Cost and Utility Estimates per Modified Rankin Scale Score up to 2 Years Post Stroke: Data to Inform Economic Evaluations From a Societal Perspective.

OBJECTIVES: Model-based health economic evaluations of ischemic stroke are in need of cost- and utility estimates related to relevant outcome measures. This study aims to describe societal cost- and utility estimates per modified Rankin Scale (mRS)-score at different time points within 2 years post stroke. METHODS: Included patients had a stroke between 3 months and 2.5 years ago. mRS and EQ-5D-5L were scored during a telephone interview. Based on the interview date, records were categorized into a time point: 3 months (3M; 3-6 months), 1 year (Y1; 6-18 months), or 2 years (Y2; 18-30 months). Patients completed a questionnaire on healthcare utilization and productivity losses in the previous 3 months. Initial stroke hospitalization costs were assessed. Mean costs and utilities per mRS and time point were derived with multiple imputation nested in bootstrapping. Cost at 3 months post stroke were estimated separately for endovascular treatment (EVT)-/non-EVT-patients. RESULTS: 1106 patients were included from 18 Dutch centers. At each time point, higher mRS-scores were associated with increasing average costs and decreasing average utility. Mean societal costs at 3M ranged from €11 943 (mRS 1, no EVT) to €55 957 (mRS 5, no EVT). For Y1, mean costs in the previous 3 months ranged from €885 (mRS 0) to €23 215 (mRS 5), and from €1655 (mRS 0) to €22 904 (mRS 5) for Y2. Mean utilities ranged from 0.07 to 0.96, depending on mRS and time point. CONCLUSIONS: The mRS-score is a major determinant of costs and utilities at different post-stroke time points. Our estimates may be used to inform future model-based health economic evaluations.

Study protocol for a multicenter randomised controlled trial on the (cost)effectiveness of biopsy combined with same-session MR-guided LITT versus biopsy alone in patients with primary irresectable glioblastoma (EMITT trial).

BACKGROUND: Glioblastoma (GBM) is the most common primary, malignant brain tumour with a 5-year survival of 5%. If possible, a glioblastoma is resected and further treated with chemoradiation therapy (CRT), but resection is not feasible in about 30% of cases. Current standard of care in these cases is a biopsy followed by CRT. Magnetic resonance (MR) imaging-guided laser interstitial thermal therapy (LITT) has been suggested as a minimally invasive alternative when surgery is not feasible. However, high-quality evidence directly comparing LITT with standard of care is lacking, precluding any conclusions on (cost-)effectiveness. We therefore propose a multicenter randomized controlled study to assess the (cost-)effectiveness of MR-guided LITT as compared to current standard of care (EMITT trial). METHODS AND ANALYSIS: The EMITT trial will be a multicenter pragmatic randomized controlled trial in the Netherlands. Seven Dutch hospitals will participate in this study. In total 238 patients will be randomized with 1:1 allocation to receive either biopsy combined with same-session MR-guided LITT therapy followed by CRT or the current standard of care being biopsy followed by CRT. The primary outcomes will be health-related quality of life (HR-QoL) (non-inferiority) using EORTC QLQ-C30 + BN20 scores at 5 months after randomization and overall survival (superiority). Secondary outcomes comprise cost-effectiveness (healthcare and societal perspective) and HR-QoL of life over an 18-month time horizon, progression free survival, tumour response, disease specific survival, longitudinal effects, effects on adjuvant treatment, ablation percentage and complication rates. DISCUSSION: The EMITT trial will be the first RCT on the effectiveness of LITT in patients with glioblastoma as compared with current standard of care. Together with the Dutch Brain Tumour Patient association, we hypothesize that LITT may improve overall survival without substantially affecting patients' quality of life. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT05318612).

Dealing With Uncertainty in Early Health Technology Assessment: An Exploration of Methods for Decision Making Under Deep Uncertainty.

OBJECTIVES: In early stages, the consequences of innovations are often unknown or deeply uncertain, which complicates early health economic modeling (EHEM). The field of decision making under deep uncertainty uses exploratory modeling (EM) in situations when the system model, input probabilities/distributions, and consequences are unknown or debated. Our aim was to evaluate the use of EM for early evaluation of health technologies. METHODS: We applied EM and EHEM to an early evaluation of minimally invasive endoscopy-guided surgery (MIS) for acute intracerebral hemorrhage and compared these models to derive differences, merits, and drawbacks of EM. RESULTS: EHEM and EM differ fundamentally in how uncertainty is handled. Where in EHEM the focus is on the value of technology, while accounting for the uncertainty, EM focuses on the uncertainty. EM aims to find robust strategies, which give relatively good outcomes over a wide range of plausible futures. This was reflected in our case study. EHEM provided cost-effectiveness thresholds for MIS effectiveness, assuming fixed MIS costs. EM showed that a policy with a population in which most patients had severe intracerebral hemorrhage was most robust, regardless of MIS effectiveness, complications, and costs. CONCLUSIONS: EHEM and EM were found to complement each other. EM seems most suited in the very early phases of innovation to explore existing uncertainty and many potential strategies. EHEM seems most useful to optimize promising strategies, yet EM methods are complex and might only add value when stakeholders are willing to consider multiple solutions to a problem and adopt flexible research and adoption strategies.

Care Pathway Analysis to Inform the Earliest Stages of Technology Development: Scoping Oncological Indications in Need of Innovation.

OBJECTIVES: Identifying unmet needs for innovative solutions across disease contexts is challenging but important for directing funding and research efforts and informing early-stage decisions during the innovation process. Our aim was to study the merits of care pathway analysis to scope disease contexts and guide the development of innovative devices. We used oncologic surgery as a case study, for which many intraoperative imaging techniques are under development. METHODS: Care pathway analysis is a mapping process, which produces graphical maps of clinical pathways using important outcomes and subsequent consequences. We performed care pathway analyses for glioblastoma, breast, bladder, prostate, renal, pancreatic, and oral cavity cancer. Differences between a "perfect" care pathway and the current care pathway in terms of percentage of inadequate margins, associated recurrences, quality of life, and 5-year overall survival were calculated to determine unmet needs. Data from The Netherlands Cancer Registry and literature were used. RESULTS: Care pathway analysis showed that highest percentages of inadequate margins were found in oral cavity cancer (72.5%), glioblastoma (48.7%), and pancreatic cancer (43.9%). Inadequate margins showed the strongest increase in recurrences in cancer of oral cavity, and bladder (absolute increases of 43.5% and 41.2%, respectively). Impact on survival was largest for bladder and oral cavity cancer with positive margins. CONCLUSIONS: Care pathway analysis provides overviews of current clinical paths in multiple indications. Disease contexts can be compared via effectiveness gaps that show the potential need for innovative solutions. This information can be used as basis for stakeholder involvement processes to prioritize care pathways in need of innovation.

The value of reducing arthroscopic partial meniscectomy in the treatment of degenerative meniscus tears: a budget impact analysis.

AIMS: Numerous studies have shown that arthroscopic partial meniscectomy (APM) is not (cost-) effective in patients with symptoms attributed to a degenerative meniscus tear. We aimed to assess the budget impact of reducing APM in routine clinical practice in this population. MATERIALS AND METHODS: A patient-level state transition model was developed to simulate patients recently diagnosed with a degenerative meniscus tear. Three strategies were compared: "current guideline" (i.e., postpone surgery to at least 3 months after diagnosis), "APM at any time" (i.e., APM available directly after diagnosis), and "nonsurgical" (i.e., APM no longer performed). Total societal costs over 5 years were calculated to determine the budget impact. Probabilistic and deterministic sensitivity analyses were conducted to address uncertainty. RESULTS: The average cost per patient over 5 years were EUR 5,077, EUR 4,577, and EUR 4,218, for the "APM at any time," "current guideline," and "nonsurgical" strategy, respectively. Removing APM from the treatment mix (i.e., 30,000 patients per year) in the Netherlands, resulted in a reduction in health care expenditures of EUR 54 million (95 percent confidence interval [CI] EUR 38 million-EUR 70 million) compared to the "current guideline strategy" and EUR 129 million (95 percent CI EUR 102 million-EUR 156 million) compared to the "APM at any time" strategy. Sensitivity analyses showed that uncertainty did not alter our conclusions. CONCLUSIONS: Substantial costs can be saved when APM is no longer performed to treat symptoms attributed to degenerative meniscus tears in the Netherlands. It is therefore recommended to further reduce the use of APM to treat degenerative meniscus tears.

A first exploration of the economic consequences of an autonomous surgical robot for lateral skull base surgery: an early health technology assessment.

OBJECTIVES: Lateral skull base procedures, such as translabyrinthine approach (TLA), are challenging. An autonomous surgical robot might be a solution to these challenges. Our aim is to explore in an early phase the economic consequences of an autonomous surgical robot compared with conventional TLA. METHODS: An early decision analytic model was constructed in order to perform a step-wise threshold analyses and a sensitivity analysis to analyze the impact of the several factors on the incremental costs. RESULTS: Using surgical robot results in incremental costs - EUR 5,562 per procedure - compared to conventional TLA. These costs are most reduced by higher number of procedures, followed by lower price of the robot, saved operation time, and reduced risk of complication, respectively. CONCLUSIONS: The incremental costs of using an autonomous surgical robot can be decreased by choosing applications with a high turnover rate, a long operation time, and a high complication rate.

Methods for Early Assessment of the Societal Value of Health Technologies: A Scoping Review and Proposal for Classification.

OBJECTIVES: Early assessments of health technologies help to better align and integrate their development and assessment. Such assessments can take many forms and serve different purposes, hampering users in their selection of the most appropriate method for a specific goal. The aim of this scoping review was to structure the large set of methods according to their specific goal. METHODS: A scoping review was conducted using PubMed and reference lists of retrieved articles, to identify review studies with a methodological focus. From the included reviews, all individual methods were listed. Based on additional literature and examples, we extracted the specific goal of each method. All goals were clustered to derive a set of subclasses and methods were grouped into these subclasses. RESULTS: Of the 404 screened, 5 reviews were included, and 1 was added when searching reference lists. The reviews described 56 methods, of which 43 (77%) were included and classified as methods to (1) explore the nature and magnitude of the problem, (2) estimate the nature and magnitude of the expected (societal) value, (3) identify conditions for the potential value to materialize, and (4) help develop and design the type of research that is needed. CONCLUSIONS: The wide range of methods for exploring the societal value of health technologies at an early stage of development can be subdivided into a limited number of classes, distinguishing methods according to their specific objective. This facilitates selection of appropriate methods, depending on the specific needs and aims.

The Use of Decision Analytic Modeling in the Evaluation of Surgical Innovations: A Scoping Review.

OBJECTIVES: The main objective of this review was to map how decision analytic models are used in surgical innovation (in which research phase, with what aim) and to understand how challenges related to the assessment of surgical interventions are incorporated. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library for studies published in 2018. We included original articles using a decision analytic model to compare surgical strategies. We included modeling studies of surgical innovations. General, innovation, and modeling characteristics were extracted, as were outcomes, recommendations, and handling of challenges related to the assessment of surgical interventions (learning curve, incremental innovation, dynamic pricing, quality variation, organizational impact). RESULTS: We included 46 studies. The number of studies increased with each research phase, from 4% (n = 2) in the preclinical phase to 40% (n = 20) in phase 3 studies. Eighty-one studies were excluded because they investigated established surgical procedures, indicating that modeling is predominantly applied after the innovation process. Regardless of the research stage, the aim to determine cost-effectiveness was most frequently identified (n = 40, 87%), whereas exploratory aims (eg, exploring when a strategy becomes cost-effective) were less common (n = 9, 20%). Most challenges related to the assessment of surgical interventions were rarely incorporated in models (eg, learning curve [n = 1, 2%], organizational impact [n = 2, 4%], and incremental innovation [n = 1, 2%]), except for dynamic pricing (n = 10, 22%) and quality variation (n = 6, 13%). CONCLUSIONS: In surgical innovation, modeling is predominantly used in later research stages to assess cost-effectiveness. The exploratory use of modeling seems still largely overlooked in surgery; therefore, the opportunity to inform research and development may not be optimally used.

Uncertainty and Coverage With Evidence Development: Does Practice Meet Theory?

OBJECTIVES: In theory, a successful coverage with evidence development (CED) scheme is one that addresses the most important uncertainties in a given assessment. We investigated the following: (1) which uncertainties were present during the initial assessment of 3 Dutch CED cases, (2) how these uncertainties were integrated in the initial assessments, (3) whether CED research plans included the identified uncertainties, and (4) issues with managing uncertainty in CED research and ways forward from these issues. METHODS: Three CED initial assessment dossiers were analyzed and 16 stakeholders were interviewed. Uncertainties were identified in interviews and dossiers and were categorized in different causes: unavailability, indirectness, and imprecision of evidence. Identified uncertainties could be mentioned, described, and explored. Issues and ways forward to address uncertainty in CED schemes were discussed during the interviews. RESULTS: Forty-two uncertainties were identified. Thirteen (31%) were caused by unavailability, 17 (40%) by indirectness, and 12 (29%) by imprecision. Thirty-four uncertainties (81%) were only mentioned, 19 (45%) were described, and the impact of 3 (7%) uncertainties on the results was explored in the assessment dossiers. Seventeen uncertainties (40%) were included in the CED research plans. According to stakeholders, research did not address the identified uncertainty, but CED research should be designed to focus on these. CONCLUSIONS: In practice, uncertainties were neither systematically nor completely identified in the analyzed CED schemes. A framework would help to systematically identify uncertainty, and this process should involve all stakeholders. Value of information analysis, and the uncertainties that are not included in this analysis should inform CED research design.

Clinical biomarker innovation: when is it worthwhile?

Background Choosing which biomarker tests to select for further research and development is not only a matter of diagnostic accuracy, but also of the clinical and monetary benefits downstream. Early health economic modeling provides tools to assess the potential effects of biomarker innovation and support decision-making. Methods We applied early health economic modeling to the case of diagnosing primary aldosteronism in patients with resistant hypertension. We simulated a cohort of patients using a Markov cohort state-transition model. Using the headroom method, we compared the currently used aldosterone-to-renin ratio to a hypothetical new test with perfect diagnostic properties to determine the headroom based on quality-adjusted life-years (QALYs) and costs, followed by threshold analyses to determine the minimal diagnostic accuracy for a cost-effective product. Results Our model indicated that a perfect diagnostic test would yield 0.027 QALYs and increase costs by €43 per patient. At a cost-effectiveness threshold of €20,000 per QALY, the maximum price for this perfect test to be cost-effective is €498 (95% confidence interval [CI]: €275-€808). The value of the perfect test was most strongly influenced by the sensitivity of the current biomarker test. Threshold analysis showed the novel test needs a sensitivity of at least 0.9 and a specificity of at least 0.7 to be cost-effective. Conclusions Our model-based approach evaluated the added value of a clinical biomarker innovation, prior to extensive investment in development, clinical studies and implementation. We conclude that early health economic modeling can be a valuable tool when prioritizing biomarker innovations in the laboratory.

In search of the most cost-effective monitoring strategy for vestibular schwannoma: A decision analytical modelling study.

OBJECTIVES: To assess the cost-effectiveness of frequently used monitoring strategies for vestibular schwannoma (VS). DESIGN: A state transition model was developed to compare six monitoring strategies for patients with VS: lifelong annual monitoring; annual monitoring for the first 10 years after diagnosis; scanning at 1-5, 7, 9, 12, 15 years after diagnosis and subsequently every 5 years; a personalised monitoring strategy for small and large tumours; scanning at 1, 2 and 5 years after diagnosis and no monitoring. Input data were derived from literature and expert opinion. Quality-adjusted life years (QALYs) and healthcare costs of each strategy were modelled over lifetime. Net monetary benefits (NMBs) were calculated to determine which strategy provided most value for money. Sensitivity analyses were performed to address uncertainty. RESULTS: Omitting monitoring is least effective with 18.23 (95% CI 16.84-19.37) QALYs per patient, and lifelong annual monitoring is most effective with 18.66 (95% CI 17.42-19.65) QALYs. Corresponding costs were €6526 (95% CI 5923-7058) and €9429 (95% CI 9197-9643) per patient, respectively. Lifelong annual monitoring provided the best value with a NMB of €363 765 (339 040-383 697), but the overall probability of being most cost-effective compared to the other strategies was still only 23%. Sensitivity analysis shows that there is large uncertainty in the effectiveness of all strategies, with largely overlapping 95% confidence intervals for all strategies. CONCLUSIONS: Due to the largely overlapping 95% confidence intervals of all monitoring strategies for VS, it is unclear which monitoring strategy provides most value for money at this moment.

THE GAP BETWEEN ECONOMIC EVALUATIONS AND CLINICAL PRACTICE: A SYSTEMATIC REVIEW OF ECONOMIC EVALUATIONS ON DABIGATRAN FOR ATRIAL FIBRILLATION.

OBJECTIVES: As model-based economic evaluations (MBEEs) are widely used to make decisions in the context of policy, it is imperative that they represent clinical practice. Here, we assess the relevance of MBEEs on dabigatran for the prevention of stroke in patients with atrial fibrillation (AF). METHODS: We performed a systematic review on the basis of a developed questionnaire, tailored to oral anticoagulation in patients with AF. Included studies had a full body text in English, compared dabigatran with a vitamin K antagonist, were not dedicated to one or more subgroup(s), and yielded an incremental cost-effectiveness ratio. The relevance of all MBEEs was assessed on the basis of ten context-independent factors, which encompassed clinical outcomes and treatment duration. The MBEEs performed for the United States were assessed on the basis of seventeen context-dependent factors, which were related to the country's target population and clinical environment. RESULTS: The search yielded twenty-nine MBEEs, of which six were performed for the United States. On average, 54 percent of the context-independent factors were included per study, and 37 percent of the seventeen context-dependent factors in the U.S. STUDIES: The share of relevant factors per study did not increase over time. CONCLUSIONS: MBEEs on dabigatran leave out several relevant factors, limiting their usefulness to decision makers. We strongly urge health economic researchers to improve the relevance of their MBEEs by including context-independent relevance factors, and modeling context-dependent factors befitting the decision context concerned.

Combining value of information analysis and ethical argumentation in decisions on participation of vulnerable patients in clinical research.

BACKGROUND: The participation of vulnerable patients in clinical research poses apparent ethical dilemmas. Depending on the nature of the vulnerability, their participation may challenge the ethical principles of autonomy, non-maleficence, or justice. On the other hand, non-participation may preclude the building of a knowledge base that is a prerequisite for defining the optimal clinical management of vulnerable patients. Such clinical uncertainty may also incur substantial economic costs. MAIN TEXT: We present the participation of pre-menopausal women with atrial fibrillation in trials of novel oral anticoagulant drugs as a case study. Due to their non-participation in pivotal trials, it is uncertain whether for them, the risks that are associated with these drugs are outweighed by the advantages compared with conventional treatment. We addressed the question whether research of this new class of drugs in this subgroup would be appropriate from both, an ethical as well an economic perspective. We used the method of specifying norms as a wider framework to resolve the apparent ethical dilemma, while incorporating the question whether research of oral anticoagulants in premenopausal women with atrial fibrillation can be justified on economic grounds. For the latter, the results of a value-of-information analysis were used. CONCLUSIONS: Further clinical research on NOACs in premenopausal women with atrial fibrillation can be justified on both, ethical and economic grounds. Addressing apparent ethical dilemmas by invoking a method such as specifying norms can improve the quality of public practical reasoning. As such, the method should also prove valuable to committees that have formally been granted the authority to review trial protocols and proposals for scientific research.

Cost-effectiveness of a new urinary biomarker-based risk score compared to standard of care in prostate cancer diagnostics - a decision analytical model.

OBJECTIVE: To assess the cost-effectiveness of a new urinary biomarker-based risk score (SelectMDx; MDxHealth, Inc., Irvine, CA, USA) to identify patients for transrectal ultrasonography (TRUS)-guided biopsy and to compare this with the current standard of care (SOC), using only prostate-specific antigen (PSA) to select for TRUS-guided biopsy. MATERIALS AND METHODS: A decision tree and Markov model were developed to evaluate the cost-effectiveness of SelectMDx as a reflex test vs SOC in men with a PSA level of >3 ng/mL. Transition probabilities, utilities and costs were derived from the literature and expert opinion. Cost-effectiveness was expressed in quality-adjusted life years (QALYs) and healthcare costs of both diagnostic strategies, simulating the course of patients over a time horizon representing 18 years. Deterministic sensitivity analyses were performed to address uncertainty in assumptions. RESULTS: A diagnostic strategy including SelectMDx with a cut-off chosen at a sensitivity of 95.7% for high-grade prostate cancer resulted in savings of €128 and a gain of 0.025 QALY per patient compared to the SOC strategy. The sensitivity analyses showed that the disutility assigned to active surveillance had a high impact on the QALYs gained and the disutility attributed to TRUS-guided biopsy only slightly influenced the outcome of the model. CONCLUSION: Based on the currently available evidence, the reduction of over diagnosis and overtreatment due to the use of the SelectMDx test in men with PSA levels of >3 ng/mL may lead to a reduction in total costs per patient and a gain in QALYs.

Uncertainty on the effectiveness and safety of rivaroxaban in premenopausal women with atrial fibrillation: empirical evidence needed.

BACKGROUND: Novel anticoagulations (NOACs) are increasingly prescribed for the prevention of stroke in premenopausal women with atrial fibrillation. Small studies suggest NOACs are associated with a higher risk of abnormal uterine bleeds than vitamin K antagonists (VKAs). Because there is no direct empirical evidence on the benefit/risk profile of rivaroxaban compared to VKAs in this subgroup, we synthesize available indirect evidence, estimate decision uncertainty on the treatments, and assess whether further research in premenopausal women is warranted. METHODS: A Markov model with annual cycles and a lifetime horizon was developed comparing rivaroxaban (the most frequently prescribed NOAC in this population) and VKAs. Clinical event rates, associated quality adjusted life years, and health care costs were obtained from different sources and adjusted for gender, age, and history of stroke. A Monte Carlo simulation with 10,000 iterations was then performed for a hypothetical cohort of premenopausal women, estimated to be reflective of the population of premenopausal women with AF in The Netherlands. RESULTS: In the simulation, rivaroxaban is the better treatment option for the prevention of ischemic strokes in premenopausal women in 61% of the iterations. Similarly, this is 98% for intracranial hemorrhages, 24% for major abnormal uterine bleeds, 1% for minor abnormal uterine bleeds, 9% for other major extracranial hemorrhages, and 23% for other minor extracranial hemorrhages. There is a 78% chance that rivaroxaban offers the most quality-adjusted life years. The expected value of perfect information in The Netherlands equals 122 quality-adjusted life years and 22 million Euros. CONCLUSIONS: There is a 22% risk that rivaroxaban offers a worse rather than a better benefit/risk profile than vitamin K antagonists in premenopausal women. Although rivaroxaban is preferred over VKAs in this population, further research is warranted, and should preferably take the shape of an internationally coordinated registry study including other NOACs.

HEADROOM BEYOND THE QUALITY- ADJUSTED LIFE-YEAR: THE CASE OF COMPLEX PEDIATRIC NEUROLOGY.

OBJECTIVES: The headroom method was introduced for the very early evaluation of the potential value of new technologies. It allows for establishing a ceiling price for technologies to still be cost-effective by combining the maximum effect a technology might yield, the maximum willingness-to-pay (WTP) for this effect, and potential downstream expenses and savings. Although the headroom method is QALY-based, not all innovations are expected to result in QALY gain. METHODS: This study explores the feasibility and usefulness of the headroom method in the evaluation of technologies that are unlikely to result in QALY gain. This will be illustrated with the diagnostic trajectory of complex pediatric neurology (CPN). RESULTS: Our headroom analysis showed a large room for improvement in the current diagnostic trajectory of CPN in terms of diagnostic yield. Combining this with a maximum WTP value for an additional diagnosis and the potential downstream expenses and savings, resulted in a total headroom of €15,028. This indicates that a new technology in this particular diagnostic trajectory, might be cost-effective as long as its costs do not exceed €15,028. CONCLUSIONS: The headroom method seems a useful tool in the very early evaluation of medical technologies, also in cases when immediate QALY gain is unlikely. It allows for allocating healthcare resources to those technologies that are most promising. It should be kept in mind, however, that the headroom assumes an optimistic scenario, and for that reason cannot guarantee future cost-effectiveness. It might be most useful for ruling out those technologies that are unlikely to be cost-effective.

Is the $1000 Genome as Near as We Think? A Cost Analysis of Next-Generation Sequencing.

BACKGROUND: The substantial technological advancements in next-generation sequencing (NGS), combined with dropping costs, have allowed for a swift diffusion of NGS applications in clinical settings. Although several commercial parties report to have broken the $1000 barrier for sequencing an entire human genome, a valid cost overview for NGS is currently lacking. This study provides a complete, transparent and up-to-date overview of the total costs of different NGS applications. METHODS: Cost calculations for targeted gene panels (TGP), whole exome sequencing (WES) and whole genome sequencing (WGS) were based on the Illumina NextSeq500, HiSeq4000, and HiSeqX5 platforms, respectively. To anticipate future developments, sensitivity analyses are performed. RESULTS: Per-sample costs were €1669 for WGS, € 792 for WES and €333 for TGP. To reach the coveted $1000 genome, not only is the long-term and efficient use of the sequencing equipment needed, but also large reductions in capital costs and especially consumable costs are also required. CONCLUSIONS: WES and TGP are considerably lower-cost alternatives to WGS. However, this does not imply that these NGS approaches should be preferred in clinical practice, since this should be based on the tradeoff between costs and the expected clinical utility of the approach chosen. The results of the present study contribute to the evaluation of such tradeoffs.

Real-life Data on Patient Characteristics, Cost and Effectiveness of Field-directed Treatment for Actinic Keratoses: An Observational Study.

Actinic keratoses (AK) occur frequently; however, real-life clinical data on personalized treatment choice and costs are scarce. This multicentre one-year observational study investigated patient-characteristics, cost and effectiveness of methylaminolaevulinate photodynamic therapy (MAL-PDT), imiquimod (IMI) and 5-fluorour-acil (5-FU) in patients with AKs on the face/scalp. A total of 104 patients preferred MAL-PDT, 106 preferred IMI and 110 preferred 5-FU. At baseline, significant differences between treatment groups were found; most patients were severely affected (mean 32.5 AK in PDT-group, 20.2 in IMI-group, 22.8 in 5-FU-group). A mean reduction in lesions of 81% after MAL-PDT, 82% after IMI and 88% after 5-FU was found after one year. Annual costs were €1,950 for MAL-PDT, €877 for IMI and €738 for 5-FU. These results show that, compared with clinical trials, in the real-life clinical setting AK patients are usually more severely affected and treatment costs are much higher. Furthermore, patient characteristics are important factors in treatment choice.

Surgical team composition has a major impact on effectiveness and costs in laparoscopic donor nephrectomy.

PURPOSE: Limited evidence exists that optimization of surgical team composition may improve effectiveness of laparoscopic donor nephrectomy (LDN). METHODS: A retrospective cohort study with 541 consecutive LDNs. From 2003 to 2012, surgical team composition was gradually optimized with regard to the surgeons' experience, proficient assistance and the use of fixed teams. RESULTS: Multivariable analysis showed that a surgical team with an experienced surgeon had a significantly shorter operation time (OT) (-18 min, 95% CI -28 to -9), less estimated blood loss (EBL) (-64 mL, 95% CI -108 to -19) and shorter length of stay (LOS) (-1 day, 95% CI -1.6 to 0). Proficient assistance was also independently associated with a shorter OT (-43 min, 95% CI -53 to -33) and reduced EBL (-58 mL, 95% CI -109 to -6), whereas those procedures performed by fixed teams were related to a shorter operation (-50 min, 95% CI -59 to -43) and warm ischemia time (-1.8, 95% CI -2.1 to -1.5), a reduced mean complication grade (-0.14 per patient, 95% CI -0.3 to -0.02) and a shorter LOS (-1.1 day, 95% CI -1.7 to -05). Health care costs for LDN by one staff surgeon with unproficient assistance were 7.707 Euro, whereas costs for LDN by two staff surgeons in fixed teams were 5.614 Euro. CONCLUSIONS: Surgical team composition has a major impact on variables that reflect the effectiveness of LDN from the donors' perspective. Health care costs are lower for LDNs performed by two experienced surgeons in fixed team composition. We advocate the use of two experienced surgeons in fixed team composition for LDN.

Cost-effectiveness modelling in diagnostic imaging: a stepwise approach.

UNLABELLED: Diagnostic imaging (DI) is the fastest growing sector in medical expenditures and takes a central role in medical decision-making. The increasing number of various and new imaging technologies induces a growing demand for cost-effectiveness analysis (CEA) in imaging technology assessment. In this article we provide a comprehensive framework of direct and indirect effects that should be considered for CEA in DI, suitable for all imaging modalities. We describe and explain the methodology of decision analytic modelling in six steps aiming to transfer theory of CEA to clinical research by demonstrating key principles of CEA in a practical approach. We thereby provide radiologists with an introduction to the tools necessary to perform and interpret CEA as part of their research and clinical practice. KEY POINTS: • DI influences medical decision making, affecting both costs and health outcome. • This article provides a comprehensive framework for CEA in DI. • A six-step methodology for conducting and interpreting cost-effectiveness modelling is proposed.