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.     

Causal inferences on the effectiveness of complex social programs: Navigating assumptions,sources of complexity and evaluation design challenges

This paper explores avenues for navigating evaluation design challenges posed by complex social programs (CSPs) and their environments when conducting studies that call for generalizable, causal inferences on the intervention’s effectiveness. A definition is provided of a CSP drawing on examples from different fields, and an evaluation case is analyzed in depth to derive seven (7) major sources of complexity that typify CSPs, threatening assumptions of textbook-recommended experimental designs for performing impact evaluations. Theoretically-supported, alternative methodological strategies are discussed to navigate assumptions and counter the design challenges posed by the complex configurations and ecology of CSPs. Specific recommendations include: sequential refinement of the evaluation design through systems thinking, systems-informed logic modeling; and use of extended term, mixed methods (ETMM) approaches with exploratory and confirmatory phases of the evaluation. In the proposed approach, logic models are refined through direct induction and interactions with stakeholders. To better guide assumption evaluation, question-framing, and selection of appropriate methodological strategies, a multiphase evaluation design is recommended.     

Step-wise group screening designs with errors in observations

The performance of step-wise group screening In terms of the expected number of runs and the expected number of incorrect decisions, Is considered. A method for obtaining optimal step-wise designs Is presented, for the cases in which the direction of each defective factor is assumed to be known a-priori and the observations are subject to error.     

Characterization of singular balanced fractional sm factorial designs derivable from balanced arrays with maximum number of constraints

An upper bound on the maximum number of constraints for s-symbol balanced arrays is derived. It is shown that balanced fractional s^m factorial designs derived from some balanced arrays with the maximum possible number of constraints become singular.     

Construction of minimum aberration blocked two-level regular factorial designs

ABSTRACT

In this article, we consider the construction of minimum aberration 2^{n ? k}: 2^p designs with respect to some existing combined wordlength patterns, where a 2^{n ? k}: 2^p design is a blocked two-level design with n treatment factors, 2^p blocks, and N = 2^q runs with q = n ? k. Two methods are proposed for two situations: n ? 2^{q ? p} ? 1 and n > N/2. These methods enable us to obtain some new minimum aberration 2^{n ? k}: 2^p designs from existing minimum aberration unblocked and blocked designs. Examples are included to illustrate the theory.     

Supersaturated design including an orthogonal base

Recently, many supersaturated designs have been proposed. A supersaturated design is a fractional factorial design in which the number of factors is greater than the number of experimental runs. The main thrust of the previous studies has been to generate more columns while avoiding large values of squared inner products among all design columns. These designs would be appropriate if the probability for each factor being active is uniformly distributed. When factors can be partitioned into two groups, namely, with high and low probabilities of each factor being active, it is desirable to maintain orthogonality among columns to be assigned to the factors in the high-probability group. We discuss a supersaturated design including an orthogonal base which is suitable for this common situation. Mathematical results on the existence of the supersaturated designs are shown, and the construction of supersaturated designs is presented. We next discuss some properties of the proposed supersaturated designs based on the squared inner products.     

On the optimality of a class of minimal covering designs

It is shown that the minimal covering designs for v=6t+5 treatments in blocks of size 3 are optimal w.r.t. a large class of optimality criteria. This class of optimality criteria includes the well-known criteria of A-, D- and E-optimality. It is conjectured that these designs are also optimal w.r.t. other criteria suggested by Takeuchi (1961).     

Estimation of parameters in survey sampling: Optimality

Some recent works on estimation in survey sampling are analyzed and extended from the perspective of the theory of optimal estimating functions.