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21.
Bayesian adaptive dose‐escalation procedures for binary and continuous responses utilizing a gain function 下载免费PDF全文
Wai Yin Yeung John Whitehead Bruno Reigner Ulrich Beyer Cheikh Diack Thomas Jaki 《Pharmaceutical statistics》2015,14(6):479-487
One of the main aims of early phase clinical trials is to identify a safe dose with an indication of therapeutic benefit to administer to subjects in further studies. Ideally therefore, dose‐limiting events (DLEs) and responses indicative of efficacy should be considered in the dose‐escalation procedure. Several methods have been suggested for incorporating both DLEs and efficacy responses in early phase dose‐escalation trials. In this paper, we describe and evaluate a Bayesian adaptive approach based on one binary response (occurrence of a DLE) and one continuous response (a measure of potential efficacy) per subject. A logistic regression and a linear log‐log relationship are used respectively to model the binary DLEs and the continuous efficacy responses. A gain function concerning both the DLEs and efficacy responses is used to determine the dose to administer to the next cohort of subjects. Stopping rules are proposed to enable efficient decision making. Simulation results shows that our approach performs better than taking account of DLE responses alone. To assess the robustness of the approach, scenarios where the efficacy responses of subjects are generated from an E max model, but modelled by the linear log–log model are also considered. This evaluation shows that the simpler log–log model leads to robust recommendations even under this model showing that it is a useful approximation to the difficulty in estimating E max model. Additionally, we find comparable performance to alternative approaches using efficacy and safety for dose‐finding. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
22.
Individual behavior under uncertainty is characterized using a new axiom, ordinal independence, which is a weakened form of the von Neumann-Morgenstern independence axiom It states that if two distributions share a tail in common, then this tail can be modified without altering the individual's preference between these distributions. Preference is determined by the tail on which the distributions differ. This axiom implies an appealing and simple functional form for a numerical representation of preferences. It generalizes the form of anticipated utility, and it explains some well-known forms of behavior, such as the Friedman-Savage paradox, that anticipated utility cannot. 相似文献
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A new class of Bayesian estimators for a proportion in multistage binomial designs is considered. Priors belong to the beta-J distribution family, which is derived from the Fisher information associated with the design. The transposition of the beta parameters of the Haldane and the uniform priors in fixed binomial experiments into the beta-J distribution yields bias-corrected versions of these priors in multistage designs. We show that the estimator of the posterior mean based on the corrected Haldane prior and the estimator of the posterior mode based on the corrected uniform prior have good frequentist properties. An easy-to-use approximation of the estimator of the posterior mode is provided. The new Bayesian estimators are compared to Whitehead's and the uniformly minimum variance estimators through several multistage designs. Last, the bias of the estimator of the posterior mode is derived for a particular case. 相似文献
26.
Jana Verstraete Isabelle Pannecoucke Bruno Meeus 《Journal of social service research》2013,39(5):665-683
People living in an institution will leave this residential context one day and have to proceed to a stable independent way of living. This transition is not without difficulties as it turns out this socially vulnerable group runs an increased risk of becoming homeless. Research in Flanders (Belgium) has shown that a considerable share of the homeless population has previously stayed in an institutional setting, mostly in youth care (48.7%), psychiatric (34.4%) and penitentiary (33.1%) institutions. Moreover, the share of homeless people with a history in one of these institutions has increased in the past decades. Institution leavers, face at least three obstacles to a stable housing situation in Flanders: a lack of affordable housing, a lack of access to (non-residential) social assistance and personal difficulties in coping with living independently. Yet, there are several programs that support institution leavers and prepare them for the transition to an independent living situation and legal developments that strengthen their position in society and on the housing market. In this paper, we explore these initiatives and developments in three case studies (Antwerp, Ghent and Leuven). Based on in-depth interviews with “street-level bureaucrats” who work in these institutions (youth care, psychiatric and penitentiary settings), social support services and social housing organizations, we reconstruct the pathways of institution leavers to the housing market, the support they receive and the experienced difficulties. 相似文献
27.
When things strike back: a possible contribution of 'science studies' to the social sciences 总被引:6,自引:0,他引:6
Bruno Latour 《The British journal of sociology》2000,51(1):107-123
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Bart Cockx Bruno Van der Linden 《International labour review / International Labour Office》2010,149(3):361-372
Belgium's systems of unemployment insurance and employment protection legislation were set up in the context of typically enduring and stable relationships between workers and firms. Economic globalization and rapid technological and organizational change, however, are now demanding more flexibility of both workers and firms. As a result, current labour market institutions are in urgent need of reform to reconcile such increased flexibility with adequate security for workers. Though the call for a “flexicurity” approach is not new, there is no single view of what institutional model the latter implies. This paper proposes a reform explicitly guided by economic principles. 相似文献
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In recent decades, accelerating processes of globalization and an increase in economic inequality in most of the world's countries have raised the question of the emergence of a new bourgeoisie integrated at the global level, sometimes described as a global super-bourgeoisie. This group would be distinguished by its unequaled level of wealth and global interconnectedness, its transnational ubiquity and concentration in the planet's major global cities, its specific culture, consumption habits, sites of sociability and shared references, and even by class consciousness and capacity to act collectively. This article successively discusses how the social sciences have examined these various dimensions of the question and begun to provide systematic empirical answers. 相似文献
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Elena D. Concepción Martin K. Obrist Marco Moretti Florian Altermatt Bruno Baur Michael P. Nobis 《Urban Ecosystems》2016,19(1):225-242
Urban growth is a major factor of global environmental change and has important impacts on biodiversity, such as changes in species composition and biotic homogenization. Most previous studies have focused on effects of urban area as a general measure of urbanization, and on few or single taxa. Here, we analyzed the impacts of the different components of urban sprawl (i.e., scattered and widespread urban growth) on species richness of a variety of taxonomic groups covering mosses, vascular plants, gastropods, butterflies, and birds at the habitat and landscape scales. Besides urban area, we considered the average age, imperviousness, and dispersion degree of urban area, along with human population density, to disentangle the effects of the different components of urban sprawl on biodiversity. The study was carried out in the Swiss Plateau that has undergone substantial urban sprawl in recent decades.Vascular plants and birds showed the strongest responses to urban sprawl, especially at the landscape scale, with non-native and ruderal plants proliferating and common generalist birds increasing at the expense of specialist birds as urban sprawl grew. Overall, urban area had the greatest contribution on such impacts, but additional effects of urban dispersion (i.e., increase of non-native plants) and human population density (i.e., increases of ruderal plants and common generalist birds) were found. Our findings support the hypothesis that negative impacts of urban sprawl on biodiversity can be reduced by compacting urban growth while still avoiding the formation of very densely populated areas. 相似文献