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BackgroundDespite the proven cost effectiveness of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion, treatment within 6 hours from symptom onset remains inaccessible for many patients. We aimed to find the optimal number and location of treatment facilities with respect to the cost effectiveness of MT in patients with AIS, first by the most cost effective implementation of comprehensive stroke centers (CSCs), and second by the most cost effective addition of complementary thrombectomy capable stroke centers (TSCs). MethodsThis study was based on nationwide observational data comprising 18 793 patients with suspected AIS potentially eligible for treatment with MT. The most cost effective solutions were attained by solving the p median facility location-allocation problem with the objective function of maximizing the incremental net monetary benefit (INMB) of MT compared with no MT in patients with AIS. Deterministic sensitivity analysis (DSA) was used as the basis of the results analysis. ResultsThe implementation strategy with seven CSCs produced the highest annual INMB per patient of all possible solutions in the base case scenario. The most cost effective implementation strategy of the extended scenario comprised seven CSCs and four TSCs. DSA revealed sensitivity to variability in MT rate and the maximum willingness to pay per quality adjusted life year gained. ConclusionThe combination of optimization modeling and cost effectiveness analysis provides a powerful tool for configuring the extent and locations of CSCs (and TSCs). The most cost effective implementation of CSCs in Sweden entails 24/7 MT services at all seven university hospitals., Funding Agencies|Center for Advanced Research in Emergency Response (CARER) at Linkoeping University, Sweden; Region Ostergotland, Sweden

Aims Previous studies on the cost-effectiveness of screening for atrial fibrillation (AF) are based on assumptions of long-term clinical effects. The STROKESTOP study, which randomised 27 975 persons aged 75/76 years into a screening invitation group and a control group, has a median follow-up time of 6.9 years. The aim of this study was to estimate the cost-effectiveness of population-based screening for AF using clinical outcomes. Methods and results The analysis is based on a Markov cohort model. The prevalence of AF, the use of oral anticoagulation, clinical event data, and all-cause mortality were taken from the STROKESTOP study. The cost for clinical events, age-specific utilities, utility decrement due to stroke, and stroke death was taken from the literature. Uncertainty in the model was considered in a probabilistic sensitivity analysis. Per 1000 individuals invited to the screening, there were 77 gained life years and 65 gained quality-adjusted life years. The incremental cost was euro1.77 million lower in the screening invitation group. Gained quality-adjusted life years to a lower cost means that the screening strategy was dominant. The result from 10 000 Monte Carlo simulations showed that the AF screening strategy was cost-effective in 99.2% and cost-saving in 92.7% of the simulations. In the base-case scenario, screening of 1000 individuals resulted in 10.6 [95% confidence interval (CI): -22.5 to 1.4] fewer strokes (8.4 ischaemic and 2.2 haemorrhagic strokes), 1.0 (95% CI: -1.9 to 4.1) more cases of systemic embolism, and 2.9 (95% CI: -18.2 to 13.1) fewer bleedings associated with hospitalization. Conclusion Based on the STROKESTOP study, this analysis shows that a broad AF screening strategy in an elderly population is cost-effective. Efforts should be made to increase screening participation., Funding Agencies|Swedish Heart and Lung foundation; Stockholm County Council; Tornspiran Foundation; King Gustav V and Queen Victorias Freemasons Foundation; Klebergska Foundation; Scientific Council of Halland Region; Southern Regional Healthcare Committee; Swedish stroke Foundation; Carl Bennet AB; Boehringer Ingelheim; Bayer; Bristol-Myers Squibb-Pfizer

Pulmonary arterial hypertension (PAH) is a progressive disease with no cure. Healthcare resource utilization (HCRU; hospitalization, outpatient visits, and drug utilization) before diagnosis and productivity loss (sick leave and disability pension) before and after PAH diagnosis are not well known. By linking several Swedish national databases, this study have estimated the societal costs in a national PAH cohort (n = 749, diagnosed with PAH in 2008-2019) 5 years before and 5 years after diagnosis and compared to an age, sex, and geographically matched control group (n = 3745, 1:5 match). HCRU and productivity loss were estimated per patient per year.The PAH group had significantly higher HCRU and productivity loss compared to the control group starting already 3 and 5 years before diagnosis, respectively. HCRU peaked the year after diagnosis in the PAH group with hospitalizations (mean +/- standard deviation; 2.0 +/- 0.1 vs. 0.2 +/- 0.0), outpatient visits (5.3 +/- 0.3 vs. 0.9 +/- 0.1), and days on sick leave (130 +/- 10 vs. 13 +/- 1) significantly higher compared to controls. Total costs during the entire 10-year period were six times higher for the PAH group than the control group. In the 5 years before diagnosis the higher costs were driven by productivity loss (76%) and hospitalizations (15%), while the 5 years after diagnosis the main cost drivers were drugs (63%), hospitalizations (16%), and productivity loss (16%). In conclusion, PAH was associated with large societal costs due to high HCRU and productivity loss, starting several years before diagnosis. The economic and clinical burden of PAH suggests that strategies for earlier diagnosis and more effective treatments are warranted., Funding Agencies|Svensk Forening for Pulmonell Hypertension; Actelion Pharmaceuticals

Background: Despite the proven cost effectiveness of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion, treatment within 6 hours from symptom onset remains inaccessible for many patients. We aimed to find the optimal number and location of treatment facilities with respect to the cost effectiveness of MT in patients with AIS, first by the most cost effective implementation of comprehensive stroke centers (CSCs), and second by the most cost effective addition of complementary thrombectomy capable stroke centers (TSCs). Methods: This study was based on nationwide observational data comprising 18 793 patients with suspected AIS potentially eligible for treatment with MT. The most cost effective solutions were attained by solving the p median facility location-allocation problem with the objective function of maximizing the incremental net monetary benefit (INMB) of MT compared with no MT in patients with AIS. Deterministic sensitivity analysis (DSA) was used as the basis of the results analysis. Results: The implementation strategy with seven CSCs produced the highest annual INMB per patient of all possible solutions in the base case scenario. The most cost effective implementation strategy of the extended scenario comprised seven CSCs and four TSCs. DSA revealed sensitivity to variability in MT rate and the maximum willingness to pay per quality adjusted life year gained. Conclusion: The combination of optimization modeling and cost effectiveness analysis provides a powerful tool for configuring the extent and locations of CSCs (and TSCs). The most cost effective implementation of CSCs in Sweden entails 24/7 MT services at all seven university hospitals.

Reimbursement programmes are used to manage care through financial incentives. However, their effects are mixed and the programmes can motivate behaviour that goes against professional values. Value-based reimbursement programmes may better align professional values with financial incentives. The aim of this study is to analyse if and how healthcare providers adapt their practices to a value-based reimbursement programme that combines bundled payment with performance-based payment. Forty-one semi-structured interviews were conducted with representatives from healthcare providers within spine surgery in Sweden. Data were analysed using thematic analysis with an abductive approach and a conceptual framework based on neo-institutional theory. Healthcare providers were positive to the idea of a value-based reimbursement programme. However, during its introduction it became evident that some aspects were easier to adapt to than others. The bundled payment provided a more comprehensive picture of the patients needs but to an increased administrative burden. Due to the financial impact of the bundled payment, healthcare providers tried to decrease the amount of post-discharge care. The performance-based payment was appreciated. However, the lack of financial impact and transparency in how the payment was calculated caused providers to neglect it. Healthcare providers adapted their practices to, but also resisted aspects of the value-based reimbursement programme. Resistance was mainly caused by lack of understanding of how to interpret and act on new information. Providers had to face unfamiliar situations, which they did not know how to handle. Better IT-facilitation and clearer definition of related care is needed to strengthen the value-based reimbursement programme among healthcare providers. A value-based reimbursement programme seems to better align professional values with financial incentives., Funding Agencies|Region Stockholm

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 liter-ature 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. (J Pediatr 2023;256:38-43)., Funding Agencies|Medical Diagnostics Karolinska

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but serious complication after a pulmonary embolism. Healthcare resource utilization (HCRU; hospitalization, outpatient visits, and drug utilization) as well as productivity loss (sick leave and disability pension) before and after the CTEPH diagnosis is sparsely studied. By linking several Swedish national databases, this study estimated the societal costs in a national CTEPH cohort (n = 369, diagnosed with CTEPH in 2008-2019) 5 years before and 5 years after diagnosis (index date) and compared to an age, sex, and geographically matched control group (n = 1845, 1:5 match). HCRU and productivity loss were estimated per patient per year. Patients were stratified as operated with pulmonary endarterectomy (PEA group) or not operated (non-PEA group). Direct and indirect societal costs were 2.1 times higher before, and 8.1 times higher after the index date for patients with CTEPH compared to the matched control groups. The higher costs were evident already several years preceding the index date. The main cost driver before the index date in both the PEA and the non-PEA groups was productivity loss. The productivity loss remained high for both groups in the 5-year period following the index date, but the main cost drivers were prescribed drugs and hospitalizations for patients that underwent PEA and prescribed drugs in the non-PEA group. In conclusion, CTEPH was associated with large societal costs related to healthcare consumption and productivity loss, both before and after diagnosis., Funding Agencies|Swedish Ethical Review Authority [Dnr 2020-02573]

Background: Whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS), with the ability to provide comprehensive genomic information, have become the focal point of research interest as novel techniques that can support precision diagnostics in routine clinical care of patients with various cancer types, including hematological malignancies. This national multi-center study, led by Genomic Medicine Sweden, aims to evaluate whether combined application of WGS and WTS (WGTS) is technically feasible and can be implemented as an efficient diagnostic tool in patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In addition to clinical impact assessment, a health-economic evaluation of such strategy will be performed. Methods and Analysis: The study comprises four phases (i.e., retrospective, prospective, real-time validation, and follow-up) including approximately 700 adult and pediatric Swedish AML and ALL patients. Results of WGS for tumor (90×) and normal/germline (30×) samples as well as WTS for tumors only will be compared to current standard of care diagnostics. Primary study endpoints are diagnostic efficiency and improved diagnostic yield. Secondary endpoints are technical and clinical feasibility for routine implementation, clinical utility, and health-economic impact. Discussion: Data from this national multi-center study will be used to evaluate clinical performance of the integrated WGTS diagnostic workflow compared with standard of care. The study will also elucidate clinical and health-economic impacts of a combined WGTS strategy when implemented in routine clinical care., On behalf of the Clinical Genomics Platform at SciLifeLab and Genomic Medicine Sweden.Funding: This work was supported by Vinnova, the Swedish Innovation Agency, the Swedish Childhood Cancer Fund, the Swedish Cancer Society, the Swedish Research Council, regional ALF funding from Region Skåne, Region Västra Götaland, Karolinska Institutet, and Karolinska University Hospital. The sequencing of the retrospective cohort was funded by the SciLifeLab National Projects (NP00043).

Background We have addressed health equity attained by fecal immunochemical testing (FIT) and primary colonoscopy (PCOL), respectively, in the randomised controlled screening trial SCREESCO conducted in Sweden. Methods We analysed data on the individuals recruited between March 2014, and March 2020, within the study registered with ClinicalTrials.gov, NCT02078804. Swedish population registry data on educational level, household income, country of birth, and marital status were linked to each 60-year-old man and woman who had been randomised to two rounds of FIT 2 years apart (n = 60,123) or once-only PCOL (n = 30,390). Furthermore, we geo-coded each study individual to his/her residential area and assessed neighbourhood-level data on deprivation, proportion of non-Western immigrants, population density, and average distance to healthcare center for colonoscopy. We estimated adjusted associations of each covariate with the colonoscopy attendance proportion out of all invited to respective arms; ie, the preferred outcome for addressing health equity. In the FIT arm, the test uptake and the colonoscopy uptake among the test positives were considered as the secondary outcomes. Findings We found a marked socioeconomic gradient in the colonoscopy attendance proportion in the PCOL arm (adjusted odds ratio [95% credibility interval] between the groups categorised in the highest vs. lowest national quartile for household income: 2.20 [2.01-2.42]) in parallel with the gradient in the test uptake of the FIT x 2 screening (2.08 [1.96-2.20]). The corresponding gradient in the colonoscopy attendance proportion out of all invited to FIT was less pronounced (1.29 [1.16-1.42]), due to higher proportions of FIT positives in socioeconomically disadvantaged groups. Interpretation The unintended risk of exacerbating inequalities in health by organised colorectal cancer screening may be higher with a PCOL strategy than a FIT strategy, despite parallel socioeconomic gradients in uptake. C, Funding Agencies|Swedish Cancer Society [20 0719]; Swedish Research Council for Health, Working life, and Welfare [2020-00962]

Introduction: Shortening the time from stroke onset to treatment increases the effectiveness of endovascular stroke therapies. Aim: This study aimed to predict the modified Rankin Scale score at 90 days post-stroke (mRS-90d score) in patients with acute ischaemic stroke (AIS) with respect to four types of treatment: conservative therapy (CVT), intravenous thrombolysis only (IVT), mechanical thrombectomy only (MT) and pretreatment with IVT before MT (IVT+MT). Patients and methods: This nationwide observational study included 124 484 confirmed cases of acute stroke in Sweden over 6 years (2012-2017). The associations between onset-to-treatment time (OTT), patient age and hospital admission National Institutes of Health Stroke Scale (NIHSS) score with the five-levelled mRS-90d score were retrospectively studied. A generalised linear model (GLM) was fitted to predict the mRS-90d scores for each patient group. Results: The fitted GLM for CVT patients is a function of age and NIHSS score. For IVT, MT and IVT+MT patients, GLMs additionally employed OTT variables. By reducing the mean OTTs by 15 min, the number needed-to-treat (NNT) for one patient to make a favourable one-step shift in the mRS was 30 for IVT, 48 for MT and 21 for IVT+MT. Discussion and conclusion: This study demonstrates linear associations of mRS-90d score with OTT for IVT, MT and IVT+MT, and shows in absolute effects measures that OTT reductions for IVT and/or MT produces substantial health gains for patients with AIS. Even moderate OTT reductions led to sharp drops in the NNT.

Reimbursement programmes are used to manage care through financial incentives. However, their effects are mixed and the programmes can motivate behaviour that goes against professional values. Value-based reimbursement programmes may better align professional values with financial incentives. The aim of this study is to analyse if and how healthcare providers adapt their practices to a value-based reimbursement programme that combines bundled payment with performance-based payment. Forty-one semi-structured interviews were conducted with representatives from healthcare providers within spine surgery in Sweden. Data were analysed using thematic analysis with an abductive approach and a conceptual framework based on neo-institutional theory. Healthcare providers were positive to the idea of a value-based reimbursement programme. However, during its introduction it became evident that some aspects were easier to adapt to than others. The bundled payment provided a more comprehensive picture of the patients needs but to an increased administrative burden. Due to the financial impact of the bundled payment, healthcare providers tried to decrease the amount of post-discharge care. The performance-based payment was appreciated. However, the lack of financial impact and transparency in how the payment was calculated caused providers to neglect it. Healthcare providers adapted their practices to, but also resisted aspects of the value-based reimbursement programme. Resistance was mainly caused by lack of understanding of how to interpret and act on new information. Providers had to face unfamiliar situations, which they did not know how to handle. Better IT-facilitation and clearer definition of related care is needed to strengthen the value-based reimbursement programme among healthcare providers. A value-based reimbursement programme seems to better align professional values with financial incentives., Funding Agencies|Region Stockholm

Background To date, evidence on the dose adjustments of biologics in the real-world treatment of psoriasis is limited. However, dose adjustments may have important clinical and economic implications. Aims To study the dose adjustments of individual biologics over time in real-world practice in Sweden. Methods A retrospective observational study of adults with moderate to severe psoriasis was conducted based on Swedish national registry data from 2010 to 2018. Treatment episodes were identified for individual patients from the date of drug dispensation to the end of the supply of the drug. Dosing data were expressed as the proportion of treatment episodes with accumulated syringes/vials equal to, above or below the recommended guidelines. Real-world costs were calculated and compared with costs predicted from dosing guidelines. Results The mean dose was above recommended levels for all biologics investigated. Weighted mean dose adjustments for adalimumab, etanercept, secukinumab and ustekinumab were 13%, 23%, 8% and 3%, respectively, over the entire treatment period. Higher doses translate to higher costs, including notable increases over time vs. expected costs for secukinumab. Conclusions Dose adjustments of biologics are frequent in clinical practice but differ for the various biologics. The mean observed increases in dose above guideline recommendations might indicate perceptions of suboptimal efficacy for biologics, with implications for the cost and cost-effectiveness of these treatments. Further research is warranted to understand the reasons for dose adjustments in clinical practice., Funding Agencies|LEO Pharma A/S

Aims A third of non-valvular atrial fibrillation (NVAF) patients are non-adherent to direct oral anticoagulants (DOACs). Estimates of the economic value of full adherence and the cost of two types of adherence improving interventions are important to healthcare planners and decision-makers. Methods A cost-utility analysis estimated the impact of non-adherence over a 20-year horizon, for a patient cohort with a mean age of 77 years, based on data from the Stockholm Healthcare database of NVAF patients with incident stroke between 2011 and 2018. Adherence was defined using a medication possession ratio (MPR) cut-off of 90%; primary outcomes were the number of ischemic strokes and associated incremental cost-utility ratio. Results Hypothetical comparisons between cohorts of 1,000 patients with varying non-adherence levels and full adherence (MPR >90%) predicted an additional number of strokes ranging from 117 (MPR = 81-90%) to 866 (MPR <60%), and years of life lost ranging from 177 (MPR = 81- 90%) to 1,318 (MPR < 60%; discounted at 3%). Chronic disease co-management intervention occurring during each DOAC prescription renewal and patient education intervention at DOAC initiation will be cost-saving to the health system if its cost is below SEK 143 and SEK 4,655, and cost-effective if below SEK 858 and SEK 28,665, respectively. Conclusion Adherence improving interventions for NVAF patients on DOACs such as chronic disease co-management and patient education can be cost-saving and cost-effective, within a range of costs that appear reasonable to the Swedish healthcare system. PLAIN LANGUAGE SUMMARY Atrial fibrillation (AF) is the most common type of chronic cardiac arrhythmia and a major risk factor for ischemic stroke (IS). The objective of this study was to compare the costs and health outcomes associated with adherence to direct oral anticoagulant (DOAC) therapy in Sweden. The study also aimed to demonstrate the potential benefits of developing in

Aims: A third of non-valvular atrial fibrillation (NVAF) patients are non-adherent to direct oral anticoagulants (DOACs). Estimates of the economic value of full adherence and the cost of two types of adherence improving interventions are important to healthcare planners and decision-makers. Methods: A cost-utility analysis estimated the impact of non-adherence over a 20-year horizon, for a patient cohort with a mean age of 77 years, based on data from the Stockholm Healthcare database of NVAF patients with incident stroke between 2011 and 2018. Adherence was defined using a medication possession ratio (MPR) cut-off of 90%; primary outcomes were the number of ischemic strokes and associated incremental cost–utility ratio. Results: Hypothetical comparisons between cohorts of 1,000 patients with varying non-adherence levels and full adherence (MPR >90%) predicted an additional number of strokes ranging from 117 (MPR = 81–90%) to 866 (MPR <60%), and years of life lost ranging from 177 (MPR = 81– 90%) to 1,318 (MPR < 60%; discounted at 3%). Chronic disease co-management intervention occurring during each DOAC prescription renewal and patient education intervention at DOAC initiation will be cost-saving to the health system if its cost is below SEK 143 and SEK 4,655, and cost-effective if below SEK 858 and SEK 28,665, respectively. Conclusion: Adherence improving interventions for NVAF patients on DOACs such as chronic disease co-management and patient education can be cost-saving and cost-effective, within a range of costs that appear reasonable to the Swedish healthcare system.

Objectives The aim of this study was to estimate the cost-effectiveness of intermittent electrocardiogram (ECG) screening for atrial fibrillation (AF) among 70-74-year old individuals in primary care. We also aimed to assess adherence to anticoagulants, severe bleeding, stroke and mortality among screening-detected AF cases at three-year follow-up. Methods A post hoc analysis based on a cross-sectional screening study for AF among 70-74-year old patients, who were registered at a single primary care center, was followed for three years for mortality. Data about adherence to anticoagulants, incidence of stroke and severe bleeding among screening-detected AF cases, were collected from patients records. Markov model and Monte Carlo simulation were used to assess the cost-effectiveness of the screening program. Results The mortality rate among screening-detected AF cases (n = 16) did not differ compared to the 274 individuals with no AF (hazard ratio 0.86, CI 0.12-6.44). Adherence to anticoagulants was 92%. There was no stroke or severe bleeding. The incremental cost-effectiveness ratio of screening versus no screening was EUR 2389/quality-adjusted life year (QALY) gained. The screening showed a 99% probability of being cost-effective compared to no screening at a willingness-to-pay threshold of EUR 20,000 per QALY. Conclusion Screening for AF among 70-74-year olds in primary care using intermittent ECG appears to be cost-effective at 3-year follow-up with high anticoagulants adherence and no increased mortality., Funding: M. R. has received research grants, lecture and consulting honoraria from the following sources. Abbott, Carl Bennett AB, Bristol Myers Squibb, Medtronic, MSD, Pfizer, Roche, Sanofi, and Zenicor. L. L. has received economic support for lecturing, advisory boards and research from AstraZeneca, Bayer, Boehringer Ingelheim and Pfizer. F. A. has received lecture fees from Bristol-Myers-Squibb, Pfizer, Boehringer-Ingelheim, and Bayer. M. A. employed by AstraZeneca.