Background Although use of comprehensive genomic profiling (CGP) was approved by a novel CMS/FDA parallel review process, the quality of the supporting evidence is unclear. We evaluated the rigor of the peer-reviewed literature cited in the National Coverage Determination Memorandum for the FoundationOne CDx (F1CDx). Methods We identified studies cited in the memorandum. Two independent researchers evaluated each study and applied a modified version of the Fryback and Thornbury hierarchy[1], an established framework for evaluating the efficacy of diagnostic tests. Studies focused on clinical outcomes were then categorized by study design, guided by recommendations from the Center for Medical Technology Policy. Results The sample included 113 scientific studies. The majority (n = 60, 53.1%) used CGP outside the course of clinical care, and there was significant heterogeneity in the cancer types assessed and sequencing depth. We found 8 (7.1%) studies that assessed whether clinical care had changed due to CGP testing, and 38 (33.6%) assessed clinical outcomes. After excluding studies that tested for five or fewer genomic alterations, 25 remained in the clinical outcomes sample: Of these, only one included a comparator group that did not receive CGP testing. Only four studies used F1CDx as the primary genomic test, none of which compared the outcomes of patients who did vs did not receive the F1CDx test. Conclusions The findings indicate gaps in the supporting evidence for broad CGP use in patients with solid tumors. More rigorous studies that assess clinical utility would better inform the approval process for novel diagnostic tests.

中文翻译：

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CMS-FDA 对癌症环境中综合基因组分析测试的平行审查的证据强度


背景尽管全面的基因组分析 （CGP） 的使用已获得新型 CMS/FDA 平行审查程序的批准，但支持证据的质量尚不清楚。我们评估了 FoundationOne CDx （F1CDx） 的全国覆盖率确定备忘录中引用的同行评审文献的严谨性。方法 我们确定了备忘录中引用的研究。两名独立研究人员评估了每项研究，并应用了 Fryback 和 Thornbury 层次结构的修改版本[1]，这是一个评估诊断测试有效性的既定框架。然后，在医疗技术政策中心的建议指导下，按研究设计对侧重于临床结果的研究进行分类。结果 样本包括 113 项科学研究。大多数 （n = 60， 53.1%） 在临床护理过程之外使用 CGP，并且评估的癌症类型和测序深度存在显着异质性。我们发现 8 项 （7.1%） 研究评估了临床护理是否因 CGP 检测而发生变化，38 项 （33.6%） 评估了临床结局。在排除了检测 5 个或更少基因组改变的研究后，临床结局样本中仍有 25 个：其中，只有 1 个包括未接受 CGP 检测的对照组。只有 4 项研究使用 F1CDx 作为主要基因组检测，没有一项研究比较接受 F1CDx 检测的患者和未接受 F1CDx 检测的患者的结局。结论 研究结果表明，在实体瘤患者中广泛使用 CGP 的支持证据存在差距。评估临床效用的更严格的研究将更好地为新型诊断测试的审批程序提供信息。