Cost-effectiveness of voretigene neparvovec in the treatment of patients with inherited retinal disease with RPE65 mutation in Switzerland

Objective: We aimed to evaluate the cost-effectiveness of voretigene neparvovec (VN) compared with standard of care (SoC) for patients with inherited retinal disease (IRD) caused by a biallelic RPE65-mutation. VN is a live, non-replicating adeno-associated virus serotype 2 (AAV2). SoC is best supportive care provided to patients with visual impairment. Patients under SoC may experience progressive vision loss leading to complete blindness. Methods: We adapted a previously published Markov cohort model for IRD. An annual cycle length, life-long time horizon, discount rate of 3% for cost and health outcomes, and Swiss health system perspective were used. Data from a randomised controlled phase III trial of VN versus SoC (ClinicalTrials.gov: NCT00999609) were used to estimate transitions between health states in the first year, after which VN patients were assumed to remain for 39 subsequent years in the health state they were in at the end of the first year. After the 40th year for VN patients and 1st year for SoC patients, visual decline was modelled based on observational data on the natural progression of the disease. Quality-adjusted life years (QALYs) were calculated based on an external study which elicited clinicians' EQ-5D-5L-based utility estimates for IRD patients with a RPE65-mutation. Costs (Swiss Francs (CHF), year 2018-2019) included drug acquisition/ administration, adverse events, testing for sufficient viable retinal cells, and healthcare-related costs of blindness. Societal costs of blindness were added in a complementary analysis. Robustness of the model results were tested in sensitivity and scenario analyses. Results: For the base-case, VN resulted in incremental costs per patient of CHF 764'402 (VN: CHF 901'654, SoC: CHF 137'252), incremental blindness-free years of 7.67 (VN: 28.32, SoC: 20.65) and incremental QALYs of 6.73 (VN: 18.35, SoC: 11.62), leading to an incremental cost-effectiveness ratio of CHF 113'526 per QALY gained. In probabilistic sensitivity analysis, the cost-effectiveness of VN was better than CHF 100,000 per QALY gained in 41% of iterations. For the scenario analysis in which a societal perspective was adopted and for which a 50% work-related productivity loss from blindness was assumed, incremental costs of CHF 423,837 and an ICER of CHF 62'947 per QALY gained were produced. The scenario assuming VN treatment effect lasts for 20 years produced an ICER of CHF 156'171 per QALY gained, whereas assuming a life-long VN treatment effect resulted in an ICER of CHF 96'384 per QALY gained. Conclusion: The incremental cost-effectiveness ratio of VN compared to the SoC was estimated to be CHF 113'526 and CHF 62'947 per QALY gained, respectively, from a Swiss healthcare system, and societal perspective assuming a 50% productivity loss. Keywords: Cost effectiveness; Health Economics; Inherited retinal disease; RPE65; Switzerland; Voretigene neparvove

Exposure of the human body to professional and domestic induction cooktops compared to the basic restrictions

We investigated whether domestic and professional induction cooktops comply with the basic restrictions defined by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). Based on magnetic field measurements, a generic numerical model of an induction cooktop was derived in order to model user exposure. The current density induced in the user was simulated for various models and distances. We also determined the exposure of the fetus and of young children. While most measured cooktops comply with the public exposure limits at the distance specified by the International Electrotechnical Commission (standard IEC 62233), the majority exceeds them at closer distances, some of them even the occupational limits. The maximum current density in the tissue of the user significantly exceeds the basic restrictions for the general public, reaching the occupational level. The exposure of the brains of young children reaches the order of magnitude of the limits for the general public. For a generic worst-case cooktop compliant with the measurement standards, the current density exceeds the 1998 ICNIRP basic restrictions by up to 24 dB or a factor of 16. The brain tissue of young children can be overexposed by 6 dB or a factor of 2. The exposure of the tissue of the central nervous system of the fetus can exceed the limits for the general public if the mother is exposed at occupational levels. This demonstrates that the methodology for testing induction cooktops according to IEC 62233 contradicts the basic restrictions. This evaluation will be extended considering the redefined basic restrictions proposed by the ICNIRP in 2010

Applications of SOI-based optical MEMS

After microelectromechanical systems (MEMS) devices have been well established, components of higher complexity are now developed. Particularly, the combination with optical components has been very successful and have led to optical MEMS. The technology of choice for us is the silicon-on-insulator (SOI) technology, which has also been successfully used by other groups. The applications presented here give an overview over what is possible with this technology. In particular, we demonstrate four completely different devices: a) a 2 × 2 optical cross connector (OXC) with an insertion loss of about 0.4 dB at a switching time of 500 μs and its extension to a 4 × 4 OXC, b) a variable optical attenuators (VOA), which has an attenuation range of more than 50 dB, c) a Fourier transform spectrometer (FTS) with a spectral resolution of 6 nm in the visible, and d) an accelerometer with optical readout that achieves a linear dynamic range of 40 dB over ±6 g. Except for the FTS, all the applications utilized optical fibers, which are held and self-aligned within the MEMS component by U-grooves and small leaf springs. All devices show high reliability and a very low power consumption

A school-based physical activity program to improve health and fitness in children aged 6–13 years ("Kinder-Sportstudie KISS"): study design of a randomized controlled trial [ISRCTN15360785]

BACKGROUND: Childhood obesity is the result of a long lasting imbalance between energy intake and energy expenditure. A major contributing factor is physical inactivity which is closely linked to bone health, cardiovascular disease risk, fitness and psychological factors. The school seems to provide an excellent setting to enhance levels of physical activity (PA). However, there is insufficient data from previous school-based intervention trials on how to enhance overall PA. It is also unknown whether an intervention aimed at increasing PA is effective in improving the children's health. The purpose of this paper is to outline the design of a school-based randomized, controlled trial (RCT) aiming to increase overall PA and to improve fitness and health in 6- to 13-year-old children. METHODS/DESIGN: 15 schools were randomized to the intervention (n = 9) or the control (n = 6) group, stratified by geographic region (urban vs. rural) and by age (1(st )and 5(th )grade). Participation was given for all children in the intervention group since in this group the intervention was part of the normal school curriculum. The intervention during one academic year consisted of: 1. two additional physical education classes per week given by trained physical education teachers adding up to a total of five PA classes per week, 2. short PA breaks (2–5 min each) during academic lessons, 3. PA home work, and 4. adaptation of recreational areas around the school. All children underwent anthropometric measurements, blood pressure assessment, fitness testing, measurement of PA and they filled out questionnaires. At least 70% of all children agreed to blood sampling and measurements of body composition and bone mineral measurements by dual energy x-ray absorptiometry. The primary endpoints of the study after one year were an increase in total PA by accelerometry, an increase in aerobic fitness measured by the 20 m shuttle run, a decrease in percent body fat derived from skinfold measurements and an increase in quality of life as assessed by the child health questionnaire in the intervention group compared to the control group. Secondary outcomes were overall fitness, differences in body composition including body fat distribution, cardiovascular risk factors, psychosocial health, bone mineral content and density of femur, lumbar spine and total body and food intake. DISCUSSION: Our preliminary data suggest that the children were representative of Swiss children with respect to sex, socio-demographic status, and body mass index. Short-term results can be expected by the beginning of 2007. We hypothesized that our intervention will lead to an increase in PA, fitness and overall health. Based on our data, we aim to provide important information regarding the influence of such an intervention on these outcome measures in school-aged children and to provide nationwide guidelines to improve PA in children

Risk Measures Based on Benchmark Loss Distributions

We introduce a class of quantile-based risk measures that generalize Value at Risk (VaR) and, likewise Expected Shortfall (ES), take into account both the frequency and the severity of losses. Under VaR a single confidence level is assigned regardless of the size of potential losses. We allow for a range of confidence levels that depend on the loss magnitude. The key ingredient is a benchmark loss distribution (BLD), that is, a function that associates to each potential loss a maximal acceptable probability of occurrence. The corresponding risk measure, called Loss VaR (LVaR), determines the minimal capital injection that is required to align the loss distribution of a risky position to the target BLD. By design, one has full flexibility in the choice of the BLD profile and, therefore, in the range of relevant quantiles. Special attention is given to piecewise constant functions and to tail distributions of benchmark random losses, in which case the acceptability condition imposed by the BLD boils down to first-order stochastic dominance. We investigate the main theoretical properties of LVaR with a focus on their comparison with VaR and ES and discuss applications to capital adequacy, portfolio risk management, and catastrophic risk

Cost-effectiveness of voretigene neparvovec in the treatment of patients with inherited retinal disease with RPE65 mutation in Switzerland

OBJECTIVE: We aimed to evaluate the cost-effectiveness of voretigene neparvovec (VN) compared with standard of care (SoC) for patients with inherited retinal disease (IRD) caused by a biallelic RPE65-mutation. VN is a live, non-replicating adeno-associated virus serotype 2 (AAV2). SoC is best supportive care provided to patients with visual impairment. Patients under SoC may experience progressive vision loss leading to complete blindness. METHODS: We adapted a previously published Markov cohort model for IRD. An annual cycle length, life-long time horizon, discount rate of 3% for cost and health outcomes, and Swiss health system perspective were used. Data from a randomised controlled phase III trial of VN versus SoC (ClinicalTrials.gov: NCT00999609) were used to estimate transitions between health states in the first year, after which VN patients were assumed to remain for 39 subsequent years in the health state they were in at the end of the first year. After the 40(th) year for VN patients and 1(st) year for SoC patients, visual decline was modelled based on observational data on the natural progression of the disease. Quality-adjusted life years (QALYs) were calculated based on an external study which elicited clinicians’ EQ-5D-5L-based utility estimates for IRD patients with a RPE65-mutation. Costs (Swiss Francs (CHF), year 2018-2019) included drug acquisition/ administration, adverse events, testing for sufficient viable retinal cells, and healthcare-related costs of blindness. Societal costs of blindness were added in a complementary analysis. Robustness of the model results were tested in sensitivity and scenario analyses. RESULTS: For the base-case, VN resulted in incremental costs per patient of CHF 764’402 (VN: CHF 901’654, SoC: CHF 137’252), incremental blindness-free years of 7.67 (VN: 28.32, SoC: 20.65) and incremental QALYs of 6.73 (VN: 18.35, SoC: 11.62), leading to an incremental cost-effectiveness ratio of CHF 113’526 per QALY gained. In probabilistic sensitivity analysis, the cost-effectiveness of VN was better than CHF 100,000 per QALY gained in 41% of iterations. For the scenario analysis in which a societal perspective was adopted and for which a 50% work-related productivity loss from blindness was assumed, incremental costs of CHF 423,837 and an ICER of CHF 62’947 per QALY gained were produced. The scenario assuming VN treatment effect lasts for 20 years produced an ICER of CHF 156’171 per QALY gained, whereas assuming a life-long VN treatment effect resulted in an ICER of CHF 96’384 per QALY gained. CONCLUSION: The incremental cost-effectiveness ratio of VN compared to the SoC was estimated to be CHF 113’526 and CHF 62’947 per QALY gained, respectively, from a Swiss healthcare system, and societal perspective assuming a 50% productivity loss. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-022-08211-y