CEO SUMMARY: Congress is gearing up for a debate on how to regulate laboratory-developed tests (LDTs) and other in vitro clinical tests (IVCTs). The VALID Act sets the stage for the FDA to take a greater role in pre-market review of LDTs, and the VITAL Act proposes to keep those tests under CLIA while calling for a modernization of clinical laboratory test oversight. Some experts believe passage of the VALID Act would cause major changes in how labs are allowed to develop and offer LDTs.
TODAY’S STATUS QUO IN HOW LABORATORY-DEVELOPED TESTS (LDTs) are regulated may soon change if Congress passes a bill to give the federal Food and Drug Administration (FDA) oversight of LDTs and in vitro clinical tests (IVCTs).
And like many things in the clinical laboratory industry these days, there is a COVID-19 angle to this debate.
Depending on how a clinical laboratory manager views the landscape, the proposed heavyweight regulation—known as the Verifying Accurate Leading-Edge IVCT Development Act of 2021, or VALID Act—could bring about more needed test validations or crush innovation under regulatory burden.
Meanwhile, a smaller bill also has been proposed, called the Verified Innovative Testing in American Laboratories Act of 2021, or VITAL Act. This bill is largely an attempt to keep LDTs and other lab testing under the auspice of the Clinical Laboratory Improvement Amendments of 1988 (CLIA).
“COVID-19 has drawn new attention to this [issue],” said Tom Sparkman, Senior Vice President of Government Affairs and Policy at the American Clinical Laboratory Association (ACLA), in an interview with The Dark Report.
“People need to be aware that there’s a genuine chance that Congress will roll up their sleeves and take a real look at how oversight can be modernized,” he added.
Debate over the passage of either bill is not imminent; expect to see congressional action in 2022.
Proposed by a bipartisan group of lawmakers, the 245-page VALID Act seeks to bring the regulation of IVCTs and LTDs under the FDA. Currently, these tests fall within CLIA oversight, but proponents believe FDA regulation is needed for in vitro diagnostic (IVD) tests because they are akin to medical devices and thus require extensive data collection.
Modernize IVD Law
“The bipartisan VALID Act is an important step toward the long-overdue modernization of the law for all diagnostic tests,” Scott Whitaker, President and CEO of the Advanced Medical Technology Association, said in a press release.
“It calls for smart reforms that will incentivize and improve the development of the advanced, reliable tests patients depend on, regardless of where those tests were developed,” he added.
The VALID Act has been introduced in the House of Representatives and Senate. Representatives Diana DeGette (D-CO) and Larry Bucshon, MD (R-IN) led the bill in the House, and Senators Richard Burr (R-NC) and Michael Bennet (D-CO) led it in the Senate. Senator Mike Braun (R-IN) cosponsored the bill.
On the other side of the argument is the VITAL Act, a seven-page proposal that calls for LDTs to remain under CLIA. The bill also seeks recommendations about how the federal government can modernize clinical laboratory oversight. Senator Rand Paul, MD (R-KY) is the bill’s only sponsor.
The VITAL Act has support from dozens of lab industry groups and parties, including the Association of Molecular Pathology (AMP), American Association for Clinical Chemistry (AACC), and various departments of pathology at hospitals and universities, all of whom sent a letter to Paul in support of the bill.
“CLIA has served this country well for decades but has not evolved with science and medicine,” according to the letter. “The advancements in laboratory medicine and pathology over the past decades warrant that this system be updated to align federal standards with those that most laboratories are already meeting or exceeding today. We are hopeful for the opportunity to work with CMS to modernize CLIA, which would be made possible by the VITAL Act.” (See the table below for a comparison of the two proposals.)
Although the CLIA-or-FDA debate over regulating tests has occurred for years, the COVID-19 pandemic amplified calls for keeping LDTs out the FDA’s oversight. In early 2020, an FDA guidance indicated that emergency use authorization for LTDs to detect the presence of the SARS-CoV-2 coronavirus fell under the agency and not CLIA. Because of that, labs could not use LTDs for COVID-19 tests, which led to a decreased availability of initial testing, according to a November 2021 article in The Yale Law Journal.
In a related development, on Nov. 15, 2021, the federal Department of Health and Human Services reversed a Trump administration policy that prevented the FDA from requiring pre-market reviews of LDTs. The Trump administration intended its policy to speed up availability of COVID tests while under emergency use authorization.
More Regulations for Industry
Generally, manufacturers of in vitro test kits and large commercial labs support the VALID Act. The manufacturers argue that they are subject to FDA oversight, so it is fair that LDTs also come under the agency. The bill offers a rare case of big business endorsing more regulations for an industry.
“Clinical labs are used to dealing with the CLIA risks and being regulated by CLIA,” Mark Birenbaum, PhD, executive director at the National Independent Laboratory Association (NILA), told The Dark Report. NILA has not taken a formal position on either bill, although the association did share detailed comments with the sponsors of the VALID Act when it was introduced earlier this year. (Visit https://www.nila-usa.org/images/nila/2021/NILAVALIDActComments.pdf to read Birenbaum’s full comments.)
“Manufacturers who produce kits and reagents that are sold to and used by a wide array of labs usually go through the FDA process and they’re very familiar with the FDA, but not so much CLIA,” Birenbaum added. “It’s been a separation where if the organization sells a piece of equipment that does 20 chemistry tests, it goes through the FDA process to get cleared for clinical use, and if the organization is a clinical lab, its testing is performed in compliance with CLIA requirements.
Different Uses for LDTs, IVDs
“Clinical laboratories develop LDTs for a variety of reasons. Because IVD tests undergo FDA approval, test manufacturers might have a disincentive to refine them because modifications to an existing IVD test may require additional regulatory review,” Birenbaum said. By comparison, LDTs do not require FDA approval, so laboratories are able to modify existing LDTs to meet patient needs.
“Manufacturers might feel that’s unfair because they are required to go through the rigorous and expensive FDA process, but labs offering LDTs do not. These labs can validate their assays under CLIA and then offer those tests,” Birenbaum said.
If FDA oversight is formalized, the associated user fees will become a major challenge for smaller laboratories. “These fees could impose unsustainable costs on community and regional laboratories and facilitate anticompetitive behavior within the laboratory and IVD industry,” Birenbaum said.
Opponents of the VALID Act argue that the cost and time associated with FDA review would be out of reach of many academic and independent clinical laboratories. This would stifle innovation when it comes to LDTs. Some critics also contend that the VALID Act will protect the existing market share of larger lab companies by building barriers of entry for smaller lab competitors.
A major provision of the VALID Act would require laboratories that seek test review to provide clinical validity data, which is a significant change from what labs provide under CLIA.
“Establishing clinical validity for a new diagnostics test takes a lot of time and money, often millions of dollars,” Birenbaum said. “The CLIA program doesn’t review clinical validity. CLIA covers what it calls ‘analytical validity,’ meaning the technical aspect of the test. Is the test accurate? Is it reproducible? Does it test for the component for which it is intended to test?
“Whereas ‘clinical validity’ [means]: Is this test medically useful?” Birenbaum added. “A lab could have the perfect test that measures the target biomarker with accuracy 100% of the time. But the relevant next question is: Do the results from this lab test help in the clinical setting? Is it useful for physicians using the test results? The answer could be no, it’s just not useful.
“So, clinical validity is a different standard,” he noted. “To establish clinical validity requires the clinical lab or other test developer to conduct clinical studies and similar supporting reviews. These are very difficult for many labs to conduct because of cost, time, and resource issues.”
Curbing LDT Development
The AACC—which supports the VITAL Act—worries that clinical laboratories will curb LDT development because it will become too expensive, should the VALID Act become law.
“Expanding oversight to include the Food and Drug Administration will divert limited laboratory resources from the provision of care to new, duplicative administrative requirements,” AACC President Stephen Master, MD, PhD, wrote in a letter to the VALID Act’s sponsors. “The additional costs associated with this bill may force many laboratories providing LDTs to discontinue this vital patient service.”
The ACLA does not view the VALID Act as a big manufacturer versus small lab contest, but instead a debate about the complexity of tests that are offered.
“You might be a high-complexity lab, but it might vary on whether you’re using high-volume IVD test kits or you’re using laboratory-developed tests,” Sparkman said. “And if you’re using laboratory-developed tests, are those [assays] simple … in-house modifications to test kits or are the assays more complex, from-the-ground-up development?”
“There are proposals [to the VALID Act] to allow more modifications, and that’s certainly what ACLA has been arguing—that there should be a greater breadth of modifications that should not require full-blown applications with months of [FDA]review and untold gigabytes of data,” he said. (See the sidebar below for further details about proposed data collection under the VALID Act.)
Regardless of where they fall in the debate between the VALID and VITAL Acts, clinical laboratory executives and managers should take the opportunity to contact their state’s Congressional members and express their thoughts.
“Don’t underestimate the power of your own voice,” Sparkman said. “Speak with legislators. All too often folks don’t think enough about what is necessary for clinical laboratories to provide high quality tests for patients.”
It is possible either proposal could become part of a larger bill. Congress often uses a major bill that is expected to pass as the vehicle to fix recognized issues, and to combine smaller bills which have widespread support among members of Congress.
The Medical Device User Fee Amendments will come up for reauthorization in 2022 and some veteran watchers of Congress consider that this legislation may be used to pass bills such as the VALID Act or VITAL Act. TDR
Contact Tom Sparkman at email@example.com; Mark Birenbaum, PhD, at firstname.lastname@example.org.
Data Collection for Proposed FDA Review
THE VERIFYING ACCURATE LEADING-EDGE IVCT DEVELOPMENT ACT OF 2021, or VALID Act, proposes to bring clinical laboratory regulation under the Food and Drug Administration for a pre-market review process.
As part of the review, test developers would need to provide a variety of data as outlined in the bill:
Description of the test’s intended use;
Explanation regarding test function and any significant performance characteristics;
Details about a test’s development and validation activities;
Synopsis of any existing alternative practices or procedures for diagnosing the disease or condition for which the in vitro clinical test is intended;
Brief description of the foreign and domestic marketing history of the test;
Summary of any studies submitted for such test, including descriptions of the objective of the study, the experimental design of the study, how the data was collected and analyzed, the results of the technical data submitted, and any nonclinical or clinical studies;
Risk assessment of the test;
Details that show the data constitutes valid scientific evidence and a discussion of any adverse effects of the test on health and proposals to mitigate those risks, if any; and,
Valid scientific evidence to support the analytical and clinical validity of the test, including raw data.
Proponents of the VALID Act contend that these data requirements bring laboratory tests more in line with other pre-market reviews, while critics argue that the provisions will be too burdensome for many labs to produce.