Regulation of Laboratory-Developed Tests in Preventive Oncology: Emerging Needs and Opportunities

Abstract

Cancer predictive or diagnostic assays, offered as Laboratory-Developed Tests (LDTs), have been subject to regulatory authority and enforcement discretion by the US Food and Drug Administration. Many LDTs enter the market without US Food and Drug Administration or any regulatory review. The Centers for Medicare & Medicaid Services under the Clinical Laboratory Improvement Amendments focuses on analytic performance, but has limited oversight of the quality or utility of LDTs, including whether patients have been harmed as a result of their use. Increasingly, LDTs for cancer risk or early detection have been marketed directly to consumers, with many LDT developers depicting these tests, requested by patients but ordered by personal or company-associated physicians, as procedures falling under the practice of medicine. This patchwork of regulation and enforcement uncertainty regarding LDTs and public concerns about accuracy of tests given emergency authorization during the COVID-19 pandemic led to the Verifying Accurate Leading-edge IVCT (in vitro clinical test) Development Act of 2021. This pending federal legislation represents an opportunity to harmonize regulatory policies and address growing concerns over quality, utility, and safety of LDTs for cancer genomics, including tests marketed directly to consumers. We review here questions regarding the potential benefits and harms of some cancer-related LDTs for cancer risk and presymptomatic molecular diagnosis, increasingly marketed to oncologists or directly to the worried well. We offer specific proposals to strengthen oversight of the accuracy and clinical utility of cancer genetic testing to ensure public safety.

FIG 1.

Timeline of FDA authorization of direct-to-consumer and COVID-19 testing. ACLA, American Clinical Laboratory Association; DAIA, Diagnostic Accuracy and Innovation Act; DTC, direct-to-consumer; FDA, US Food and Drug Administration; HHS, Department of Health and Human Services; IVCT, in vitro clinical test; LDT, laboratory-developed test; PGx, pharmacogenomic; VALID, Verifying Accurate, Leading-edge IVCT Development.