Designing longitudinal studies is generally a very challenging problem because of the complex optimization problems. We show the popular nature-inspired metaheuristic algorithm, Particle Swarm Optimization (PSO), can find different types of optimal exact designs for longitudinal studies with different correlation structures for different types of models. In particular, we demonstrate PSO-generated D-optimal longitudinal studies for the widely used Michaelis-Menten model with various correlation structures agree with the reported analytically derived locally D-optimal designs in the literature when there are only 2 observations per subject, and their numerical D-optimal designs when there are 3 and 4 observations per subject. We further show the usefulness of PSO by applying it to generate new locally D-optimal designs to estimate model parameters when there are 5 or more observations per subject. Additionally, we find various optimal longitudinal designs for a growth curve model commonly used in animal studies and for a nonlinear HIV dynamic model for studying T-cells in AIDS subjects. In particular, c-optimal exact designs for estimating one or more functions of model parameters (c-optimality) were found, along with other types of multiple objectives optimal designs.
The continuation-ratio (CR) model is frequently used in dose response studies to model a three-category outcome as the dose levels vary. Design issues for a CR model defined on an unrestricted dose interval have been discussed for estimating model parameters or a selected function of the model parameters. This paper uses metaheuristics to address design issues for a CR model defined on any compact dose interval when there are one or more objectives in the study and some are more important than others. Specifically, we use an exemplary nature-inspired metaheuristic algorithm called particle swarm optimization (PSO) to find locally optimal designs for estimating a few interesting functions of the model parameters, such as the most effective dose ($MED$), the maximum tolerated dose ($MTD$) and for estimating all parameters in a CR model. We demonstrate that PSO can efficiently find locally multiple-objective optimal designs for a CR model on various dose intervals and a small simulation study shows it tends to outperform the popular deterministic cocktail algorithm (CA) and another competitive metaheuristic algorithm called differential evolutionary (DE). We also discuss hybrid algorithms and their flexible applications to design early Phase 2 trials or tackle biomedical problems, such as different strategies for handling the recent pandemic.