Here, the Senators (Blumenthal, Durbin, etc) had asked the Office of Policy and Management to assure that the FDA do their jobs and assue that Lyme testing was valid. The FDA spells out what is a valid test and why they have to address the Dearborn criteria, now: ===================================================== SEE PAGES 5-8 of this pdf (dated July 31, 2014) fda.gov/downloads/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm407409.pdf 1. Regulatory History of LDTs In 1976, Congress enacted the Medical Device Amendments (MDA), which amended the FD&C Act to create a comprehensive system for the regulation of medical devices intended for use in humans. At that time, the definition of a device was amended to make explicit that it encompasses IVDs.7 The definition of a device applies equally to IVDs manufactured by conventional device manufacturers and those manufactured by laboratories. An IVD, therefore, meets the device definition irrespective of where and by whom it is manufactured. However, since the implementation of the MDA of 1976, FDA has generally exercised enforcement discretion so that the Agency has generally not enforced applicable provisions under the FD&C Act and FDA regulations with respect to LDTs. Enforcement discretion for LDTs developed as a matter of general practice, following the implementation of the 1976 MDA. The Centers for Medicare & Medicaid Services (CMS) has regulated laboratories, including those that develop LDTs, under the Clinical Laboratory Improvement Amendments (CLIA) (42 U.S.C. 263a) since 1988. CLIA governs the accreditation, inspection and certification process for laboratories. CLIA requirements, however, address different functions than the requirements under the FD&C Act. Namely, CLIA requirements address the laboratory’s testing process (i.e., the ability to perform laboratory testing in an accurate and reliable manner). Under CLIA, accreditors do not evaluate test validation prior to marketing nor do they assess the clinical validity of a LDT (i.e., the accuracy with which the test identifies, measures, or predicts the presence or absence of a clinical condition or predisposition in a patient). **** Under the FD&C Act, the FDA assures both the analytical validity (e.g., analytical specificity and sensitivity, accuracy and precision - SEE ACTIONLYME, CHAPTER ONE OF CRYME DISEASE- KMD) and clinical validity of diagnostic tests through its premarket clearance or approval process. **** In addition to premarket review, FDA requirements provide other controls to ensure appropriate design, manufacture, and safety and effectiveness of the device. As a result, while CLIA oversight is important, it alone does not ensure that LDTs are properly designed, consistently manufactured, and are safe and effective for patients. 2. Evolution of LDT Technology, Marketing, and Business Models and the Need for Increased Regulatory Oversight of LDTs Since 1976, when Congress clarified that IVDs were medical devices under the FD&C Act and FDA opted to exercise enforcement discretion with respect to LDTs under this authority, the industry has grown and evolved in significant ways, as summarized in the discussion below. FDA finds that in the absence of appropriate oversight of LDTs, there is the potential for increased risk for patients. In 1976, LDTs were mostly manufactured in small volumes by local laboratories. Many laboratories manufactured LDTs that were similar to well-characterized, standard diagnostic devices, as well as other LDTs that were intended for use in diagnosing rare diseases or for other uses to meet the needs of a local patient population. LDTs at the time tended to rely on the manual techniques used by laboratory personnel. LDTs were typically used and interpreted directly by physicians and pathologists working within a single institution that was responsible for the patient. In addition, historically, LDTs were manufactured using components that were legally marketed for clinical use.8 Although some laboratories today still manufacture LDTs in this “traditional” manner, the landscape for laboratory testing in general, and LDTs along with it, has changed dramatically since 1976. Today, LDTs are often used in laboratories that are independent of the healthcare delivery entity. Additionally, today, LDTs are frequently manufactured with components and instruments that are not legally marketed for clinical use and also rely more heavily on high-tech instrumentation and software to generate results and clinical interpretations. Moreover, technological advances have increased the use of diagnostic services in guiding critical clinical management decisions for high-risk diseases and conditions, particularly in the context of personalized medicine. …. [SKIP TO PAGE 8] 3. Gaps in Regulatory Oversight of LDTs Due to changes in the complexity and use of LDTs and the associated increased risks, as described above, FDA believes the policy of general enforcement discretion towards LDTs is no longer appropriate. Although the CLIA requirements are essential for ensuring that laboratories and their personnel maintain standards of high quality, FDA is concerned that compliance with CLIA regulations alone does not ensure that the diagnostic devices themselves are safe and effective as required by the FD&C Act. Specifically, CLIA regulations: • Do not assure the safety and effectiveness of LDTs. o Under CLIA, the laboratory’s analytical validation of a LDT is reviewed during its routine biennial survey, which means that the evaluation of analytical validation occurs after the laboratory has already started testing rather than before it markets a test to the public. Performance of analytical validation (i.e., proof that the device accurately detects analytes) is required by CLIA regulations for a laboratory’s use of its test system in its own laboratory prior to reporting outpatient result, but this is generally only assessed after the device is marketed to the public. Moreover, the routine CLIA survey does not include a review of the clinical validation of a LDT – that is, the accuracy with which the test identifies, measures, or predicts the presence or absence of a clinical condition or predisposition in a patient. Accordingly, there is no assurance that the devices are clinically relevant. Under the FD&C Act, both analytical validation and clinical validation are required and assessed before the devices are offered for clinical use. • Do not require adverse event reporting, which makes it difficult for regulators to detect devices that are inaccurate, ineffective, or unsafe. • Do not require removal of unsafe devices from the market. • Do not assess quality manufacturing of devices, a critical area of device oversight. o CLIA regulation focuses on laboratory processes for using devices, rather than on the design and manufacture of the devices themselves. • Do not require informed consent for patients who participate in LDT clinical studies and do not establish procedures for the conduct of such studies. The Agency has serious concerns regarding the lack of independent review of the evidence of clinical validity of LDTs. Clinical validity is the ability of a diagnostic device to measure or detect the clinical condition for which the device is intended. Clinical validity is not evaluated under CLIA regulations. LDTs that have not been properly clinically validated for their intended use10 and are used to make critical clinical decisions potentially put patients at risk of missed or incorrect diagnosis, failure to administer appropriate treatment or administration of potentially harmful treatment with no benefit. Further, the FDA is aware that, while clinical laboratories perform some level of analytical validation for LDTs to meet CLIA requirements (42 CFR 493.1253(b)(2)), the protocols used for that purpose are not adequate to assure the safety and effectiveness of many LDTs. The CLIA survey process reviews LDT analytical validation data, but this is generally conducted onsite after the device is already in use for providing clinical diagnostic results. CLIA oversight is not designed to ensure that LDTs are appropriately analytically validated for their intended use before the test is used clinically. In addition, CLIA does not require or assess the clinical validity of any test. Accordingly, with respect to LDTs, compliance with CLIA regulations alone does not adequately protect patient safety. FDA premarket review under the FD&C Act and FDA regulations is intended to ensure safety and effectiveness.
Posted on: Sun, 07 Sep 2014 07:16:29 +0000
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