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.

Extrapolating empirical long-term survival data: the impact of updated follow-up data and parametric extrapolation methods on survival estimates in multiple myeloma.

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

Cost-Effectiveness of a Cardiac Rehabilitation Program Specifically Designed for Patients With Obesity Within the OPTICARE XL Randomized Controlled Trial.

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

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.

An implantable device to treat multiple sclerosis: A discrete choice experiment on patient preferences in three European countries.

BACKGROUND: Persons with multiple sclerosis (MS) take their treatment via pills, injections or infusions. A novel mode of disease-modifying treatment administration, an implantable device, is under development. This study determined MS patient preferences for three modes of first-line treatment administration (implant, pills, injectables), and trade-offs regarding treatment characteristics. METHODS: A survey including a discrete choice experiment was conducted among MS patients in the Netherlands, France, and the United Kingdom. Respondents had to repeatedly choose between various treatment scenarios with four treatment characteristics: risk of relapse, reduction of disease progression, risk of side effects and mode of administration. Data was analysed using a panel latent class logit model. RESULTS: Based on the preferences of 753 MS patients (response rate 7%: 753/11202), two latent classes were identified (class probability of 74% vs 26%). Persons with relapsing-remitting MS and who administered medication via injections generally preferred any treatment over no treatment. Patients who could walk without an aid were more likely to prefer no treatment. Reducing disease progression was the most important treatment characteristic class 1. Mode of administration was the most important characteristic in class 2. Patients were willing to accept an increase in risk of relapse and disease progression to get their treatment via an implant rather than injections. Predicted uptake was the highest for the implant, followed by pills, injections, and no treatment. CONCLUSION: We found that a drug-delivery implant could be a potential addition to the MS treatment landscape: MS patients are willing to trade-off risk of relapse and disease progression for an implant, and predicted uptake for an implant is relatively high.

Innovative Medical Technology and the Treatment Decision-Making Process in Multiple Sclerosis: A Focus Group Study to Examine Patient Perspectives.

BACKGROUND: Disease-modifying therapies are given to people with multiple sclerosis (MS) to reduce disease progression and relapse frequency. Current modes of administration include oral, injectable and infusion therapy and the treatment decision-making process is complex. A novel mode of treatment administration, an implantable device, is currently under development, yet patient attitudes about the device are unknown. The aim of this study was 1) to understand the treatment decision-making process from the patient perspective and 2) to explore the possible acceptance of an implant to treat MS. METHODS: Focus groups with people with MS were conducted in the Netherlands. Three topics were addressed: the treatment decision-making process, the current treatment landscape, and attitudes about the implantable device. All focus groups were recorded and transcribed and data were analyzed by raw data coding and creating themes. An online survey was conducted in the Netherlands to quantify interest in an implant. RESULTS: Two focus group sessions were held (n=16 participants) and n=93 persons filled out the survey. The main theme that emerged was the constant uncertainty persons with MS face throughout their disease course and during treatment decisions (when to start, stop, continue or switch treatment). Patients were generally positive towards the implant but felt that efficacy and safety should be guaranteed. CONCLUSION: People with MS want some form of control over their disease and treatment course. New medical technologies, such as an implant, may enhance the treatment landscape and with caution we postulate that it may be accepted by patients as a new mode of administration, though further research is needed. For medical technologies to be successful, patients should be engaged early on in the design process.

A Systematic Review of Cost-Effectiveness Studies of Interventions With a Personalized Nutrition Component in Adults.

OBJECTIVES: Important links between dietary patterns and diseases have been widely applied to establish nutrition interventions. However, knowledge about between-person heterogeneity regarding the benefits of nutrition intervention can be used to personalize the intervention and thereby improve health outcomes and efficiency. We performed a systematic review of cost-effectiveness analyses (CEAs) of interventions with a personalized nutrition (PN) component to assess their methodology and findings. METHODS: A systematic search (March 2019) was performed in 5 databases: EMBASE, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar. CEAs involving interventions in adults with a PN component were included; CEAs focusing on clinical nutrition or undernutrition were excluded. The CHEERS checklist was used to assess the quality of CEAs. RESULTS: We identified 49 eligible studies among 1792 unique records. Substantial variation in methodology was found. Most studies (91%) focused only on psychological concepts of PN such as behavior and preferences. Thirty-four CEAs were trial-based, 13 were modeling studies, and 4 studies were both trial- and model-based. Thirty-two studies used quality-adjusted life year as an outcome measure. Different time horizons, comparators, and modeling assumptions were applied, leading to differences in costs/quality-adjusted life years. Twenty-eight CEAs (49%) concluded that the intervention was cost-effective, and 75% of the incremental cost-utility ratios were cost-effective given a willingness-to-pay threshold of $50 000 per quality-adjusted life year. CONCLUSIONS: Interventions with PN components are often evaluated using various types of models. However, most PN interventions have been considered cost-effective. More studies should examine the cost-effectiveness of PN interventions that combine psychological and biological concepts of personalization.

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.

Future of Data Analytics in the Era of the General Data Protection Regulation in Europe.

The development of evidence to demonstrate 'value for money' is regarded as an important step in facilitating the search for the optimal allocation of limited resources and has become an essential component in healthcare decision making. Real-world evidence collected from de-identified individuals throughout the continuum of healthcare represents the most valuable source in technology evaluation. However, in the European Union, the value assessment based on real-world data has become challenging as individuals have recently been given the right to have their personal data erased in the case of consent withdrawal or when the data are regarded as being no longer necessary. This act may limit the usefulness of data in the future as it may introduce information bias. Among healthcare stakeholders, this has become an important topic of discussion because it relates to the importance of data on one side and to the need for personal data protection on the other side, especially when it comes to "personal data related to the physical or mental health of a natural person, including the provision of health care services, which reveals information about his or her health status". At the forefront of these discussions are data protection issues as well as the population's trust in digital services. It seems that the new era has begun, where citizens and patients will have the ability to manage their personal or self-generated data. The European Commission has laid the groundwork for this paradigm shift that will steadily emerge in the coming years. To prepare for this change, we believe attention should be given to data security and other rules of data privacy. It has become increasingly important to ensure that individuals are properly introduced into complex environments with multiple sources of Big Data for clinical and behavioral purposes to provide an optimal balance between societal and individual benefits. In this article, a number of issues are considered and discussed, based upon the authors' experience, with the aim of helping the reader better understand the implications of the use of Big Data and the importance of data protection in the coming years.

Patient needs and preferences in relapsing-remitting multiple sclerosis: A systematic review.

BACKGROUND: Considering the multiple treatments approved for multiple sclerosis (MS) by the Food and Drug Administration (FDA) and European Medicines Agency (EMA), determining a treatment strategy for patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS) can be challenging. To date, an overview of the needs and preferences of patients at each treatment decision-making moment is lacking. Therefore, the aim of this systematic review is to examine the existing literature about the needs and preferences of patients with CIS and RRMS when making treatment decisions. METHODS: A systematic search was done using Embase, Medline, PsychINFO, Web of Science and Google Scholar. Eligibility criteria included whether the article described a study of adults with CIS/RRMS and reported patient needs or preferences regarding first-line disease modifying treatment (DMT) decisions. Publications were categorized by treatment decision: initiation of first DMT (D1), DMT adherence/discontinuation (D2a/D2b), and switch to a second DMT (D3). A separate category was created for stated preference studies such as discrete choice experiment methods to examine the relative importance of different treatment attributes. Publications were compared to identify key factors. RESULTS: The search yielded 2789 articles after removal of duplicates and 434 full-text publications were reviewed for eligibility. Twenty-four articles fulfilled all criteria: n = 5 (D1), n = 12 (D2a), n = 13 (D2b), and n = 3 (D3); six articles studied more than one treatment decision. The need for social support is important during D1. The most commonly reported reasons for adherence/discontinuation/switch included forgetfulness, side-effects, and injection-related reasons. Eight articles described preference studies; the most important DMT attributes were efficacy, mode and frequency of administration, and side-effect profile. CONCLUSIONS: Understanding the needs and preferences of CIS/RRMS patients regarding DMT attributes and non-treatment related attributes are important to improve treatment decision-making and reduce non-adherence. Studies are needed to understand patient preferences upon treatment initiation. Furthermore, preference studies should include attributes based on the patient perspective.

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.

Health-related quality of life and its determinants in patients with metastatic renal cell carcinoma.

PURPOSE: Based on improvements of progression-free survival (PFS), new agents for metastatic renal cell carcinoma (mRCC) have been approved. It is assumed that one of the benefits is a delay in health-related quality of life (HRQoL) deterioration as a result of a delay in progression of disease. However, little data are available supporting this relationship. This study aims to provide insight into the most important determinants of HRQoL (including progression of disease) of patients with mRCC. METHODS: A patient registry (PERCEPTION) was created to evaluate treatment of patients with (m)RCC in the Netherlands. HRQoL was measured, using the EORTC QLQ-C30 and EQ-5D-5L, every 3 months in the first year of participation in the study, and every 6 months in the second year. Participation started as soon as possible following a diagnosis of (m)RCC. Random effects models were used to study associations between HRQoL and patient and disease characteristics, symptoms and treatment. RESULTS: Eighty-seven patients with mRCC completed 304 questionnaires. The average EORTC QLQ-C30 global health status was 69 (SD, 19) before progression and 61 (SD, 22) after progression of disease. Similarly, the average EQ-5D utility was 0.75 (SD, 0.19) before progression and 0.66 (SD, 0.30) after progression of disease. The presence of fatigue, pain, dyspnoea, and the application of radiotherapy were associated with significantly lower EQ-5D utilities. CONCLUSIONS: Key drivers for reduced HRQoL in mRCC are disease symptoms. Since symptoms increase with progression of disease, targeted therapies that increase PFS are expected to postpone reductions in HRQoL in mRCC.

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.

Potential health gains for patients with metastatic renal cell carcinoma in daily clinical practice: A real-world cost-effectiveness analysis of sequential first- and second-line treatments.

INTRODUCTION: Randomised controlled trials have shown that targeted therapies like sunitinib are effective in metastatic renal cell carcinoma (mRCC). Little is known about the current use of these therapies, and their associated costs and effects in daily clinical practice. We estimated the real-world cost-effectiveness of different treatment strategies comprising one or more sequentially administered drugs. METHODS: Analyses were performed using patient-level data from a Dutch population-based registry including patients diagnosed with primary mRCC from January 2008 to December 2010 (i.e., treated between 2008 and 2013). The full disease course of these patients was estimated using a patient-level simulation model based on regression analyses of the registry data. A healthcare sector perspective was adopted; total costs included healthcare costs related to mRCC. Cost-effectiveness was expressed in cost per life-year and cost per quality-adjusted life-year (QALY) gained. Probabilistic sensitivity analysis was conducted to estimate the overall uncertainty surrounding cost-effectiveness. RESULTS: In current daily practice, 54% (336/621) of all patients was treated with targeted therapies. Most patients (84%; 282/336) received sunitinib as first-line therapy. Of the patients receiving first-line therapy, 30% (101/336) also received second-line therapy; the majority was treated with everolimus (40%, 40/101) or sorafenib (28%, 28/101). Current treatment practice (including patients not receiving targeted therapy) led to 0.807 QALYs; mean costs were €58,912. This resulted in an additional €105,011 per QALY gained compared to not using targeted therapy at all. Forty-six percent of all patients received no targeted therapy; of these patients, 24% (69/285) was eligible for sunitinib. If these patients were treated with first-line sunitinib, mean QALYs would improve by 0.062-0.076 (where the range reflects the choice of second-line therapy). This improvement is completely driven by the health gain seen amongst patients eligible to receive sunitinib but did not receive it, who gain 0.558-0.684 QALYs from sunitinib. Since additional costs would be €7,072-9,913, incremental costs per QALY gained are €93,107-111,972 compared to current practice. DISCUSSION: Health can be gained if more treatment-eligible patients receive targeted therapies. Moreover, it will be just as cost-effective to treat these patients with sunitinib as current treatment practice.

Cost-effectiveness analysis of new generation coronary CT scanners for difficult-to-image patients.

AIMS: New generation dual-source coronary CT (NGCCT) scanners with more than 64 slices were evaluated for patients with (known) or suspected of coronary artery disease (CAD) who are difficult to image: obese, coronary calcium score > 400, arrhythmias, previous revascularization, heart rate > 65 beats per minute, and intolerance of betablocker. A cost-effectiveness analysis of NGCCT compared with invasive coronary angiography (ICA) was performed for these difficult-to-image patients for England and Wales. METHODS AND RESULTS: Five models (diagnostic decision model, four Markov models for CAD progression, stroke, radiation and general population) were integrated to estimate the cost-effectiveness of NGCCT for both suspected and known CAD populations. The lifetime costs and effects from the National Health Service perspective were estimated for three strategies: (1) patients diagnosed using ICA, (2) using NGCCT, and (3) patients diagnosed using a combination of NGCCT and, if positive, followed by ICA. In the suspected population, the strategy where patients only undergo a NGCCT is a cost-effective option at accepted cost-effectiveness thresholds. The strategy of using NGCCT in combination with ICA is the most favourable strategy for patients with known CAD. The most influential factors behind these results are the percentage of patients being misclassified (a function of both diagnostic accuracy and the prior likelihood), the complication rates of the procedures, and the cost price of a NGCCT scan. CONCLUSION: The use of NGCCT might be considered cost-effective in both populations since it is cost-saving compared to ICA and generates similar effects.