Alternative strategies in cardiac preclinical research and new clinical trial formats

An efficient and safe drug development process is crucial for the establishment of new drugs on the market aiming to increase quality of life and life-span of our patients. Despite technological advances in the past decade, successful launches of drug candidates per year remain low. We here give an overview about some of these advances and suggest improvements for implementation to boost preclinical and clinical drug development with a focus on the cardiovascular field. We highlight advantages and disadvantages of animal experimentation and thoroughly review alternatives in the field of three-dimensional cell culture as well as preclinical use of spheroids and organoids. Microfluidic devices and their potential as organ-on-a-chip systems, as well as the use of living animal and human cardiac tissues are additionally introduced. In the second part, we examine recent gold standard randomized clinical trials and present possible modifications to increase lead candidate throughput: adaptive designs, master protocols, and drug repurposing. In silico and N-of-1 trials have the potential to redefine clinical drug candidate evaluation. Finally, we briefly discuss clinical trial designs during pandemic times.

Automated summary

An efficient and safe drug development process plays a crucial role in improving patients' quality of life and lifespan. This article provides an overview of recent technological advances in the field of cardiovascular drug development and suggests improvements to enhance preclinical and clinical drug development. It discusses the advantages and disadvantages of animal experimentation and explores alternative methods such as three-dimensional cell culture, spheroids, and organoids. The potential of microfluidic devices as organ-on-a-chip systems and the use of living animal and human cardiac tissues are also introduced. The article further examines recent randomized clinical trials and proposes modifications to increase lead candidate throughput. In addition, it explores the potential of in silico and N-of-1 trials to redefine the evaluation of clinical drug candidates. Finally, it briefly discusses clinical trial designs during pandemic times.