No Arabic abstract
We propose a method for constructing optimal block designs for experiments on networks. The response model for a given network interference structure extends the linear network effects model to incorporate blocks. The optimality criteria are chosen to reflect the experimental objectives and an exchange algorithm is used to search across the design space for obtaining an efficient design when an exhaustive search is not possible. Our interest lies in estimating the direct comparisons among treatments, in the presence of nuisance network effects that stem from the underlying network interference structure governing the experimental units, or in the network effects themselves. Comparisons of optimal designs under different models, including the standard treatment models, are examined by comparing the variance and bias of treatment effect estimators. We also suggest a way of defining blocks, while taking into account the interrelations of groups of experimental units within a network, using spectral clustering techniques to achieve optimal modularity. We expect connected units within closed-form communities to behave similarly to an external stimulus. We provide evidence that our approach can lead to efficiency gains over conventional designs such as randomized designs that ignore the network structure and we illustrate its usefulness for experiments on networks.
Blocking is often used to reduce known variability in designed experiments by collecting together homogeneous experimental units. A common modelling assumption for such experiments is that responses from units within a block are dependent. Accounting for such dependencies in both the design of the experiment and the modelling of the resulting data when the response is not normally distributed can be challenging, particularly in terms of the computation required to find an optimal design. The application of copulas and marginal modelling provides a computationally efficient approach for estimating population-average treatment effects. Motivated by an experiment from materials testing, we develop and demonstrate designs with blocks of size two using copula models. Such designs are also important in applications ranging from microarray experiments to experiments on human eyes or limbs with naturally occurring blocks of size two. We present methodology for design selection, make comparisons to existing approaches in the literature and assess the robustness of the designs to modelling assumptions.
In paired comparison experiments respondents usually evaluate pairs of competing options. For this situation we introduce an appropriate model and derive optimal designs in the presence of second-order interactions when all attributes are dichotomous.
Optimal two-treatment, $p$ period crossover designs for binary responses are determined. The optimal designs are obtained by minimizing the variance of the treatment contrast estimator over all possible allocations of $n$ subjects to $2^p$ possible treatment sequences. An appropriate logistic regression model is postulated and the within subject covariances are modeled through a working correlation matrix. The marginal mean of the binary responses are fitted using generalized estimating equations. The efficiencies of some crossover designs for $p=2,3,4$ periods are calculated. The effect of misspecified working correlation matrix on design efficiency is also studied.
Interval designs are a class of phase I trial designs for which the decision of dose assignment is determined by comparing the observed toxicity rate at the current dose with a prespecified (toxicity tolerance) interval. If the observed toxicity rate is located within the interval, we retain the current dose; if the observed toxicity rate is greater than the upper boundary of the interval, we deescalate the dose; and if the observed toxicity rate is smaller than the lower boundary of the interval, we escalate the dose. The most critical issue for the interval design is choosing an appropriate interval so that the design has good operating characteristics. By casting dose finding as a Bayesian decision-making problem, we propose new flexible methods to select the interval boundaries so as to minimize the probability of inappropriate dose assignment for patients. We show, both theoretically and numerically, that the resulting optimal interval designs not only have desirable finite- and large-sample properties, but also are particularly easy to implement in practice. Compared to existing designs, the proposed (local) optimal design has comparable average performance, but a lower risk of yielding a poorly performing clinical trial.
The issue of determining not only an adequate dose but also a dosing frequency of a drug arises frequently in Phase II clinical trials. This results in the comparison of models which have some parameters in common. Planning such studies based on Bayesian optimal designs offers robustness to our conclusions since these designs, unlike locally optimal designs, are efficient even if the parameters are misspecified. In this paper we develop approximate design theory for Bayesian $D$-optimality for nonlinear regression models with common parameters and investigate the cases of common location or common location and scale parameters separately. Analytical characterisations of saturated Bayesian $D$-optimal designs are derived for frequently used dose-response models and the advantages of our results are illustrated via a numerical investigation.