Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Weill Cornell Medical College, New York, NY.
J Clin Oncol. 2023 Jan 1;41(1):11-21. doi: 10.1200/JCO.22.00995. Epub 2022 Aug 9.
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.
癌症预测或诊断检测，作为实验室开发的检测（LDT），一直受到美国食品和药物管理局的监管机构和执法自由裁量权的约束。许多 LDT 在未经美国食品和药物管理局或任何监管审查的情况下进入市场。医疗保险和医疗补助服务中心（Centers for Medicare & Medicaid Services）根据临床实验室改进修正案（Clinical Laboratory Improvement Amendments）专注于分析性能，但对 LDT 的质量或实用性的监督有限，包括患者是否因使用这些检测而受到伤害。越来越多的用于癌症风险或早期检测的 LDT 已直接向消费者销售，许多 LDT 开发商将这些由患者要求但由私人或公司相关医生订购的检测描述为属于医学实践的程序。这种关于 LDT 的监管和执法不确定性的拼凑，以及公众对在 COVID-19 大流行期间紧急授权的检测准确性的担忧，导致了 2021 年的验证准确前沿体外临床检测（Verifying Accurate Leading-edge IVCT）发展法案。这项悬而未决的联邦立法代表着协调监管政策的机会，并解决了人们对癌症基因组学中 LDT 的质量、实用性和安全性日益增长的担忧，包括直接向消费者销售的检测。我们在这里审查了一些与癌症风险和无症状分子诊断相关的 LDT 的潜在益处和危害的问题，这些 LDT 越来越多地向肿瘤学家或直接向担忧的健康人群销售。我们提出了具体的建议，以加强对癌症基因检测准确性和临床实用性的监督，以确保公众安全。
