FDA于去年10月份发布了一份指南草案，提出了针对实验室开发的测试（laboratory developed tests，LDTs）的监管框架。FDA表示将与临床实验室改进修正案(Clinical Laboratory Improvement Amendments，CLIA)下负责管理临床实验室的医保和医疗服务中心 (Centers for Medicare and Medicaid Services，CMS)一道，共同监管临床实验室检测的质量。曾有同行对这两个机构的职能分工表示困惑，并关注其潜在的重复性工作。现在，为了协调两部门工作，FDA与CMS将成立联合工作组（The Diagnostic Test Working Group），以继续扩展在LDT领域的监管合作。这一工作组汇集了两部门在相关领域的主要领导与专家，旨在回应包括LDT质量要求在内的一系列问题。
Health care providers and their patients expect that laboratory tests used in clinical management of patients should be consistent and of high quality.
Under FDA's proposed framework for the oversight of laboratory developed tests (LDTs), outlined in draft guidance documents issued in October 2014, FDA would oversee the quality of these laboratory tests, alongside the Centers for Medicare and Medicaid Services (CMS), which regulate the laboratories themselves through the Clinical Laboratory Improvement Amendments (CLIA). We have heard stakeholder confusion about the roles of the two agencies in ensuring quality and concerns about potentially duplicative efforts. To coordinate efforts across the Department, FDA and CMS are establishing an interagency task force that will continue and expand on our collaboration related to the oversight of LDTs, which are tests intended for clinical use and designed, manufactured, and used within a single lab. The task force, comprised of leaders and subject matter experts from each agency, will work to address a range of issues, including those involving quality requirements for LDTs.
LDTs can be used to measure or detect a wide variety of analytes (substances such as proteins, chemical compounds like glucose or cholesterol, or DNA), in a sample taken from a human body. Some LDTs are relatively simple tests that measure single analytes, such as a test that measures the level of sodium. Other LDTs are complex and measure or detect numerous analytes. For example, DNA variations can be detected from a blood sample, which can be used to help diagnose a genetic disease. Various levels of chemicals can be measured to help diagnose a patient's state of health, such as levels of cholesterol or sodium. According to the American Clinical Laboratory Association (ACLA), more than 11,000 laboratories are authorized to develop and perform LDTs, and the majority of them do.
FDA first obtained comprehensive authority to regulate all in vitro diagnostics as devices in 1976. Some LDTs are now more complex, have a nation-wide reach and present higher risks, such as detection of risk for breast cancer and Alzheimer's disease, which are similar to those of other IVDs that have undergone premarket review.
During the lecture of Margaret A. Hamburg, M.D., Former Commissioner of Food and Drugs, She Specially introduct the progress in LDTs regulatory. We proposed a risk-based framework for laboratory developed tests (LDTs) to help ensure patients and providers have access to safe, accurate and reliable tests, while continuing to promote innovation of diagnostic tests to help guide treatment decisions.
Some lawmakers and stakeholders balk at the thought of FDA's increased involvement. Alan Mertz, president of ACLA and a witness at the FDA hearing, argued that the proposed regulations would discourage labs from developing innovative new tests and prevent them from adjusting the tests quickly for new uses. Mertz, along with several representatives, also challenged FDA's authority to regulate LDTs, arguing that they are not “devices” but rather services provided to a patient, and are already regulated effectively under CLIA.
Under the proposed LDT framework, FDA would phase in enforcement of premarket review requirements and the quality system regulation for some LDTs. FDA's oversight of LDTs will assure that the tests are both analytically valid (able to accurately detect analytes) and clinically valid (able to measure or detect the clinical condition for which the test is intended). FDA is currently reviewing public comments on the draft guidances that it received through an open public docket and a two-day public meeting. In response to public comments, FDA may modify the proposed framework when we issue final guidance.
CMS, under CLIA, oversees the labs' processes, rather than the tests they develop. CLIA and its implementing regulations include requirements for establishing and maintaining quality laboratory operations and ensuring the lab is staffed by qualified personnel. These laws do not require premarket review of tests or any evidence that a test is clinically valid.
When FDA's proposed framework is implemented, both FDA and CMS will play a role in ensuring that LDTs are high quality—CMS through CLIA by continuing to focus on laboratory operations including the testing process and FDA by enforcing compliance with the agency's quality systems regulation pertaining to the design and manufacture of the laboratory tests.
The goals of the FDA/CMS Task Force on LDT Quality Requirements include:
identifying areas of similarity between the FDA quality system regulation and requirements under CLIA;
working together to clarify responsibilities for laboratories that fall under the purview of both agencies; and
leveraging joint resources to avoid duplication and maximize efficiency.
The task force is currently exploring areas where collaboration may realize greater oversight efficiency and produce the greatest benefit to patients, providers, and laboratories. The task force understands stakeholders' concerns about differences in terminology used by FDA and CMS. We intend to clarify the terms used so that labs may better understand what is expected of them.
