Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Abramson Family Cancer Research Institute, Philadelphia, 19104-4283, USA.
J Transl Med. 2010 Mar 16;8:26. doi: 10.1186/1479-5876-8-26.
Correlative studies are a primary mechanism through which insights can be obtained about the bioactivity and potential efficacy of candidate therapeutics evaluated in early-stage clinical trials. Accordingly, well designed and performed early-stage correlative studies have the potential to strongly influence further clinical development of candidate therapeutic agents, and correlative data obtained from early stage trials has the potential to provide important guidance on the design and ultimate successful evaluation of products in later stage trials, particularly in the context of emerging clinical trial paradigms such as adaptive trial design. Historically the majority of early stage trials have not generated meaningful correlative data sets that could guide further clinical development of the products under evaluation. In this review article we will discuss some of the potential limitations with the historical approach to performing correlative studies that might explain at least in part the to-date overall failure of such studies to adequately support clinical trial development, and present emerging thought and approaches related to comprehensiveness and quality that hold the promise to support the development of correlative plans which will provide meaningful correlative data that can effectively guide and support the clinical development path for candidate therapeutic agents.
相关性研究是一种主要机制，可以深入了解在早期临床试验中评估的候选治疗药物的生物活性和潜在疗效。因此，精心设计和执行的早期相关性研究有可能强烈影响候选治疗药物的进一步临床开发，并且从早期试验中获得的相关性数据有可能为产品在后期试验中的设计和最终成功评估提供重要指导，特别是在新兴临床试验模式（如适应性试验设计）的背景下。从历史上看，大多数早期试验并未产生有意义的相关性数据集，这些数据集可以指导正在评估的产品的进一步临床开发。在这篇综述文章中，我们将讨论在进行相关性研究方面历史方法存在的一些潜在局限性，这些局限性至少可以部分解释迄今为止此类研究未能充分支持临床试验开发的总体失败，并介绍与全面性和质量相关的新兴思想和方法，这些方法有可能支持相关性计划的开发，这些计划将提供有意义的相关性数据，能够有效地指导和支持候选治疗药物的临床开发路径。
