity of statin therapy a patient can safely receive), with or without ezetimibe. Main Outcomes and Measures: Major cardiovascular events (myocardial infarction, ischemic stroke, and cardiovascular death), costs, quality-adjusted life-years, and incremental cost-effectiveness ratios. Results: Evolocumab was associated with both increased costs and improved outcomes when added to standard background therapy. Incremental costs ranged from $22 228 to $3411, depending on the varying level of risk within the defined population. Incremental quality-adjusted life years ranged from 0.39 to 0.44. Incremental cost-effectiveness ratios ranged from $56 655 to $7667 per quality-adjusted life-year gained. For a range of baseline cardiovascular event rates in patients with very high-risk atherosclerotic cardiovascular disease, incremental cost-effectiveness ratios were below the generally accepted willingness-to-pay thresholds. Moreover, the ratios were below the threshold of $50 000 per quality-adjusted life-years gained for any baseline rate of 6.9 or more events per 100 patient-years. Conclusions and Relevance: At its current list price, the addition of evolocumab to standard background therapy meets accepted cost-effectiveness thresholds across a range of baseline cardiovascular event rates in patients with very high-risk atherosclerotic cardiovascular disease as defined by the 2018 ACC/AHA guideline.

Health-related quality of life and mortality in patients with pulmonary embolism: a prospective cohort study in seven European countries.

PURPOSE: Little is known about the quality of life following pulmonary embolism (PE). The aim of the study was to assess the 12-month illness burden in terms of health-related quality of life (HrQoL) and mortality, in relation to differences in patient characteristics. METHODS: The PREFER in VTE registry, a prospective, observational study conducted in seven European countries, was used. Within 2 weeks following an acute symptomatic PE, patients were recruited and followed up for 12 months. Associations between patient characteristics and HrQoL (EQ-5D-5L) and mortality were examined using a regression approach. RESULTS: Among 1399 PE patients, the EQ-5D-5L index score at baseline was 0.712 (SD 0.265), which among survivors gradually improved to 0.835 (0.212) at 12 months. For those patients with and without active cancer, the average index score at baseline was 0.658 (0.275) and 0.717 (0.264), respectively. Age and previous stroke were significant factors for predicting index scores in those with/without active cancer. Bleeding events but not recurrences had a noticeable impact on the HrQoL of patients without active cancer. The 12-month mortality rate post-acute period was 8.1%, ranging from 1.4% in Germany, Switzerland, and Austria to 16.8% in Italy. Mortality differed between patients with active cancer and those without (42.7% vs. 4.7%). CONCLUSION: PE is associated with a substantial decrease in HrQoL at baseline which normalizes following treatment. PE is associated with a high mortality rate especially in patients with cancer, with significant country variation. Bleeding events, in particular, impact the burden of PE.

Comparison of quality of life measurements: EQ-5D-5L versus disease/treatment-specific measures in pulmonary embolism and deep vein thrombosis.

INTRODUCTION: There is a lack of performance comparisons of the generic quality of life tool EQ-5D-5L against disease- and treatment-specific measures in venous thromboembolism (VTE). The aim of this study was to compare EQ-5D-5L against the pulmonary embolism (PE)-specific PEmb-QoL and the deep vein thrombosis (DVT)-specific VEINES-QOL/Sym, and PACT-Q2 (treatment-specific) questionnaires in five language settings. METHODS: PREFER in VTE was a non-interventional disease registry conducted between 2013 and 2014 in primary and secondary care across seven European countries with five languages, including English, French, German, Italian and Spanish. Consecutive patients with acute PE/DVT were enrolled and followed over 12 months. Only patients who completed all three questionnaires at baseline were included in the study sample. The psychometric properties examined included acceptability (missing, ceiling and floor effects), validity (convergent and known-groups validity), and responsiveness. Known groups validity and responsiveness were assessed using both effect size (Cohen's d) and relative efficiency (F-statistic). All analyses were conducted in each language version and the total sample across all languages. RESULTS: A total of 1054 PE and 1537 DVT patients were included. 14% of PE and 10% of DVT patients had the maximum EQ-5D-5L index score. EQ-5D-5L was low to moderately correlated with other measures (r < 0.5). EQ-5D-5L was associated with larger effect size/relative efficiency in most of known group comparisons in both VTE groups. Similar results were observed for responsiveness. EQ-5D-5L performed relatively better in French, Italian and Spanish language versions. CONCLUSION: Overall EQ-5D-5L is comparable to PEmb-QoL, VEINES-QOL/Sym and PACT-Q2 in terms of acceptability, validity and responsiveness in both PE and DVT populations in English, French, German, Italian and Spanish language version. Nevertheless, it should be noted that each measure is designed to capture different aspects of health-related quality of life.

Overview, Update, and Lessons Learned From the International EQ-5D-5L Valuation Work: Version 2 of the EQ-5D-5L Valuation Protocol.

A standardized 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5L) valuation protocol was first used in national studies in the period 2012 to 2013. A set of problems encountered in this initial wave of valuation studies led to the subsequent refinement of the valuation protocol. To clarify lessons learned and how the protocol was updated when moving from version 1.0 to the current version 2.1 and 2.0, this article will (1) present the challenges faced in EQ-5D-5L valuation since 2012 and how these were resolved and (2) describe in depth a set of new challenges that have become central in currently ongoing research on how EQ-5D-5L health states should be valued and modeled.

A new method for valuing health: directly eliciting personal utility functions.

BACKGROUND: Standard methods for eliciting the preference data upon which 'value sets' are based generally have in common an aim to 'uncover' people's preferences by asking them to evaluate a subset of health states, then using their responses to infer their preferences over all dimensions and levels. An alternative approach is to ask people directly about the relative importance to them of the dimensions, levels and interactions between them. This paper describes a new stated preference approach for directly eliciting personal utility functions (PUFs), and reports a pilot study to test its feasibility for valuing the EQ-5D. METHODS: A questionnaire was developed, designed to directly elicit PUFs from general public respondents via computer-assisted personal interviews, with a focus on helping respondents to reflect and deliberate on their preferences. The questionnaire was piloted in England. RESULTS: Seventy-six interviews were conducted in December 2015. Overall, pain/discomfort and mobility were found to be the most important of the EQ-5D dimensions. The ratings for intermediate improvements in each dimension show heterogeneity, both within and between respondents. Almost a quarter of respondents indicated that no EQ-5D health states are worse than dead. DISCUSSION: The PUF approach appears to be feasible, and has the potential to yield meaningful, well-informed preference data from respondents that can be aggregated to yield a value set for the EQ-5D. A deliberative approach to health state valuation also has the potential to complement and develop existing valuation methods. Further refinement of some elements of the approach is required.

Methodology of a Novel Risk Stratification Algorithm for Patients with Multiple Myeloma in the Relapsed Setting.

INTRODUCTION: Risk stratification tools provide valuable information to inform treatment decisions. Existing algorithms for patients with multiple myeloma (MM) were based on patients with newly diagnosed disease, and these have not been validated in the relapsed setting or in routine clinical practice. We developed a risk stratification algorithm (RSA) for patients with MM at initiation of second-line (2L) treatment, based on data from the Czech Registry of Monoclonal Gammopathies. METHODS: Predictors of overall survival (OS) at 2L treatment were identified using Cox proportional hazards models and backward selection. Risk scores were obtained by multiplying the hazard ratios for each predictor. The K-adaptive partitioning for survival (KAPS) algorithm defined four groups of stratification based on individual risk scores. RESULTS: Performance of the RSA was assessed using Nagelkerke's R2 test and Harrell's concordance index through Kaplan-Meier analysis of OS data. Prognostic groups were successfully defined based on real-world data. Use of a multiplicative score based on Cox modeling and KAPS to define cut-off values was effective. CONCLUSION: Through innovative methods of risk assessment and collaboration between physicians and statisticians, the RSA was capable of stratifying patients at 2L treatment by survival expectations. This approach can be used to develop clinical decision-making tools in other disease areas to improve patient management. FUNDING: Amgen Europe GmbH.

The impact of co-morbidity on the disease burden of VTE.

Venous thromboembolism (VTE) is often accompanied by co-morbidities, which complicate and confound data interpretation concerning VTE-related mortality, costs and quality of life. We aimed to assess the contribution of co-morbidities to the burden of VTE. The PREFER in VTE registry, across seven European countries, documented and followed acute VTE patients over 12 months. Patients with co-morbidities were grouped in major co-morbidity groups: cancer, cardiovascular (CV) comorbidity (other than VTE), CV risks, venous, renal, liver, respiratory, bone and joint diseases, and lower extremity paralysis. Mortality rates and health-related quality of life (HrQoL) utility values grouped per co-morbidity were compared to the UK general population. Regression analyses were performed to determine the impact of co-morbidities on mortality and HrQoL. VTE were analyzed together and separately as pulmonary embolism (PE) and deep vein thrombosis (DVT). In total, 3455 patients were included, 40.5% with PE and 59.5% with DVT. 13% and 16% of the PE and DVT patients had no co-morbidities and had a 12-month mortality rate of 1.8% and 1.7%, respectively. Frequency and severity of co-morbidities increased mortality rates up to 30%. The EQ-5D-5L index in patients without co-morbidities were 0.826 and 0.838 for PE and DVT. These scores decreased to 0.638 and 0.555 in the presence of co-morbidities. Co-morbidities in VTE patients are common. VTE had an impact on mortality and HrQoL, and additional impact of co-morbidities was seen. Awareness of the presence of co-morbidities is important when making VTE-related treatment decisions. The presence of co-morbidities in PE and DVT patients is common and their frequency and severity in VTE patients have a substantial impact on mortality rates and HrQoL. When adjusting for co-morbidities, the impact of VTE on mortality as well as health-related quality of life remains present. Assessing patients without consideration of co-morbidities might lead to misinterpretations of the disease burden of PE and DVT.

Pulmonary embolism in Europe - Burden of illness in relationship to healthcare resource utilization and return to work.

OBJECTIVES: Pulmonary embolism (PE) is associated with a substantial economic burden. However evidence from patients in Europe is scarce. The aim of this study was to report the impacts of PE on healthcare resource utilization (HCRU) and return to work using the PREFER in VTE registry. METHODS: The PREFER in VTE registry was a prospective, observational, multicenter study in seven European countries, aiming to provide data concerning treatment patterns, HCRU, mortality, quality of life and work-loss. Patients with a first-time or recurrent PE were included and followed up at 1, 3, 6 and 12 months. Treatment patterns, re-hospitalization rates, length of hospital stays (LOS), and ambulatory/office visits, as well as proportion of patients returning to work, were assessed. Subgroups by country and with/without active cancer were examined separately. Zero-inflated negative binomial and Cox regression were applied to investigate the relationship between baseline characteristics and LOS and return to work, respectively. RESULTS: Amongst 1399 patients with PE, 53.2% were male and the average age was 62.3 ±â€¯17.1 years old. Overall, patients were treated with combinations of heparin, vitamin K antagonists (VKA) and the non-VKA oral anticoagulants (NOACs) (50.0% treated with the combination of heparin with VKA). Patients with active cancer were primarily treated with heparin (84.9%). NOACs were used more frequently in DACH (Germany, Austria and Switzerland) and France (55.2% and 32.6%) compared to Italy and Spain (4.5% and 6.1%). The VTE-related re-hospitalization rate within 12 months and the average LOS varied substantially between countries, from 26.2% in UK to 12.3% in France, and from 12.9 days in Italy to 3.9 days in France. PE patients were often co-managed by general practitioners in France and DACH (>84%), and less frequently in other countries (<47%). The regression results confirmed the country variation of HCRU. Of the employed patients (n = 385), 60% returned to work at 1 month but 27.8% had not after one year. PE patients with DVT were more likely to return to work. Active cancer was a significant predictor for not returning to work, as well as smoking history. CONCLUSIONS: Medical treatment of PE differed between patients with active cancer and patients without active cancer. VTE-related resource utilization differed markedly between countries. While the reported 'not return to work' was high for patients with PE, this may at least in part reflect the presence of co-morbidities such as cancer.