Properties of the weighted log‐rank test in the design of confirmatory studies with delayed effects

Proportional hazards are a common assumption when designing confirmatory clinical trials in oncology. This assumption not only affects the analysis part but also the sample size calculation. The presence of delayed effects causes a change in the hazard ratio while the trial is ongoing since at the beginning we do not observe any difference between treatment arms, and after some unknown time point, the differences between treatment arms will start to appear. Hence, the proportional hazards assumption no longer holds, and both sample size calculation and analysis methods to be used should be reconsidered. The weighted log‐rank test allows a weighting for early, middle, and late differences through the Fleming and Harrington class of weights and is proven to be more efficient when the proportional hazards assumption does not hold. The Fleming and Harrington class of weights, along with the estimated delay, can be incorporated into the sample size calculation in order to maintain the desired power once the treatment arm differences start to appear. In this article, we explore the impact of delayed effects in group sequential and adaptive group sequential designs and make an empirical evaluation in terms of power and type‐I error rate of the of the weighted log‐rank test in a simulated scenario with fixed values of the Fleming and Harrington class of weights. We also give some practical recommendations regarding which methodology should be used in the presence of delayed effects depending on certain characteristics of the trial.     

Comparison of Four New General Classes of Search Designs

A factor screening experiment identifies a few important factors from a large list of factors that potentially influence the response. If a list consists of m factors each at three levels, a design is a subset of all possible 3 ^m runs. This paper considers the problem of finding designs with small numbers of runs, using the search linear model introduced in Srivastava (1975). The paper presents four new general classes of these 'search designs', each with 2 m −1 runs, which permit, at most, two important factors out of m factors to be searched for and identified. The paper compares the designs for 4 ≤ m ≤ 10, using arithmetic and geometric means of the determinants, traces and maximum characteristic roots of particular matrices. Two of the designs are found to be superior in all six criteria studied. The four designs are identical for m = 3 and this design is an optimal design in the class of all search designs under the six criteria. The four designs are also identical for m = 4 under some row and column permutations.     

Implied Preference for Seismic Design Level and Earthquake Insurance

Seismic risk can be reduced by implementing newly developed seismic provisions in design codes. Furthermore, financial protection or enhanced utility and happiness for stakeholders could be gained through the purchase of earthquake insurance. If this is not so, there would be no market for such insurance. However, perceived benefit associated with insurance is not universally shared by stakeholders partly due to their diverse risk attitudes. This study investigates the implied seismic design preference with insurance options for decisionmakers of bounded rationality whose preferences could be adequately represented by the cumulative prospect theory (CPT). The investigation is focused on assessing the sensitivity of the implied seismic design preference with insurance options to model parameters of the CPT and to fair and unfair insurance arrangements. Numerical results suggest that human cognitive limitation and risk perception can affect the implied seismic design preference by the CPT significantly. The mandatory purchase of fair insurance will lead the implied seismic design preference to the optimum design level that is dictated by the minimum expected lifecycle cost rule. Unfair insurance decreases the expected gain as well as its associated variability, which is preferred by risk-averse decisionmakers. The obtained results of the implied preference for the combination of the seismic design level and insurance option suggest that property owners, financial institutions, and municipalities can take advantage of affordable insurance to establish successful seismic risk management strategies.     

Examples of the use of an equivalence theorem in constructing optimum experimental designs for random-effects nonlinear regression models

The problem considered is that of finding an optimum measurement schedule to estimate population parameters in a nonlinear model when the patient effects are random. The paper presents examples of the use of sensitivity functions, derived from the General Equivalence Theorem for D-optimality, in the construction of optimum population designs for such schedules. With independent observations, the theorem applies to the potential inclusion of a single observation. However, in population designs the observations are correlated and the theorem applies to the inclusion of an additional measurement schedule. In one example, three groups of patients of differing size are subject to distinct schedules. Numerical, as opposed to analytical, calculation of the sensitivity function is advocated. The required covariances of the observations are found by simulation.     

Efficient designs based on orthogonal arrays of type I and type II for experiments using units ordered over time or space

For a wide variety of applications, experiments are based on units ordered over time or space. Models for these experiments generally may include one or more of: correlations, systematic trends, carryover effects and interference effects. Since the standard optimal block designs may not be efficient in these situations, orthogonal arrays of type I and type II, which were introduced in 1961 by C.R. Rao [Combinatorial arrangements analogous to orthogonal arrays, Sankhya A 23 (1961) 283–286], have been recently used to construct optimal and efficient designs for many of these experiments. Results in this area are unified and the salient features are outlined.     

Robustness of a Class of Partial Diallel Cross Designs to the Unavailability of a Complete Block of Observations

Complete and partial diallel cross designs are examined as to their construction and robustness against the loss of a block of observations. A simple generalized inverse is found for the information matrix of the line effects, which allows evaluation of expressions for the variances of the line-effect differences with and without the missing block. A-efficiencies, based on average variances of the elementary contrasts of the line-effects, suggest that these designs are fairly robust. The loss of efficiency is generally less than 10%, but it is shown that specific comparisons might suffer a loss of efficiency of as much as 40%.     

斜腿刚构桥几何布局的优化设计

采用数学规划的方法从静力和动力两方面对斜腿刚构桥的几何布局进行优化设计。静力优化设计的优化目标是截面截面应力平方均值最小，动力优化设计的优化目标是结构自振周期平方和最小。采用了直接搜索法寻优。通过算例可知，这两种优化设计方法均可行，且均为刚性设计。     

Three-level main-effects designs exploiting prior information about model uncertainty

To explore the projection efficiency of a design, Tsai, et al [2000. Projective three-level main effects designs robust to model uncertainty. Biometrika 87, 467–475] introduced the Q criterion to compare three-level main-effects designs for quantitative factors that allow the consideration of interactions in addition to main effects. In this paper, we extend their method and focus on the case in which experimenters have some prior knowledge, in advance of running the experiment, about the probabilities of effects being non-negligible. A criterion which incorporates experimenters’ prior beliefs about the importance of each effect is introduced to compare orthogonal, or nearly orthogonal, main effects designs with robustness to interactions as a secondary consideration. We show that this criterion, exploiting prior information about model uncertainty, can lead to more appropriate designs reflecting experimenters’ prior beliefs.     

Some results on optimality in models with heteroscedastic errors from partial optimum designs

This paper studies optimum designs for linear models when the errors are heteroscedastic. Sufficient conditions are given in order to obtainD-, A- andE-optimum designs for a complete regression model from partial optimum designs for some sub-parameters. A result about optimality for a complete model from the optimality for the submodels is included. Supported by Junta de Andalucía, research group FQM244.     

Optimal designs for generalized linear models

Summary This paper solves some D-optimal design problems for certain Generalized Linear Models where the mean depends on two parameters and two explanatory variables. In all of the cases considered the support point of the optimal designs are found to be independent of the unknown parameters. While in some cases the optimal design measures are given by two points with equal weights, in others the support is given by three point with weights depending on the unknown parameters, hence the designs are locally optimal in general. Empirical results on the efficiency of the locally optimal designs are also given. Some of the designs found can also be used for planning D-optimal experiments for the normal linear model, where the mean must be positive. This research was carried out in part at University College, London as an M.Sc. project. Thanks are due to Prof. I. Ford (University of Glasgow) and Prof. A. Giovagnoli (University of Perugia) for their valuable suggestions and critical observations.