Department of Equity, Ethics and Policy, Rm 1155, School of Population and Global Health, McGill University, 2001 McGill College, Montreal, QC H3A 1L7, Canada.
Department of Equity, Ethics and Policy, Rm 1155, School of Population and Global Health, McGill University, 2001 McGill College, Montreal, QC H3A 1L7, Canada.
Med. 2024 Oct 11;5(10):1227-1236. doi: 10.1016/j.medj.2024.07.014. Epub 2024 Aug 7.
Early-phase trials and innovative care draw support from basic science, preclinical studies, and clinical research. Such evidential diversity presents a challenge for traditional ways of synthesizing evidence. In what follows, we review the limitations of existing approaches for communicating supporting evidence for early-phase trials. We then offer a structured approach, PATH (preclinical assessment for translation to humans). PATH is grounded in the premise that the case for administering novel strategies to patients requires connecting the dots between nine mechanistic steps supporting a clinical claim. Using PATH entails first parsing supporting evidence, assessing the strength of evidence at each step, and then assessing the strength of a chain of evidence linking drug administration to clinical effect. While PATH requires further refinement, the approach reduces some of the opacity, arbitrariness, and biases in current ways of presenting and assessing scientific support for early-phase trials and innovative care.
早期阶段的试验和创新护理得到基础科学、临床前研究和临床研究的支持。这种证据多样性对传统的综合证据方法提出了挑战。在接下来的内容中，我们将回顾现有的沟通早期阶段试验支持证据方法的局限性。然后，我们提供了一种结构化的方法，即 PATH（转化至人体的临床前评估）。PATH 的基本前提是，向患者应用新型策略的理由需要在支持临床主张的九个机制步骤之间建立联系。使用 PATH 需要首先解析支持性证据，评估每个步骤的证据强度，然后评估将药物给药与临床效果联系起来的证据链的强度。虽然 PATH 需要进一步完善，但该方法减少了目前呈现和评估早期阶段试验和创新护理科学支持的一些不透明性、任意性和偏见。
