The Pareto approach to optimal experimental design simultaneously considers multiple objectives by constructing a set of Pareto optimal designs while explicitly considering trade-offs between opposing criteria. Various algorithms have been proposed to populate Pareto fronts of designs, and evaluating and comparing these fronts–and by extension the algorithms that produce them–is crucial. In this paper, we first propose a framework for comparing algorithm-generated Pareto fronts based on a refined hypervolume indicator. We then theWe consider the optimal design of controlled experimental epidemics or transmission experiments, whose purpose is to inform the practitioner about disease transmission and recovery rates. Our methodology employs Gaussian diffusion approximations, applicable to epidemics that can be modeled as density-dependent Markov processes and involving relatively large numbers of organisms. We focus on finding (i) the optimal times at which to collect data about the state of the system for a small number of discrete observations, (ii) the optimal numbers of susceptible and infective individuals to begin an experiment with, and (iii) the optimal number of replicate epidemics to use. We adopt the popular D-optimality criterion as providing an appropriate objective function for designing our experiments, since this leads to estimates with maximum precision, subject to valid assumptions about parameter values. We demonstrate the broad applicability of our methodology using a diverse array of compartmental epidemic models: a time-homogeneous SIS epidemic, a time-inhomogeneous SI epidemic with exponentially decreasing transmission rates and a partially observed SIR epidemic where the infectious period for an individual has a gamma distribution.oretically address how the choice of the reference point affects comparisons of Pareto fronts, and demonstrate that our approach is Pareto compliant. Based on our theoretical investigation, we provide rules for choosing reference points when two-dimensional Pareto fronts are compared. Because theoretical results for three-dimensional fronts are difficult to obtain, we propose an empirical rule for the three-dimensional case by making an analogy to the rules for two dimensions. We also consider the use of our procedure in evaluating the progress of a front-constructing algorithm, and illustrate our work with two examples from the literature.