Radiology AI Deployment and Assessment Rubric (RADAR) to bring value-based AI into radiological practice.

OBJECTIVE: To provide a comprehensive framework for value assessment of artificial intelligence (AI) in radiology. METHODS: This paper presents the RADAR framework, which has been adapted from Fryback and Thornbury's imaging efficacy framework to facilitate the valuation of radiology AI from conception to local implementation. Local efficacy has been newly introduced to underscore the importance of appraising an AI technology within its local environment. Furthermore, the RADAR framework is illustrated through a myriad of study designs that help assess value. RESULTS: RADAR presents a seven-level hierarchy, providing radiologists, researchers, and policymakers with a structured approach to the comprehensive assessment of value in radiology AI. RADAR is designed to be dynamic and meet the different valuation needs throughout the AI's lifecycle. Initial phases like technical and diagnostic efficacy (RADAR-1 and RADAR-2) are assessed pre-clinical deployment via in silico clinical trials and cross-sectional studies. Subsequent stages, spanning from diagnostic thinking to patient outcome efficacy (RADAR-3 to RADAR-5), require clinical integration and are explored via randomized controlled trials and cohort studies. Cost-effectiveness efficacy (RADAR-6) takes a societal perspective on financial feasibility, addressed via health-economic evaluations. The final level, RADAR-7, determines how prior valuations translate locally, evaluated through budget impact analysis, multi-criteria decision analyses, and prospective monitoring. CONCLUSION: The RADAR framework offers a comprehensive framework for valuing radiology AI. Its layered, hierarchical structure, combined with a focus on local relevance, aligns RADAR seamlessly with the principles of value-based radiology. CRITICAL RELEVANCE STATEMENT: The RADAR framework advances artificial intelligence in radiology by delineating a much-needed framework for comprehensive valuation. KEYPOINTS: • Radiology artificial intelligence lacks a comprehensive approach to value assessment. • The RADAR framework provides a dynamic, hierarchical method for thorough valuation of radiology AI. • RADAR advances clinical radiology by bridging the artificial intelligence implementation gap.

Incorporating risk preferences of patients in the valuation of immune checkpoint inhibitors for non-small cell lung cancer.

Immunotherapy offers a distinctive mechanism of action compared to traditional treatments, arising from additional value dimensions that may not be captured in standard health technology assessments. Cancer patients may have the expectation that immunotherapy provides durable, long-term survival gains. Moreover, some patients may be willing to take a 'risk' to undergo immunotherapy to achieve better survival outcomes. We reviewed quantitative methods that explored patients' risk preferences in their non-small cell lung cancer (NSCLC) treatment choices, in PubMed (MEDLINE), from January 1, 2015, until July 1, 2022. The consideration of a value dimension ('hope') based on patients' risk-seeking preferences is specifically addressed for the valuation of immune checkpoint inhibitors in NSCLC. We reported that the quantitative methods that aim to measure patients' risk preferences or 'hope' empirically are emerging. Value assessments should not only comprise survival improvements for the mean or median patient but also consider methods that reflect durable, long-term overall survival gains for risk-seeking patients. However, the published evidence for incorporating 'hope' based on patients' stated preferences for uncertain treatment profiles is not strong, and future research could strengthen this evidence base. We encourage further research on the development and validation of quantification methods to incorporate 'hope' and risk preferences of patients treated with immunotherapy for NSCLC and beyond.

Cost-effectiveness of first line nivolumab-ipilimumab combination therapy for advanced non-small cell lung cancer: A systematic review and methodological quality assessment.

To assess the methodological quality of cost-effectiveness analyses (CEA) of nivolumab in combination with ipilimumab, we conducted a systematic literature review in the first-line treatment of patients with recurrent or metastatic non-small cell lung cancer (NSCLC), whose tumors express programmed death ligand-1, with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations. PubMed, Embase, and the Cost-Effectiveness Analysis Registry were searched, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The methodological quality of the included studies was assessed by the Philips checklist and the Consensus Health Economic Criteria (CHEC) checklist. 171 records were identified. Seven studies met the inclusion criteria. Cost-effectiveness analyses differed substantially due to the applied modeling methods, sources of costs, health state utilities, and key assumptions. Quality assessment of the included studies highlighted shortcomings in data identification, uncertainty assessment, and methods transparency. Our systematic review and methodology assessment revealed that the methods of estimation of long-term outcomes, quantification of health state utility values, estimation of drug costs, the accuracy of data sources, and their credibility have important implications on the cost-effectiveness outcomes. None of the included studies fulfilled all of the criteria reported in the Philips and the CHEC checklists. To compound the economic consequences presented in these limited number of CEAs, ipilimumab's drug action as a combination therapy poses significant uncertainty. We encourage further research to address the economic consequences of these combination agents in future CEAs and the clinical uncertainties of ipilimumab for NSCLC in future trials.

Long-Term Effects of Dexmedetomidine versus Propofol During the Implantation of a Neurostimulator-A Post-Trial Follow-Up Analysis.

OBJECTIVE: The success of neurostimulation depends partly on the amount of coverage of the neurostimulation-induced paresthesia of the painful area. This is often achieved by asking feedback from patients intraoperatively. If sedation analgesia is used, it is important that the patient is comfortable during sedation and easily arousable. If the patient is not well sedated or experiences residual effects of the sedation during testing, this can directly influence the ideal placement of the leads and indirectly the long-term effect of the treatment. It is our hypothesis that the quality of the sedation is directly coupled to the adequacy of lead placement and in this way in the result of the treatment. Dexmedetomidine is known for its easy production of arousable sedation. The aim of the present study was to compare the long-term effect of using dexmedetomidine versus propofol during the implantation of a neurostimulator. MATERIALS AND METHODS: This is a post-trial follow-up analysis of the DexMedPro cohort. The primary outcome was global perceived effect (GPE). The secondary outcomes were the course of pain intensity, the emotional and physical functioning at the time of follow-up, and the course of neurostimulation treatment. In this study, we used the patient satisfaction with sedation as a measure for sedation quality. RESULTS: Regarding the GPE, no statistically significant differences were found between the experimental groups in either subscale (ie, recovery (p=0.82) and satisfaction with the neurostimulation treatment at follow-up (p=0.06)). The same was found regarding the secondary parameters. A correlation was found between patient satisfaction with sedation during the lead implantation (side effects and procedural recall) and satisfaction at follow-up. CONCLUSION: Regarding the long-term efficacy of neurostimulation treatment, no statistically significant differences were found between the dexmedetomidine and the propofol group. We observed a trend towards greater satisfaction with the neurostimulation treatment at follow-up in the dexmedetomidine group, compared to the propofol group.

Cost-effectiveness of Mechanical Thrombectomy More Than 6 Hours After Symptom Onset Among Patients With Acute Ischemic Stroke.

Importance: Two 2018 randomized controlled trials (DAWN and DEFUSE 3) demonstrated the clinical benefit of mechanical thrombectomy (MT) more than 6 hours after onset in acute ischemic stroke (AIS). Health-economic evidence is needed to determine whether the short-term health benefits of late MT translate to a cost-effective option during a lifetime in the United States. Objective: To compare the cost-effectiveness of 2 strategies (MT added to standard medical care [SMC] vs SMC alone) for various subgroups of patients with AIS receiving care more than 6 hours after symptom onset. Design, Setting, and Participants: This economic evaluation study used the results of the DAWN and DEFUSE 3 trials to populate a cost-effectiveness model from a US health care perspective combining a decision tree and Markov trace. The DAWN and DEFUSE 3 trials enrolled 206 international patients from 2014 to 2017 and 182 US patients from 2016 to 2017, respectively. Patients were followed until 3 months after stroke. The clinical outcome at 3 months was available for 29 subgroups of patients with AIS and anterior circulation large vessel occlusions. Data analysis was conducted from July 2018 to October 2019. Exposures: MT with SMC in the extended treatment window vs SMC alone. Main Outcomes and Measures: Expected costs and quality-adjusted life-years (QALYs) during lifetime were estimated. Deterministic results (incremental costs and effectiveness, incremental cost-effectiveness ratios, and net monetary benefit) were presented, and probabilistic analyses were performed for the total populations and 27 patient subgroups. Results: In the DAWN study, the MT group had a mean (SD) age of 69.4 (14.1) years and 42 of 107 (39.3%) were men, and the control group had a mean (SD) age of 70.7 (13.2) years and 51 of 99 (51.5%) were men. In the DEFUSE 3 study, the MT group had a median (interquartile range) age of 70 (59-79) years, and 46 of 92 (50.0%) were men, and the control group had a median (interquartile range) age of 71 (59-80) years, and 44 of 90 (48.9%) were men. For the total trial population, incremental cost-effectiveness ratios were $662/QALY and $13 877/QALY based on the DAWN and DEFUSE 3 trials, respectively. MT with SMC beyond 6 hours had a probability greater than 99.9% of being cost-effective vs SMC alone at a willingness-to-pay threshold of $100 000/QALY. Subgroup analyses showed a wide range of probabilities for MT with SMC to be cost-effective at a willingness-to-pay threshold of $50 000/QALY, with the greatest uncertainty observed for patients with a National Institute of Health Stroke Scale score of at least 16 and for those aged 80 years or older. Conclusions and Relevance: The results of this study suggest that late MT added to SMC is cost-effective in all subgroups evaluated in the DAWN and DEFUSE 3 trials, with most results being robust in probabilistic sensitivity analyses. Future MT evidence-gathering could focus on older patients and those with National Institute of Health Stroke Scale scores of 16 and greater.

Use of data-mining to support real-world cost analyses: An example using HER2-positive breast cancer in Iran.

INTRODUCTION: Patient registries play an important role in obtaining real-world evidence of the cost-effectiveness of treatments. However, their implementation is costly and sometimes infeasible in many middle-income countries (MICs). We explored the combination of data-mining and a large claims database to estimate the direct healthcare costs of HER2-positive breast cancer (BC) treatment in Iran and the fraction of total costs from trastuzumab use. METHOD: We performed a retrospective analysis of claims data from the Iran Social Security Organization, a health insurer which covers approximately 50%(~40 million) of the Iranian population, in the period of 21/03/2011-20/03/2014. A data-mining algorithm using R software and validated using patient dossiers in the Cancer Research Center identified 1295 patients and divided them into the three main HER2-positive breast cancer stages (early, loco-regional and advanced). A payer perspective was used to calculate the absolute and relative direct costs of healthcare services associated with the treatment of HER2-positive breast cancer in the public and private healthcare systems. RESULTS: The number of women totaled 802 (early), 125 (loco-regional) and 218 (advanced). The mean age[SD] was 45[10], 46[10] and 48[10] years, respectively, while mean follow-up in all stages was approximately one year. Average costs of direct healthcare care in early, loco-regional and advanced stages were €11,796 (95%CI: €9,356-€12,498), €8,253 (95%CI: €6,843-€10,002), and €17,742 (95%CI: €15,720-€19,505), respectively. Trastuzumab accounted for the largest share of total costs in all three stages (range: 53-76%). CONCLUSION: Wherever comprehensive patient registries are infeasible or costly, real-world costs can be estimated through claims databases and data-mining strategies. Using this method, real-world costs have been estimated in Iran. The stage-specific cost estimates derived from this study can be used to perform real-world cost-effectiveness analyses of therapies for HER2-positive BC and support healthcare financing decisions.

Author Correction to: Adjuvant Trastuzumab Therapy for Early HER2-Positive Breast Cancer in Iran: A Cost-Effectiveness and Scenario Analysis for an Optimal Treatment Strategy.

ABSTARCT: Page 95, Table 2, final row, second column: the mean Advanced treatment annual cost which.

Adjuvant Trastuzumab Therapy for Early HER2-Positive Breast Cancer in Iran: A Cost-Effectiveness and Scenario Analysis for an Optimal Treatment Strategy.

INTRODUCTION: Clinical guidelines have recommended a 1-year trastuzumab regimen as standard care for early human epidermal growth factor receptor 2 (HER2)-positive breast cancer; however, this recommendation can have a dramatic impact on total drug expenditures in middle-income countries (MICs). We performed a cost-effectiveness analysis from the Iranian healthcare perspective to find an optimum duration of trastuzumab use in Iran. METHOD: We compared four treatment strategies comprising chemotherapy and varying durations of trastuzumab use (no trastuzumab, 6, 9 months, and 1 year), and a Markov model and probabilistic sensitivity analysis were used to estimate the costs and effects of the strategies. We then examined the cost effectiveness of the strategies at different willingness-to-pay (WTP) thresholds and ages at onset of treatment. RESULTS: Incremental costs (versus no trastuzumab) were €8826 (6 months), €13,808 (9 months) and €18,588 (12 months), while incremental quality-adjusted life-years (QALYs) were 0.65 (6 months), 0.87 (9 months) and 1.14 (12 months). At a threshold of 3 × gross domestic product (GDP)/capita (€21,000/QALY) and for patients younger than 59 years, the 6-month protocol was most likely to be cost effective (probability of 42%). At a threshold of 4 × GDP/capita (€28,000/QALY), the 6-month and 1-year regimens were essentially equal in cost effectiveness (37 and 35%, respectively). At this WTP threshold, the 6-month and 1-year regimens were optimal strategies only for patients up to 66 and 44 years of age, respectively. CONCLUSION: In contrast to clinical guidelines, 6 months of trastuzumab may be the most cost-effective option for Iran. The lower absolute WTP threshold and lower life expectancy compared with high-income countries are two crucial parameters in the cost effectiveness of interventions in MICs. It is therefore necessary to strike a balance between maximum population health and maintaining affordability in these countries.

Cost-effectiveness of enzyme replacement therapy with alglucosidase alfa in adult patients with Pompe disease.

BACKGROUND: Pompe disease is a rare, progressive, metabolic disease, and the first treatable inheritable muscle disorder. Enzyme replacement therapy (ERT) with alglucosidase alfa is disease specific and the only medicinal product authorized for the treatment of Pompe disease. Costs of ERT are very high as for most orphan drugs. This study investigates the cost-effectiveness of ERT compared to supportive treatment in adult patients with Pompe disease. METHODS: Survival probabilities were estimated from an international observational dataset (n = 283) using a time-dependent Cox model. Quality of life was estimated on a Dutch observational dataset using a previously developed conceptual model which links clinical factors to quality of life. Costs included costs of ERT, costs of drug administration and other healthcare costs. Cost-effectiveness was estimated using a patient-level simulation model (n = 90), synthesising the information from underlying models for survival, quality of life and costs. The cost-effectiveness model estimated the (difference in) lifetime effects and costs for both treatments. Two scenarios were modelled: (1) a worse case scenario with no extrapolation of the survival gain due to ERT beyond the observed period (i.e. from 10 years onwards); and (2) a best case scenario with lifetime extrapolation of the survival gain due to ERT. Effects were expressed in (quality adjusted) life years (QALYs). Costs were discounted at 4.0% and effects at 1.5%. RESULTS: Substantial increases in survival were estimated - discounted incremental life years of ERT ranged from 1.9 years to 5.4 years in the scenarios without and with extrapolation of survival gains beyond the observed period. Quality of life was also significantly better for patients receiving ERT. Incremental costs were considerable and primarily consisted of the costs of ERT. Incremental costs per QALY were €3.2 million for scenario 1 and €1.8 million for scenario 2. CONCLUSIONS: The availability of extended, prospectively collected, longitudinal observational data on the most important input parameters required to construct a cost-effectiveness model is quite exceptional for orphan diseases. The cost-effectiveness model showed substantial survival gains from ERT. Despite these substantial gains, ERT was not cost-effective in the treatment of adult Pompe disease because of the high cost of treatment.

Which Questionnaire Should Be Used to Measure Quality-of-Life Utilities in Patients with Acute Leukemia? An Evaluation of the Validity and Interpretability of the EQ-5D-5L and Preference-Based Questionnaires Derived from the EORTC QLQ-C30.

OBJECTIVES: The aim of this study was to assess the validity and interpretability of different preference-based questionnaires (generic 5-level EuroQol five-dimensional questionnaire [EQ-5D-5L], cancer-specific Quality of Life Questionnaire Preference-Based Measure, and European Organization of Randomized Controlled Trials 8 Dimension [EORTC-8D]) in patients with acute leukemia. METHODS: Patients who participated in Hemato-Oncologie voor Volwassenen Nederland (HOVON - the Haemato Oncology Foundation for Adults in the Netherlands) clinical trials between 1999 and 2011 at a single hospital were invited to complete the questionnaires. Interpretability was evaluated by the frequency of incomplete data and highest and lowest possible scores. Content validity was evaluated by exploring the health-related quality-of-life domains included in the questionnaires. Construct validity was assessed using correlations with other quality-of-life scales (EQ-visual analogue scale score and global quality-of-life scale of the EORTC Quality of Life Questionnaire) and ability to distinguish between patients with different health statuses. RESULTS: Questionnaires were returned by 89% (111 of 125) of the patients. Six to seven respondents did not return full questionnaires. Perfect health on the EQ-5D-5L was reported by 32 respondents and many of them (N = 17) did report health problems on other questionnaires. All questionnaires were strongly correlated (range 0.61-0.78) with other quality-of-life scales and yielded substantially different utility values for patients with different health statuses. Nevertheless, the disease-specific preference-based questionnaires showed greater discriminatory power. CONCLUSIONS: Although the Quality of Life Questionnaire Preference-Based Measure and the EORTC-8D appear to have better validity, this study does not provide any strong evidence against the use of the EQ-5D-5L for measuring quality-of-life utilities in acute leukemia. However, our findings need to be confirmed in larger longitudinal studies.

Individualized Angiotensin-Converting Enzyme (ACE)-Inhibitor Therapy in Stable Coronary Artery Disease Based on Clinical and Pharmacogenetic Determinants: The PERindopril GENEtic (PERGENE) Risk Model.

BACKGROUND: Patients with stable coronary artery disease (CAD) constitute a heterogeneous group in which the treatment benefits by angiotensin-converting enzyme (ACE)-inhibitor therapy vary between individuals. Our objective was to integrate clinical and pharmacogenetic determinants in an ultimate combined risk prediction model. METHODS AND RESULTS: Clinical, genetic, and outcomes data were used from 8726 stable CAD patients participating in the EUROPA/PERGENE trial of perindopril versus placebo. Multivariable analysis of phenotype data resulted in a clinical risk score (range, 0-21 points). Three single-nucleotide polymorphisms (rs275651 and rs5182 in the angiotensin-II type I-receptor gene and rs12050217 in the bradykinin type I-receptor gene) were used to construct a pharmacogenetic risk score (PGXscore; range, 0-6 points). Seven hundred eighty-five patients (9.0%) experienced the primary endpoint of cardiovascular mortality, nonfatal myocardial infarction or resuscitated cardiac arrest, during 4.2 years of follow-up. Absolute risk reductions ranged from 1.2% to 7.5% in the 73.5% of patients with PGXscore of 0 to 2. As a consequence, estimated annual numbers needed to treat ranged from as low as 29 (clinical risk score ≥10 and PGXscore of 0) to 521 (clinical risk score ≤6 and PGXscore of 2). Furthermore, our data suggest that long-term perindopril prescription in patients with a PGXscore of 0 to 2 is cost-effective. CONCLUSIONS: Both baseline clinical phenotype, as well as genotype determine the efficacy of widely prescribed ACE inhibition in stable CAD. Integration of clinical and pharmacogenetic determinants in a combined risk prediction model demonstrated a very wide range of gradients of absolute treatment benefit.

Using meta-regression analyses in addition to conventional systematic review methods to examine the variation in cost-effectiveness results - a case study.

BACKGROUND: Systematic reviews of cost-effectiveness analyses summarize results and describe study characteristics. Variability in the study results is often explained qualitatively or based on sensitivity analyses of individual studies. However, variability due to input parameters and study characteristics (e.g., funding or study quality) is often not statistically explained. As a case study, a systematic review on the cost-effectiveness of drug-eluting stents (DES) versus bare-metal stents (BMS) using meta-regression analyses is performed to explore the usefulness of such methods compared with conventional review methods. METHODS: We attempted to identify and review all modelling studies published until January 2012 that compared costs and consequences of DES versus BMS. We extracted general study information (e.g., funding), modelling methods, values of input parameters, and quality of the model using the Philips et al. checklist. Associations between study characteristics and the incremental costs and effectiveness of individual analyses were explored using regression analyses corrected for study ID. RESULTS: Sixteen eligible studies were identified, with a combined total of 508 analyses. The overall quality of the models was moderate (59% ± 15%). This study showed associations (e.g., type of lesion) that were expected (based on individual studies), however the meta-regression analyses revealed also unpredicted associations: e.g., model quality was negatively associated with repeat revascularizations avoided. CONCLUSIONS: Meta-regressions can be of added value, identifying significant associations that could not be identified using conventional review methods or by sensitivity analyses of individual studies. Furthermore, this study underlines the need to examine input parameters and perform a quality check of studies when interpreting the results.

A conceptual disease model for adult Pompe disease.

BACKGROUND: Studies in orphan diseases are, by nature, confronted with small patient populations, meaning that randomized controlled trials will have limited statistical power. In order to estimate the effectiveness of treatments in orphan diseases and extrapolate effects into the future, alternative models might be needed. The purpose of this study is to develop a conceptual disease model for Pompe disease in adults (an orphan disease). This conceptual model describes the associations between the most important levels of health concepts for Pompe disease in adults, from biological parameters via physiological parameters, symptoms and functional indicators to health perceptions and final health outcomes as measured in terms of health-related quality of life. METHODS: The structure of the Wilson-Cleary health outcomes model was used as a blueprint, and filled with clinically relevant aspects for Pompe disease based on literature and expert opinion. Multiple observations per patient from a Dutch cohort study in untreated patients were used to quantify the relationships between the different levels of health concepts in the model by means of regression analyses. RESULTS: Enzyme activity, muscle strength, respiratory function, fatigue, level of handicap, general health perceptions, mental and physical component scales and utility described the different levels of health concepts in the Wilson-Cleary model for Pompe disease. Regression analyses showed that functional status was affected by fatigue, muscle strength and respiratory function. Health perceptions were affected by handicap. In turn, self-reported quality of life was affected by health perceptions. CONCLUSIONS: We conceptualized a disease model that incorporated the mechanisms believed to be responsible for impaired quality of life in Pompe disease. The model provides a comprehensive overview of various aspects of Pompe disease in adults, which can be useful for both clinicians and policymakers to support their multi-faceted decision making.

Which factors may determine the necessary and feasible type of effectiveness evidence? A mixed methods approach to develop an instrument to help coverage decision-makers.

OBJECTIVES: Reimbursement decisions require evidence of effectiveness and, in general, a blinded randomised controlled trial (RCT) is the preferred study design to provide it. However, there are situations where a cohort study, or even patient series, can be deemed acceptable. The aim of this study was to develop an instrument that first examines which study characteristics of a blinded RCT are necessary, and then, if particular characteristics are considered necessary, examines whether these characteristics are feasible. DESIGN: We retrospectively studied 22 interventions from 20 reimbursement reports concerning medical specialist care made by the Dutch National Health Care Institute (ZIN) to identify any factors that influenced the necessity and feasibility of blinded RCTs, and their constituent study characteristics, that is, blinding, randomisation and a control group. A literature review was performed to identify additional factors. Additional expertise was included by interviewing eight experts in epidemiology, medicine and ethics. The resulting instrument was called the FIT instrument (Feasible Information Trajectory), and was prospectively validated using three consecutive reimbursement reports. RESULTS: (Blinded) RCT evidence was lacking in 5 of 11 positive reimbursement decisions and 3 of 11 negative decisions. In the reimbursement reports, we found no empirical evidence supporting situations where a blinded RCT is unnecessary. The literature also revealed few arguments against the necessity of a blinded RCT. In contrast, many factors influencing the feasibility of randomisation, a control group and blinding, were found in the reimbursement reports and the literature; for example, when a patient population is too small or when an intervention is common practice, randomisation will be hindered. CONCLUSIONS: Policy regarding the necessity and feasibility of different types of evidence of effectiveness would benefit from systematic guidance. The FIT instrument has the potential to support transparent, reproducible and well-founded decisions on appropriate evidence of effectiveness in medical specialist care.

Access to orphan drugs in western Europe: can more systematic policymaking really help to avoid different decisions about the same drug?

When the Scottish government recently launched a £21 million fund to provide patients with rare diseases access to treatment, Alex Neill, the Scottish Health Secretary, stated that 'it was only right that Scottish patients with rare conditions had access to innovative medicines which were clinically justified, and that they were not disadvantaged due to the very high cost of these treatments'. This statement raises questions about the criteria that play a role in reimbursement decisions on orphan drugs. This editorial examines the criteria that were used in the decisions about the reimbursement of an orphan drug for Pompe disease and explores methods to improve the transparency and consistency of reimbursement decisions for orphan drugs in general.

Cost-effectiveness of enzyme replacement therapy with alglucosidase alfa in classic-infantile patients with Pompe disease.

BACKGROUND: Infantile Pompe disease is a rare metabolic disease. Patients generally do not survive the first year of life. Enzyme replacement therapy (ERT) has proven to have substantial effects on survival in infantile Pompe disease. However, the costs of therapy are very high. In this paper, we assess the cost-effectiveness of enzyme replacement therapy in infantile Pompe disease. METHODS: A patient simulation model was used to compare costs and effects of ERT with costs of effects of supportive therapy (ST). The model was filled with data on survival, quality of life and costs. For both arms of the model, data on survival were obtained from international literature. In addition, survival as observed among 20 classic-infantile Dutch patients, who all received ERT, was used. Quality of life was measured using the EQ-5D and assumed to be the same in both treatment groups. Costs included the costs of ERT (which depend on a child's weight), infusions, costs of other health care utilization, and informal care. A lifetime time horizon was used, with 6-month time cycles. RESULTS: Life expectancy was significantly longer in the ERT group than in the ST group. On average, ST receiving patients were modelled not to survive the first half year of life; whereas the life expectancy in the ERT patients was modelled to be almost 14 years. Lifetime incremental QALYs were 6.8. Incremental costs were estimated to be € 7.0 million, which primarily consisted of treatment costs (95%). The incremental costs per QALY were estimated to be € 1.0 million (range sensitivity analyses: € 0.3 million - € 1.3 million). The incremental cost per life year gained was estimated to be € 0.5 million. CONCLUSIONS: The incremental costs per QALY ratio is far above the conventional threshold values. Results from univariate and probabilistic sensitivity analyses showed the robustness of the results.

DRG systems in Europe: variations in cost accounting systems among 12 countries.

BACKGROUND: Diagnosis-related group (DRG)-based hospital payment systems have gradually become the principal means of reimbursing hospitals in many European countries. Owing to the absence or inaccuracy of costs related to DRGs, these countries have started to routinely collect cost accounting data. The aim of the present article was to compare the cost accounting systems of 12 European countries. METHODS: A standardized questionnaire was developed to guide comprehensive cost accounting system descriptions for each of the 12 participating countries. RESULTS: The cost accounting systems of European countries vary widely by the share of hospital costs reimbursed through DRG payment, the presence of mandatory cost accounting and/or costing guidelines, the share of cost collecting hospitals, costing methods and data checks on reported cost data. Each of these aspects entails a trade-off between accuracy of the cost data and feasibility constraints. CONCLUSION: Although a 'best' cost accounting system does not exist, our cross-country comparison gives insight into international differences and may help regulatory authorities and hospital managers to identify and improve areas of weakness in their cost accounting systems. Moreover, it may help health policymakers to underpin the development of a cost accounting system.

Beliefs about medicines in Dutch acenocoumarol and phenprocoumon users.

AIMS: Adherence to the generally complex regimen of coumarin derivatives is vital in order to keep patients in the adequate International Normalized Ratio range. Patients' beliefs about medicines are associated with the level of therapy adherence. Our first aim was to assess beliefs about coumarins. Secondly, we compared the beliefs about coumarins with the beliefs about other cardiovascular drugs. METHODS: The Beliefs about Medicines Questionnaire was used to assess medication beliefs. The questionnaire was completed by new users of coumarins indicated for venous thromboembolism or atrial fibrillation. A necessity score and a concerns score were calculated for all patients. The analyses were repeated for users of antihypertensive drugs or statins (not using coumarins). RESULTS: Three hundred and twenty patients were included in the analysis of the beliefs about coumarins. The mean necessity score was 15.3, the concerns score 12.3 and the necessity-concerns differential 3.0. Patients with venous thromboembolism (n = 71) had higher necessity scores than patients with atrial fibrillation (n = 249; 16.8 vs. 14.9, P < 0.001). The mean necessity score in 493 users of other cardiovascular drugs was 16.1, the concerns score 13.5 and the necessity-concerns differential 2.6. The necessity score was higher in chronic cardiovascular drug users (n = 192) than in new users (n = 301; 17.9 vs. 14.9, P < 0.001). CONCLUSIONS: Coumarin users score higher on the necessity scale than on the concerns scale, which is also the case in users of other cardiovascular drugs. Patients with atrial fibrillation have a less positive attitude towards these drugs than patients with venous thromboembolism, and could therefore benefit more from specific attention.