Dirk Müller

The use of O-(2-18F-fluoroethyl)-L-tyrosine PET for treatment management of bevacizumab and irinotecan in patients with recurrent high-grade glioma: a cost-effectiveness analysis

To date, the use of structural MR imaging (including contrast-enhanced and T2-weighted or fluid-attenuated inversion recovery–weighted images) is the standard method to diagnose tumor progression and to assess antiangiogenic treatment effects. However, several studies have suggested that O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) PET adds valuable clinical information to the information derived from structural MR imaging alone. We evaluated the effectiveness and cost-effectiveness of the addition of 18F-FET PET to structural MR imaging for the management of treatment with bevacizumab and irinotecan (BEV/IR) in patients with recurrent high-grade glioma compared with MR imaging alone from the perspective of the German Statutory Health Insurance. Methods: To evaluate the incremental cost-effectiveness of the additional use of 18F-FET PET, a decision tree model was used. Effectiveness of 18F-FET PET was defined as correct identification of both tumor progression before BEV/IR treatment initiation and BEV/IR treatment response and was evaluated for the combination of 18F-FET PET and MR imaging compared with MR imaging alone. Costs were estimated for a baseline scenario and for a more expensive scenario. The robustness of the results was tested using deterministic and probabilistic sensitivity analyses. Results: The use of 18F-FET PET resulted in a number needed to diagnose of 2.4, that is, 3 additional patients have to be diagnosed to avoid 1 wrong diagnosis. The incremental cost-effectiveness ratio of 18F-FET PET/MR imaging compared with MR imaging alone was €5,725 (€1 ≈

Thyroid nodules with indeterminate cytology: molecular imaging with 99m Tc-methoxyisobutylisonitrile (MIBI) is more cost-effective than the Afirma® gene expression classifier

1.30) for the baseline scenario and €8,145 for the more expensive scenario per additional correct diagnosis. The probabilistic sensitivity analysis confirmed the robustness of the results. Conclusion: The model suggests that the additional use of 18F-FET PET in the management of patients with recurrent high-grade glioma treated with BEV/IR may be cost-effective. Integration of 18F-FET PET has the potential to avoid overtreatment and corresponding costs, as well as unnecessary side effects to the patient.

Cost-Effectiveness of Different Strategies for Selecting and Treating Individuals at Increased Risk of Osteoporosis or Osteopenia: A Systematic Review

PurposeTo compare the cost-effectiveness of 99mTc-methoxyisobutylisonitrile (MIBI) thyroid scintigraphy and the Afirma® gene expression classifier for the assessment of cytologically indeterminate thyroid nodules.MethodsA decision tree model was used. Costs were calculated from the perspective of the German health insurance system. The robustness of the results was assessed with probabilistic sensitivity analyses using a Monte Carlo simulation.ResultsLife expectancy was 34.3xa0years (estimated costs per patient €1,459xa0–xa0€2,224) for the MIBI scan and 34.1xa0years (estimated costs €3,560xa0–xa0€4,071) for the molecular test. These results were confirmed by the Monte Carlo simulation.ConclusionMIBI thyroid scintigraphy is more cost-effective than the gene expression classifier.

Cost Effectiveness of Rivaroxaban for Stroke Prevention in German Patients with Atrial Fibrillation

OBJECTIVESnTo compare cost-effectiveness modeling analyses of strategies to prevent osteoporotic and osteopenic fractures either based on fixed thresholds using bone mineral density or based on variable thresholds including bone mineral density and clinical risk factors.nnnMETHODSnA systematic review was performed by using the MEDLINE database and reference lists from previous reviews. On the basis of predefined inclusion/exclusion criteria, we identified relevant studies published since January 2006. Articles included for the review were assessed for their methodological quality and results.nnnRESULTSnThe literature search resulted in 24 analyses, 14 of them using a fixed-threshold approach and 10 using a variable-threshold approach. On average, 70% of the criteria for methodological quality were fulfilled, but almost half of the analyses did not include medication adherence in the base case. The results of variable-threshold strategies were more homogeneous and showed more favorable incremental cost-effectiveness ratios compared with those based on a fixed threshold with bone mineral density. For analyses with fixed thresholds, incremental cost-effectiveness ratios varied from €80,000 per quality-adjusted life-year in women aged 55 years to cost saving in women aged 80 years. For analyses with variable thresholds, the range was €47,000 to cost savings.nnnCONCLUSIONSnRisk assessment using variable thresholds appears to be more cost-effective than selecting high-risk individuals by fixed thresholds. Although the overall quality of the studies was fairly good, future economic analyses should further improve their methods, particularly in terms of including more fracture types, incorporating medication adherence, and including or discussing unrelated costs during added life-years.

A multi-perspective cost-effectiveness analysis comparing rivaroxaban with enoxaparin sodium for thromboprophylaxis after total hip and knee replacement in the German healthcare setting

ObjectiveThe aim of this study was to assess the cost effectiveness of the novel fixed-dose anticoagulant rivaroxaban compared with the current standard of care, warfarin, for the prevention of stroke in patients with atrial fibrillation (AF).MethodsA Markov model was constructed to model the costs and health outcomes of both treatments, potential adverse events, and resulting health states over 35xa0years. Analyses were based on a hypothetical cohort of 65-year-old patients with non-valvular AF at moderate to high risk of stroke. The main outcome measure was cost per quality-adjusted life-year (QALY) gained over the lifetime, and was assessed from the German Statutory Health Insurance (SHI) perspective. Costs and utility data were drawn from public data and the literature, while event probabilities were derived from both the literature and rivaroxaban’s pivotal ROCKET AF trial.ResultsStroke prophylaxis with rivaroxaban offers health improvements over warfarin treatment at additional cost. From the SHI perspective, at baseline the incremental cost-effectiveness ratio of rivaroxaban was €15,207 per QALY gained in 2014. The results were robust to changes in the majority of variables; however, they were sensitive to the price of rivaroxaban, the hazard ratios for stroke and intracranial hemorrhage, the time horizon, and the discount rate.ConclusionsOur results showed that the substantially higher medication costs of rivaroxaban were offset by mitigating the shortcomings of warfarin, most notably frequent dose regulation and bleeding risk. Future health economic studies on novel oral anticoagulants should evaluate the cost effectiveness for secondary stroke prevention and, as clinical data from direct head-to-head comparisons become available, new anticoagulation therapies should be compared against each other.

Cost-effectiveness of rituximab in addition to fludarabine and cyclophosphamide (R-FC) for the first-line treatment of chronic lymphocytic leukemia.

BackgroundPatients undergoing major orthopaedic surgery (MOS), such as total hip (THR) or total knee replacement (TKR), are at high risk of developing venous thromboembolism (VTE). For thromboembolism prophylaxis, the oral anticoagulant rivaroxaban has recently been included in the German diagnosis related group (DRG) system. However, the cost-effectiveness of rivaroxaban is still unclear from both the German statutory health insurance (SHI) and the German hospital perspective.ObjectivesTo assess the cost-effectiveness of rivaroxaban from the German statutory health insurance (SHI) perspective and to analyse financial incentives from the German hospital perspective.MethodsBased on data from the RECORD trials and German cost data, a decision tree was built. The model was run for two settings (THR and TKR) and two perspectives (SHI and hospital) per setting.ResultsProphylaxis with rivaroxaban reduces VTE events (0.02 events per person treated after TKR; 0.007 after THR) compared with enoxaparin. From the SHI perspective, prophylaxis with rivaroxaban after TKR is cost saving (€27.3 saving per patient treated). However, the cost-effectiveness after THR (€17.8 cost per person) remains unclear because of stochastic uncertainty. From the hospital perspective, for given DRGs, the hospital profit will decrease through the use of rivaroxaban by €20.6 (TKR) and €31.8 (THR) per case respectively.ConclusionsBased on our findings, including rivaroxaban for reimbursement in the German DRG system seems reasonable. Yet, adequate incentives for German hospitals to use rivaroxaban are still lacking.

Impact of small study bias on cost-effectiveness acceptability curves and value of information analyses

Abstract The cost-effectiveness of rituximab in combination with fludarabine/cyclophosphamide (R-FC) for the first line treatment of chronic lymphocytic leukemia (CLL) was evaluated. Based on long-term clinical data (follow-up of 5.9 years) from the CLL8-trial, a Markov-model with three health states (Free from disease progression, Progressive disease, Death) was used to evaluate the cost per quality-adjusted life-year (QALY) and cost per life years gained (LYG) of R-FC from the perspective of the German statutory health insurance (SHI). The addition of rituximab to FC chemotherapy results in a gain of 1.1 quality-adjusted life-years. The incremental cost-effectiveness ratio (ICER) of R-FC compared with FC was €17 979 per QALY (€15 773 per LYG). Results were robust in deterministic and probabilistic sensitivity analyses. From the German SHI perspective, rituximab in combination with FC chemotherapy represents good value for first-line treatment of patients with CLL and compares favorably with chemotherapy alone.

Ethical Objections Against Including Life-Extension Costs in Cost-Effectiveness Analysis: A Consistent Approach

AbstractnIt is well known that small, randomized, controlled trials (RCTs) have limited validity. When comparing the results of meta-analyses with those of later large trials or with those of large trials removed from the meta-analyses, discrepancies were reported. This paper addresses two issues: (1) how measures of the uncertainty in cost-effectiveness, i.e., cost-effectiveness acceptability curves (CEACs), and the expected value of perfect information (EVPI) are affected by the limited validity of small trials and (2) how to deal with this bias. To this end, the paper adopts a Bayesian approach. Using empirical estimates for the validity of small RCTs compared to larger RCTs, the probability of cost-effectiveness drops by almost 10xa0%, while the EVPI is three times higher. In conclusion, traditional CEACs and EVPI analyses based on (small) RCTs may need careful appraisal. Ignoring prior evidence on the validity of small-size trials leads to an underestimation of uncertainty in cost-effectiveness. For future economic analyses, it is important to incorporate aspects of uncertainty which are caused by flawed data on effectivenessn.

Cost-effectiveness of hip protector use on a geriatric ward in Germany: a Markov model

One of the major ethical concerns regarding cost-effectiveness analysis in health care has been the inclusion of life-extension costs (“it is cheaper to let people die”). For this reason, many analysts have opted to rule out life-extension costs from the analysis. However, surprisingly little has been written in the health economics literature regarding this ethical concern and the resulting practice. The purpose of this work was to present a framework and potential solution for ethical objections against life-extension costs. This work found three levels of ethical concern: (i) with respect to all life-extension costs (disease-related and -unrelated); (ii) with respect to disease-unrelated costs only; and (iii) regarding disease-unrelated costs plus disease-related costs not influenced by the intervention. Excluding all life-extension costs for ethical reasons would require—for reasons of consistency—a simultaneous exclusion of savings from reducing morbidity. At the other extreme, excluding only disease-unrelated life-extension costs for ethical reasons would require—again for reasons of consistency—the exclusion of health gains due to treatment of unrelated diseases. Therefore, addressing ethical concerns regarding the inclusion of life-extension costs necessitates fundamental changes in the calculation of cost effectiveness.

Economic burden of clinical trials in lung cancer in a German Comprehensive Cancer Center

SummaryIn this study, we determined the cost-effectiveness of hip protector use compared with no hip protector on a geriatric ward in Germany. From both the societal and the statutory health insurance (SHI) perspectives, the cost-effectiveness ratios for the provision of hip protectors were below €12,000/quality-adjusted life year (QALY) even if unrelated costs in added life years were included.IntroductionThe aim of this study is to determine the cost-effectiveness of the provision of hip protectors compared with no hip protectors on a geriatric ward in Germany.MethodsA lifetime decision-analytic Markov model was developed. Costs were measured from the societal and from the statutory health insurance (SHI) perspectives and comprised direct medical, non-medical and unrelated costs in additional life years gained. Health outcomes were measured in terms of quality-adjusted life years (QALYs). To reflect several levels of uncertainty, first- and second-order Monte Carlo simulation (MCS) approaches were applied.ResultsHip protector use compared with no hip protector results in savings (costs, −5.1/QALYs, 0.003) for the societal perspective. For the SHI perspective, the incremental cost-effectiveness ratio was €4416 €/QALY (costs, +13.4). If unrelated costs in life years gained were included, the cost-effectiveness ratio increases to €9794/QALY for the societal perspective and to €11,426/QALY for the SHI perspective. In the MCS, for the societal perspective without unrelated costs, 47xa0% of simulations indicated hip protectors to be cost saving (i.e. lower costs and higher effects).ConclusionAlthough the gain in QALYs due to the provision of providing hip protectors to patients on geriatric wards is small, all scenarios showed acceptable cost-effectiveness ratios or even savings.