Introducing an Artificial Neural Network for Virtually Increasing the Sample Size of Bioequivalence Studies

Sample size is a key factor in bioequivalence and clinical trials. An appropriately large sample is necessary to gain valuable insights into a designated population. However, large sample sizes lead to increased human exposure, costs, and a longer time for completion. In a previous study, we introduced the idea of using variational autoencoders (VAEs), a type of artificial neural network, to synthetically create in clinical studies. In this work, we further elaborate on this idea and expand it in the field of bioequivalence (BE) studies. A computational methodology was developed, combining Monte Carlo simulations of 2 × 2 crossover BE trials with deep learning algorithms, specifically VAEs. Various scenarios, including variability levels, the actual sample size, the VAE-generated sample size, and the difference in performance between the two pharmaceutical products under comparison, were explored. All simulations showed that incorporating AI generative algorithms for creating virtual populations in BE trials has many advantages, as less actual human data can be used to achieve similar, and even better, results. Overall, this work shows how the application of generative AI algorithms, like VAEs, in clinical/bioequivalence studies can be a modern tool to significantly reduce human exposure, costs, and trial completion time.