Historical Advances in Clinical Trial Design and Expanding Representation as the New Frontier for Innovation.

Abstract

Since its establishment in 1962, the Vaccine and Treatment Evaluation Units (VTEUs) have employed cutting-edge technologies to develop novel vaccines and therapeutics to mitigate emerging public health threats in the United States and globally. Clinical trial innovation has been the hallmark of these efforts as novel approaches to testing countermeasures are investigated in pace with advances in technology and evolving public health needs. The spectrum of trials conducted by the VTEUs ranges from proof-of-concept or first-in-human phase 1 to late-phase trials that establish efficacy and inform licensure decisions or "real world" vaccine usage such as with the coronavirus disease 2019 (COVID-19) and rotavirus mix-and-match trials aimed to inform standard of care. The VTEUs have also been instrumental in developing experimental wild-type challenge studies to preliminarily assess vaccine immunogenicity against influenza, shigellosis, cholera, enterotoxigenic Escherichia coli, enteropathogenic E. coli, and malaria to help select promising vaccine candidates for further development. During the COVID-19 pandemic, novel strategies for recruitment and improved accessibility of vaccine clinical trials emerged. However, the pandemic also highlighted the need for improved representation in clinical trials and underscored the importance of community engagement. As we consider what challenges to address in the upcoming years, engagement of the population in clinical trials is critical to establishing safety and efficacy and community acceptance of vaccines and therapeutics. It is imperative to develop skills that engender community advocacy while staying on the cutting edge of science, henceforth serving as the guideposts for new frontiers in clinical trial innovation.