FDA's risk-based oversight of lab tests closes key gap

Diagnostic tests are increasingly a cornerstone of the modern health care system, providing critical information at every stage of patient care. Advanced molecular diagnostics are at the heart of an ongoing revolution in early detection of disease and in personalized medicine, helping to tailor treatments to individual patients and enabling people to survive conditions that just a few years ago would have been terminal. 

Given the relevance of these innovations to improving patient management and outcomes, it is most important that their use is fully realized. A critical element in the realized utility of these innovations lies in the ability of physicians and the public to have confidence in the quality and ultimate reliability of test results. The increasing prevalence of laboratory-developed tests (LDTs) for conditions like cancer and other life-threatening diseases, which often do not undergo FDA review, requires a modern regulatory framework to help ensure accurate, reliable and consistent test results. 

ADVERTISEMENT
FDA’s new risk-based approach to oversight of LDTs, outlined in the agency’s Sept. 30 proposed guidance document, would begin to bring LDT regulation in-line with the growing criticality of test results and represents a positive move towards closing a critical gap in patient safety and public health under the current two-tiered system for oversight of diagnostic tests. 

Under the current system, test kits manufactured by traditional diagnostics companies are treated differently from tests developed and used in a lab (LDTs). While the former typically require FDA oversight and review for safety and effectiveness, the latter do not. 

While FDA has the authority under the law to regulate all diagnostic tests, it historically has exercised enforcement discretion and not imposed regulatory requirements for LDTs. The FDA believes this arrangement worked well in the past, when LDTs typically were low-risk tests with well-established test methods or were used in low volumes. Now, LDTs encompass even the most complex and advanced molecular diagnostics, such as genetic tests used to guide choices among cancer treatments for personalized medicine, or tests used in the diagnosis and treatment of other life-threatening diseases. 

The FDA has identified problems with high-risk LDTs including “claims that are not adequately supported with evidence; lack of appropriate controls yielding erroneous results; and falsification of data.” The agency has further noted that “LDTs that have not been properly validated for their intended use put patients at risk. Risks include risk of missed diagnosis, wrong diagnosis and failure to receive appropriate treatment.” Under the new framework, FDA would impose regulatory requirements including premarket reviews for higher-risk LDTs. 

As the CEO of a company that makes innovative, high-quality molecular diagnostic tests for infectious disease, virology, oncology and other applications, I believe it is critical to ensure that patients and health care providers have confidence in the accuracy and reliability of tests that may be critical to their health and care, no matter where the tests are made or performed. It is also essential to promote innovation by ensuring a level regulatory playing field for industry in development of next-generation tests. 

Overall, FDA’s proposal begins to strike a good balance between patient safety and continued innovation. Maintaining the current status quo on LDT oversight, on the other hand, would continue to permit the use of high-risk tests without sufficient clinical data, and stifle investment in high quality products that are assured to be safe and effective for patients. 

In addressing the need for appropriate, balanced LDT oversight for the modern era, FDA’s proposal includes important safeguards to ensure continued patient access to essential tests as well as future innovations. For example, the proposal allows a five-year phase-in period for regulatory requirements for high-risk LDTs, and a nine-year phase-in period for moderate-risk LDTs. FDA also plans to exempt from review several categories of LDTs, including low-risk tests and tests for rare diseases. Recognizing the critical role that academic medical centers play in the modern innovation ecosystem, the agency also will exempt tests developed by medical institutions for their own patients when there is no equivalent FDA cleared or approved test available. 

As molecular tests and personalized medicine in particular become an increasingly integral part of cutting-edge American health care, with a potentially significant impact on a greater number of health care decisions and patient outcomes, the necessity is increasingly clear for FDA to provide oversight of higher-risk LDTs. Indeed, FDA and the National Institutes of Health noted in the New England Journal of Medicine that an appropriate risk-based regulatory framework is now “critical” to ensuring the clinical validity of LDTs. 

Americans expect and deserve the best health care available. Accordingly, the diagnostics industry supports FDA’s risk-based approach to LDT oversight as key to ensuring patient safety and public health, as well as continued access to life-changing innovation. We look forward to working with the agency to address needed refinements for its final guidance, and toward a smooth implementation. 

Bishop is chairman and CEO of Cepheid, and chairman of AdvaMedDx. AdvaMedDx member companies produce innovative, safe and effective in vitro diagnostic tests that facilitate evidence-based medicine, improve quality of patient care, promote wellness, enable early detection of disease and reduce overall health care costs.