Digital Alcohol Interventions Could Be Part of the Societal Response to Harmful Consumption, but We Know Little About Their Long-Term Costs and Health Outcomes.

Alcohol consumption causes both physical and psychological harm and is a leading risk factor for noncommunicable diseases. Digital alcohol interventions have been found to support those looking for help by giving them tools for change. However, whether digital interventions can help tackle the long-term societal consequences of harmful alcohol consumption in a cost-effective manner has not been adequately evaluated. In this Viewpoint, we propose that studies of digital alcohol interventions rarely evaluate the consequences of wider dissemination of the intervention under study, and that when they do, they do not take advantage of modeling techniques that allow for appropriately studying consequences over a longer time horizon than the study period when the intervention is tested. We argue that to help decision-makers to prioritize resources for research and dissemination, it is important to model long-term costs and health outcomes. Further, this type of modeling gives important insights into the context in which interventions are studied and highlights where more research is required and where sufficient evidence is available. The viewpoint therefore invites the researcher not only to reflect on which interventions to study but also how to evaluate their long-term consequences.

Is a larger patient benefit always better in healthcare priority setting?

When considering the introduction of a new intervention in a budget constrained healthcare system, priority setting based on fair principles is fundamental. In many jurisdictions, a multi-criteria approach with several different considerations is employed, including severity and cost-effectiveness. Such multi-criteria approaches raise questions about how to balance different considerations against each other, and how to understand the logical or normative relations between them. For example, some jurisdictions make explicit reference to a large patient benefit as such a consideration. However, since patient benefit is part of a cost-effectiveness assessment it is not clear how to balance considerations of greater patient benefit against considerations of severity and cost-effectiveness. The aim of this paper is to explore the role of a large patient benefit as an independent criterion for priority setting in a healthcare system also considering severity and cost-effectiveness. By taking the opportunity cost of new interventions (i.e., the health forgone in patients already receiving treatment) into account, we argue that patient benefit has a complex relationship to priority setting. More specifically, it cannot be reasonably concluded that large patient benefits should be given priority if severity, cost-effectiveness, and opportunity costs are held constant. Since we cannot find general support for taking patient benefit into account as an independent criterion from any of the most discussed theories about distributive justice: utilitarianism, prioritarianism, telic egalitarianism and sufficientarianism, it is reasonable to avoid doing so. Hence, given the complexity of the role of patient benefit, we conclude that in priority practice, a large patient benefit should not be considered as an independent criterion, on top of considerations of severity and cost-effectiveness.

Disease Progression Modeling for Economic Evaluation in Nonalcoholic Fatty Liver Disease-A Systematic Review.

BACKGROUND & AIMS: Globally, 25% of people have nonalcoholic fatty liver disease (NAFLD), and, currently, there are no approved pharmacologic treatments for NAFLD. With a slow disease progression, long-term impact of pharmacologic treatments can be assessed only by complementing emerging clinical trial evidence with data from other sources in disease progression modeling. Although this modeling is crucial for economic evaluation studies assessing the clinical and economic consequences of new treatments, the approach to modeling the natural history of NAFLD differs in contemporary research. This systematic literature review investigated modeling of the natural history of NAFLD. METHODS: A systematic literature review was conducted searching PubMed, Scopus, Cochrane, and the National Health Service Economic Evaluation Database to identify articles focusing on modeling of the natural history of NAFLD. Model structure and transition probabilities were extracted from included studies. RESULTS: Of the 28 articles identified, differences were seen in model structure and data input. Clear definitions of nonalcoholic steatohepatitis and NAFLD often were lacking; differences in the granularity of modeling fibrosis progression, the approach to disease regression, and modeling of advanced liver disease varied across studies. Observed transition probabilities for F0 to F1, F1 to F2, F2 to F3, and F3 to compensated cirrhosis varied between 0.059 to 0.095, 0.023 to 0.140, 0.018 to 0.070, and 0.040 to 0.118, respectively. CONCLUSIONS: The difference in disease progression modeling for seemingly similar models warrants further inquiry regarding how to model the natural course of NAFLD. Such differences may have a large impact when assessing the value of emerging pharmacologic treatments.

Cost-Effectiveness of Newborn Screening for Phenylketonuria and Congenital Hypothyroidism.

OBJECTIVE: To evaluate the long-term costs and health effects of the Swedish newborn screening program for classic phenylketonuria (PKU) alone and in combination with congenital hypothyroidism compared with no screening. STUDY DESIGN: A decision-analytic model was developed to estimate and compare the long-term (80 years) costs and health effects of newborn screening for PKU and congenital hypothyroidism. Data were obtained from the literature and translated to Swedish conditions. A societal perspective was taken, including costs falling on health care providers, municipal care and services, as well as production loss due to morbidity. RESULTS: Screening 100 000 newborns for PKU resulted in 73 gained quality-adjusted life-years (QALYs) compared with no screening. When adding congenital hypothyroidism, the number of gained QALYs was 232 compared with PKU alone, adding up to a total of 305 QALYs gained. Corresponding cost estimates were $80.8, $70.3, and $10.05 million USD for no screening, PKU screening, and PKU plus congenital hypothyroidism screening, respectively, indicating that screening for PKU plus congenital hypothyroidism was more effective and less costly compared with the other strategies. The majority of cost savings with PKU plus congenital hypothyroidism screening was due to reductions in productivity losses and municipal care and services costs. CONCLUSION: The Swedish newborn screening program for PKU and congenital hypothyroidism saves substantial costs for society while generating additional QALYs, emphasizing the importance of public investments in early diagnosis and treatment.

A rapid, non-invasive, clinical surveillance for CachExia, sarcopenia, portal hypertension, and hepatocellular carcinoma in end-stage liver disease: the ACCESS-ESLD study protocol.

BACKGROUND: Liver cirrhosis, the advanced stage of many chronic liver diseases, is associated with escalated risks of liver-related complications like decompensation and hepatocellular carcinoma (HCC). Morbidity and mortality in cirrhosis patients are linked to portal hypertension, sarcopenia, and hepatocellular carcinoma. Although conventional cirrhosis management centered on treating complications, contemporary approaches prioritize preemptive measures. This study aims to formulate novel blood- and imaging-centric methodologies for monitoring liver cirrhosis patients. METHODS: In this prospective study, 150 liver cirrhosis patients will be enrolled from three Swedish liver clinics. Their conditions will be assessed through extensive blood-based markers and magnetic resonance imaging (MRI). The MRI protocol encompasses body composition profile with Muscle Assement Score, portal flow assessment, magnet resonance elastography, and a abbreviated MRI for HCC screening. Evaluation of lifestyle, muscular strength, physical performance, body composition, and quality of life will be conducted. Additionally, DNA, serum, and plasma biobanking will facilitate future investigations. DISCUSSION: The anticipated outcomes involve the identification and validation of non-invasive blood- and imaging-oriented biomarkers, enhancing the care paradigm for liver cirrhosis patients. Notably, the temporal evolution of these biomarkers will be crucial for understanding dynamic changes. TRIAL REGISTRATION: Clinicaltrials.gov, registration identifier NCT05502198. Registered on 16 August 2022. Link: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05502198 .

Laparoscopic distal pancreatectomy is more cost-effective than open resection: results from a Swedish randomized controlled trial.

BACKGROUND: Laparoscopic distal pancreatectomy is being implemented worldwide. The aim of this study was to perform a cost-effectiveness analysis from a health care perspective. METHODS: This cost-effectiveness analysis was based on the randomized controlled trial LAPOP, where 60 patients were randomized to open or laparoscopic distal pancreatectomy. For the follow-up of two years, resource use from a health care perspective was recorded, and health-related quality of life was assessed using the EQ-5D-5L. The per-patient mean cost and quality-adjusted life years (QALYs) were compared using nonparametric bootstrapping. RESULTS: Fifty-six patients were included in the analysis. The mean health care costs were lower, €3863 (95% CI: -€8020 to €385), for the laparoscopic group. Postoperative quality of life improved with laparoscopic resection and resulted in a gain in QALYs of 0.08 (95% CI: -0.09 to 0.25). The laparoscopic group had lower costs and improved QALYs in 79% of bootstrap samples. With a cost-per-QALY threshold of €50 000, 95.4% of the bootstrap samples were in favour of laparoscopic resection. CONCLUSION: Laparoscopic distal pancreatectomy is associated with numerically lower health care costs and improvements in QALYs compared with the open approach. The results support the ongoing transition from open to laparoscopic distal pancreatectomies.

Clinical decision support for familial hypercholesterolemia (CDS-FH): Rationale and design of a cluster randomized trial in primary care.

BACKGROUND: Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder with high risk of premature atherosclerotic cardiovascular disease and death. Clinical decision support (CDS) systems have the potential to aid in the identification and management of patients with FH. Prior studies using computer-based systems to screen patients for FH have shown promising results, but there has been no randomized controlled trial conducted. The aim of the current cluster randomized study is to evaluate if a CDS can increase the identification of FH. METHODS: We have developed a CDS integrated in the electronic health records that will be activated in patients with elevated cholesterol levels (total cholesterol >8 mmol/L or low-density lipoprotein-cholesterol >5.5 mmol/L, adjusted for age, ongoing lipid lowering therapy and presence of premature coronary artery disease) at increased risk for FH. When activated, the CDS will urge the physician to send an automatically generated referral to the local lipid clinic for further evaluation. To evaluate the effects of the CDS, all primary care clinics will be cluster randomized 1:1 to either CDS intervention or standard care in a Swedish region with almost 500,000 inhabitants. The primary endpoint will be the number of patients diagnosed with FH at 30 months. Resource use and long-term health consequences will be estimated to assess the cost-effectiveness of the intervention. CONCLUSION: Despite increasing awareness of FH, the condition remains underdiagnosed and undertreated. The present study will investigate whether a CDS can increase the number of patients being diagnosed with FH.

Inequality and heterogeneity in health-related quality of life: findings based on a large sample of cross-sectional EQ-5D-5L data from the Swedish general population.

PURPOSE: This study aimed to investigate inequality and heterogeneity in health-related quality of life (HRQoL) and to provide EQ-5D-5L population reference data for Sweden. METHODS: Based on a large Swedish population-based survey, 25,867 respondents aged 30‒104 years, HRQoL is described by sex, age, education, income, economic activity, health-related behaviours, self-reported diseases and conditions. Results are presented by EQ-5D-5L dimensions, respondents rating of their overall health on the EQ visual analogue scale (EQ VAS), VAS index value and TTO (time trade-off) index value allowing for calculation of quality-adjusted life years (QALYs). Ordinary Least Squares and multivariable logistic regression analyses were used to study inequalities in observed EQ VAS score between socioeconomic groups and the likelihood to report problems on the dimensions, respectively, adjusted for confounders. RESULTS: In total, 896 different health states were reported; 24.1% did not report any problems. Most problems were reported with pain/discomfort. Women reported worse HRQoL than men, and health deteriorated with age. The strongest association between diseases and conditions and EQ VAS score was seen for depression and mental health problems. There was a socioeconomic gradient in HRQoL; adjusting for health-related behaviours, diseases and conditions slightly reduced the differences between educational groups and income groups, but socioeconomic inequalities largely remained. CONCLUSION: EQ-5D-5L population reference (norms) data are now available for Sweden, including socioeconomic differentials. Results may be used for comparisons with disease-specific populations and in health economic evaluations. The observed socioeconomic inequality in HRQoL should be of great importance for policy makers concerned with equity aspects.

Should we accept a higher cost per health improvement for orphan drugs? A review and analysis of egalitarian arguments.

In recent years, the issue of accepting a higher cost per health improvement for orphan drugs has been the subject of discussion in health care policy agencies and the academic literature. This article aims to provide an analysis of broadly egalitarian arguments for and against accepting higher costs per health improvement. More specifically, we aim to investigate which arguments one should agree upon putting aside and where further explorations are needed. We identify three kinds of arguments in the literature: considerations of substantial equality, formal equality, and opportunity cost. We argue that considerations of substantial equality do not support higher costs per health improvement orphan drugs, even if such considerations are considered valid. On the contrary, arguments of formal equality may support accepting a higher cost per health improvement for orphan drugs. However, in order to do so, a number of both normative and empirical issues must be resolved; these issues are identified in the article. For instance, it must be settled to what extent the opportunity cost in terms of foregone health for other patients is acceptable in order to uphold formal equality. We conclude that certain arguments can be set aside, and future focus should be put on the unresolved normative and empirical issues related to formal equality and opportunity cost.

On the role of cost-effectiveness thresholds in healthcare priority setting.

In the past few years, empirical estimates of the marginal cost at which health care produces a quality-adjusted life year (QALY, k) have begun to emerge. In theory, these estimates could be used as cost-effectiveness thresholds by health-maximizing decision makers, but prioritization decisions in practice often include other considerations than just efficiency. Pharmaceutical reimbursement in Sweden is one such example, where the reimbursement authority (TLV) uses a threshold range to give priority to disease severity and rarity. In this paper, we argue that estimates of k should not be used to inform threshold ranges. Instead, they are better used directly in health technology assessment (HTA) to quantify how much health is forgone when a new technology is funded in place of other healthcare services. Using a recent decision made by TLV as a case, we show that an estimate of k for Sweden implies that reimbursement meant forgoing 8.6 QALYs for every QALY that was gained. Reporting cost-effectiveness evidence as QALYs forgone per QALY gained has several advantages: (i) it frames the decision as assigning an equity weight to QALYs gained, which is more transparent about the trade-off between equity and efficiency than determining a monetary cost per QALY threshold, (ii) it makes it less likely that decision makers neglect taking the opportunity cost of reimbursement into account by making it explicit, and (iii) it helps communicate the reason for sometimes denying reimbursement in a way that might be less objectionable to the public than current practice.

Health Care Costs of Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease Are Nearly Twice Those of Matched Controls.

BACKGROUND & AIMS: Data on healthcare resource use and costs associated with nonalcoholic fatty liver disease (NAFLD) in clinical practice are lacking. We compared real-life healthcare costs of patients with NAFLD to matched controls. METHODS: We performed a retrospective study of 646 patients with biopsy-proven NAFLD in Sweden from 1971 through 2009. Each patient was matched for age, sex, and county of residence with 10 persons from the general population (controls). We retrieved all healthcare contacts through Dec 31, 2014 from national registers. Unit costs were assigned to arrive at a total healthcare cost (in USD [$]) per study subject. RESULTS: During a mean follow-up of 19.9 years, we recorded a mean of 0.27 hospitalizations per year for patients with NAFLD vs 0.16 for controls (P < .001). This corresponded to an incremental cost of $635 per year for patients with NAFLD. Patients with NAFLD had a higher mean use of outpatient care visits: 1.46 contacts per year compared with 0.86 per year in controls, corresponding to $255 in additional costs (P < .001). Total costs incurred by patients with stage 3-4 fibrosis were higher than by patients with fibrosis stage 0-2 (mean annual costs, $4397 vs $629). Cumulative costs were higher for all stages of fibrosis compared to controls. CONCLUSIONS: Healthcare costs are nearly twice as high in patients with NAFLD than in matched controls. This is mostly attributable to higher costs for hospitalizations, but also to more outpatient visits. Patients with advanced fibrosis had the highest costs.

MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool.

Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bind in the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.

Do not despair about severity-yet.

In a recent extended essay, philosopher Daniel Hausman goes a long way towards dismissing severity as a morally relevant attribute in the context of priority setting in healthcare. In this response, we argue that although Hausman certainly points to real problems with how severity is often interpreted and operationalised within the priority setting context, the conclusion that severity does not contain plausible ethical content is too hasty. Rather than abandonment, our proposal is to take severity seriously by carefully mapping the possibly multiple underlying accounts to well-established ethical theories, in a way that is both morally defensible and aligned with the term's colloquial uses.

Severity as a Priority Setting Criterion: Setting a Challenging Research Agenda.

Priority setting in health care is ubiquitous and health authorities are increasingly recognising the need for priority setting guidelines to ensure efficient, fair, and equitable resource allocation. While cost-effectiveness concerns seem to dominate many policies, the tension between utilitarian and deontological concerns is salient to many, and various severity criteria appear to fill this gap. Severity, then, must be subjected to rigorous ethical and philosophical analysis. Here we first give a brief history of the path to today's severity criteria in Norway and Sweden. The Scandinavian perspective on severity might be conducive to the international discussion, given its long-standing use as a priority setting criterion, despite having reached rather different conclusions so far. We then argue that severity can be viewed as a multidimensional concept, drawing on accounts of need, urgency, fairness, duty to save lives, and human dignity. Such concerns will often be relative to local mores, and the weighting placed on the various dimensions cannot be expected to be fixed. Thirdly, we present what we think are the most pertinent questions to answer about severity in order to facilitate decision making in the coming years of increased scarcity, and to further the understanding of underlying assumptions and values that go into these decisions. We conclude that severity is poorly understood, and that the topic needs substantial further inquiry; thus we hope this article may set a challenging and important research agenda.

Balancing early access with uncertainties in evidence for drugs authorized by prospective case series - systematic review of reimbursement decisions.

AIMS: To review clinical and cost-effectiveness evidence underlying reimbursement decisions relating to drugs whose authorization mainly is based on evidence from prospective case series. METHODS: A systematic review of all new drugs evaluated in 2011-2016 within a health care profession-driven resource prioritization process, with a market approval based on prospective case series, and a reimbursement decision by the Swedish Dental and Pharmaceutical Benefits Agency (TLV). Public assessment reports from the European Medicines Agency, published pivotal studies, and TLV, Scottish Medicines Consortium and National Institute of Health and Care Excellence decisions and guidance documents were reviewed. RESULTS: Six drug cases were assessed (brentuximab vedotin, bosutinib, ponatinib, idelalisib, vismodegib, ceritinib). The validity of the pivotal studies was hampered by the use of surrogate primary outcomes and the absence of recruitment information. To quantify drug treatment effect sizes, the reimbursement agencies primarily used data from another source in indirect comparisons. TLV granted reimbursement in five cases, compared with five in five cases for Scottish Medicines Consortium and four in five cases for National Institute of Health and Care Excellence. Decision modifiers, contributing to granted reimbursement despite hugely uncertain cost-effectiveness ratios, were, for example, small population size, occasionally linked to budget impact, severity of disease, end of life and improved life expectancy. CONCLUSION: For drugs whose authorization is based on prospective case series, most applications for reimbursement within public health care are granted. The underlying evidence has limitations over and above the design per se, and decision modifiers are frequently referred to in the value-based pricing decision making.

Cost-effectiveness of comprehensive geriatric assessment at an ambulatory geriatric unit based on the AGe-FIT trial.

BACKGROUND: Older people with multi-morbidity are increasingly challenging for today's healthcare, and novel, cost-effective healthcare solutions are needed. The aim of this study was to assess the cost-effectiveness of comprehensive geriatric assessment (CGA) at an ambulatory geriatric unit for people ≥75 years with multi-morbidity. METHOD: The primary outcome was the incremental cost-effectiveness ratio (ICER) comparing costs and quality-adjusted life years (QALYs) of a CGA strategy with usual care in a Swedish setting. Outcomes were estimated over a lifelong time horizon using decision-analytic modelling based on data from the randomized AGe-FIT trial. The analysis employed a public health care sector perspective. Costs and QALYs were discounted by 3% per annum and are reported in 2016 euros. RESULTS: Compared with usual care CGA was associated with a per patient mean incremental cost of approximately 25,000 EUR and a gain of 0.54 QALYs resulting in an ICER of 46,000 EUR. The incremental costs were primarily caused by intervention costs and costs associated with increased survival, whereas the gain in QALYs was primarily a consequence of the fact that patients in the CGA group lived longer. CONCLUSION: CGA in an ambulatory setting for older people with multi-morbidity results in a cost per QALY of 46,000 EUR compared with usual care, a figure generally considered reasonable in a Swedish healthcare context. A rather simple reorganisation of care for older people with multi-morbidity may therefore cost effectively contribute to meet the needs of this complex patient population. TRIAL REGISTRATION: The trial was retrospectively registered in clinicaltrial.gov, NCT01446757 . September, 2011.

How is disease severity associated with quality of life in psoriasis patients? Evidence from a longitudinal population-based study in Sweden.

BACKGROUND: Assessing the impact of disease severity on generic quality of life (QOL) is a critical step in outcomes research and in the development of decision-analytic models structured around health states defined by clinical measures. While data from routine clinical practice found in healthcare registers are increasingly used for research, more attention should be paid to understanding the relationship between clinical measures of disease severity and QOL. The purpose of this work was therefore to investigate this relationship in psoriasis using a population-based dataset. METHODS: Severity was measured by the Psoriasis Area and Severity Index (PASI), which combines severity of erythema, induration, and desquamation into a single value ranging from 0 to 72. The generic EQ-5D-3L utility instrument, under the UK tariff, was used to measure QOL. The association between PASI and EQ-5D-3L was estimated using a population-based dataset of 2674 patients with moderate to severe psoriasis enrolled over ten years in the Swedish psoriasis register (PsoReg). Given the repeated measurement of patients in the register data, a longitudinal fixed-effects model was employed to control for unobserved patient-level heterogeneity. RESULTS: Marginal changes in PASI are associated with a non-linear response in EQ-5D-3L: Moving from PASI 10 to 9 (1 to 0) is associated with an increase of 0.0135 (0.0174) in EQ-5D-3L. Furthermore, unobserved patient-level heterogeneity appears to be an important source of confounding when estimating the relationship between QOL and PASI. CONCLUSIONS: Using register data to estimate the impact of disease severity on QOL while controlling for unobserved patient-level heterogeneity shows that PASI appears to have a larger impact on QOL than previously estimated. Routine collection of generic QOL data in registers should be encouraged to enable similar applications in other disease areas. TRIAL REGISTRATION: Not applicable.

Cardiovascular risk in post-myocardial infarction patients: nationwide real world data demonstrate the importance of a long-term perspective.

AIMS: Long-term disease progression following myocardial infarction (MI) is not well understood. We examined the risk of subsequent cardiovascular events in patients discharged after MI in Sweden. METHODS AND RESULTS: This was a retrospective, cohort study linking morbidity, mortality, and medication data from Swedish national registries. Of 108 315 patients admitted to hospital with a primary MI between 1 July 2006 and 30 June 2011 (index MI), 97 254 (89.8%) were alive 1 week after discharge and included in this study. The primary composite endpoint of risk for non-fatal MI, non-fatal stroke, or cardiovascular death was estimated for the first 365 days post-index MI and Day 366 to study completion. Risk and risk factors were assessed by Kaplan-Meier analysis and Cox proportional hazards modelling, respectively. Composite endpoint risk was 18.3% during the first 365 days post-index MI. Age [60-69 vs. <60 years: HR (95% CI): 1.37 (1.30-1.45); 70-79 vs. <60 years: 2.13 (2.03-2.24); >80 vs. <60 years: 3.96 (3.78-4.15)], prior MI [1.44 (1.40-1.49)], stroke [1.49 (1.44-1.54)], diabetes [1.37 (1.34-1.40)], heart failure [1.57 (1.53-1.62)] and no index MI revascularisation [1.88 (1.83-1.93)] were each independently associated with a higher risk of ischaemic events or death. For patients without a combined endpoint event during the first 365 days, composite endpoint risk was 20.0% in the following 36 months. CONCLUSIONS: Risk of cardiovascular events appeared high beyond the first year post-MI, indicating a need for prolonged surveillance, particularly in patients with additional risk factors.

Swedish experience-based value sets for EQ-5D health states.

PURPOSE: To estimate Swedish experience-based value sets for EQ-5D health states using general population health survey data. METHODS: Approximately 45,000 individuals valued their current health status by means of time trade off (TTO) and visual analogue scale (VAS) methods and answered the EQ-5D questionnaire, making it possible to model the association between the experience-based TTO and VAS values and the EQ-5D dimensions and severity levels. The association between TTO and VAS values and the different severity levels of respondents' answers on a self-rated health (SRH) question was assessed. RESULTS: Almost all dimensions (except usual activity) and severity levels had less impact on TTO valuations compared with the UK study based on hypothetical values. Anxiety/depression had the greatest impact on both TTO and VAS values. TTO and VAS values were consistently related to SRH. The inclusion of age, sex, education and socioeconomic group affected the main effect coefficients and the explanatory power modestly. CONCLUSIONS: A value set for EQ-5D health states based on Swedish valuations has been lacking. Several authors have recently advocated the normative standpoint of using experience-based values. Guidelines of economic evaluation for reimbursement decisions in Sweden recommend the use of experience-based values for QALY calculations. Our results that anxiety/depression had the greatest impact on both TTO and VAS values underline the importance of mental health for individuals' overall HRQoL. Using population surveys is in line with recent thinking on valuing health states and could reduce some of the focusing effects potentially appearing in hypothetical valuation studies.