Skip to main content
Premium Trial:

Request an Annual Quote

Senate HELP Committee Holds Hearing to Discuss Best Path Forward for Lab Test Regulation

This article has been updated from an earlier version to correctly reflect the scope of a 2010 report cited by Sen. Lamar Alexander during the hearing that estimated the cost of FDA approval and clearance for medical devices.

NEW YORK (GenomeWeb) – As senators on the Committee on Health, Education, Labor, & Pensions mull legislative solutions to regulate lab-developed tests (LDTs) they have to try to advance a framework that facilitates rapid access to tests while ensuring patients can rely on the results.

Achieving this balance will be a challenge for the HELP Committee as it considers the impact of regulation on the lab industry and on diagnostic manufacturers, and reviews different legislative proposals from groups representing pathologists, a coalition of testing firms and labs called the Diagnostic Test Working Group, and the US Food and Drug Administration (see GenomeWeb white paper). 

Historically, life sciences stakeholders have been divided on how to address regulation of LDTs, which in the era of molecularly guided precision care, has grown rapidly. At the Senate committee hearing, four witnesses — two pathologists, a regulatory expert at a diagnostics company, and the head of a cancer-focused policy group — agreed at a basic level that any regulatory framework needs to ensure that patients get access to critical tests quickly and that these tests are safe and effective. But there was little consensus on the level of regulation needed to maintain innovation in laboratory testing and which agency — the FDA, the Centers for Medicare & Medicaid Services, or an entirely new entity — should oversee such tests.

These disagreements have held up the FDA's attempts to oversee LDTs since 1992, and maintained regulation in the hands of CMS since the enactment of the Clinical Laboratory Improvement Amendments of 1988. Two years ago, the FDA released a draft guidance outlining a risk-based framework for regulating LDTs, noting the increasing number and technological complexity of tests on the market. But the proposal has been challenged by the pathologist and lab community as a threat to innovation and timely patient care. 

At the HELP Committee hearing, Republican congressmen focused on these points as an argument against FDA regulation, which they characterized as too plodding to keep up with innovation in the molecular diagnostics space. Noting that there are 60,000 lab tests on the market, Committee Chairman Lamar Alexander (R-TN) worried that each of them would need to be approved by the FDA, which would limit patients' ability to receive critical tests and would become financially unsustainable to labs.

Alexander cited a 2010 survey of 200 medical technology companies, in which researchers found that patients in the US waited on average two years longer to get access to products than patients in Europe. According to the report, the average total cost of bringing a low- to moderate-risk medical devices to market with 510(k) clearance was $31 million, of which $24 million was attributable to FDA-related regulatory activities. The total average cost of bringing high-risk medical devices to market with premarket approval was estimated to be $94 million, with $75 million attributable to additional FDA requirements. (Editor's note: This report, funded by a number of medical technology and device interest groups, estimates the cost of bringing medical devices to market with FDA approval or clearance. Alexander represented these numbers as reflecting the cost of FDA premarket review for LDTs, which according to the FDA falls under the broader category of a medical device, although the lab industry maintains LDTs aren't medical devices at all.)

The difficulty with estimating the impact of FDA regulation of LDTs has been that it's unclear at the moment precisely how many of the 60,000 tests — an estimate put forth by healthcare technology firm NextGxDx — will be deemed high risk under FDA's regulatory proposal and therefore subject to the most stringent oversight via PMA, how many will be moderate risk and subject to 510(k) clearance, and how many will be low risk, grandfathered in, or subject to lesser requirements because they address an unmet need. 

A year ago, at a hearing of the House Energy & Commerce Committee on LDT regulation, the FDA estimated there were more than 11,000 LDTs on the market, 50 percent of which would fall into the low-risk category and wouldn't require premarket approval, while 2 percent of high-risk and 48 percent of moderate-risk tests would have varying levels of commitments. The lab industry hasn't been reassured by these figures in the absence of further guidance from the FDA on how it plans to determine which tests fall in to which category.

Karen Kaul, chair of the pathology department and laboratory medicine at the NorthShore University HealthSystem, testified before the HELP Committee that her facility develops and performs hundreds of LDTs, of which around 50 are in the area of personalized medicine. David Klimstra, chairman of the pathology department at Memorial Sloan Kettering Cancer Center, testified that his facility conducts 350 LDTs, and highlighted that the center had performed a test that gauges more than 460 cancer-related genes on more than 12,000 patients in the last few years.

While Kaul acknowledged that there were areas where oversight of lab tests could be improved, she preferred these changes be made to the existing framework under CLIA, which already inspects labs, considers the analytical accuracy of tests performed, and evaluates performance between labs through proficiency testing. Klimstra noted that in addition to CLIA requirements, his lab at MSKCC is subject to oversight from the New York State Department of Health, which also requires premarket test approval.

Kaul and Klimstra both said that additional FDA oversight of LDTs would financially hobble their labs and they'd have to stop offering some of their most innovative tests in the area of personalized medicine. They further testified that FDA regulation would slow their ability to bring critical tests to market, citing now infamous examples in EGFR and KRAS testing, where LDTs for characterizing patient response to cancer drugs based on these genetic markers came to market years before FDA-approved test kits.

DNA testing for diagnosing Herpes simplex encephalitis, an infection that can become life threatening in hours, has been available since 1995, Kaul highlighted. "Labs rallied together to set up assays, compare results, and [set up] standard protocols for proficiency testing, all the things we regularly do under CLIA," she said, noting that an FDA-approved test became available 20 years later. "So, during those 20 years should we have waited for the kit?"

Jeff Allen, CEO of Friends of Cancer Research, pointed out that LDTs often come to market before an FDA-approved kit not necessarily due to delays from the agency but because it's currently voluntary for labs to take their tests through the agency's premarket review process. It has long been standard practice in the lab community to launch a test as an LDT first, and then submit the test for FDA approval.

For example, Foundation Medicine announced in August that it would submit its next-generation sequencing cancer profiling test FoundationOne for parallel review by the FDA and CMS. The test, which has been available as an LDT for a number of years, will be reviewed by the FDA through its Expedited Access Pathway for breakthrough devices. 

Friends of Cancer Research worked with stakeholders and Congress to bring about the law that created the breakthrough therapy designation, which the FDA uses to expedite the review of promising drugs for life-threatening conditions. Allen told the HELP committee that drugs are increasingly relying on tests to identify patients who will benefit and highlighted that 18 out of the 48 treatments with breakthrough therapy designation have a biomarker-associated research program.

Allen was supportive of the FDA playing a leading role in regulating all diagnostic tests and recognized that the agency had demonstrated flexibility in its recently issued draft guidances on oversight of next-generation sequencing tests. "Any test that is used to guide medical decision making should be held to the same standards no matter where it's developed," referring to the current bifurcated system under which FDA regulates test kits performed at multiple labs while CMS oversees LDTs performed at a single lab.

Attempting to address the concerns of some Republican senators about the added burden FDA regulation would place on labs, Allen attempted to clarify that not all 60,000 LDTs on the market would be subject to premarket approval. However, this didn't appease Alexander and others who continued to insist that any FDA oversight would slow innovation and increase costs for labs.

Alexander noted that both CMS and FDA are trying to do too much with too little funds, and instead of trying to fit old regulatory systems to new tests using rapidly evolving technologies, perhaps it would be better to create a whole new agency. "Sometimes when you own an old house, you invite the contractor in and he looks the house over and says, 'You know, it'd be easier, and cheaper and quicker to tear it down and start over,'" he said.

Brad Spring, VP of regulatory affairs and compliance at the BD Life Sciences business of diagnostic and medical technologies firm Becton Dickinson, told the senators that industry players had worked together to come up a with a new framework for regulating LDTs that wouldn't be duplicative, but would leverage the expertise of FDA, CMS, and state health regulators. BD was a key player in crafting the DTWG's regulatory proposal, which would create a new test category, in vitro clinical tests, and establish FDA's authority over test development and validation, keep CMS in charge of traditional lab activities necessary to perform tests, and maintain state oversight of interpreting test results.

Spring noted that among stakeholders that had worked on this proposal there was agreement that any new regulatory framework should be risk based; protect patients and ensure access to innovative tests; apply the same principles for tests regardless of where they are developed; ensure analytical and clinical validity; establish clear jurisdiction between FDA, CMS, and the states; improve transparency; and create expedited pathways to ensure access to tests for unmet needs.

The House Energy & Commerce Committee used the DTWG's plan as the backbone of a draft legislative proposal, on which stakeholders provided feedback. The fact that Spring gave testimony today discussing the DTWG's proposal suggests that framework is still alive and under consideration by the HELP Committee.

Committee member Elizabeth Warren (D-MA), who got the last word by coming in at end of the hearing, focused on the gaps in the current system in ensuring that LDTs are reliable and not harming patients.

"We have identified a problem," she said. "We're not getting the same kinds of tests. They're not reliable. And that means we've got to hammer out a way to make sure that if you get the test done in Alaska that the odds are at least above 99 percent that you're going to get the same type of result if you had that test done in Massachusetts," she said, noting that the best personalized medicine won't get to the patients who need them if they are given based on inaccurate lab results.

"Some of my Republican colleagues have suggested that we choose between innovation and verifying whether or not the tests are accurate," she continued. "But innovation without proven accuracy is not a medical advance. I believe we can have sensible oversight that can encourage more innovation." Warren added that she would work with Republican colleagues on the committee to try to accomplish that.