College of Medicine, University of Arizona Health Sciences, Tucson, Arizona.
College of Medicine, University of Arizona Health Sciences, Tucson, Arizona.
Transl Res. 2020 Dec;226:105-115. doi: 10.1016/j.trsl.2020.06.010. Epub 2020 Jun 26.
Recent innovations in translational research have ushered an exponential increase in the discovery of novel biomarkers, thereby elevating the hope for deeper insights into "personalized" medicine approaches to disease phenotyping and care. However, a critical gap exists between the fast pace of biomarker discovery and the successful translation to clinical use. This gap underscores the fundamental biomarker conundrum across various acute and chronic disorders: how does a biomarker address a specific unmet need? Additionally, the gap highlights the need to shift the paradigm from a focus on biomarker discovery to greater translational impact and the need for a more streamlined drug approval process. The unmet need for biomarkers in acute respiratory distress syndrome (ARDS) is for reliable and validated biomarkers that minimize heterogeneity and allow for stratification of subject selection for enrollment in clinical trials of tailored therapies. This unmet need is particularly highlighted by the ongoing SARS-CoV-2/COVID-19 pandemic. The unprecedented numbers of COVID-19-induced ARDS cases has strained health care systems across the world and exposed the need for biomarkers that would accelerate drug development and the successful phenotyping of COVID-19-infected patients at risk for development of ARDS and ARDS mortality. Accordingly, this review discusses the current state of ARDS biomarkers in the context of the drug development pipeline and highlight gaps between biomarker discovery and clinical implementation while proposing potential paths forward. We discuss potential ARDS biomarkers by category and by context of use, highlighting progress in the development continuum. We conclude by discussing challenges to successful translation of biomarker candidates to clinical impact and proposing possible novel strategies.
近年来，转化研究的创新带来了新型生物标志物的发现呈指数级增长，从而为深入了解疾病表型和治疗的“个体化”医学方法带来了更大的希望。然而，在生物标志物的发现速度和成功转化为临床应用之间存在着一个关键的差距。这一差距突显了各种急性和慢性疾病中存在的基本生物标志物难题：生物标志物如何解决特定的未满足的需求？此外，这一差距还强调了需要将重点从生物标志物的发现转移到更大的转化影响，并需要更精简的药物审批流程。急性呼吸窘迫综合征（ARDS）对生物标志物的未满足需求是需要可靠和经过验证的生物标志物，以最大限度地减少异质性，并允许对接受个体化治疗临床试验的受试者进行分层选择。这一未满足的需求在当前的 SARS-CoV-2/COVID-19 大流行中尤为突出。COVID-19 引起的 ARDS 病例数量之多前所未有，使世界各地的医疗系统都承受了压力，这凸显了需要生物标志物来加速药物开发，并对有发生 ARDS 和 ARDS 死亡风险的 COVID-19 感染患者进行成功的表型分析。因此，本综述讨论了 ARDS 生物标志物在药物开发管道中的现状，并强调了生物标志物发现与临床实施之间的差距，同时提出了潜在的前进方向。我们按类别和使用背景讨论了潜在的 ARDS 生物标志物，突出了开发连续体中的进展。最后，我们讨论了将生物标志物候选物成功转化为临床影响所面临的挑战，并提出了可能的新策略。
