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Government investment in preparing for pandemics has never been more relevant. The COVID-19 pandemic has stimulated debate regarding the trade-offs societies are prepared to make between health and economic activity. What is not known is: (1) how much the public in different countries are prepared to pay in forgone GDP to avoid mortality from future pandemics; and (2) which health and economic policies the public in different countries want their government to invest in to prepare for and respond to the next pandemic. Using a future-focused, multi-national discrete choice experiment, we quantify these trade-offs and find that the tax-paying public is prepared to pay $3.92 million USD (Canada), $4.39 million USD (UK), $5.57 million USD (US) and $7.19 million USD (Australia) in forgone GDP per death avoided in the next pandemic. We find the health policies that taxpayers want to invest in before the next pandemic and the economic policies they want activated once the next pandemic hits are relatively consistent across the countries, with some exceptions. Such results can inform economic policy responses and government investment in health policies to reduce the adverse impacts of the next pandemic.

When healthcare interventions prolong life, people consume medical and non-medical goods during the years of life they gain. It has been argued that the costs for medical consumption should be included in cost-effectiveness analyses from both a healthcare and societal perspective, and the costs for non-medical consumption should additionally be included when a societal perspective is applied. Standardized estimates of these so-called future costs are available in only a few countries and the impact of inclusion of these costs is likely to differ between countries. In this paper we present and compare future costs for five European countries and estimate the impact of including these costs on the cost-effectiveness of life-prolonging interventions. As countries differ in the availability of data, we illustrate how both individual- and aggregate-level data sources can be used to construct standardized estimates of future costs. Results show a large variation in costs between countries. The medical costs for the Netherlands, Germany, and the United Kingdom are large compared to Spain and Greece. Non-medical costs are higher in Germany, Spain, and the United Kingdom than in Greece. The impact of including future costs on the ICER similarly varied between countries, ranging from €1000 to €35,000 per QALY gained. The variation between countries in impact on the ICER is largest when considering medical costs and indicate differences in both structure and level of healthcare financing in these countries. Case study analyses were performed in which we highlight the large impact of including future costs on ICER relative to willingness-to-pay thresholds.

Background: End-stage liver disease (ESLD) patients carry heavy symptom burdens and risk receiving aggressive and sometimes unwanted care at end of life. Palliative care (PC), which aims to alleviate symptoms and facilitate goal-concordant care in serious illness, may offer substantial benefits for ESLD patients but is not widely provided. Objectives: To assess the impact of PC integrated within hepatology (PCIH) services on health care utilization, advance care planning (ACP), and hospice enrollment. Design: We compared patients who received PCIH (n = 55) to a retrospective cohort (n = 57) receiving usual care in an outpatient hepatology clinic. Setting/Subjects: From June 2016 to November 2017, we enrolled patients receiving care in a U.S. public hospital clinic who met the following inclusion criteria: (1) ESLD with a Model for End-Stage Liver Disease score ≥20, (2) hepatology approval for PC referral, and (3) at least one advanced complication of ESLD. Measurements: We assessed patient demographics, clinical information, health care insurance status, health care utilization, completion of psychosocial assessments, and ACP using two-sided Fisher's exact test and Mann-Whitney U tests. Results: Patients receiving PCIH more frequently had goals of care discussions (87.3% vs. 21.2% p ≤ 0.01), completed ACP documentation (56.4% vs. 7.0%, p ≤ 0.01), psychosocial assessments (98.2% vs. 35.1%, p ≤ 0.01), and hospice enrollment (25.5% vs. 7.0%, p = 0.01). Patients receiving PCIH who were hospitalized also had fewer mean hospitalization days (13 vs. 19.7 days, p ≤ 0.01). Conclusions: Embedding PC services in a hepatology clinic is a promising strategy to improve care for ESLD patients in public hospitals.

Objective: To assess the cost-effectiveness of a cardiac rehabilitation (CR) program specifically designed for cardiac patients with obesity vs standard CR. Design: Cost-effectiveness analysis based on observations in a randomized controlled trial. Setting: Three regional CR centers in the Netherlands. Participants: Cardiac patients (N=201) with obesity (BMI≥30 kg/m2) referred to CR. Interventions: Participants were randomized to a CR program specifically designed for patients with obesity (OPTICARE XL; N=102) or standard CR. OPTICARE XL included aerobic and strength exercise and behavioral coaching on diet and physical activity during 12 weeks, followed by a 9-month after-care program with “booster” educational sessions. Standard CR consisted of a 6- to 12-week aerobic exercise program, supplemented with cardiovascular lifestyle education. Main Outcome Measures: An economic evaluation, with an 18-month time horizon, in terms of quality-adjusted life years (QALYs) and costs from the societal perspective was performed. Costs were reported in 2020 Euros, discounted at a 4% annual rate, and health effects were discounted at a 1.5% annual rate. Results: OPTICARE XL CR and standard CR resulted in comparable health gain per patient (0.958 vs 0.965 QALYs, respectively; P=.96). Overall, OPTICARE XL CR saved costs (-€4542) compared with the standard CR group. The direct costs for OPTICARE XL CR were higher than for standard CR (€10,712 vs €9951), whereas indirect costs were lower (€51,789 vs €57,092), but these differences were not significant. Conclusions: This economic evaluation showed no differences between OPTICARE XL CR and standard CR in health effects and costs in cardiac patients with obesity.

The prevalence of multimorbidity among rheumatoid arthritis (RA) patients is increasing and associated with worse outcomes. Therefore, management of multimorbid patients requires a multidisciplinary approach. However, healthcare systems consist of mono-disciplinary subsystems, which limits collaboration across subsystems. To study the importance of a multidisciplinary, integrated approach, associations between expenditures and multimorbidity are assessed in real-life data. Retrospective data on RA patients from a Dutch single-hospital are analyzed and compared to the Dutch RA population data. The Elixhauser index is used to measure the multimorbidity prevalence. Regression analyses were conducted to derive the relationship between multimorbidity, healthcare costs and self-reported quality of life (e.g. EQ-5D). When analyzing the impact of multimorbidity within RA patients in context of a single-hospital context, multimorbidity is only partially captured: 13% prevalence versus 24% of the Dutch population. Multimorbidity is associated with higher care expenditures. Depending on the type of multimorbidity, expenditures are €43–€5821 higher in a single-hospital and from €2259–€9648 in population data. Finally, medication use associated with chronic diseases and self-reported aspects of well-being are associated with similar increases in healthcare expenditures as multimorbidity based on hospital care. Within RA, a single-hospital approach underestimates the association between multimorbidity and healthcare expenditures as 43% of healthcare utilization and expenditures are missed. To overcome a single-provider perspective in healthcare and efficiently coordinate multimorbid patients, besides providing holistic care, professionals also need to use data providing comprehensive pictures of patients.

Health-related discrete choice experiments (DCEs) information can be used to inform decision-making on the development, authorisation, reimbursement and marketing of drugs and devices as well as treatments in clinical practice. Discrete choice experiment is a stated preference method based on random utility theory (RUT), which imposes strong assumptions on respondent choice behaviour. However, respondents may use choice processes that do not adhere to the normative rationality assumptions implied by RUT, applying simplifying decision rules that are more selective in the amount and type of processed information (i.e., simplifying heuristics). An overview of commonly detected simplifying heuristics in health-related DCEs is lacking, making it unclear how to identify and deal with these heuristics; more specifically, how researchers might alter DCE design and modelling strategies to accommodate for the effects of heuristics. Therefore, the aim of this paper is three-fold: (1) provide an overview of common simplifying heuristics in health-related DCEs, (2) describe how choice task design and context as well as target population selection might impact the use of heuristics, (3) outline DCE design strategies that recognise the use of simplifying heuristics and develop modelling strategies to demonstrate the detection and impact of simplifying heuristics in DCE study outcomes.

BACKGROUND AND OBJECTIVES: Case 2 best-worst scaling (BWS-2) is an increasingly popular method to elicit patient preferences. Because BWS-2 potentially has a lower cognitive burden compared with discrete choice experiments, the aim of this study was to compare treatment preference weights and relative importance scores.METHODS: Patients with neuromuscular diseases completed an online survey at two different moments in time, completing one method per occasion. Patients were randomly assigned to either first a discrete choice experiment or BWS-2. Attributes included: muscle strength, energy endurance, balance, cognition, chance of blurry vision, and chance of liver damage. Multinomial logit was used to calculate overall relative importance scores and latent class logit was used to estimate heterogeneous preference weights and to calculate the relative importance scores of the attributes for each latent class.RESULTS: A total of 140 patients were included for analyses. Overall relative importance scores showed differences in attribute importance rankings between a discrete choice experiment and BWS-2. Latent class analyses indicated three latent classes for both methods, with a specific class in both the discrete choice experiment and BWS-2 in which (avoiding) liver damage was the most important attribute. Ex-post analyses showed that classes differed in sex, age, level of education, and disease status. The discrete choice experiment was easier to understand compared with BWS-2.CONCLUSIONS: This study showed that using a discrete choice experiment and BWS-2 leads to different outcomes, both in preference weights as well as in relative importance scores, which might have been caused by the different framing of risks in BWS-2. However, a latent class analysis revealed similar latent classes between methods. Careful consideration about method selection is required, while keeping the specific decision context in mind and pilot testing the methods.

Objectives: This study aimed to introduce a parsimonious modeling approach that enables the estimation of interaction effects in health state valuation studies. Methods: Instead of supplementing a main-effects model with interactions between each and every level, a more parsimonious optimal scaling approach is proposed. This approach is based on the mapping of health state levels onto domain-specific continuous scales. The attractiveness of health states is then determined by the importance-weighted optimal scales (ie, main effects) and the interactions between these domain-specific scales (ie, interaction effects). The number of interaction terms only depends on the number of health domains. Therefore, interactions between dimensions can be included with only a few additional parameters. The proposed models with and without interactions are fitted on 3 valuation data sets from 2 different countries, that is, a Dutch latent-scale discrete choice experiment (DCE) data set with 3699 respondents, an Australian time trade-off data set with 400 respondents, and a Dutch DCE with duration data set with 788 respondents. Results: Important interactions between health domains were found in all 3 applications. The results confirm that the accumulation of health problems within health states has a decreasing marginal effect on health state values. A similar effect is obtained when so-called N3 or N5 terms are included in the model specification, but the inclusion of 2-way interactions provides superior model fits. Conclusions: The proposed interaction model is parsimonious, produces estimates that are straightforward to interpret, and accommodates the estimation of interaction effects in health state valuation studies with realistic sample size requirements. Not accounting for interactions is shown to result in biased value sets, particularly in stand-alone DCE with duration studies.

Rheumatoid Arthritis (RA) is a chronic disease that impacts patients’ quality of life. Sophisticated organization of care delivery drives quality improvement. Therefore, the study objective was establishing a validated process map of the care cycle for RA patients. Hence, increasing transparency and optimizing care delivery and identifying areas of improvement. To map the RA care cycle, the care delivery value chain (CDVC) approach was used as framework to document activities and resources systematically. A mixed method study was conducted where quantitative data on activities were collected from health records and unstructured interviews with medical staff were held. Consequently, the process map was separately validated in a consensus meeting with a delegation of the medical staff and patient advisory board. At the start of the care cycle, the focus is predominantly on defining the treat-to-target strategy and examining disease activity. Towards the monitoring phase, tapering medication and managing the disease through patient-reported outcome measures are becoming increasingly important. Although patient’s functioning, quality of care and patient’s evaluation of received care are monitored, reflection of CDVC and engaging patients in the evaluation process resulted in improvement actions on outcome and process level. Mapping the RA care cycle following a systematic approach, provides insight and transparency in delivered activities, involved resources and the engagement of patients and caregivers at multiple levels, contributing to a system facilitating value-based care delivery. The CDVC framework and applied methodology is recommended in other conditions. Future research will focus at assigning outcomes and costs to activities and evaluating interventions to explore patient value.

Elisabeth M Jongbloed,1 Hedwig M Blommestein,2 Hannah M van Schoubroeck,2 John WM Martens,1 Saskia M Wilting,1 Carin A Uyl-de Groot,2 Agnes Jager1 1Department of Medical Oncology; Erasmus MC Cancer Institute, Rotterdam, the Netherlands; 2Erasmus School of Health Policy and Management, Erasmus University, Rotterdam, the NetherlandsCorrespondence: Elisabeth M Jongbloed, Department of Medical Oncology; Erasmus MC Cancer Institute, Dr. Molenwaterplein 40, Rotterdam, 3014 GD, the Netherlands, Tel +31 107044375, Email e.jongbloed@erasmusmc.nlPurpose: The addition of two years of abemaciclib treatment to standard adjuvant endocrine therapy in all patients with high risk ER+, HER2- early breast cancer (EBC) has been approved by the US Food and Drug Administration (FDA). Pre-selection of patients with an immediate risk of recurrence within the group of clinically high risk patients using detection of minimal residual disease (MRD) using patient-informed circulating tumor DNA assays during follow-up could enhance efficacy. Here, we investigate the cost-effectiveness of the addition of two years abemaciclib in all high risk HR+, HER2- patients and in MRD-guided high risk patients only.Methods: Two semi-Markov models were developed to evaluate the cost-effectiveness of adding two years of abemaciclib compared to “standard treatment”: 1) “abemaciclib all” and 2) “MRD-guided abemaciclib” using MRD-guidance. Data of the MonarchE trial were used to model the invasive disease-free survival (iDFS). Since iDFS and overall survival (OS) data of abemaciclib were currently limited, abemaciclib effects were extrapolated using a favorable, intermediate and unfavorable effect scenario.Results: The addition of abemaciclib in all high-risk EBC patients prolonged iDFS slightly (0.04 additional quality adjusted life years (QALYs)) and led to higher costs compared to standard ET, leading to a high incremental cost effectiveness ratio (ICER) of € 1,551,876/QALY. Neither the favorable effect scenario (additional 1.09 QALYs) was cost-effective (ICER € 62,935/QALY), using a willingness-to-pay threshold of € 50,000/QALY. The “MRD-guided abemaciclib” strategy resulted in lower costs and an increase in QALYs (1.27) compared to “standard treatment” in the unfavorable effect scenario.Conclusion: The addition of abemaciclib to adjuvant endocrine therapy in all high-risk ER+, HER2- EBC patients is not cost-effective. However, using MRD detection to justify the addition of abemaciclib treatment dominates standard treatment in this cost-effectiveness analysis. Further evaluation of MRD detection in EBC by means of prospective clinical trials assessing clinical utility is recommended and promising in terms of cost-effectiveness.Keywords: breast cancer, minimal residual disease, circulating tumor DNA, cost-effectiveness, abemaciclib

OBJECTIVES: This study aimed to investigate the cost-effectiveness, budget impact (BI), and impact of uncertainty of future developments concerning whole-genome sequencing (WGS) as a clinical diagnostic test compared with standard of care (SoC) in patients with locally advanced and metastatic non-small cell lung cancer.METHODS: A total of 3 likely scenarios to take place within 5 years (according to experts) were simulated using a previously developed, peer reviewed, and published decision model. The scenarios concerned "WGS results used for treatment selection" (scenario 1), "WGS-based biomarker for immunotherapy" (scenario 2), and "off-label drug approval for WGS results" (scenario 3). Two diagnostic strategies of the original model, "SoC" and "WGS as a diagnostic test" (base model), were used to compare our scenarios with. Outcomes were reported for the base model, all scenarios separately, combined (combined unweighted), and weighted by likelihood (combined weighted). Cost-effectiveness, BI, and value of information analyses were performed for WGS compared with SoC.RESULTS: Total costs and quality-adjusted life-years for SoC in metastatic non-small cell lung cancer were €149 698 and 1.235. Incremental outcomes of WGS were €1529/0.002(base model), -€222/0.020(scenario 1), -€2576/0.023(scenario 2), €388/0.024(scenario 3), -€5041/0.060(combined unweighted), and -€1715/0.029(combined weighted). The annual BI for adopting WGS for this population in The Netherlands ranged between €682 million (combined unweighted) and €714 million (base model). The consequences of uncertainty amounted to €3.4 million for all scenarios (combined weighted) and to €699 000 for the diagnostic yield of WGS alone (combined weighted).CONCLUSIONS: Our findings suggest that it is likely for WGS to become cost-effective within the near future if it identifies more patients with actionable targets and show the impact of uncertainty regarding its diagnostic yield. Modeling future scenarios can be useful to consider early adoption of WGS while timely anticipating on unforeseen developments before final conclusions are reached.

Item does not contain fulltext BACKGROUND: Immune checkpoint inhibitors and targeted therapies have dramatically improved outcomes in patients with advanced melanoma, but approximately half these patients will not have a durable benefit. Phase 1-2 trials of adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) have shown promising responses, but data from phase 3 trials are lacking to determine the role of TILs in treating advanced melanoma. METHODS: In this phase 3, multicenter, open-label trial, we randomly assigned patients with unresectable stage IIIC or IV melanoma in a 1:1 ratio to receive TIL or anti-cytotoxic T-lymphocyte antigen 4 therapy (ipilimumab at 3 mg per kilogram of body weight). Infusion of at least 5×10(9) TILs was preceded by nonmyeloablative, lymphodepleting chemotherapy (cyclophosphamide plus fludarabine) and followed by high-dose interleukin-2. The primary end point was progression-free survival. RESULTS: A total of 168 patients (86% with disease refractory to anti-programmed death 1 treatment) were assigned to receive TILs (84 patients) or ipilimumab (84 patients). In the intention-to-treat population, median progression-free survival was 7.2 months (95% confidence interval [CI], 4.2 to 13.1) in the TIL group and 3.1 months (95% CI, 3.0 to 4.3) in the ipilimumab group (hazard ratio for progression or death, 0.50; 95% CI, 0.35 to 0.72; P

BACKGROUND AND OBJECTIVES: EQ-5D-Y-3L health states are commonly valued by asking adults to complete stated preference tasks, 'given their views about a 10-year-old child' (hereafter referred to as proxy 1). The use of this perspective has been a source of debate. In this paper, we investigated an alternative proxy perspective: i.e. adults considered what they think a 10-year old-child would decide for itself (hereafter, proxy 2 (substitute)]. Our main objective was to explore how the outcomes, dispersion and response patterns of a composite time trade-off valuation differ between proxy 1 and proxy 2.METHODS: A team of four trained interviewers completed 402 composite time trade-off interviews following the EQ-5D-Y-3L protocol. Respondents were randomly allocated to value health states in either the proxy 1 or proxy 2 (substitute) perspective. Each respondent valued ten health states with the perspective they were assigned to, as well as one health state with the alternative perspective (33333).RESULTS: The use of different proxy perspectives yielded differences in EQ-5D-Y-3L valuation. For states in which children had considerable pain and were very worried, sad or unhappy, respondents' valuations were lower in proxy 1 than in proxy 2 (substitute) perspectives, by about 0.2. Within-subject variation across health states was lower for proxy 2 (substitute) than proxy 1 perspectives. Analyses of response patterns suggest that data for proxy 2 (substitute) perspectives were less clustered.CONCLUSIONS: There are systematic differences between composite time trade-off responses given by adults deciding for children and adults considering what children would want for themselves. In addition to warranting further qualitative exploration, such differences contribute to the ongoing normative discussion surrounding the source and perspective used for valuation of child and adolescent health.

Objectives: Decisions about health often involve risk, and different decision makers interpret and value risk information differently. Furthermore, an individual's attitude toward health-specific risks can contribute to variation in health preferences and behavior. This study aimed to determine whether and how health-risk attitude and heterogeneity of health preferences are related. Methods: To study the association between health-risk attitude and preference heterogeneity, we selected 3 discrete choice experiment case studies in the health domain that included risk attributes and accounted for preference heterogeneity. Health-risk attitude was measured using the 13-item Health-Risk Attitude Scale (HRAS-13). We analyzed 2 types of heterogeneity via panel latent class analyses, namely, how health-risk attitude relates to (1) stochastic class allocation and (2) systematic preference heterogeneity. Results: Our study did not find evidence that health-risk attitude as measured by the HRAS-13 distinguishes people between classes. Nevertheless, we did find evidence that the HRAS-13 can distinguish people's preferences for risk attributes within classes. This phenomenon was more pronounced in the patient samples than in the general population sample. Moreover, we found that numeracy and health literacy did distinguish people between classes. Conclusions: Modeling health-risk attitude as an individual characteristic underlying preference heterogeneity has the potential to improve model fit and model interpretations. Nevertheless, the results of this study highlight the need for further research into the association between health-risk attitude and preference heterogeneity beyond class membership, a different measure of health-risk attitude, and the communication of risks.

This study undertook a head-to-head comparison of best-worst, best-best and ranking discrete choice experiments (DCEs) to help decide which method to use if moving beyond traditional single-best DCEs. Respondents were randomized to one of three preference elicitation methods. Rank-ordered (exploded) mixed logit models and respondent-reported data were used to compare methods and first and second choices. First choices differed from second choices and preferences differed between elicitation methods, even beyond scale and scale dynamics. First choices of best-worst had good choice consistency, scale dynamics and statistical efficiency, but this method's second choices performed worst. Ranking performed best on respondent-reported difficulty and preference; best-best's second choices on statistical efficiency. All three preference elicitation methods improve efficiency of data collection relative to using first choices only. However, differences in preferences between first and second choices challenge moving beyond single-best DCE. If nevertheless doing so, best-best and ranking are preferred over best-worst DCE.

Background aims: Drug prices are regarded as one of the most influential factors in determining accessibility and affordability to novel therapies. Cell and gene therapies such as OTL-200 (brand name: Libmeldy) and AVXS-101 (brand name: Zolgensma) with (expected) list prices of 3.0 million EUR and 1.9 million EUR per treatment, respectively, spark a global debate on the affordability of such therapies. The aim of this study was to use a recently published cost-based pricing model to calculate prices for cell and gene therapies, with OTL-200 and AVXS-101 as case study examples. Methods: Using the pricing model proposed by Uyl-de Groot and Löwenberg, we estimated a price for both therapies. We searched the literature and online public sources to estimate (i) research and development (R&D) expenses adjusted for risk of failure and cost of capital, (ii) the eligible patient population and (iii) costs of drug manufacturing to calculate a base-case price for OTL-200 and AVXS-101. All model input parameters were varied in a stepwise, deterministic sensitivity analysis and scenario analyses to assess their impact on the calculated prices. Results: Prices for OTL-200 and AVXS-101 were estimated at 1 048 138 EUR and 380 444 EUR per treatment, respectively. In deterministic sensitivity analyses, varying R&D estimates had the greatest impact on the price for OTL-200, whereas for AVXS-101, changes in the profit margin changed the calculated price substantially. Highest prices in scenario analyses were achieved when assuming the lowest number of patients for OTL-200 and highest R&D expenses for AVXS-101. The lowest R&D expenses scenario resulted in lowest prices for either therapy. Conclusions: Our results show that, using the proposed model, prices for both OTL-200 and AVXS-101 lie substantially below the currently (proposed) list prices for both therapies. Nevertheless, the uncertainty of the used model input parameters is considerable, which translates in a wide range of estimated prices. This is mainly because of a lack of transparency from pharmaceutical companies regarding R&D expenses and the costs of drug manufacturing. Simultaneously, the disease indications for both therapies remain heavily understudied in terms of their epidemiological profile. Despite the considerable variation in the estimated prices, our results may support the public debate on value-based and cost-based pricing models, and on “fair” drug prices in general.

Maureen PMH Rutten-van Mölken,1 Elisabeth Sophia Hartgers-Gubbels,2 Michael Chambers3 1Erasmus School of Health Policy & Management, Erasmus University Rotterdam, Rotterdam, the Netherlands; 2Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany; 3MC Healthcare Evaluation, London, UKCorrespondence: Elisabeth Sophia Hartgers-Gubbels, Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany, Email lisa.hartgers-gubbels@boehringer-ingelheim.comAbstract: How is a cost-effectiveness analysis constructed and used? In this episode of the Value Insider podcast, host Mike Chambers speaks with Prof. Maureen Rutten-van Mölken about economic evaluations in healthcare and how value is considered in these evaluations. Prof. Rutten-van Mölken is professor of Economic Evaluation of Innovations for Health at the Erasmus University Rotterdam in the Netherlands. She leads the Erasmus HTA department and is Scientific Director of the Institute for Medical Technology Assessment (iMTA). Prof Rutten-van Mölken explains how comparative assessments can help us understand which treatments offer the best value-for-money as reimbursement can only be allocated to a selection of all possible treatments.Keywords: market access, healthcare reimbursement, health technology assessment, HTA, value demonstration, health economics and outcomes research, payer

The importance of integrated care will increase in future health systems due to aging populations and patients with chronic multimorbidity, however, such complex healthcare interventions are often developed and implemented in higher income countries. For Central and Eastern European (CEE) countries it is important to investigate which integrated care models are transferable to their setting and facilitate the implementation of relevant models by identifying barriers to their implementation. This study investigates the relative importance of integrated care models and the most critical barriers for their implementation in CEE countries. Experts from Croatia, Hungary, Poland, Romania and Serbia were invited to complete an online survey within the SELFIE H2020 project. 81 respondents completed the survey. Although experts indicated that some integrated care models were already being implemented in CEE countries, the survey revealed a great need for further improvement in the integration of care, especially the managed care of oncology patients, coordinated palliative care of terminally ill patients, and nursing care of elderly with multimorbidity. Lack of long-term financial sustainability as well as of dedicated financing schemes were seen the most critical implementation barriers, followed by the lack of integration between health and social care providers and insufficient availability of human resources. These insights can guide future policy making on integrated care in CEE countries.

In the Netherlands, about one-third of the adult population provides unpaid care. Providing informal caregiving can be very straining in normal times, but the impact of a public health crisis on caregivers is largely unknown. This study focuses on the question of how caregiver burden changed following the COVID-19 pandemic, and what characteristics were related to these changes. We use self-reported data from a sample of 965 informal caregivers from the Netherlands 3 months into the pandemic to investigate how the objective burden (i.e. hours spent on caregiving) and the subjective burden had changed, and what their care-related quality of life (CarerQol) was. We found that on average the subjective burden had increased slightly (from 4.75 to 5.04 on a 0–10 scale). However, our analysis revealed that some caregivers were more affected than others. Most affected caregivers were women, and those with low income, better physical health, decreased psychological health, childcare responsibilities, longer duration of caregiving and those caring for someone with decreased physical and psychological health. On average, time spent on care remained the same (a median of 15 h per week), but certain groups of caregivers did experience a change, being those caring for people in an institution and for people with a better psychological health before the pandemic. Furthermore, caregivers experiencing changes in objective burden did not have the same characteristics as those experiencing changes in perceived burden and quality of life. This shows that the consequences of a public health crisis on caregivers cannot be captured by a focus on either objective or subjective burden measures or quality of life alone. Long-term care policies aiming to support caregivers to persevere during a future crisis should target caregivers at risk of increased subjective burden and a lower CarerQol, such as women, people with a low income and people with childcare responsibilities. Such policies should consider that reducing objective burden may not necessarily lead to a reduction in subjective burden for all caregivers.

Objectives: To introduce the garbage class mixed logit (MIXL) model as a convenient alternative to manually screening and accounting for respondents with low data quality in discrete choice experiments. Methods: Garbage classes are typically used in latent class logit analyses to designate or identify group(s) of respondents with low data quality. Yet, the same concept can be applied to MIXL models as well. Results: Based on a reanalysis of 4 discrete choice experiments that were originally analyzed using a standard MIXL model, it is shown that garbage class MIXL models can achieve the same effect as manually screening for (and excluding) respondents with low data quality based on the more commonly used root likelihood test, but with less effort and ambiguity. Conclusions: Including a garbage class in MIXL models removes the influence of respondents with a random choice pattern from the MIXL model estimates, provides an estimate of the number of low-quality respondents in the dataset, and avoids having to manually screen for respondents with low data quality based on internal or statistical validity tests. Although less versatile than the combination of standard MIXL estimates with separate assessments of data quality and sensitivity analyses, the proposed garbage class MIXL model provides an attractive alternative.

Ian P Smith,1,* Mirko Ancillotti,2,* Esther W de Bekker-Grob,3,4 Jorien Veldwijk2– 4 1Julius Center for Health and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; 2Centre for Research Ethics and Bioethics, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; 3Erasmus Choice Modelling Centre, Erasmus University Rotterdam, Rotterdam, the Netherlands; 4Erasmus School of Health Policy & Management, Erasmus University Rotterdam, Rotterdam, the Netherlands*These authors contributed equally to this workCorrespondence: Ian P Smith, Julius Center for Health and Primary Care, University Medical Center Utrecht, Str. 6.131, P.O. Box 85500 3508 GA, Utrecht, the Netherlands, Tel +31 88 75 69 616, Fax +31 88 75 554 84, Email i.p.smith@umcutrecht.nlPurpose: Studies assessing framing effects in discrete choice experiments (DCE) primarily focused on attributes related to mortality/survival information. Little is known about framing effects for other attributes in health-related DCEs. This study aimed to investigate how framing treatment outcome as effective, failure, or a combined frame impacts respondent choices and DCE outcomes.Patients and Methods: Three Bayesian D-efficient designed DCE surveys measuring preferences for antibiotic treatments were randomly distributed to a representative sample of the Swedish population aged 18– 65 years (n=1119). Antibiotic treatments were described using five attributes. Four attributes were static: Contribution to Antibiotic Resistance, Treatment Duration, Likelihood of Side-Effects, and Costs. A fifth treatment attribute was framed in three ways: Effectiveness, Failure Rate, or both. Mixed logit models were used to analyze attribute level estimates, importance value, and choice predictions.Results: Significant differences between the frames were found for the parameter estimates of the attributes of Treatment Duration and Likelihood of Side-Effects, but not Treatment Outcome which was the alternatively framed attribute. Contribution to Antibiotic Resistance and Costs were the most important attributes for all participants regardless of framing. Choice predictions for the “best option” antibiotic only slightly differed between the groups based on the frame seen (95.2– 92.4%).Conclusion: Our study showed that attribute framing can impact preferences regardless of the attribute’s importance value in alternative valuation. However, the practical implication of this effect may be limited. A theoretical discussion is needed to identify how researchers should accommodate and report any potential framing effect in their studies.Keywords: patient preferences, patient-centered care, DCE

BACKGROUND AND OBJECTIVE: There is increasing interest in preference-accompanied measures of health for paediatric populations. The child-friendly EQ-5D version, EQ-5D-Y-3L, is one such instrument, but the lack of a Dutch value set prevents its use in economic evaluations of healthcare interventions in the Netherlands. This study aims at covering this gap by collecting preferences using a standardised protocol for deriving EQ-5D-Y-3L value sets.METHODS: Composite time trade-off data were collected using videoconferencing interviews, with each respondent completing ten composite time trade-off tasks. Discrete choice experiment data were collected using an online survey, with respondents each completing 15 paired comparisons. Respondents completed these tasks considering what they prefer for a hypothetical 10-year-old child. Discrete choice experiment data were analysed using a ten-parameter mixed-logit model and anchored to the quality-adjusted life-year scale using the mean observed composite time trade-off values.RESULTS: The study collected preferences for 197 respondents using composite time trade-off and for 959 respondents using a discrete choice experiment. The discrete choice experiment sample was representative for the Dutch population in terms of age and sex. The level 3 weight for pain/discomfort was the largest, followed by feeling worried, sad or unhappy, usual activities, mobility and self-care. Health state values ranged between -0.218 and 1.CONCLUSIONS: This study generated a Dutch value set for the EQ-5D-Y-3L, which can be used for the computation of quality-adjusted life-years for economic evaluations of healthcare interventions in paediatric populations.

Background: Preference differences between countries and populations justify the use of country-specific value sets for the EQ-5D instruments. There are no clear criteria based on which the selection of value sets for countries without a national value set should be made. As part of the European PECUNIA project, this study aimed to identify factors contributing to differences in preference-based valuations and develop supra-national value sets for homogenous country clusters in Europe. Methods: A literature review was conducted to identify factors relevant to variations in the EQ-5D-3L/5L health state valuations across countries. Factors fulfilling the pre-specified criteria of validity, reliability, international feasibility and comparability were used to group 27 European Union member states, the European Free Trade Association countries and the UK. Clusters of countries were developed based on the frequency of their appearance in the same grouping. The supra-national value sets were estimated for these clusters from the coefficients of existing published valuation studies using the ordinary least-squares model. Results: Ten factors were identified from 69 studies. From these, five grouping variables: (1) culture and religion; (2) linguistics; (3) healthcare system typology; (4) healthcare system financing; and (5) sociodemographic aspects were derived to define the groups of homogenous countries. Frequency-based grouping revealed five cohesive clusters: English-speaking, Nordic, Central-Western, Southern and Eastern European. Conclusions: European countries were clustered considering variables that may relate to differences in health state valuations. Supra-national value sets provide optimised proxy value set selection in the lack of a national value set and/or for regional decision making.

Objectives: The estimation of lifetime quality-adjusted life-years (QALYs) requires the extrapolation of both length and quality of life (QoL). The extrapolation of QoL has received little attention in the literature. Here we explore the predictive value of “time to death” (TTD) for extrapolating QoL in oncology. Methods: We used QoL and survival data from the Patient Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship registry, which is linked to The Netherlands Cancer Registry. QoL was assessed with EQ-5D and SF-6D. We tested the relationship between TTD and QoL using linear, 2-part, and beta regression models. Incremental QALYs were compared using the TTD approach and an annual age-related disutility approach using artificial survival data with varying mortality rates. Results: A total of 6 samples with >100 patients each were used for the analysis. A declining pattern in QoL was observed when patients were closer to death, confirming the predictive value of TTD for QoL. The declining pattern in QoL was most pronounced when QoL was measured with SF-6D. Proximity to death had a larger impact on QoL than age. Incremental QALYs were higher using the TTD approach than annual age-related disutility, ranging from +0.139 to +0.00003 depending on mortality rates. Conclusions: TTD is a predictor variable for QoL. Using TTD allows cost-effectiveness models that lack QoL data to extrapolate morbidity using overall survival estimates. The TTD approach generates more incremental QALYs than an annual age-related disutility, most notably for longer survival periods.

Objectives: This study aimed to investigate how multicriteria decision analysis (MCDA) could complement cost-effectiveness analysis (CEA) to support investment decisions in elderly care at local level. Methods: We used an integrated elderly care program in The Netherlands as a case study to demonstrate the application of both methods. In a 12-month quasi-experimental study (n = 384), data on the following outcome measures were collected: quality-adjusted life-years (CEA) and physical functioning, psychological well-being, social relationships and participation, enjoyment of life, resilience, person centeredness, continuity of care, and costs (MCDA). We performed regression analysis on inversed probability weighted data and controlled for potential confounders to obtain a double robust estimate of the outcomes. Probabilistic sensitivity analyses determined uncertainty for both methods. Results: The integrated elderly care program was not likely (ie, 36%) to be cost-effective according to the CEA (incremental cost-effectiveness ratios: €88 249 from a societal perspective) using the conventional Dutch willingness-to-pay threshold (ie, €50 000). The MCDA demonstrated that informal caregivers and professionals slightly preferred the intervention over usual care, driven by enjoyment of life and person centeredness. Patients did not prefer either the intervention or usual care, whereas payers and policy makers slightly preferred usual care, mainly due to higher costs of the intervention. Conclusions: MCDA could provide local-level decision makers with a broader measurement of effectiveness by including outcomes beyond health and longevity and the preferences of multiple stakeholders. This additional information could foster the acceptability and implementability of cost-effective innovations in elderly care.

Purpose For an integrated care programme to be successful, preferences of the stakeholders involved should be aligned. The aim of this study is to investigate to which extent outcomes beyond health are valued and to study the heterogeneity of preferences of those involved in integrated care. Methods A discrete choice experiment (DCE) was conducted to elicit preferences for eight Triple Aim outcomes, i.e., physical functioning, psychological well-being, social relationships & participation, enjoyment of life, resilience, person-centeredness, continuity of care and total health and social care costs. Stakeholders were recruited among Dutch persons with multi-morbidity, informal caregivers, professionals, payers, and policymakers. A Bayesian mixed-logit model was used to analyse the data. Subsequently, a latent class analysis was performed to identify stakeholders with similar preferences. Results 739 stakeholders completed the DCE. Enjoyment of life was perceived as the most important outcome (relative importance: 0.221) across stakeholders, while total health and social care costs were perceived as least important (0.063). The latent class analysis identified four classes. The first class (19.9%) put most weight on experience with care outcomes. The second class (39%) favoured enjoyment of life. The third class (18%) focused relatively more on physical health. The fourth class (24%) had the least consistent preferences. Conclusion This study has highlighted the heterogeneity in views of stakeholders in integrated care on what is important in health(care) for persons with multi-morbidity. To accurately value integrated care a variety of outcomes beyond health–e.g., enjoyment of life and experience with care–should be taken into account.

INTRODUCTION: To support shared decision-making (SDM) between patients and providers surrounding biologic treatments, we created IBD&me ( ibdandme.org )-a freely available, unbranded, interactive decision aid. We performed a multicenter comparative effectiveness trial comparing the impact of IBD&me on SDM vs a biologics fact sheet developed by the Crohn's & Colitis Foundation. METHODS: We enrolled patients with inflammatory bowel disease (IBD) being seen at a clinic within IBD Qorus-a multicenter adult IBD learning health system-between March 5, 2019, and May 14, 2021. Eligible patients included those with recent IBD-related symptoms who reported that they wanted to discuss biologics with their provider during their upcoming visit. Patients were randomized 1:1 using stratified block randomization and received an e-mail 1 week before their visit inviting them to review either IBD&me or a fact sheet. The primary outcome was patient perception of SDM as measured by the 9-Item SDM Questionnaire (0-100 scale; higher = better); the Student t test was used to compare outcomes between arms. RESULTS: Overall, 152 patients were randomized (biologics fact sheet 75, IBD&me 77); most patients had Crohn's disease (66.4%) and were biologic-experienced (82.9%). No differences were seen between groups regarding SDM (fact sheet 72.6 ± 25.6, IBD&me 75.0 ± 20.8; P = .57). Most patients stated they would be likely to recommend the fact sheet (79.6%) or IBD&me (84.9%; P = .48) to another patient with IBD. DISCUSSION: No differences in outcomes were seen between IBD&me and the biologics fact sheet in this comparative effectiveness study; patients reported high satisfaction with both resources. Further study, particularly among biologic naïve patients, is needed to determine the utility of interactive components to IBD decision aids.

BACKGROUND: Disease modifying treatments (DMTs) currently under development for Alzheimer's disease, have the potential to prevent or postpone institutionalization and more expensive care and might delay institutionalization of persons with dementia. OBJECTIVE: The current study estimates costs of living in a nursing home for persons with dementia in the Netherlands to help inform economic evaluations of future DMTs. METHODS: Data were collected during semi-structured interviews with healthcare professionals and from the financial administration of a healthcare organization with several nursing homes. Personnel costs were calculated using a bottom-up approach by valuing the time estimates. Non-personnel costs were calculated using information from the financial administration of the healthcare organization. RESULTS: Total costs of a person with dementia per 24 hours, including both care staff and other healthcare providers, were € 151 for small-scale living wards and € 147 for independent living wards. Non-personnel costs were € 37 per day. CONCLUSION: This study provides Dutch estimates for total healthcare costs per day for institutionalized persons with dementia. These cost estimates can be used in cost-effectiveness analyses for future DMTs in dementia.

Health technology assessment (HTA) of medical devices (MDs) increasingly rely on real-world evidence (RWE). The aim of this study was to evaluate the type and the quality of the evidence used to assess the (cost-)effectiveness of high risk MDs (Class III) by HTA agencies in Europe (four European HTA agencies and EUnetHTA), with particular focus on RWE. Data were extracted from HTA reports on the type of evidence demonstrating (cost-)effectiveness, and the quality of observational studies of comparative effectiveness using the Good Research for Comparative Effectiveness principles. 25 HTA reports were included that incorporated 28 observational studies of comparative effectiveness. Half of the studies (46%) took important confounding and/or effect modifying variables into account in the design and/or analyses. The most common way of including confounders and/or effect modifiers was through multivariable regression analysis. Other methods, such as propensity score matching, were rarely employed. Furthermore, meaningful analyses to test key assumptions were largely omitted. Resulting recommendations from HTA agencies on MDs is therefore (partially) based on evidence which is riddled with uncertainty. Considering the increasing importance of RWE it is important that the quality of observational studies of comparative effectiveness are systematically assessed when used in decision-making.

ObjectivesThe COVID-19 pandemic necessitates time-sensitive policy and implementation decisions regarding new therapies in the face of uncertainty. The aim of this study was to quantify consequences of approving therapies or pursuing further research: either immediate approval, use only in research, approval with research (e.g., Emergency Use Authorization), or reject.MethodsUsing a cohort state-transition model for hospitalized COVID-19 patients, we estimated quality-adjusted life years (QALYs) and costs associated with the following interventions: Hydroxychloroquine, Remdesivir, Casirivimab-Imdevimab, Dexamethasone, Baricitinib-Remdesivir, Tocilizumab, Lopinavir-Ritonavir, and Interferon beta-1a, and usual care. We used the model outcomes to conduct cost-effectiveness and value of information analyses from a US healthcare perspective and a lifetime horizon.ResultsAssuming a $100,000-per-QALY willingness-to-pay-threshold, only Remdesivir, Casirivimab-Imdevimab, Dexamethasone, Baricitinib-Remdesivir and Tocilizumab were (cost-) effective (incremental net health benefit 0.252, 0.164, 0.545, 0.668 and 0.524 QALYs and incremental net monetary benefit $25,249, $16,375, $54,526, $66,826 and $52,378). Our value of information analyses suggest that most value can be obtained if these 5 therapies are approved for immediate use rather than requiring additional RCTs (net value $20.6 Billion, $13.4 Billion, $7.4 Billion, $54.6 Billion and $7.1 Billion); Hydroxychloroquine (net value $198 Million) only used in further RCTs if seeking to demonstrate decremental cost-effectiveness, and otherwise rejected; and Interferon beta-1a and Lopinavir-Ritonavir are rejected (i.e., neither approved nor additional RCTs).Conclusions and RelevanceEstimating the real-time value of collecting additional evidence during the pandemic can inform policymakers and clinicians about the optimal moment to implement therapies and whether to perform further research.

Objectives: This study aimed to identify the most commonly used internal validity tests in the discrete choice experiment (DCE) literature and establish their sensitivity and specificity. Methods: A structured literature review of recent DCE articles (2018-2020Q1) published in the health, marketing, transport economics, and environmental science literature was used to identify commonly used internal validity tests. The 2 most frequently used internal validity tests were incorporated in 4 new data collections. Respondent preferences in each application were summarized using a mixed logit model, which served as the benchmark for the subsequent sensitivity and specificity calculations. The performance of the internal validity tests was also compared with that of the root likelihood (RLH) test, which is a likelihood-based statistical validity test that is commonly used in marketing applications. Results: Dominant and repeated choice tasks were most commonly included in health-related DCE designs. Based on 4 applications, their specificity and sensitivity depend on the type of incorrect response pattern to be detected and on design characteristics such as the number of choice options per choice task and the number of internal validity tests as included in the experimental design. In all but one scenario, the performance of the dominant and repeated choice tasks was considerably worse than that of the RLH test. Conclusions: Dominant and repeated choice tasks are unreliable screening tests and costly in terms of statistical power. The RLH test, which is a statistical test that does not require additional choice tasks to be included in the DCE design, provides a more reliable alternative.

Objective: Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have been shown to reduce the risk of cardiovascular complications, which largely drive diabetes’ health and economic burdens. Trial results indicated that SGLT2i are cost effective. However, these findings may not be generalizable to the real-world target population. This study aims to evaluate the cost effectiveness of SGLT2i in a routine care type 2 diabetes population that meets Dutch reimbursement criteria using the MICADO model. Methods: Individuals from the Hoorn Diabetes Care System cohort (N = 15,392) were filtered to satisfy trial inclusion criteria (including EMPA-REG, CANVAS, and DECLARE-TIMI58) or satisfy the current Dutch reimbursement criteria for SGLT2i. We validated a health economic model (MICADO) by comparing simulated and observed outcomes regarding the relative risks of events in the intervention and comparator arm from three trials, and used the validated model to evaluate the long-term health outcomes using the filtered cohorts’ baseline characteristics and treatment effects from trials and a review of observational studies. The incremental cost-effectiveness ratio (ICER) of SGLT2i, compared with care-as-usual, was assessed from a third-party payer perspective, measured in euros (2021 price level), using a discount rate of 4% for costs and 1.5% for effects. Results: From Dutch individuals with diabetes in routine care, 15.8% qualify for the current Dutch reimbursement criteria for SGLT2i. Their characteristics were significantly different (lower HbA1c, higher age, and generally more preexisting complications) than trial populations. After validating the MICADO model, we found that lifetime ICERs of SGLT2i, when compared with usual care, were favorable (

A cost-effectiveness analysis has become an important method to inform allocation decisions and reimbursement of new technologies in healthcare. A cost-effectiveness analysis requires a threshold to which the cost effectiveness of a new intervention can be compared. In principle, the threshold ought to reflect opportunity costs of reimbursing a new technology. In this paper, we contrast the practical use of this threshold within a CEA with its theoretical underpinnings. We argue that several assumptions behind the theoretical models underlying this threshold are violated in practice. This implies that a simple application of the decision rules of CEA using a single estimate of the threshold does not necessarily improve population health or societal welfare. Conceptual differences regarding the interpretation of the threshold, widely varying estimates of its value, and an inconsistent use within and outside the healthcare sector are important challenges in informing policy makers on optimal reimbursement decision and setting appropriate healthcare budgets.

Tumour DNA and germline testing, based on DNA-wide sequencing analysis, are becoming more and more routine in clinical-oncology practice. A promising step in medicine, but at the same time leading to challenging ethicolegal questions. An important one is under what conditions individuals (patients and their relatives, research participants) should be recontacted with new information, even if many years have passed since the last contact. Based on legal- and ethical study, we developed a tool to help professionals to decide whether or not to recontact an individual in specific cases. It is based on four assessment criteria: (1) professional relationship (2) clinical impact (3) individual's preferences and (4) feasibility. The tool could also serve as a framework for guidelines on the topic.

Background In economic evaluations, survival is often extrapolated to smooth out the Kaplan-Meier estimate and because the available data (e.g., from randomized controlled trials) are often right censored. Validation of the accuracy of extrapolated results can depend on the length of follow-up and the assumptions made about the survival hazard. Here, we analyze the accuracy of different extrapolation techniques while varying the data cut-off to estimate long-term survival in newly diagnosed multiple myeloma (MM) patients. Methods Empirical data were available from a randomized controlled trial and a registry for MM patients treated with melphalan + prednisone, thalidomide, and bortezomib- based regimens. Standard parametric and spline models were fitted while artificially reducing follow-up by introducing database locks. The maximum follow-up for these locks varied from 3 to 13 years. Extrapolated (conditional) restricted mean survival time (RMST) was compared to the Kaplan-Meier RMST and models were selected according to statistical tests, and visual fit. Results For all treatments, the RMST error decreased when follow-up and the absolute number of events increased, and censoring decreased. The decline in RMST error was highest when maximum follow-up exceeded six years. However, even when censoring is low there can still be considerable deviations in the extrapolated RMST conditional on survival until extrapolation when compared to the KM-estimate. Conclusions We demonstrate that both standard parametric and spline models could be worthy candidates when extrapolating survival for the populations examined. Nevertheless, researchers and decision makers should be wary of uncertainty in results even when censoring has decreased, and the number of events has increased.

Background: Gene expression profiling tests can predict the risk of disease recurrence and select patients who are expected to benefit from therapy, while allowing other patients to forgo therapy. For breast cancers, these tests were initially designed to tailor chemotherapy decisions, but recent evidence suggests that they may also guide the use of endocrine therapy. This study evaluated the cost effectiveness of a prognostic test, MammaPrint®, to guide the use of adjuvant endocrine therapy in patients eligible according to Dutch treatment guidelines. Methods: We constructed a Markov decision model to calculate the lifetime costs (in 2020 Euros) and effects (survival and quality-adjusted life-years) of MammaPrint® testing versus usual care (endocrine therapy for all patients) in a simulated cohort of patients. The population of interest includes patients for whom MammaPrint® testing is currently not indicated, but for whom it may be possible to safely omit endocrine therapy. We applied both a health care perspective and a societal perspective and discounted costs (4%) and effects (1.5%). Model inputs were obtained from published research (including randomized controlled trials), nationwide cancer registry data, cohort data and publicly available data sources. Scenario and sensitivity analyses were conducted to explore the impact of uncertainty around input parameters. Additionally, threshold analyses were performed to identify under which circumstances MammaPrint® testing would be cost effective. Results: Adjuvant endocrine therapy guided by MammaPrint® resulted in fewer side effects, more (quality-adjusted) life-years (0.10 and 0.07 incremental QALYS and LYs, respectively) and higher costs (€18,323 incremental costs) compared with the usual care strategy in which all patients receive endocrine therapy. While costs for hospital visits, medication costs and productivity costs were somewhat higher in the usual care strategy, these did not outweigh costs of testing in the MammaPrint® strategy. The incremental cost-effectiveness ratio was €185,644 per QALY gained from a healthcare perspective and €180,617 from a societal perspective. Sensitivity and scenario analyses showed that the conclusions remained the same under changed input parameters and assumptions. Our results show that MammaPrint® can become a cost-effective strategy when either the price of the test is reduced (> 50%), or the proportion of patients for which treatment is altered (i.e. those with ultra-low risk) increases to > 26%. Conclusion: Standard MammaPrint® testing to guide the use of endocrine therapy in our simulated patient population appears not to be a cost-effective strategy compared with usual care. The cost effectiveness of the test can be improved by reducing the price or preselecting a population more likely to benefit from the test.

Aim: Estimating the burden of obesity in five European countries (Germany, Greece, the Netherlands, Spain and the UK) and the potential health benefits and changes in health care costs associated with a reduction in body mass index (BMI). Materials and Methods: A Markov model was used to estimate the long-term burden of obesity. Health states were based on the occurrence of diabetes, ischaemic heart disease and stroke. Multiple registries and literature sources were used to derive the demographic, epidemiological and cost input parameters. For the base-case analyses, the model was run for a starting cohort of healthy obese people with a BMI of 30 and 35 kg/m2 aged 40 years to estimate the lifetime impact of obesity and the impact of a one-unit decrease in BMI. Different scenario and sensitivity analyses were performed. Results: The base-case analyses showed that total lifetime health care costs (for obese people aged 40 and BMI 35 kg/m2) ranged from €75 376 in Greece to €343 354 in the Netherlands, with life expectancies ranging from 37.9 years in Germany to 39.7 years in Spain. A one-unit decrease in BMI showed gains in life expectancy ranging from 0.65 to 0.68 year and changes in total health care costs varying from −€1563 to +€4832. Conclusions: The economic burden of obesity is substantial in the five countries. Decreasing BMI results in health gains, reductions in obesity-related health care costs, but an increase in non-obesity related health care costs, which emphasizes the relevance of including all costs in decision making on implementation of preventive interventions.

Artificial intelligence (AI) based algorithms for classification of suspicious skin lesions have been implemented in mobile phone apps (mHealth), but their effect on healthcare systems is undocumented. In 2019, a large Dutch health insurance company offered 2.2 million adults free access to an mHealth app for skin cancer detection. To study the impact on dermatological healthcare consumption, we conducted a retrospective population-based pragmatic study. We matched 18,960 mHealth-users who completed at least one successful assessment with the app to 56,880 controls who did not use the app and calculated odds ratios (OR) to compare dermatological claims between both groups in the first year after granting free access. A short-term cost-effectiveness analysis was performed to determine the cost per additional detected (pre)malignancy. Here we report that mHealth-users had more claims for (pre)malignant skin lesions than controls (6.0% vs 4.6%, OR 1.3 (95% CI 1.2–1.4)) and also a more than threefold higher risk of claims for benign skin tumors and nevi (5.9% vs 1.7%, OR 3.7 (95% CI 3.4–4.1)). The costs of detecting one additional (pre)malignant skin lesion with the app compared to the current standard of care were €2567. Based on these results, AI in mHealth appears to have a positive impact on detecting more cutaneous (pre)malignancies, but this should be balanced against the for now stronger increase in care consumption for benign skin tumors and nevi.

Background: Active surveillance is propagated as an alternative for hemithyroidectomy in the management of Bethesda III thyroid nodules. Methods: A cross-sectional survey questioned respondents on their willingness to accept risks related to active surveillance and hemithyroidectomy. Results: In case of active surveillance, respondents (129 patients, 46 clinicians, and 66 healthy controls) were willing to accept a risk of 10%–15% for thyroid cancer and 15% for needing more extensive surgery in the future. Respondents were willing to accept a risk of 22.5%–30% for hypothyroidism after hemithyroidectomy. Patients and controls were willing to accept a higher risk on permanent voice changes compared with clinicians (10% vs. 3%, p < 0.001). Conclusion: Real-life risks associated which active surveillance and hemithyroidectomy for Bethesda III nodules are equivalent or less than the risks people are willing to accept. Clinicians accepted less risk for permanent voice changes.

Background: Evidence regarding health-related quality of life (HRQoL) in patients with steroid-refractory acute graft-versus-host disease (SR-aGvHD) is lacking. Evaluating HRQoL was a secondary objective of the HOVON 113 MSC trial. Here we describe the outcomes of the EQ-5D-5L, EORTC QLQ-C30, and FACT-BMT for all adult patients who completed these questionnaires at baseline (i.e., before the start of treatment; n = 26). Methods: Descriptive statistics were used to describe baseline patient and disease characteristics, EQ-5D dimension scores and values, EQ VAS scores, EORTC QLQ-C30 scale/item and summary scores, and FACT-BMT subscale and total scores. Results: The mean EQ-5D value was 0.36. In total, 96% of the patients reported problems with usual activities, 92% with pain/discomfort, 84% with mobility, 80% with self-care, and 72% with anxiety/depression. The mean EORTC QLQ-C30 summary score was 43.50. Mean scale/item scores ranged from 21.79 to 60.00 for functioning scales, from 39.74 to 75.21 for symptom scales, and from 5.33 to 91.67 for single items. The mean FACT-BMT total score was 75.31. Mean subscale scores ranged from 10.09 for physical well-being to 23.94 for social/family well-being. Conclusion: Our study showed that HRQoL in patients with SR-aGvHD is poor. Improving HRQoL and symptom management in these patients should be a top priority.

BACKGROUND: Time-driven activity-based costing (TDABC) can support value-based healthcare (VBHC) programs by providing insights into the actual relationships between time spent by the medical staff and the costs associated with specific care cycles. However, the robustness of time estimates (time variation) as well as the effort required to obtain these estimates are major challenges of the TDABC methodology, given the heterogeneity in patients' needs and the presence of (multi)morbidity. To allow for the variation in time estimates in an efficient manner, this study uses fuzzy logic (FL) to estimate the TDABC model parameters (FL-TDABC).METHODS: A standardized care path was used to calculate the annual costs (per patient) and cost drivers of the Rheumatoid arthritis (RA) care cycle following the FL-TDABC methodology. Cost information (2018) was derived from hospital reports concerning financial, human resource and business intelligence data from a Dutch top clinical research hospital, Maasstad Hospital. Time estimates of procedures were obtained by interviewing the medical staff and relevant care activities were extracted from electronic health records. For analytical and validation purposes, FL-TDABC estimates were compared with TDABC and ABC cost estimates.RESULTS: The RA care cycle annual costs totaled €1497 per patient (2018 prices) based on the FL-TDABC methodology. Maximum RA cycle costs (€1684) were some 22% higher than minimum costs (€1317) observed from FL-TDABC. Cost drivers explaining the cost variation are predominantly the number of consultations with rheumatologists and pharmacy costs related to RA. Based on TDABC and ABC, annual costs per patient were €1609 and €1604, respectively.CONCLUSIONS: The FL-TDABC methodology offers a more precise and efficient estimate of care cycle costs, allowing for the subjective (fuzzy) nature of healthcare time estimates made by the medical staff. As a result, the FL-TDABC provides insight into the practice variation, and hence it can promote the transition from a volume-based system to a VBHC system.

Background: The processes that operationalize the evaluation framework for new medicines are implemented to reach the system objectives of public health, financial sustainability, and equitability. However, when the activities and procedures of these processes are misaligned, the objectives of the system may be at risk. Objectives: To evaluate the supporting processes for introducing new medicines in public healthcare services in Malta. Methods: We first reviewed literature on the Maltese reimbursement system and subsequently conducted semi-structured interviews based on the Hutton Framework. Interviewees included policy makers, committee members, procurement staff, medical specialists, pharmacists, and pharmaceutical industry representatives. After validation, we analysed the data with a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis. Results: Most medicines are assessed for introduction on the Government Formulary List. Exceptional requests fall outside this policy and pass through the Exceptional Medicinal Treatment route. Efficiency, quality, and transparency are major weaknesses across the supporting processes. Taking up responsibility, however, is considered the most important factor in reaching system objectives. Stakeholders tend to shift responsibilities to other processes, start/stop activities that impact the activities of subsequent processes whilst dismissing any contribution to the weaknesses of the system. Consequently, system objectives cannot be reached in an optimum manner. Conclusions: The Maltese case showed that recommendations for introducing new medicines in the public healthcare setting are influenced beyond the choice of HTA tools and criteria. Earmarked budgets, political steering, delays, and uninformed applicants as well as HTA capacity are impeding on system goals of public health, equity, and sustainability.

Objectives: Following protocol, adults value EQ-5D-Y-3L health states from the perspective of a 10-year-old child. It remains unclear why adults value health states differently for themselves than for a 10-year-old child and whether the latter perspective is representative of adults’ preferences for the 8 to 15 years age range of the EQ-5D-Y-3L. This study examines the reasons underlying (potential) differences in adults’ health-state preferences for themselves, a 10-year-old child, and 15-year-old adolescent. Methods: We conducted semistructured interviews using a think-aloud protocol with 25 participants who performed valuation tasks in July 2020 to August 2020. Using the Framework Method, we developed 28 categories grouped under 5 themes that illustrated the differences emerging from the interviews. Results: Participants (A) deemed it more straining to perform valuation tasks for a 10-year-old child and 15-year-old adolescent than for themselves, (B) had a stable self-image, but varied in whom they imagined as 10-year-old child and 15-year-old adolescent, (C) focused on different dimensions and levels for a 15-year-old adolescent than for a 10-year-old child and themselves, (D) had various thoughts about nonhealth-related factors that influenced their preferences, and (E) gave up relatively few life-years for a 10-year-old child and 15-year-old adolescent, also to avoid others bearing a grudge against them. Conclusions: Our results indicate that differences in adults’ health-state preferences for themselves and a 10-year-old child largely result from differences in thoughts about nonhealth-related factors. They further indicate that health-state preferences for a 10-year-old child may not be representative of such preferences for the full EQ-5D-Y-3L age range.

INTRODUCTION: To broadly disseminate 5 user-centered educational videos for patients with inflammatory bowel disease and their family and friends on social media. METHODS: Relevant social media users were iteratively identified based on their online behavior. For each video, 2 different accompanying texts were tested. RESULTS: We reached 4.2 million social media users of whom 320,302 watched at least 50% of the video. A short description resulted in higher view rates than posing an open-ended question. DISCUSSION: We showed the feasibility of large-scale dissemination of health-related educational videos through social media. Our findings can inform future online dissemination approaches of educational content.

Objective: To assess the effectiveness of duloxetine in addition to usual care in patients with chronic osteoarthritis (OA) pain. The cost-effectiveness and whether the presence of symptoms of centralized pain alters the response to duloxetine were secondary objectives. Methods: We conducted an open-label, cluster-randomized trial. Patients with chronic hip or knee OA pain who had an insufficient response to acetaminophen and nonsteroidal antiinflammatory drugs were included. Randomization took place at the general practice level, and patients received duloxetine (60 mg/day) in addition to usual care or usual care alone. The presence of centralized pain was defined as a modified PainDETECT Questionnaire score >12. The primary outcome measure was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores (scale 0–20) at 3 months after the initiation of treatment. Our aim was to detect a difference between the groups of a clinically relevant effect of 1.9 points (effect size 0.4). We used a linear mixed model with repeated measurements to analyze the data. Results: In total, 133 patients were included, and 132 patients were randomized into treatment groups. A total of 66 patients (at 31 practices) were randomized to receive duloxetine in addition to usual care, and 66 patients (at 35 practices) were randomized to receive usual care alone. We found no differences in WOMAC pain scores between the groups at 3 months (adjusted difference –0.58 [95% confidence interval (95% CI) –1.80, 0.63]) or at 12 months (adjusted difference –0.26 [95% CI –1.86, 1.34]). In the subgroup of patients with centralized pain symptoms, we also found no effect of duloxetine compared to usual care alone (adjusted difference –0.32 [95% CI –2.32, 1.67]). Conclusion: We found no effect of duloxetine added to usual care compared to usual care alone in patients with chronic knee or hip OA pain. Another trial including patients with centralized pain symptoms should be conducted to validate our results.

OBJECTIVE Lumbar discectomy is a frequently performed procedure to treat sciatica caused by lumbar disc herniation. Multiple surgical techniques are available, and the popularity of minimally invasive surgical techniques is increasing worldwide. Clinical outcomes between these techniques may not show any substantial differences. As lumbar discectomy is an elective procedure, patients’ own preferences play an important role in determining the procedure they will undergo. The aims of the current study were to determine the relative preference weights patients apply to various attributes of lumbar discectomy, determine if patient preferences change after surgery, identify preference heterogeneity for choosing surgery for sciatica, and calculate patient willingness to pay for other attributes. METHODS A discrete choice experiment (DCE) was conducted among patients with sciatica caused by lumbar disc herniation. A questionnaire was administered to patients before they underwent surgery and to an independent sample of patients who had already undergone surgery. The DCE required patients to choose between two surgical techniques or to opt out from 12 choice sets with alternating characteristic levels: waiting time for surgery, out-of-pocket costs, size of the scar, need of general anesthesia, need for hospitalization, effect on leg pain, and duration of the recovery period. RESULTS A total of 287 patients were included in the DCE analysis. All attributes, except scar size, had a significant influence on the overall preferences of patients. The effect on leg pain was the most important characteristic in the decision for a surgical procedure (by 44.8%). The potential out-of-pocket costs for the procedure (28.8%), the wait time (12.8%), need for general anesthesia (7.5%), need for hospitalization (4.3%), and the recovery period (1.8%) followed. Preferences were independent of the scores on patient-reported outcome measures and baseline characteristics. Three latent classes could be identified with specific preference patterns. Willingness-to-pay was the highest for effectiveness on leg pain, with patients willing to pay €3133 for a treatment that has a 90% effectiveness instead of 70%. CONCLUSIONS Effect on leg pain is the most important factor for patients in deciding to undergo surgery for sciatica. Not all proposed advantages of minimally invasive spine surgery (e.g., size of the scar, no need of general anesthesia) are necessarily perceived as advantages by patients. Spine surgeons should propose surgical techniques for sciatica, not only based on own ability and proposed eligibility, but also based on patient preferences as is part of shared decision making.

ImportanceDifferences in the organization and financing of health systems may produce more or less equitable outcomes for advantaged vs disadvantaged populations. We compared treatments and outcomes of older high- and low-income patients across 6 countries.ObjectiveTo determine whether treatment patterns and outcomes for patients presenting with acute myocardial infarction differ for low- vs high-income individuals across 6 countries.Design, Setting, and ParticipantsSerial cross-sectional cohort study of all adults aged 66 years or older hospitalized with acute myocardial infarction from 2013 through 2018 in the US, Canada, England, the Netherlands, Taiwan, and Israel using population-representative administrative data.ExposuresBeing in the top and bottom quintile of income within and across countries.Main Outcomes and MeasuresThirty-day and 1-year mortality; secondary outcomes included rates of cardiac catheterization and revascularization, length of stay, and readmission rates.ResultsWe studied 289 376 patients hospitalized with ST-segment elevation myocardial infarction (STEMI) and 843 046 hospitalized with non-STEMI (NSTEMI). Adjusted 30-day mortality generally was 1 to 3 percentage points lower for high-income patients. For instance, 30-day mortality among patients admitted with STEMI in the Netherlands was 10.2% for those with high income vs 13.1% for those with low income (difference, −2.8 percentage points [95% CI, −4.1 to −1.5]). One-year mortality differences for STEMI were even larger than 30-day mortality, with the highest difference in Israel (16.2% vs 25.3%; difference, −9.1 percentage points [95% CI, −16.7 to –1.6]). In all countries, rates of cardiac catheterization and percutaneous coronary intervention were higher among high- vs low-income populations, with absolute differences ranging from 1 to 6 percentage points (eg, 73.6% vs 67.4%; difference, 6.1 percentage points [95% CI, 1.2 to 11.0] for percutaneous intervention in England for STEMI). Rates of coronary artery bypass graft surgery for patients with STEMI in low- vs high-income strata were similar but for NSTEMI were generally 1 to 2 percentage points higher among high-income patients (eg, 12.5% vs 11.0% in the US; difference, 1.5 percentage points [95% CI, 1.3 to 1.8 ]). Thirty-day readmission rates generally also were 1 to 3 percentage points lower and hospital length of stay generally was 0.2 to 0.5 days shorter for high-income patients.Conclusions and RelevanceHigh-income individuals had substantially better survival and were more likely to receive lifesaving revascularization and had shorter hospital lengths of stay and fewer readmissions across almost all countries. Our results suggest that income-based disparities were present even in countries with universal health insurance and robust social safety net systems.

Objectives: Efficacy of venetoclax plus obinutuzumab (VenO) compared with chlorambucil plus obinutuzumab (ClbO) for treatment-naïve adult patients with chronic lymphocytic leukemia (CLL) with coexisting medical conditions was investigated in CLL14 (NCT02242942). Our aim was to evaluate the cost-effectiveness of VenO versus ClbO for these patients from a Dutch societal perspective. Methods: A 3-state partitioned survival model was constructed to evaluate the cost-effectiveness of VenO. The outcome of the analysis was the incremental cost-effectiveness ratio (ICER) with effectiveness measured in quality-adjusted life-years (QALYs) gained. Uncertainty was explored through deterministic and probabilistic sensitivity analyses, scenario analyses, and value of information analysis (VOI). Results: The base case resulted in a discounted ICER −49 928 EUR/QALY gained (with incremental negative costs and positive effects). None of the ICERs resulted from deterministic sensitivity and scenario analyses exceeded the chosen willingness-to-pay threshold of 20 000 EUR/QALY, and > 99% of the iterations in the probabilistic sensitivity analysis were cost-effective. VOI analyses showed a maximum expected value of eliminating all model parameter uncertainty of 183 591 EUR. Conclusions: Our study demonstrated VenO being dominant over ClbO in treatment-naïve adult patients with CLL assuming a Dutch societal perspective. We concluded that our results are robust as tested through sensitivity and scenario analyses. Additionally, the VOI analyses confirmed that our current evidence base is strong enough to generate reliable results for our study. Nevertheless, further research based on real-world data or longer follow-up period could further contribute to the robustness of the current study's conclusions.

Benefit-risk assessment is commonly conducted by drug and medical device developers and regulators, to evaluate and communicate issues around benefit-risk balance of medical products. Quantitative benefit-risk assessment (qBRA) is a set of techniques that incorporate explicit outcome weighting within a formal analysis to evaluate the benefit-risk balance. This report describes emerging good practices for the 5 main steps of developing qBRAs based on the multicriteria decision analysis process. First, research question formulation needs to identify the needs of decision makers and requirements for preference data and specify the role of external experts. Second, the formal analysis model should be developed by selecting benefit and safety endpoints while eliminating double counting and considering attribute value dependence. Third, preference elicitation method needs to be chosen, attributes framed appropriately within the elicitation instrument, and quality of the data should be evaluated. Fourth, analysis may need to normalize the preference weights, base-case and sensitivity analyses should be conducted, and the effect of preference heterogeneity analyzed. Finally, results should be communicated efficiently to decision makers and other stakeholders. In addition to detailed recommendations, we provide a checklist for reporting qBRAs developed through a Delphi process conducted with 34 experts.

Background Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory diseases that often affect the wrist and, when affected, can lead to impaired wrist function and progressive joint destruction if inadequately treated. Standard care consists primarily of disease-modifying anti-rheumatic drugs (DMARDs), often supported by systemic corticosteroids or intra-articular corticosteroid injections (IACSI). IACSI, despite their use worldwide, show poor response in a substantial group of patients. Arthroscopic synovectomy of the wrist is the surgical removal of synovitis with the goal to relieve pain and improve wrist function. The primary objective of this study is to evaluate wrist function following arthroscopic synovectomy compared to IACSI in therapy-resistant patients with rheumatoid or psoriatic arthritis. Secondary objectives include radiologic progress, disease activity, health-related quality of life, work participation and cost-effectiveness during a 1-year follow-up. Methods This protocol describes a prospective, randomized controlled trial. RA and PsA patients are eligible with prominent wrist synovitis objectified by a rheumatologist, not responding to at least 3 months of conventional DMARDs and naïve to biological DMARDs. For 90% power, an expected loss to follow-up of 5%, an expected difference in mean Patient-Rated Wrist Evaluation score (PRWE, range 0–100) of 11 and α = 0.05, a total sample size of 80 patients will be sufficient to detect an effect size. Patients are randomized in a 1:1 ratio for arthroscopic synovectomy with deposition of corticosteroids or for IACSI. Removed synovial tissue will be stored for an ancillary study on disease profiling. The primary outcome is wrist function, measured with the PRWE score after 3 months. Secondary outcomes include wrist mobility and grip strength, pain scores, DAS28, EQ-5D-5L, disease progression on ultrasound and radiographs, complications and secondary treatment. Additionally, a cost-effectiveness analysis will be performed, based on healthcare costs (iMCQ questionnaire) and productivity loss (iPCQ questionnaire). Follow-up will be scheduled at 3, 6 and 12 months. Patient burden is minimized by combining study visits with regular follow-ups. Discussion Persistent wrist arthritis continues to be a problem for patients with rheumatic joint disease leading to disability. This is the first randomized controlled trial to evaluate the effect, safety and feasibility of arthroscopic synovectomy of the wrist in these patients compared to IACSI. Trial registration Dutch trial registry (CCMO), NL74744.100.20. Registered on 30 November 2020. ClinicalTrials.gov NCT04755127. Registered after the start of inclusion on 15 February 2021.