Validation of novel imaging methodologies for use as cancer clinical trial end-points
Validation of novel imaging methodologies for use as cancer clinical trial end-points
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DOI：
10.1016/j.ejca.2008.10.030
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发表时间：
2009-01-01
影响因子：
8.4
通讯作者：
Shankar, L. K.
中科院分区：
文献类型：
--
作者：
Sargent, D. J.;Rubinstein, L.;Shankar, L. K.
任何阶段的临床试验的成功或失败，关键取决于适当的主要终点的选择。在II期和III期癌症临床试验的背景下，成像终点在历史上并且目前继续在确定治疗功效中发挥主要作用。本文的主要目的是讨论基于成像的标志物作为癌症治疗II期临床试验终点的有效性。具体而言，我们概述了必须考虑的问题，以及需要满足的标准，以补充或可能取代RECIST定义的肿瘤状态作为II期临床试验终点的成像终点。建议用于判断新终点效用的关键标准主要涉及其准确和可重复预测最终III期终点治疗效果的能力，通常通过两组之间无进展生存期或总生存期的差异进行评估，无论是在患者还是更重要的是在试验水平。正如将要证明的那样，正式和充分验证新的成像标记物作为II期试验的适当终点所需的证据水平是相当大的。在许多情况下，只有通过进行一系列协调的前瞻性设计的多中心临床试验，最终进行正式的荟萃分析，才能获得这种水平的证据。我们还讨论了相对于理想的严格评估，可能需要灵活性的情况，以适应不可避免的现实世界的可行性约束。(C)2008爱思唯尔有限公司保留所有权利。
The success or failure of a clinical trial, of any phase, depends critically on the choice of an appropriate primary end-point. In the setting of phases II and III cancer clinical trials, imaging end-points have historically, and continue presently to play a major role in determining therapeutic efficacy. The primary goal of this paper is to discuss the validation of imaging-based markers as end-points for phase II clinical trials of cancer therapy. Specifically, we outline the issues that must be considered, and the criteria that would need to be satisfied, for an imaging end-point to supplement or potentially replace RECIST-defined tumour status as a phase II clinical trial end-point. The key criteria proposed to judge the utility of a new end-point primarily relate to its ability to accurately and reproducibly predict the eventual phase III end-point for treatment effect, which is usually assessed by a difference between two arms on progression free or overall survival, both at the patient and more importantly at the trial level. As will be demonstrated, the level of evidence required to formally and fully validate a new imaging marker as an appropriate end-point for phase II trials is substantial. In many cases, this level of evidence will only become available by conducting a series of coordinated prospectively designed multicentre clinical trials culminating in a formal meta-analysis. We also include a discussion of situations where flexibility may be required, relative to the ideal rigorous evaluation, to accommodate inevitable real-world feasibility constraints. (C) 2008 Elsevier Ltd. All rights reserved.