Department of Medicine, Firestone Institute for Respiratory Health, McMaster University and The Research Institute of St. Joe's Hamilton, Hamilton, ON, Canada.
Methods Mol Biol. 2021;2299:291-321. doi: 10.1007/978-1-0716-1382-5_21.
The drug discovery pipeline, from discovery of therapeutic targets through preclinical and clinical development phases, to an approved product by health authorities, is a time-consuming and costly process, where a lead candidates' success at reaching the final stage is rare. Although the time from discovery to final approval has been reduced over the last decade, there is still potential to further optimize and streamline the evaluation process of each candidate as it moves through the different development phases. In this book chapter, we describe our preclinical strategies and overall decision-making process designed to evaluate the tolerability and efficacy of therapeutic candidates suitable for patients diagnosed with fibrotic lung disease. We also describe the benefits of conducting preliminary discovery trials, to aid in the selection of suitable primary and secondary outcomes to be further evaluated and assessed in subsequent internal and external validation studies. We outline all relevant research methodologies and protocols routinely performed by our research group and hope that these strategies and protocols will be a useful guide for biomedical and translational researchers aiming to develop safe and beneficial therapies for patients with fibrotic lung disease.
药物发现管道，从治疗靶点的发现到临床前和临床开发阶段，再到卫生当局批准的产品，是一个耗时且昂贵的过程，先导候选药物成功进入最后阶段的情况很少见。尽管过去十年中从发现到最终批准的时间已经缩短，但在候选药物通过不同的开发阶段时，仍然有潜力进一步优化和简化每个候选药物的评估过程。在本章中，我们描述了我们的临床前策略和整体决策过程，旨在评估适合诊断为肺纤维化疾病的患者的治疗候选药物的耐受性和疗效。我们还描述了进行初步发现试验的好处，以帮助选择适合进一步评估和评估的主要和次要结局，并在随后的内部和外部验证研究中进行评估。我们概述了我们研究小组常规进行的所有相关研究方法和方案，并希望这些策略和方案将为旨在为肺纤维化疾病患者开发安全有效的治疗方法的生物医学和转化研究人员提供有用的指导。
