Strength of evidence underlying the CMS-FDA parallel review of comprehensive genomic profiling tests in the cancer setting.

Background: Although use of comprehensive genomic profiling was approved by a novel Centers for Medicare & Medicaid Services-US Food and Drug Administration 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 FoundationOneCDx (Foundation Medicine, Inc, Cambridge, MA).

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, 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 (60/113 [53.1%]) used comprehensive genomic profiling outside the course of clinical care, and there was substantive heterogeneity in the cancer types assessed and the sequencing depth. We found 8 (7.1%) studies that assessed whether clinical care had changed due to comprehensive genomic profiling testing, and 38 (33.6%) assessed clinical outcomes. After excluding studies that tested for 5 or fewer genomic alterations, 25 remained in the clinical outcomes sample: Of these, only 1 included a comparator group that did not receive comprehensive genomic profiling testing. Only 4 studies used FoundationOneCDx as the primary genomic test, none of which compared the outcomes of patients who did vs did not receive the test.

Conclusions: The findings indicate gaps in the supporting evidence for broad comprehensive genomic profiling use in patients with solid tumors. More rigorous studies that assess clinical utility would better inform the approval process for novel diagnostic tests.