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.     

Choosing Aggregation Rules for Composite Indicators

From a formal point of view, a composite indicator is an aggregate of all dimensions, objectives, individual indicators and variables used for its construction. This implies that what defines a composite indicator is the set of properties underlying its mathematical aggregation convention. In this article, I try to revise the theoretical debate on aggregation rules by looking at contributions from both voting theory and multi-criteria decision analysis. This cross-fertilization helps in clarifying many ambiguous issues still present in the literature and allows discussing the key assumptions that may change the evaluation of an aggregation rule easily, when a composite indicator has to be constructed.     

Public Support for Sickle-Cell Disease Funding: Does Race Matter?

Despite the fact that sickle-cell disease (SCD) is perhaps the most “racialized” medical condition in the USA, very little is known about how “race” impacts public support for health policies related to the condition. We embedded an experiment within the 2011 Cooperative Congressional Election Study in order to assess perceptions about SCD among 1250 participants from diverse backgrounds and evaluate the extent to which these perceptions were associated with support for government spending on SCD-related benefits. We manipulated the racial phenotype of SCD advocates who requested additional government funding and asked participants to indicate how much the government should provide. Overall, participants expressed moderately positive attitudes about SCD, and there were no differences in funding support based on the race of the advocate. However, white participants supported less funding compared to nonwhite participants, even after adjusting for a number of demographic and attitudinal covariates. These findings suggest that a complex relationship between racial identification and implicit racism may shape public perceptions about SCD that negatively influences perceivers’ support for SCD-related policy.     

Reciprocal Family,Friendship and Church Support Networks of African Americans: Findings from the National Survey of American Life

This study examined reciprocal support networks involving extended family, friends and church members among African Americans. Our analysis examined specific patterns of reciprocal support (i.e., received only, gave only, both gave and received, neither gave or received), as well as network characteristics (i.e., contact and subjective closeness) as correlates of reciprocal support. The analysis is based on the African American subsample of the National Survey of American Life. Overall, our findings indicate that African Americans are very involved in reciprocal support networks with their extended family, friends and church members. Respondents were most extensively involved in reciprocal supports with extended family members, followed closely by friends and church networks. Network characteristics (i.e., contact and subjective closeness) were significantly and consistently associated with involvement with reciprocal support exchanges for all three networks. These and other findings are discussed in detail. This study complements previous work on the complementary roles of family, friend and congregational support networks, as well as studies of racial differences in informal support networks.     

Bootstrap Testing of Hypotheses on Co‐Integration Relations in Vector Autoregressive Models

It is well known that the finite‐sample properties of tests of hypotheses on the co‐integrating vectors in vector autoregressive models can be quite poor, and that current solutions based on Bartlett‐type corrections or bootstrap based on unrestricted parameter estimators are unsatisfactory, in particular in those cases where also asymptotic χ² tests fail most severely. In this paper, we solve this inference problem by showing the novel result that a bootstrap test where the null hypothesis is imposed on the bootstrap sample is asymptotically valid. That is, not only does it have asymptotically correct size, but, in contrast to what is claimed in existing literature, it is consistent under the alternative. Compared to the theory for bootstrap tests on the co‐integration rank (Cavaliere, Rahbek, and Taylor, 2012), establishing the validity of the bootstrap in the framework of hypotheses on the co‐integrating vectors requires new theoretical developments, including the introduction of multivariate Ornstein–Uhlenbeck processes with random (reduced rank) drift parameters. Finally, as documented by Monte Carlo simulations, the bootstrap test outperforms existing methods.     

On the robustness of the generalized fused lasso to prior specifications

Using networks as prior knowledge to guide model selection is a way to reach structured sparsity. In particular, the fused lasso that was originally designed to penalize differences of coefficients corresponding to successive features has been generalized to handle features whose effects are structured according to a given network. As any prior information, the network provided in the penalty may contain misleading edges that connect coefficients whose difference is not zero, and the extent to which the performance of the method depend on the suitability of the graph has never been clearly assessed. In this work we investigate the theoretical and empirical properties of the adaptive generalized fused lasso in the context of generalized linear models. In the fixed \(p\) setting, we show that, asymptotically, adding misleading edges in the graph does not prevent the adaptive generalized fused lasso from enjoying asymptotic oracle properties, while forgetting suitable edges can be more problematic. These theoretical results are complemented by an extensive simulation study that assesses the robustness of the adaptive generalized fused lasso against misspecification of the network as well as its applicability when theoretical coefficients are not exactly equal. Our contribution is also to evaluate the applicability of the generalized fused lasso for the joint modeling of multiple sparse regression functions. Illustrations are provided on two real data examples.     

The West,Russia, and China in Central Asia: What Kind of Game Is Being Played in the Region?

The article discusses the nature of the tangled interaction between the ex-Soviet Central Asian republics and the outside great powers – Russia, the United States and China. Although the so-called Great Game model is often used to explain the geopolitical rivalry in the region, the current pattern of relations between various international actors is much more complex than a traditional tug-of-war between the old colonial empires. While Russia's strategic role in Central Asia appears to be on the rise, the capacity of the West to influence political developments in the region has diminished. However, the overall situation in Central Asia remains volatile and its geopolitical landscape is far from being settled.     

Changes in HIV/AIDS knowledge and testing behavior in Africa: how much and for whom?

Demographic and Health Survey data from nine African countries make it clear that HIV/AIDS prevention knowledge has been increasing. Still, in many cases, fewer than half of adult respondents can identify specific prevention behaviors. Knowledge is lowest in rural areas and among women. HIV testing generally remains rare but is highly variable across countries, likely reflecting differences in the supply of testing services. In most cases, schooling and wealth impacts on prevention knowledge have either been stable or have increased; hence, in the majority of contexts, initial disparities in knowledge by education and wealth levels have persisted or widened.

Welfare analysis of a tax reform for Germany: a comparison of the unitary and collective models of household labour supply

We compare results of a tax reform analysis obtained with the collective and unitary models of household behaviour. We simulate real world micro-data by means of a collective approach, using a compound procedure of estimation and calibration based on the 1998 wave of the German socio-economic panel. We estimate a unitary model on this ‘collective’ data set. Investigating a move from joint to individual taxation on the basis of both models, we obtain important discrepancies between predicted adjustments to labour supply and distortions in the welfare analysis of the reform on the basis of unitary estimates.      

Understanding changes in Māori incomes and income inequality 1997–2003

This paper examines recent changes in weekly income levels and dispersion for Māori, New Zealand’s indigenous ethnic group. Changes in the Māori income distribution between 1997 and 2003 reflect rapid increases in economic growth and employment rate. A reduced proportion of people had zero or benefit-level incomes and a higher proportion had high incomes. Income inequality declined for working-aged Māori and was stable for employed Māori. The average income gap between Māori and Europeans declined. The increased Māori employment rate during this period was the single most important driver of changes in the Māori income distribution.