Bayesian adaptive dose‐escalation designs for simultaneously estimating the optimal and maximum safe dose based on safety and efficacy

The main purpose of dose‐escalation trials is to identify the dose(s) that is/are safe and efficacious for further investigations in later studies. In this paper, we introduce dose‐escalation designs that incorporate both the dose‐limiting events and dose‐limiting toxicities (DLTs) and indicative responses of efficacy into the procedure. A flexible nonparametric model is used for modelling the continuous efficacy responses while a logistic model is used for the binary DLTs. Escalation decisions are based on the combination of the probabilities of DLTs and expected efficacy through a gain function. On the basis of this setup, we then introduce 2 types of Bayesian adaptive dose‐escalation strategies. The first type of procedures, called “single objective,” aims to identify and recommend a single dose, either the maximum tolerated dose, the highest dose that is considered as safe, or the optimal dose, a safe dose that gives optimum benefit risk. The second type, called “dual objective,” aims to jointly estimate both the maximum tolerated dose and the optimal dose accurately. The recommended doses obtained under these dose‐escalation procedures provide information about the safety and efficacy profile of the novel drug to facilitate later studies. We evaluate different strategies via simulations based on an example constructed from a real trial on patients with type 2 diabetes, and the use of stopping rules is assessed. We find that the nonparametric model estimates the efficacy responses well for different underlying true shapes. The dual‐objective designs give better results in terms of identifying the 2 real target doses compared to the single‐objective designs.     

Activation and social inclusion: challenges and possibilities

The last two decades have seen an increasing focus on the activation of individuals receiving welfare benefits. This has entailed an attempt to transform employment assistance and social security systems to make them more employment‐friendly through the development of explicit linkages between social protection policies, labour market participation and labour market programs. At the same time there has been a growing interest in the concept of social inclusion, and social inclusion has been a commonly stated goal of activation programs. However, despite some synergies between these two approaches, in other respects it is not clear that they are always compatible. This paper explores the extent to which activation programs are central to the social inclusion approach and the similarities and differences between these approaches. It then briefly examines the evidence regarding the ability of activation programs to enhance social inclusion.     

The Distribution of Returns to Education for People with Disabilities

This article takes a first look at the distribution of returns to education for people with disabilities, a particularly disadvantaged group whose labor market performances have not been well studied or documented. Using a nonparametric approach, we uncover significant heterogeneity in the returns to education for these workers, which is drastically masked by conventional parametric methods. Based on these estimates, we construct the Sharpe ratio of human capital investment (taking into account its substantial risk), and our results corroborate the claimed importance of human capital in improving these workers’ wages. Our stochastic dominance tests show that the returns to education for workers with disabilities, as a group, may have been affected more adversely in the most recent recession, relative to their non-disabled counterparts.     

The Inability of Self-affirmations to Decrease Defensive Bias Toward an Alcohol-Related Risk Message Among High-Risk College Students

Abstract

Objective: To examine the efficacy of a self-affirmation task in deterring college alcohol misuse and the importance of preexisting beliefs in predicting subsequent behavior change. Participants: Heavy-drinking undergraduates (N = 110) participated during the 2011–2012 academic year. Methods: Participants were randomized to complete an affirmation or control task before reading an alcohol risk message. Alcohol-related beliefs and behaviors were assessed. Participants completed a 2-week online follow-up assessing alcohol-related behaviors. Results: Both groups reported increased perceived problem importance, but neither group displayed changes in personal risk. Follow-up assessment revealed similar, significant declines in peak consumption in both groups, with no significant between-group differences. Preexisting beliefs accounted for 5% to 10% of variance in drinking outcomes. Conclusions: An affirmation task does not seem to decrease defensive processing or alter high-risk drinking behaviors among college students and should not be utilized in lieu of more effective strategies.     

The Multi-dimensional Characteristics of Wellbeing: How Different Aspects of Wellbeing Interact and Do Not Interact with Each Other

Because wellbeing is a multi-varied and dynamic phenomenon, social scientists need to better understand how different aspects of people’s wellbeing are tied together and how these ties differ between individuals at one point in time and within individuals over time. The paper outlines a general model that considers the multidimensional structure of wellbeing. We utilize the potential of latent variable modelling on a unique Swedish database: the Panel Survey of Ageing and the Elderly (PSAE). An inclusive and flexible model that considers the interactions between semi-autonomous domains (material resources, health, psychosocial factors, lifestyle, etc.) is developed. Our empirical study is based on cross-sectional PSAE data and focuses on people 55 years or older (N = 5,374). The analysis takes advantage of recent developments in statistical theory in the field of latent variable modelling to bring about a more dynamic and theory confirming analysis of a multifaceted phenomenon such as wellbeing.     

Deferred life annuities: on the combined effects of stochastic mortality and interest rates

The paper analyzes the systematic risk which is inherent in a portfolio of deferred life annuities. We take into account stochastic mortality as well as stochastic interest rates. For the specification of the mortality rate dynamics, we consider a pure diffusion model as well as a compound Poisson jump model. The interest rate dynamics are given by a one-factor Hull–White model. All models, interest rate and mortality rate, are calibrated to financial market as well as demographic data. We use Monte Carlo simulations to approximate the variance of the discounted cash flow and its decomposition into a pooling and a non-pooling risk part. We also consider pricing effects using the principle of zero expected utility and the quantile principle. The estimated risk premiums are benchmarked to the equivalence premium. Finally, we focus on solvency requirements which are based on the investment decisions and the associated shortfall probability of the annuity provider.     

城市的精神

面对全球化的挑战,城市风尚具有越来越重要的政治意蕴.这是因为,全球化正在使不同的文化传统、不同的生活方式迅速同一化和均质化,在国家层面,对抗这种同一化和均质化是相当困难的,而在城市层面,城市风尚的培养或恢复可以有效地保护文化多样性.     

Does product complexity matter for competition in experimental retail markets?

We describe a first experiment on whether product complexity affects competition and consumers in retail markets. We are unable to detect a significant effect of product complexity on prices, except insofar as the demand elasticity for complex products is higher. However, there is qualified evidence that complex products have the potential to induce consumers to buy more than they would otherwise. In this sense, consumer exploitability in quantities cannot be ruled out. We also find evidence for shaping effects: consumers’ preferences are shaped by past experience with prices, and firms may in principle exploit this to sell more.