Shi Qian, Sargent Daniel J
Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Int J Clin Oncol. 2009 Apr;14(2):102-11. doi: 10.1007/s10147-009-0885-4. Epub 2009 Apr 24.
The identification and validation of putative surrogate endpoints in oncology is a great challenge to medical investigators, statisticians, and regulators. A putative surrogate endpoint must be validated at both individual-level and trial-level before it can be used to replace the clinical endpoint in a future clinical trial. Recently, meta-analytic methods for evaluating potential surrogates have become widely accepted in cancer clinical trials. In this review, after addressing multiple complications and general issues surrounding surrogate endpoints, we review various proposed and adopted meta-analytic methodologies pertaining to the application of these methods to oncology clinical trials with different tumor types. In oncology, several applications have successfully identified useful surrogates. For example, disease-free survival and progression-free survival have been validated through meta-analyses as acceptable surrogates for overall survival in adjuvant colon cancer and advanced colorectal cancer, respectively. We also discuss several limitations of surrogate endpoints, including the critical issues that the extrapolation of the validity of a surrogate is always context-dependent and that such extrapolation should be exercised with caution.
在肿瘤学中，确定和验证假定的替代终点对医学研究人员、统计学家和监管机构来说是一项巨大挑战。一个假定的替代终点必须在个体层面和试验层面都得到验证，才能在未来的临床试验中用于替代临床终点。最近，用于评估潜在替代指标的荟萃分析方法在癌症临床试验中已被广泛接受。在本综述中，在解决围绕替代终点的多种复杂情况和一般问题之后，我们回顾了各种已提出并采用的荟萃分析方法，这些方法涉及将这些方法应用于不同肿瘤类型的肿瘤学临床试验。在肿瘤学中，一些应用已成功识别出有用的替代指标。例如，无病生存期和无进展生存期已通过荟萃分析分别被验证为辅助性结肠癌和晚期结直肠癌总生存期的可接受替代指标。我们还讨论了替代终点的几个局限性，包括关键问题，即替代指标有效性的外推始终依赖于具体情况，并且这种外推应谨慎进行。
