Extended two-stage adaptive designswith three target responses forphase II clinical trials

We develop a nature-inspired stochastic population-based algorithm and call it discrete particle swarm optimization tofind extended two-stage adaptive optimal designs that allow three target response rates for the drug in a phase II trial.Our proposed designs include the celebrated Simon’s two-stage design and its extension that allows two target responserates to be specified for the drug. We show that discrete particle swarm optimization not only frequently outperformsgreedy algorithms, which are currently used to find such designs when there are only a few parameters; it is also capableof solving design problems posed here with more parameters that greedy algorithms cannot solve. In stage 1 of ourproposed designs, futility is quickly assessed and if there are sufficient responders to move to stage 2, one tests one ofthe three target response rates of the drug, subject to various user-specified testing error rates. Our designs aretherefore more flexible and interestingly, do not necessarily require larger expected sample size requirements thantwo-stage adaptive designs. Using a real adaptive trial for melanoma patients, we show our proposed design requires onehalf fewer subjects than the implemented design in the study

On optimal designs for clinical trials: An updated review

Optimization of clinical trial designs can help investigators achieve higher qualityresults for the given resource constraints. The present paper gives an overviewof optimal designs for various important problems that arise in different stages ofclinical drug development, including phase I dose–toxicity studies; phase I/II studiesthat consider early efficacy and toxicity outcomes simultaneously; phase IIdose–response studies driven by multiple comparisons (MCP), modeling techniques(Mod), or their combination (MCP–Mod); phase III randomized controlled multiarmmulti-objective clinical trials to test difference among several treatment groups;and population pharmacokinetics–pharmacodynamics experiments. We find thatmodern literature is very rich with optimal design methodologies that can be utilizedby clinical researchers to improve efficiency of drug development

T-optimal designs formulti-factor polynomial regressionmodelsvia a semidefinite relaxation method

We consider T-optimal experiment design problems for discriminating multi-factor polynomial regression models wherethe design space is defined by polynomial inequalities and the regression parameters are constrained to given convex sets.Our proposed optimality criterion is formulated as a convex optimization problem with a moment cone constraint. When theregression models have one factor, an exact semidefinite representation of the moment cone constraint can be applied to obtainan equivalent semidefinite program.When there are two or more factors in the models, we apply a moment relaxation techniqueand approximate the moment cone constraint by a hierarchy of semidefinite-representable outer approximations. When therelaxation hierarchy converges, an optimal discrimination design can be recovered from the optimal moment matrix, and itsoptimality can be additionally confirmed by an equivalence theorem. The methodology is illustrated with several examples

Minimum aberration designs for discrete choice experiments

A discrete choice experiment (DCE) is a survey method that givesinsight into individual preferences for particular attributes.Traditionally, methods for constructing DCEs focus on identifyingthe individual effect of each attribute (a main effect). However, aninteraction effect between two attributes (a two-factor interaction)better represents real-life trade-offs, and provides us a better understandingof subjects’ competing preferences. In practice it is oftenunknown which two-factor interactions are significant. To address theuncertainty, we propose the use of minimum aberration blockeddesigns to construct DCEs. Such designs maximize the number ofmodels with estimable two-factor interactions in a DCE with two-levelattributes. We further extend the minimum aberration criteria toDCEs with mixed-level attributes and develop some general theoreticalresults

d-QPSO: A Quantum-Behaved Particle Swarm Technique for Finding D-Optimal Designs With Discrete and Continuous Factors and a Binary Response

Identifying optimal designs for generalized linear models with a binary response can be a challengingtask, especially when there are both discrete and continuous independent factors in the model. Theoreticalresults rarely exist for such models, and for the handful that do, they usually come with restrictive assumptions.In this article, we propose the d-QPSO algorithm, a modified version of quantum-behaved particleswarm optimization, to find a variety of D-optimal approximate and exact designs for experiments withdiscrete and continuous factors and a binary response. We show that the d-QPSO algorithm can efficientlyfind locally D-optimal designs even for experiments with a large number of factors and robust pseudo-Bayesian designs when nominal values for the model parameters are not available. Additionally, we investigaterobustness properties of the d-QPSO algorithm-generated designs to variousmodel assumptions andprovide real applications to design a bio-plastics odor removal experiment, an electronic static experiment,and a 10-factor car refueling experiment. Supplementary materials for the article are available online