Validation of surrogate endpoints in advanced solid tumors: systematic review of statistical methods, results, and implications for policy makers.

摘要: Objectives: Licensing of, and coverage decisions on, new therapies should rely on evidence from patient-relevant endpoints such as overall survival (OS). Nevertheless, surrogate may also be useful, it not only expedite the regulatory approval of but inform decisions. It is, therefore, essential that candidate properly validated. However, there is no consensus statistical methods for validation how thus derived applied by policy makers. Methods: We review current approaches to surrogate-endpoint based meta-analysis in various advanced-tumor settings. assessed suitability two surrogates (progression-free [PFS] time-to-progression [TTP]) using three frameworks: Elston Taylor's framework, German Institute Quality Efficiency Health Care's (IQWiG) framework Biomarker-Surrogacy Evaluation Schema (BSES3). Results: A wide variety have been used assess surrogacy. The strength association between OS was generally low. level (observation-level versus treatment-level) available varied considerably cancer type, evaluation tools always consistent even within one specific type. Conclusions: Not all solid tumors treatment-level PFS or TTP has investigated. According IQWiG's achieved acceptable surrogacy metastatic colorectal ovarian treated with cytotoxic agents. Our study emphasizes challenges importance building development frameworks.