Dealing with selective dropout in clinical trials

Clinical trials in severely diseased populations often suffer from a high dropout rate that is related to the investigated target morbidity. These dropouts can bias estimates and treatment comparisons, particularly in the event of an imbalance. Methods to describe such selective dropout are presented that use the time in study distribution to generate so‐called population evolution charts. These charts show the development of a distribution of a covariate or the target morbidity measure as it changes as a result of the dropout process during the follow‐up time. The selectiveness of the dropout process with respect to a variable can be inferred from the change in its distribution. Different types of selective dropout are described with real data from several studies in metastatic bone disease, where marked effects can be seen. A general strategy to cope with selective dropout seems to be the inclusion of dropout events into the endpoint. Within a time‐to‐event analysis framework this simple approach can lead to valid conclusions and still retains conservative elements. Morbidity measures that are based on (recurrent) event counts react differently in the presence of selective dropout. They differ mainly in the way dropout is included. One simple measure achieves good performance under selective dropout by introducing a non‐specific penalty for premature study termination. The use of a prespecified scoring system to assign a weight for each works well. This simple and transparent approach performs well even in the presence of unbalanced selective dropout. Copyright © 2002 John Wiley & Sons, Ltd.     

Variable-population extensions of social aggregation theorems

This paper examines principles for social evaluation under uncertainty in environments with a variable population. In contrast to most of the literature, we employ a model that is formulated in terms of prospects rather than lotteries. Starting from a fixed-population result, a multi-profile variant of Harsanyi’s social aggregation theorem is extended to a variable-population environment. Two nested classes of population principles under uncertainty are characterized. Each is a variable-population extension of ex-ante utilitarianism. The results continue to apply if the probability distribution may vary, as long as probabilities are objectively known or agreed upon by all individuals and society.     

Optimal adaptive sequential designs for crossover bioequivalence studies

In prior works, this group demonstrated the feasibility of valid adaptive sequential designs for crossover bioequivalence studies. In this paper, we extend the prior work to optimize adaptive sequential designs over a range of geometric mean test/reference ratios (GMRs) of 70–143% within each of two ranges of intra‐subject coefficient of variation (10–30% and 30–55%). These designs also introduce a futility decision for stopping the study after the first stage if there is sufficiently low likelihood of meeting bioequivalence criteria if the second stage were completed, as well as an upper limit on total study size. The optimized designs exhibited substantially improved performance characteristics over our previous adaptive sequential designs. Even though the optimized designs avoided undue inflation of type I error and maintained power at 80%, their average sample sizes were similar to or less than those of conventional single stage designs. Copyright © 2015 John Wiley & Sons, Ltd.     

Evaluating a multiple-family group access intervention for refugees with PTSD

The purpose of this study was to analyze the effects of a multiple-family group in increasing access to mental health services for refugees with posttraumatic stress disorder (PTSD). This study investigated a nine-session multiple-family group called Coffee and Families Education and Support with refugee families from Bosnia-Herzegovina in Chicago. Adults with PTSD (n = 197) and their families were randomly assigned to receive either the intervention or a control condition. The results indicated that a multiple-family group was effective in increasing access to mental health services and that depression and family comfort with discussing trauma mediated the intervention effect. Further well-designed studies of family interventions are needed for developing evidence-based interventions for refugee families.     

Location optimization of strategic alert sites for homeland defense

This research uses a location analysis approach for selecting aircraft alert sites for the defense of important national areas of interest identified by the US Department of Defense. Solutions are generated in a two step approach where the minimum number of sites is first identified using the location set covering problem and then the result is improved by finding the minimum aggregate network distance or p-median solution from the alternate optimal solutions to the LSCP. This approach also identifies the p-center solution to the problem ensuring equitable response to all areas of interest. Sensitivity analysis is performed to determine the impact of altering aircraft launch and flying times on the number of required alert sites and the amount of coverage provided by selecting fewer locations. Results indicate a significant increase in the number of alert locations needed in comparison to original military estimates. The research points out significant implications about future military base closure decisions and the trade-offs between cost and required response times of aircraft in a defense emergency.     

东方智慧文学和创世神话——兼谈对古希腊宇宙开创论的影响

我们对柏拉图之前的希腊情况知之甚少,然而公元前6世纪出现的一种特殊文学样式留下了宝贵的历史资料。在这个时期曾经有一些视野较为宽阔的关于宇宙及其起源的书籍问世,它们在特殊的环境中获得繁荣。这些书籍主要由两条支流——思想和文学汇集而成,它们超越了狭小的地域边界,广为流传的是：智慧的宣言和宇宙开创的神话。到目前为止,我们没有理由将希腊人——荷马,赫西俄德或俄耳甫斯神话的宇宙发生论从其东方副本（极相似的人或物）中分离出来。很明显,它们出自同一个家庭,而且有不少证据显示出前苏格拉底的哲学家们依然在步东方宇宙发生论的后尘。