Virtual Patients in Clinical Trials for Drug Development: A Narrative Review.

The pharmaceutical industry faces significant challenges due to the prolonged development timelines, high failure rates of innovative drugs, and escalating regulatory demands for robust data. A novel solution to address these challenges is the utilization of virtual patient cohorts to simulate drug effects in computer models. This review article provides an overview of the application of virtual patient cohorts in drug development and the diverse methodologies employed, based on a comprehensive literature review. Complementing previous reviews, this work emphasizes the practical applications of virtual patients across various disease conditions, especially rare diseases where patient recruitment is particularly challenging. It also highlights the challenges of conventional trial methodologies, such as limited generalizability, ethical concerns, and recruitment barriers, and discusses virtual patients as a potential solution to these longstanding issues. Since all literature was included according to the judgment of a single reviewer, a potential selection bias must be taken into account when reading this article. Virtual patients can be generated as digital twins through statistical inference or by randomly assigning parameters, followed by plausibility assessments, with the method choice depending upon study objectives and available data. These cohorts find utility across all clinical phases of drug development. The principal advantages of leveraging virtual patient cohorts include potential cost savings through heightened development success and increased innovation. Moreover, they offer improved representation of patient groups often marginalized in drug development efforts. However, it is imperative to acknowledge the computational nature of virtual patients, which can yield erroneous outcomes and necessitate substantial expertise and computational resources. Currently, there is a lack of standardized protocols for generating and utilizing virtual patient cohorts. Nonetheless, virtual patient cohorts hold promise in fundamentally transforming drug development and patient treatment approaches. By creating realistic virtual patients, more efficient and personalized drug development strategies can be pursued. Integrating this technology alongside in vitro and in vivo studies, while considering their respective limitations, might significantly enhance the success rate of drug development across the pipeline, ultimately advancing patient health outcomes.