No Arabic abstract
While generic drugs offer a cost-effective alternative to brand name drugs, regulators need a method to assess therapeutic equivalence in a post market setting. We develop such a method in the context of assessing the therapeutic equivalence of immediate release (IM) venlafaxine, based on a large insurance claims dataset provided by OptumLabstextsuperscript{textregistered}. To properly address this question, our methodology must deal with issues of non-adherence, secular trends in health outcomes, and lack of treatment overlap due to sharp uptake of the generic once it becomes available. We define, identify (under assumptions) and estimate (using G-computation) a causal effect for a time-to-event outcome by extending regression discontinuity to survival curves. We do not find evidence for a lack of therapeutic equivalence of brand and generic IM venlafaxine.
One of the most significant barriers to medication treatment is patients non-adherence to a prescribed medication regimen. The extent of the impact of poor adherence on resulting health measures is often unknown, and typical analyses ignore the time-varying nature of adherence. This paper develops a modeling framework for longitudinally recorded health measures modeled as a function of time-varying medication adherence or other time-varying covariates. Our framework, which relies on normal Bayesian dynamic linear models (DLMs), accounts for time-varying covariates such as adherence and non-dynamic covariates such as baseline health characteristics. Given the inefficiencies using standard inferential procedures for DLMs associated with infrequent and irregularly recorded response data, we develop an approach that relies on factoring the posterior density into a product of two terms; a marginal posterior density for the non-dynamic parameters, and a multivariate normal posterior density of the dynamic parameters conditional on the non-dynamic ones. This factorization leads to a two-stage process for inference in which the non-dynamic parameters can be inferred separately from the time-varying parameters. We demonstrate the application of this model to the time-varying effect of anti-hypertensive medication on blood pressure levels from a cohort of patients diagnosed with hypertension. Our model results are compared to ones in which adherence is incorporated through non-dynamic summaries.
Two different Master Equation approaches have been formally derived to address the dynamics of open quantum systems interacting with a thermal environment (such as sunlight). They have led to two different physical results: non-secular equations that show noise-induced (Fano) coherences and secular equations that do not. An experimental test for the appearance of non-secular terms is proposed using Ca atoms in magnetic fields excited by broadband incoherent radiation. Significantly different patterns of fluorescence are predicted, allowing for a clear test for the validity of the secular and non-secular approach and for the observation of Fano coherences.
A finite mixture model is used to learn trends from the currently available data on coronavirus (COVID-19). Data on the number of confirmed COVID-19 related cases and deaths for European countries and the United States (US) are explored. A semi-supervised clustering approach with positive equivalence constraints is used to incorporate country and state information into the model. The analysis of trends in the rates of cases and deaths is carried out jointly using a mixture of multivariate Gaussian non-linear regression models with a mean trend specified using a generalized logistic function. The optimal number of clusters is chosen using the Bayesian information criterion. The resulting clusters provide insight into different mitigation strategies adopted by US states and European countries. The obtained results help identify the current relative standing of individual states and show a possible future if they continue with the chosen mitigation technique
Gaussian random fields have been one of the most popular tools for analyzing spatial data. However, many geophysical and environmental processes often display non-Gaussian characteristics. In this paper, we propose a new class of spatial models for non-Gaussian random fields on a sphere based on a multi-resolution analysis. Using a special wavelet frame, named spherical needlets, as building blocks, the proposed model is constructed in the form of a sparse random effects model. The spatial localization of needlets, together with carefully chosen random coefficients, ensure the model to be non-Gaussian and isotropic. The model can also be expanded to include a spatially varying variance profile. The special formulation of the model enables us to develop efficient estimation and prediction procedures, in which an adaptive MCMC algorithm is used. We investigate the accuracy of parameter estimation of the proposed model, and compare its predictive performance with that of two Gaussian models by extensive numerical experiments. Practical utility of the proposed model is demonstrated through an application of the methodology to a data set of high-latitude ionospheric electrostatic potentials, generated from the LFM-MIX model of the magnetosphere-ionosphere system.
The algorithms used for optimal management of ambulances require accurate description and prediction of the spatio-temporal evolution of emergency interventions. In the last years, several authors have proposed sophisticated statistical approaches to forecast the ambulance dispatches, typically modelling the events as a point pattern occurring on a planar region. Nevertheless, ambulance interventions can be more appropriately modelled as a realisation of a point process occurring along a network of lines, such as a road network. The constrained spatial domain raises specific challenges and unique methodological problems that cannot be ignored when developing a proper statistical model. Hence, this paper proposes a spatiotemporal model to analyse the ambulance interventions that occurred in the road network of Milan (Italy) from 2015 to 2017. We adopt a non-separable first-order intensity function with spatial and temporal terms. The temporal component is estimated semi-parametrically using a Poisson regression model, while the spatial dimension is estimated nonparametrically using a network kernel function. A set of weights is included in the spatial term to capture space-time interactions, inducing non-separability in the intensity function. A series of maps and graphical tests show that our approach successfully models the ambulance interventions and captures the space-time patterns.