Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany.
REBIRTH Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.
Cardiovasc Res. 2022 Feb 21;118(3):746-762. doi: 10.1093/cvr/cvab075.
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.
建立旨在提高患者生活质量和延长寿命的新药市场，需要高效且安全的药物开发流程。尽管过去十年技术取得了进步，但每年成功推出的候选药物数量仍然很低。在此，我们概述了其中的一些进展，并提出了实施建议，以推动以心血管领域为重点的临床前和临床药物开发。我们强调了动物实验的优缺点，并彻底审查了三维细胞培养领域以及球体和类器官的临床前应用的替代方案。微流控设备及其作为器官芯片系统的潜力，以及活体动物和人类心脏组织的使用也被引入。在第二部分中，我们检查了最近的黄金标准随机临床试验，并提出了可能的修改方案，以提高先导候选药物的通量：适应性设计、主方案和药物再利用。计算和 N-of-1 试验有可能重新定义临床候选药物的评估。最后，我们简要讨论了大流行时期的临床试验设计。
