Is progression-free survival associated with a better health-related quality of life in patients with lung cancer? : Evidence from two randomised trials with afatinib

Acknowledgements Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Suzanne Patel during the preparation of this article. Funding This study was supported by Boehringer Ingelheim.Peer reviewedPublisher PD

DETC2003/DAC-48759 ANALYSIS OF SUPPORT VECTOR REGRESSION FOR APPROXIMATION OF COMPLEX ENGINEERING ANALYSES

ABSTRACT A variety of metamodeling techniques have been developed in the past decade to reduce the computational expense of computer-based analysis and simulation codes. Metamodeling is the process of building a "model of a model" that provides a fast surrogate for a computationally expensive computer code. Common metamodeling techniques include response surface methodology, kriging, radial basis functions, and multivariate adaptive regression splines. In this paper, we present Support Vector Regression (SVR) as an alternative technique for approximating complex engineering analyses. The computationally efficient theory behind SVR is presented, and SVR approximations are compared against the aforementioned four metamodeling techniques using a testbed of 22 engineering analysis functions. SVR achieves more accurate and more robust function approximations than these four metamodeling techniques and shows great promise for future metamodeling applications

DETC2003/DAC-48759 ANALYSIS OF SUPPORT VECTOR REGRESSION FOR APPROXIMATION OF COMPLEX ENGINEERING ANALYSES

ABSTRACT A variety of metamodeling techniques have been developed in the past decade to reduce the computational expense of computer-based analysis and simulation codes. Metamodeling is the process of building a "model of a model" that provides a fast surrogate for a computationally expensive computer code. Common metamodeling techniques include response surface methodology, kriging, radial basis functions, and multivariate adaptive regression splines. In this paper, we present Support Vector Regression (SVR) as an alternative technique for approximating complex engineering analyses. The computationally efficient theory behind SVR is presented, and SVR approximations are compared against the aforementioned four metamodeling techniques using a testbed of 22 engineering analysis functions. SVR achieves more accurate and more robust function approximations than these four metamodeling techniques and shows great promise for future metamodeling applications

Budget impact of sequential treatment with first-line afatinib versus first-line osimertinib in non-small-cell lung cancer patients with common EGFR mutations

Background The therapeutic landscape for non-small-cell lung cancer (NSCLC) patients that have common epidermal growth factor receptor (EGFR) mutations has changed radically in the last decade. The availability of these treatment options has an economic impact, therefore a budget impact analysis was performed. Methods A budget impact analysis was conducted from a Dutch healthcare perspective over a 5-year time horizon in EGFR-mutant NSCLC patients receiving first-line afatinib (Gilotrif(R)) versus first-line osimertinib (Tagrisso(R)), followed by subsequent treatments. A decision analysis model was constructed in Excel. Scenario analyses and one-way sensitivity analysis were used to test the models' robustness. Results Sequential treatment with afatinib versus first-line treatment with osimertinib showed mean total time on treatment (ToT) of 29.1 months versus 24.7 months, quality-adjusted life months (QALMs) of 20.2 versus 17.4 with mean cost of euro108,166 per patient versus euro143,251 per patient, respectively. The 5-year total budget impact was euro110.4 million for the afatinib sequence versus euro158.6 million for the osimertinib sequence, leading to total incremental cost savings of euro48.15 million. Conclusions First-line afatinib treatment in patients with EGFR-mutant NSCLC had a lower financial impact on the Dutch healthcare budget with a higher mean ToT and QALM compared to osimertinib sequential treatment

Variation of health-related quality of life assessed by caregivers and patients affected by severe childhood infections.

BACKGROUND: The agreement between self-reported and proxy measures of health status in ill children is not well established. This study aimed to quantify the variation in health-related quality of life (HRQOL) derived from young patients and their carers using different instruments. METHODS: A hospital-based cross-sectional survey was conducted between August 2010 and March 2011. Children with meningitis, bacteremia, pneumonia, acute otitis media, hearing loss, chronic lung disease, epilepsy, mild mental retardation, severe mental retardation, and mental retardation combined with epilepsy, aged between five to 14 years in seven tertiary hospitals were selected for participation in this study. The Health Utilities Index Mark 2 (HUI2), and Mark 3 (HUI3), and the EuroQoL Descriptive System (EQ-5D) and Visual Analogue Scale (EQ-VAS) were applied to both paediatric patients (self-assessment) and caregivers (proxy-assessment). RESULTS: The EQ-5D scores were lowest for acute conditions such as meningitis, bacteremia, and pneumonia, whereas the HUI3 scores were lowest for most chronic conditions such as hearing loss and severe mental retardation. Comparing patient and proxy scores (n = 74), the EQ-5D exhibited high correlation (r = 0.77) while in the HUI2 and HUI3 patient and caregiver scores were moderately correlated (r = 0.58 and 0.67 respectively). The mean difference between self and proxy-assessment using the HUI2, HUI3, EQ-5D and EQ-VAS scores were 0.03, 0.05, -0.03 and -0.02, respectively. In hearing-impaired and chronic lung patients the self-rated HRQOL differed significantly from their caregivers. CONCLUSIONS: The use of caregivers as proxies for measuring HRQOL in young patients affected by pneumococcal infection and its sequelae should be employed with caution. Given the high correlation between instruments, each of the HRQOL instruments appears acceptable apart from the EQ-VAS which exhibited low correlation with the others

On the Valuation of Fader and Discrete Barrier Options in Heston's Stochastic Volatility Model

We focus on closed-form option pricing in Heston's stochastic volatility model, in which closed-form formulas exist only for few option types. Most of these closed-form solutions are constructed from characteristic functions. We follow this approach and derive multivariate characteristic functions depending on at least two spot values for different points in time. The derived characteristic functions are used as building blocks to set up (semi-) analytical pricing formulas for exotic options with payoffs depending on finitely many spot values such as fader options and discretely monitored barrier options. We compare our result with different numerical methods and examine accuracy and computational times

Measuring and Valuing Health-Related Quality of Life among Children and Adolescents in Mainland China - A Pilot Study

Background: The Child Health Utility 9D (CHU9D), a new generic preference-based health-related quality of life (HRQoL) instrument, has been validated for use in young people in both the UK and Australia. The main objectives of this study were to examine the feasibility of using a Chinese version of the CHU9D (CHU9D-CHN) to assess HRQoL and to investigate the association of physical activity, homework hours and sleep duration with HRQoL in children and adolescents in Mainland China. Methods: Data were collected using a multi-stage sampling method from grades 4–12 students in May 2013 in Nanjing, China. Consenting participants (N = 815) completed a self-administered questionnaire including the CHU9D-CHN instrument and information on physical activity, homework and sleep duration, self-reported health status, and socio-demographic characteristics. Descriptive and multivariate linear regression analyses were undertaken. CHU9D-CHN utility scores were generated by employing two scoring algorithms currently available for the instrument, the first derived from UK adults utilising the standard gamble (SG) valuation method and the second derived from Australian adolescents utilising the bestworst scaling (BWS) method. Results: It was found that CHU9D utility scores discriminated well in relation to self-reported health status and that better health status was significantly associated with higher utility scores regardless of which scoring algorithm was employed (both p,0.001). The adjusted mean utilities were significantly higher for physically active than inactive students (0.023 by SG, 0.029 by BWS scoring methods, p,0.05). An additional hour of doing homework and sleep duration were, separately, associated with mean utilities of 20.019 and 0.032 based on SG, and 20.021 and 0.040 according to BWS scoring algorithms (p,0.01). Conclusion: The CHU9D-CHN shows promise for measuring and valuing the HRQoL of children and adolescents in China. Levels of self-reported physical activity, homework and sleep time were important influencers of utility scores

HEE-GER: a systematic review of German economic evaluations of health care published 1990–2004

BACKGROUND: Studies published in non-English languages are systematically missing in systematic reviews of growth and quality of economic evaluations of health care. The aims of this study were: to characterize German evaluations, published in English or German-language, in terms of various key parameters; to investigate methods to derive quality-of-life weights in cost-utility studies; and to examine changes in study characteristics over the years. METHODS: We conducted a country-specific systematic review of the German and English-language literature of German economic evaluations (assessment of or application to the German health care system) published 1990–2004. Generic and specialized health economic databases were searched. Two independent reviewers verified fulfillment of inclusion criteria and extracted study characteristics. RESULTS: The fulltexts of 730 articles were reviewed of which 283 fulfilled all entry criteria. 32% of included studies were published in German-language. 51% of studies evaluated pharmaceuticals and 63% were cost-effectiveness analyses. Economic appraisals concentrate on few disease categories and important health areas are strongly underrepresented. Declaration of sponsorship was associated with article language (49% English articles vs. 29% German articles, p < 0.001). The methodology used to obtain quality-of-life weights in published cost-utility studies was very diverse, poorly reported and most studies did not use German patients' or community health state valuations. CONCLUSION: Many of the German-language evaluations included in our study are likely to be missing in international reviews and may be systematically different from English-language reviews from Germany. Lack of transparency and adherence to recommended reporting practices constitute a serious problem in German economic evaluations

Cost-effectiveness of MRI compared to mammography for breast cancer screening in a high risk population

<p>Abstract</p> <p>Background</p> <p>Breast magnetic resonance imaging (MRI) is a sensitive method of breast imaging virtually uninfluenced by breast density. Because of the improved sensitivity, breast MRI is increasingly being used for detection of breast cancer among high risk young women. However, the specificity of breast MRI is variable and costs are high. The purpose of this study was to determine if breast MRI is a cost-effective approach for the detection of breast cancer among young women at high risk.</p> <p>Methods</p> <p>A Markov model was created to compare annual breast cancer screening over 25 years with either breast MRI or mammography among young women at high risk. Data from published studies provided probabilities for the model including sensitivity and specificity of each screening strategy. Costs were based on Medicare reimbursement rates for hospital and physician services while medication costs were obtained from the Federal Supply Scale. Utilities from the literature were applied to each health outcome in the model including a disutility for the temporary health state following breast biopsy for a false positive test result. All costs and benefits were discounted at 5% per year. The analysis was performed from the payer perspective with results reported in 2006 U.S. dollars. Univariate and probabilistic sensitivity analyses addressed uncertainty in all model parameters.</p> <p>Results</p> <p>Breast MRI provided 14.1 discounted quality-adjusted life-years (QALYs) at a discounted cost of $18,167 while mammography provided 14.0 QALYs at a cost of$4,760 over 25 years of screening. The incremental cost-effectiveness ratio of breast MRI compared to mammography was $179,599/QALY. In univariate analysis, breast MRI screening became <$50,000/QALY when the cost of the MRI was < $315. In the probabilistic sensitivity analysis, MRI screening produced a net health benefit of -0.202 QALYs (95$50,000/QALY. Breast MRI screening was superior in 0%, < $50,000/QALY in 22$50,000/QALY in 34%, and inferior in 44% of trials.</p> <p>Conclusion</p> <p>Although breast MRI may provide health benefits when compared to mammographic screening for some high risk women, it does not appear to be cost-effective even at willingness to pay thresholds above $120,000/QALY.</p

Evaluating and Minimizing Distributed Cavity Phase Errors in Atomic Clocks

We perform 3D finite element calculations of the fields in microwave cavities and analyze the distributed cavity phase errors of atomic clocks that they produce. The fields of cylindrical cavities are treated as an azimuthal Fourier series. Each of the lowest components produces clock errors with unique characteristics that must be assessed to establish a clock's accuracy. We describe the errors and how to evaluate them. We prove that sharp structures in the cavity do not produce large frequency errors, even at moderately high powers, provided the atomic density varies slowly. We model the amplitude and phase imbalances of the feeds. For larger couplings, these can lead to increased phase errors. We show that phase imbalances produce a novel distributed cavity phase error that depends on the cavity detuning. We also design improved cavities by optimizing the geometry and tuning the mode spectrum so that there are negligible phase variations, allowing this source of systematic error to be dramatically reduced.Comment: To appear in Metrologi