Statistical testing strategies for assessing treatment efficacy and marker accuracy in phase III trials

When a candidate predictive marker is available, but evidence on its predictive ability is not sufficiently reliable, all‐comers trials with marker stratification are frequently conducted. We propose a framework for planning and evaluating prospective testing strategies in confirmatory, phase III marker‐stratified clinical trials based on a natural assumption on heterogeneity of treatment effects across marker‐defined subpopulations, where weak rather than strong control is permitted for multiple population tests. For phase III marker‐stratified trials, it is expected that treatment efficacy is established in a particular patient population, possibly in a marker‐defined subpopulation, and that the marker accuracy is assessed when the marker is used to restrict the indication or labelling of the treatment to a marker‐based subpopulation, ie, assessment of the clinical validity of the marker. In this paper, we develop statistical testing strategies based on criteria that are explicitly designated to the marker assessment, including those examining treatment effects in marker‐negative patients. As existing and developed statistical testing strategies can assert treatment efficacy for either the overall patient population or the marker‐positive subpopulation, we also develop criteria for evaluating the operating characteristics of the statistical testing strategies based on the probabilities of asserting treatment efficacy across marker subpopulations. Numerical evaluations to compare the statistical testing strategies based on the developed criteria are provided.     

孙中山与德国——兼论"中德苏联盟"的构想

1917年参战纠纷发生以后,孙中山就一直坚持接近德国的政策,这种政策是出于战略的考虑,因为孙中山希望得到德国的政治、军事和技术援助;巴黎和会以后,孙中山的亲德政策与亲苏政策相联结,形成了"中德苏联盟"的构想,亲德和亲苏政策是一体推进的,其政策来源于孙中山的"大亚洲主义";孙中山认为受凡尔赛—华盛顿体系压迫的民族应该通过中德苏三国联合来抵抗英美强权,孙中山的思想成为后来中国国民党联俄政策和聘请德国军事顾问团的基础;尽管孙中山及其广州政府并没有与德国建立正式的外交关系,其联俄政策也因为他的逝世而最终放弃,但在整个20世纪30-40年代,这种中德苏合作的政策总是时隐时现地贯穿于中国政治家的认识中。     

A multiattribute decision time theory

In this study, we analyze choice in the presence of some conflict that affects the decision time (response time), a subject that has been documented in the literature. We axiomatize a multiattribute decision time (MDT) representation, which is a dynamic extension of the classic multiattribute expected utility theory that allows potentially incomplete preferences. Under this framework, one alternative is preferred to another in a certain period if and only if the weighted sum of the attribute-dependent expected utility induced by the former alternative is larger than that induced by the latter for all attribute weights in a closed and convex set. MDT uniquely determines the decision time as the earliest period at which the ranking between alternatives becomes decisive. The comparative statics result indicates that the decision time provides useful information to locate indifference curves in a specific setting. MDT also explains various empirical findings in economics and other relevant fields.     

A global count of the extreme poor in 2012: data issues,methodology and initial results

The 2014 release of a new set of purchasing power parity (PPP) conversion factors (PPPs) for 2011 has prompted a revision of the World Bank’s international poverty line. In revising the line, we have sought to minimize changes to the real purchasing power of the earlier $1.25 line (in 2005 PPPs), so as to preserve the integrity of the goalposts for international targets such as the Sustainable Development Goals (SDGs) and the World Bank’s twin goals – which were set with respect to that line. In particular, the new line was obtained by inflating the same fifteen national poverty lines – originally used by Ravallion et al. (World Bank Econ. Rev. 23(2): 163–184 2009) to construct the $1.25 line – to 2011 prices in local currency units, and then converting them to US dollars using 2011 PPP conversion factors. With a small approximation, this procedure yields a new international poverty line of $1.90 per person per day. In combination with other changes described in the paper, this revision leads to relatively small changes in global poverty incidence for 2011: from 14.5 % using the old method to 14.1 % using the new method. In 2012, the new reference year for the global count, we find 12.7 % of the world’s population, or 897 million people, are living in extreme poverty. There are changes in the regional composition of poverty, but they are also relatively small. This paper documents methodological decisions taken in the process of updating both the poverty line and the consumption and income distributions at the country level, including issues of inter-temporal and spatial price adjustments. It also describes various caveats and limitations of the approach taken.     

A Single Garbage Can Model and the Degree of Anarchy in Japanese Firms

This paper refreshes an empirical examination ofthe garbage can model, particularly in a sample drawnfrom Japanese firms. The garbage can model oforganizational decision making was originally developed by Cohen, March, and Olsen (1972) to describeorganized anarchy. This paper incorporates twomethodologies in an attempt to both validate and extendthe garbage can model: Simulation is first used togenerate a research hypothesis, then several surveys areconducted to test that hypothesis and to empiricallydevelop an ex-post model of decision ambiguity, flight,and anarchy. The data support our hypothesis and we find out new conditions of ambiguity:(i) fluid participation, (ii) divorce of solution fromdiscussion, and (iii) job performance rather thansubjective assessments, which are clearly related to the simulation assumption of our single garbagecan model. By using our new conditions of ambiguity, wedevelop a measure of degree of anarchy, and theregression analysis indicates a linear relationship between the flight ratio and the degree ofanarchy.     

TITE‐BOIN‐ET: Time‐to‐event Bayesian optimal interval design to accelerate dose‐finding based on both efficacy and toxicity outcomes

One of the primary purposes of an oncology dose‐finding trial is to identify an optimal dose (OD) that is both tolerable and has an indication of therapeutic benefit for subjects in subsequent clinical trials. In addition, it is quite important to accelerate early stage trials to shorten the entire period of drug development. However, it is often challenging to make adaptive decisions of dose escalation and de‐escalation in a timely manner because of the fast accrual rate, the difference of outcome evaluation periods for efficacy and toxicity and the late‐onset outcomes. To solve these issues, we propose the time‐to‐event Bayesian optimal interval design to accelerate dose‐finding based on cumulative and pending data of both efficacy and toxicity. The new design, named “TITE‐BOIN‐ET” design, is nonparametric and a model‐assisted design. Thus, it is robust, much simpler, and easier to implement in actual oncology dose‐finding trials compared with the model‐based approaches. These characteristics are quite useful from a practical point of view. A simulation study shows that the TITE‐BOIN‐ET design has advantages compared with the model‐based approaches in both the percentage of correct OD selection and the average number of patients allocated to the ODs across a variety of realistic settings. In addition, the TITE‐BOIN‐ET design significantly shortens the trial duration compared with the designs without sequential enrollment and therefore has the potential to accelerate early stage dose‐finding trials.     

New types of shrinkage estimators of Poisson means under the normalized squared error loss

In estimating p( ? 2) independent Poisson means, Clevenson and Zidek (1975) have proposed a class of estimators that shrink the unbiased estimator to the origin and dominate the unbiased one under the normalized squared error loss. This class of estimators was subsequently enlarged in several directions. This article deals with the problem and proposes new classes of dominating estimators using prior information pertinently. Dominance is shown by partitioning the sample space into disjoint subsets and averaging the loss difference over each subset. Estimation of several Poisson mean vectors is also discussed. Further, simultaneous estimation of Poisson means under order restriction is treated and estimators which dominate the isotonic regression estimator are proposed for some types of order restrictions.     

On Efron's Parameterization

This paper discusses a curved exponential family of distributions which is defined by a differential equation with respect to the expectation parameters in the two–dimensional exponential family. The differential equation considered here is the same as the one given by Efron (1975) for the trinomial distribution. This equation is extended here to a general exponential family, and called Efron's parameterization in the two–dimensional exponential family. The solution of Efron's parameterization is obtained explicitly in an exponential family, although Kumagai & Inagaki (1996) showed that there exists no proper solution of Efron's equation for the trinomial distribution, in line with the counterexample given by Efron (1975 p. 1206). The paper gives some characterizations of Efron's parameterization with special reference to Fisher's circle model. The implications of these characterizations are the two–dimensional normal distribution and a spiral curve in the plane.     

Estimation of Ordered Means of Two Poisson Distributions

In this article, we discuss the estimation of linear functions of two Poisson means, on which an order restriction is given. We give a necessary and sufficient condition on the coefficients of the linear function for the maximum likelihood estimator (MLE) which satisfies the order restriction to dominate the unbiased estimator under squared error loss. Furthermore, simultaneous estimation of two ordered Poisson means is considered and we suggest the Clevenson–Zidek type modification of MLE which dominates the MLE under normalized squared error loss. We also improve the estimator proposed by Clevenson and Zidek (1975 Clevenson , M. , Zidek , J. ( 1975 ). Simultaneous estimation of the means of independent Poisson laws . J. Amer. Statist. Assoc. 70 : 698 – 705 . [CSA] [CROSSREF] [Taylor & Francis Online], [Web of Science ®] , [Google Scholar]) which ignores the order restriction.     

Relationship between state anxiety and success rate in game performance, coach's evaluation among Japanese university volleyball players

The purpose of this study is to examine the relationship between state anxiety and individual athletic game performance. The subjects were 54 male players of 4 teams (The average age was 20.5 (SD=1.09) years), who participated in the Kanto university men's volleyball league games in the spring of year 2010. The subjects were asked to respond to a Japanese version of the State Trait Anxiety Inventory (STAI), which was measured at 4 time periods (the day before, the day of game, just before the game, just after the game) for each of a total of 40 games (each team played 10 games). The results were as follows: (1) Relationships between state anxiety and success rate in game performance (spike, reception, block) showed different correlation depending on each game performance. (2) The group of players who performed well in games collected by coaches scored lower than the more badly-performing group in the score of state anxiety on the day of game and just after the game. (3) The temporal change of the score of state anxiety from just before the game to just after the game was different depending on whether they performed well or not in games.