Alternative strategies in cardiac preclinical research and new clinical trial formats

• Published in: Cardiovascular research Vol. 118; no. 3; pp. 746 - 762
• Main Authors: Kreutzer, Fabian Philipp, Meinecke, Anna, Schmidt, Kevin, Fiedler, Jan, Thum, Thomas
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 21.02.2022
• Subjects: Animals; Clinical Trials as Topic; Drug Evaluation, Preclinical; Heart; Humans; Lab-On-A-Chip Devices; Organoids; Quality of Life; Reviews; Adaptive design; Alternatives to animal models; Pandemic trials; Clinical trials; 3D cell culture; Organ-on-a-chip; Preclinical research; Master protocols N-of-1 trials
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/cvab075

Abstract 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. Graphical Abstract