Department of Experimental Neurology, Charité-Universitätsmedizin, Berlin, Germany.
BIH QUEST Center for Transforming Biomedical Research, Berlin Institute of Health, Berlin, Germany.
Elife. 2021 Jan 12;10:e62101. doi: 10.7554/eLife.62101.
The purpose of preclinical research is to inform the development of novel diagnostics or therapeutics, and the results of experiments on animal models of disease often inform the decision to conduct studies in humans. However, a substantial number of clinical trials fail, even when preclinical studies have apparently demonstrated the efficacy of a given intervention. A number of large-scale replication studies are currently trying to identify the factors that influence the robustness of preclinical research. Here, we discuss replications in the context of preclinical research trajectories, and argue that increasing validity should be a priority when selecting experiments to replicate and when performing the replication. We conclude that systematically improving three domains of validity - internal, external and translational - will result in a more efficient allocation of resources, will be more ethical, and will ultimately increase the chances of successful translation.
临床前研究的目的是为新的诊断或治疗方法提供信息,并且疾病动物模型实验的结果通常会影响在人类中进行研究的决策。然而,即使在临床前研究显然证明了某种干预措施的有效性的情况下,仍有大量临床试验失败。目前,许多大规模的复制研究正试图确定影响临床前研究稳健性的因素。在这里,我们在临床前研究轨迹的背景下讨论了复制,并认为在选择要复制的实验和进行复制时,提高有效性应该是优先事项。我们的结论是,系统地提高内部、外部和转化三个有效性领域的水平将导致更有效地分配资源,更符合伦理道德,并最终增加成功转化的机会。