Senate committee weighs in on laboratory developed test regulation

Issue: October 2016

The U.S. Senate Committee on Health, Education, Labor and Pensions, or HELP, fielded expert testimonies Tuesday on laboratory developed tests for infectious diseases and cancers, and discussed whether these tests should be subject to FDA regulation.

Patty Murray

Lamar Alexander

“I’m concerned that the FDA already has a full plate of responsibilities, and the agency has said it needs more money to meet those responsibilities,” Sen. Lamar Alexander, R-Tenn., HELP chairman, said in his opening remarks. “I look forward today to hearing whether additional, or different, regulation of laboratory developed tests (LDTs) is necessary.”

LDTs are developed by individual labs to provide prompt detection or quantification in situations where commercial assays are unavailable. Currently, LDTs are validated by the labs and indirectly regulated by CMS through the Clinical Laboratory Improvement Amendments (CLIA), or in some cases by state organizations.

On Oct. 3, 2014, the FDA released draft guidance proposing a regulatory framework that would require most of the 60,000 established LDTs to undergo a costly and time-consuming review process to receive approval. This proposal has since been criticized by laboratory diagnostics experts and clinical societies.

“I’ve heard views from a wide range of stakeholders about this proposal and how the FDA’s policies would impact their work,” Sen. Patty Murray, D-Wash., ranking member, said during the hearing. “I think that there are ways that the agency’s proposal could be improved, but even though everyone wants to make sure the tests offered to patients work as advertised, and that we allow researchers and clinicians to continue to innovate and advance precision medicine, there is not wide agreement about the best regulatory approach.”

David S. Klimstra, MD, attending pathologist and chairman at Memorial Sloan Kettering Cancer Center, described the advantages LDTs offer his institution.

“We use LDTs because the tests can be customized to provide the specific information we need,” Klimstra said to the committee. “They can be adapted to study a range of different types of specimens, and they can bring the tests to clinical care quickly relative to FDA-approved tests, which have been slower to come to market.”

Klimstra added that LDTs are independently verified by laboratory experts and their peers before use, and in certain states, such as New York, they are also subject to state oversight. These concerns, as well as those of cost, led Klimstra to speak against the FDA’s proposal.

“We believe that additional regulatory oversight of our labs … would be duplicative and unnecessary,” he said. “I would also raise concerns about the cost of additional regulations, both monetary and in terms of patient access to cutting-edge diagnostics. Maintaining a regulatory infrastructure is already costly, and additional costs of obtaining a regulatory approval of individual tests may prohibit academic laboratories from developing LDTs.”

Elizabeth Warren

Bill Cassidy

Jeff Allen, PhD, president and CEO of the nonprofit organization Friends of Cancer Research, raised concerns about the uniformity of LDTs without a standard of regulation. This issue is especially important given the rapid advancement of new technology, he said, and could potentially compromise test results critical to a patient’s care.

“When a patient is told they have cancer or any other debilitating disease, they are flooded with confusion, fear, anger and the thought of losing the life of a loved one, or their own,” Allen said. “While their journey will undoubtedly include periods of confusion and uncertainty, they shouldn’t be left to wonder if the results of a test, which their physician used to decide the course of their treatment, was right or not.”

There are numerous instances where tests critical to the treatment of infectious diseases preceded those approved by the FDA, according to Karen Kaul, MD, PhD, chair of the department of pathology and laboratory medicine, NorthShore University HealthSystem. After referencing how a collaboration of laboratory experts established PCR as the standard for herpes simplex virus detection 20 years before the availability of a commercial assay, she advised the committee members to consider ways that the existing system could be adapted to fit the needs for uniformity and efficiency.

“Labs have a history of operating successfully under CLIA, and there’s published data to support this,” Kaul said. “CLIA does need expansion and modernization, however. Goals for test performance can be defined by clinical groups prior to tests being launched, and we do need an expanded review of data coming out of labs who are performing this testing.

“Labs currently have the infrastructure to support an expanded CLIA program without expensive additional programs, but this is not so for FDA oversight. FDA has an important role, but only for those products that are truly [in vitro diagnostic] kits manufactured to work in an array of settings around the country.”

Following their testimonies, committee members questioned the experts on a number of issues and benefits that would result from FDA regulation. Major concerns included the awareness of physicians and patients of their tests’ validity, the inability of smaller- or lesser-known test developers to receive prompt approval and the potential for inaccurate tests to be used before receiving CLIA oversight. In addition, Sen. Bill Cassidy, MD, R-La., questioned the experts on the potential for an alternative “crowdsource” system and whether such a process could quickly and accurately gauge novel LDTs, while Sen. Elizabeth Warren, D-Mass., noted the issue of inconsistent care between states without lab regulation programs or highly regarded clinical laboratories.

“The best personalized medicine in the world won’t work if it’s given to patients who are unlikely to benefit from them because the treatment was based on bad lab results,” Warren said. “I believe that we can have sensible oversight that will encourage more innovation, and I look forward to working … with this committee to accomplish this goal.” – by Dave Muoio

Reference:

FDA. Framework for regulatory oversight of laboratory developed tests (LDTs) Draft Guidance.http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm416685.pdf. Accessed September 20, 2016.

Disclosure: Infectious Disease News was unable to determine relevant financial disclosures at the time of publication.

Editor’s Note: This article has been updated to clarify that Elizabeth Warren is a Senator from Massachusetts. The editors regret the error.