F. Hoffmann-La Roche AG, Basel, Switzerland.
Genentech Inc. - A Member of the Roche Group, South San Francisco, USA.
Ther Innov Regul Sci. 2021 Sep;55(5):1066-1074. doi: 10.1007/s43441-021-00308-6. Epub 2021 May 27.
Next-generation sequencing (NGS) and decreased costs of genomic testing are changing the paradigm in precision medicine and continue to fuel innovation. Integration of NGS into clinical drug development has the potential to accelerate clinical trial conduct and ultimately will shape the landscape of clinical care by making it easier to identify patients who would benefit from particular therapy(ies) and to monitor treatment outcomes with less invasive tests. This has led to an increased use of NGS service providers by pharmaceutical sponsors: to screen patients for clinical trials eligibility and for patient stratification, expanded Companion Diagnostic (CDx) development for treatment recommendations and Comprehensive Genomic profiling (CGP). These changes are reshaping the face of clinical quality considerations for precision medicine. Although some clinical quality considerations do exist in Health Authorities (HA) guidances and regulations (e.g., International Conference of Harmonization Good Clinical Practices-GCP), there is currently no holistic GxP-like detailed framework for pharmaceutical sponsors using NGS service providers in clinical trials, or for the development of CDx and CGP. In this research, we identified existing and applicable regulations, guidelines and recommendations that could be translated into clinical quality considerations related to technology, data quality, patients and oversight. We propose these considerations as a basis for pharmaceutical sponsors using NGS service providers in clinical drug development to develop a set of guidelines for NGS clinical quality.
下一代测序 (NGS) 和基因组检测成本的降低正在改变精准医学的范式，并继续推动创新。将 NGS 整合到临床药物开发中有可能加速临床试验的进行，并最终通过更容易识别将从特定治疗中受益的患者以及使用侵入性较小的测试来监测治疗效果，从而改变临床护理的格局。这导致制药赞助商越来越多地使用 NGS 服务提供商：筛选临床试验的患者资格和患者分层，扩大伴随诊断 (CDx) 的开发以提供治疗建议和综合基因组分析 (CGP)。这些变化正在重塑精准医学临床质量考虑的面貌。尽管在卫生当局 (HA) 的指南和法规中存在一些临床质量考虑因素（例如，国际协调会议良好临床规范-GCP），但目前尚无针对制药赞助商在临床试验中使用 NGS 服务提供商或开发 CDx 和 CGP 的整体类似 GxP 的详细框架。在这项研究中，我们确定了现有的和适用的法规、指南和建议，这些法规、指南和建议可以转化为与技术、数据质量、患者和监督相关的临床质量考虑因素。我们建议将这些考虑因素作为制药赞助商在临床药物开发中使用 NGS 服务提供商的基础，制定一套 NGS 临床质量指南。
