Statistical considerations in clinical trial design with event-free survival as the primary efficacy endpoint

In late-phase confirmatory clinical trials in the oncology field, time-to-event (TTE) endpoints are commonly used as primary endpoints for establishing the efficacy of investigational therapies. Among these TTE endpoints, overall survival (OS) is always considered as the gold standard. However, OS data can take years to mature, and its use for measurement of efficacy can be confounded by the use of post-treatment rescue therapies or supportive care. Therefore, to accelerate the development process and better characterize the treatment effect of new investigational therapies, other TTE endpoints such as progression-free survival and event-free survival (EFS) are applied as primary efficacy endpoints in some confirmatory trials, either as a surrogate for OS or as a direct measure of clinical benefits. For evaluating novel treatments for acute myeloid leukemia, EFS has been gradually recognized as a direct measure of clinical benefits. However, the application of an EFS endpoint is still controversial mainly due to the debate surrounding definition of treatment failure (TF) events. In this article, we investigate the EFS endpoint with the most conservative definition for the timing of TF, which is Day 1 since randomization. Specifically, the corresponding non-proportional hazard pattern of the EFS endpoint is investigated with both analytical and numerical approaches.     

Conditional Akaike Information Criteria for a Class of Poisson Mixture Models with Random Effects

Focusing on the model selection problems in the family of Poisson mixture models (including the Poisson mixture regression model with random effects and zero‐inflated Poisson regression model with random effects), the current paper derives two conditional Akaike information criteria. The criteria are the unbiased estimators of the conditional Akaike information based on the conditional log‐likelihood and the conditional Akaike information based on the joint log‐likelihood, respectively. The derivation is free from the specific parametric assumptions about the conditional mean of the true data‐generating model and applies to different types of estimation methods. Additionally, the derivation is not based on the asymptotic argument. Simulations show that the proposed criteria have promising estimation accuracy. In addition, it is found that the criterion based on the conditional log‐likelihood demonstrates good model selection performance under different scenarios. Two sets of real data are used to illustrate the proposed method.     

Sum,product and ratio of Pareto and gamma variables

The exact distributions of X+Y, X Y and X/(X+Y) are studied when X and Y are independent Pareto and gamma random variables. Applications are discussed, to real problems in clinical trials, computer networks and economics.     

Simulating random variables using moment-generating functions and the saddlepoint approximation

When we are given only a transform such as the moment-generating function of a distribution, it is rare that we can efficiently simulate random variables. Possible approaches such as the inverse transform using numerical inversion of the transform are computationally very expensive. However, the saddlepoint approximation is known to be exact for the Normal, Gamma, and inverse Gaussian distribution and remarkably accurate for a large number of others. We explore the efficient use of the saddlepoint approximation for simulating distributions and provide three examples of the accuracy of these simulations.     

A multiple warm standby δ-shock system with a repairman having multiple vacations

In this article, a warm standby n-unit system is studied. The system is operational as long as there is one unit normal. The unit online, which has a lifetime distribution governed by a phase-type distribution, is also attacked by a shock from some external causes. Assume that shocks arrive according to a Poisson process. Whenever an interarrival time of shock is less than a threshold, the unit online fails. The lifetimes of the units in warm standby is exponentially distributed. A repairman who can take multiple vacations repairs the failed units based on the “first-in-first-out” rule. The repair times and the vacation times of repairman are governed by different phase-type distributions. For this system, the Markov process governing the system is constructed. The system is studied in a transient and stationary regime; the availability, the reliability, the rates of occurrence of the different types of failures, and the working probability of the repairman are calculated. A numerical application is performed to illustrate the calculations.     

Decomposition of Variance for Spatial Cox Processes

Abstract. Spatial Cox point processes is a natural framework for quantifying the various sources of variation governing the spatial distribution of rain forest trees. We introduce a general criterion for variance decomposition for spatial Cox processes and apply it to specific Cox process models with additive or log linear random intensity functions. We moreover consider a new and flexible class of pair correlation function models given in terms of normal variance mixture covariance functions. The proposed methodology is applied to point pattern data sets of locations of tropical rain forest trees.     

Cumulants of random sum distributions

Consider a random variable S being the sum of a number N of independent and identically distributed random variables X_j (j = 1, 2, ...) where the number N is itself a non-negative integer-valued random variable independent of the X_j An explicit expression of the r-th cumulant of S is given in terms of the cumulants of N and X_j, Asymptotic properties of the distribution of S are also discussed.     

A class of integral operators generated by random variables

H. Kres Statistisehe Tafeln zur multlvariaten Analysis. Springer-Verlag, Berlin- Heidel-berg-New York 1975, XVIII, 431 S., 26 Tab., DM 48.

D. Rasch: Einführung in die mathematische Statistik - WahrscheinUcllkeitsrechnung und Grundlagen der mathematlsehan Statistlk. VEB Deutscher Verlag delr Wissenschaften, Berlin 1976, 371 S., 37 Abb., 46 'I'ab., 40,– M.

D. Rasch: Einführung in die muthematisehe Statlstik - II .Anweuduugen, VEB Deutscher Verlag der Wissenschaften, Berlin 1976.

Donald L. Snyder: Random Point Processes. -JohnWiley &; Sons, New York 1975,485 S.     

A strong law of large numbers for independent random variables under non-additive probabilities

Abstract

Under non‐additive probabilities, cluster points of the empirical average have been proved to quasi-surely fall into the interval constructed by either the lower and upper expectations or the lower and upper Choquet expectations. In this paper, based on the initiated notion of independence, we obtain a different Marcinkiewicz-Zygmund type strong law of large numbers. Then the Kolmogorov type strong law of large numbers can be derived from it directly, stating that the closed interval between the lower and upper expectations is the smallest one that covers cluster points of the empirical average quasi-surely.     

企业无力清偿欠薪的法律应对:基于香港的经验

1980-1982年经济危机爆发后,香港因大量企业倒闭引发欠薪浪潮,欠薪优先权机制出现失灵.以国外经验为模本,香港构设了欠薪保障基金制度.该制度依托完善的法律程序将欠薪纳入专门基金予以垫付,并逐渐提高垫付标准.这种法律设计特点鲜明,实际运行数据也证明比较成功.这为解决当前农民工极端讨薪事件频发、欠薪问题季节性爆发的顽疾,提供了极具参考价值的制度化思路.我国应当鼓励地方探索和构建企业欠薪保障制度.