Biometric Research Branch, EPN-8122, National Cancer Institute, Bethesda, MD 20892, USA.
J Natl Cancer Inst. 2010 Feb 3;102(3):152-60. doi: 10.1093/jnci/djp477. Epub 2010 Jan 14.
Clinical biomarker tests that aid in making treatment decisions will play an important role in achieving personalized medicine for cancer patients. Definitive evaluation of the clinical utility of these biomarkers requires conducting large randomized clinical trials (RCTs). Efficient RCT design is therefore crucial for timely introduction of these medical advances into clinical practice, and a variety of designs have been proposed for this purpose. To guide design and interpretation of RCTs evaluating biomarkers, we present an in-depth comparison of advantages and disadvantages of the commonly used designs. Key aspects of the discussion include efficiency comparisons and special interim monitoring issues that arise because of the complexity of these RCTs. Important ongoing and completed trials are used as examples. We conclude that, in most settings, randomized biomarker-stratified designs (ie, designs that use the biomarker to guide analysis but not treatment assignment) should be used to obtain a rigorous assessment of biomarker clinical utility.
临床生物标志物检测有助于制定治疗决策，将在实现癌症患者的个体化医疗方面发挥重要作用。这些生物标志物的临床实用性的明确评估需要进行大型随机临床试验 (RCT)。因此，高效的 RCT 设计对于及时将这些医学进展引入临床实践至关重要，为此提出了各种设计方案。为了指导评估生物标志物的 RCT 的设计和解释，我们深入比较了常用设计的优缺点。讨论的关键方面包括由于这些 RCT 的复杂性而出现的效率比较和特殊的中期监测问题。重要的正在进行和已完成的试验被用作示例。我们的结论是，在大多数情况下，应使用随机生物标志物分层设计（即使用生物标志物来指导分析而不是治疗分配的设计）来严格评估生物标志物的临床实用性。
