Evaluating Field Trial Designs for Genetically Modified Mosquito Interventions: An In-Silico Simulation Approach

Mosquito control strategies based on the mass release of modified males, such as genetically modified mosquitoes (GMMs), aim to suppress wild populations by impairing reproduction. Evaluating these interventions requires resource-intensive field trials, but a lack of standardized implementation practices, particularly regarding release ratios of modified males to wild female mosquitoes and trial timing, has led to variable outcomes. This study's objective is to propose a modeling tool for the "in-silico" simulation of trial designs before field implementation. To this aim, we developed an agent-based model of mosquito population dynamics. As a case study, we calibrated the model using 2019-2023 Aedes aegypti surveillance data from Miami-Dade County, Florida, and compared two GMM trial designs: a "constant-release" design (fixed releases based on a baseline entomological survey) and an "adaptive-release" design (releases adjusted weekly to the population of the control arm). Our results show that the constant-release design's effectiveness is highly dependent on the trial's start date relative to mosquito seasonality, creating large outcome uncertainty. For a 6-month trial with a 4:1 GMM:wild ratio and constant-release, the median effectiveness across all start dates was 71.4%, with an interquartile range (IQR) spanning from 55.3% to 90.0%. In contrast, the adaptive-release design yielded similar median effectiveness but with a narrower IQR regardless of the start date, trial duration, and release ratio. Overall, effectiveness is closely linked to the total number of mosquitoes released but also dependent on the timing, frequency of releases, release ratio, mosquito fitness, and duration of interventions. Our findings suggest that "in-silico" simulation is a valuable tool for improving trial protocol design, allowing stakeholders to test strategies and reduce outcome uncertainty before committing to a fieldwork experiment.