IN PREPARED REMARKS at a clinical lab industry meeting last month, FDA Commissioner Scott Gottlieb, MD, outlined steps the federal Food and Drug Administration would take to reduce the regulatory burden on labs that develop next-generation gene sequencing and lab-developed tests. He also explained some of the ways that the agency could be more flexible in the way it assesses the analytical and clinical validity of new clinical laboratory tests.
THE DARK REPORT presented Gottlieb’s key themes in its last issue. (See “FDA’s Gottlieb Favors Flexibility with LDTs, NGS,” TDR, Mar. 26, 2018.)
Concerns About Oversight
At the annual meeting of the American Clinical Laboratory Association, Gottlieb described how the FDA was considering efforts to qualify third-party reviewers, such as the New York State Department of Health, to help speed reviews and approvals for clinical laboratory tests, including LDTs. He said it also might be possible to exempt from premarket review certain individual tests that meet specific standards when the agency has confidence in the lab’s underlying standards.
The clinical laboratory industry is likely to welcome such comments from the commissioner, especially given that, in October 2014, the FDA released draft guidance on a proposal that it called an oversight framework for LDTs and in vitro diagnostic tests.
At the time, pathologists, clinical lab directors, and physicians in academic institutions and other settings expressed concerns that the proposed oversight would slow innovation, create a needlessly burdensome and expensive review process, and potentially jeopardize patient care and continuing advances in personalized medicine.
Not all observers opposed the proposal, however. Some medical directors for health insurers, for example, were among those who expressed support for the FDA’s oversight framework on LDTs.
In his remarks last month, Gottlieb said he was concerned that the FDA should be able to ensure that regulations keep pace with innovations as they occur in the market.
One reader of THE DARK REPORT responded to the story about Gottlieb’s comments and provided a counterpoint. The reader asked not to be named.
The Self-Regulation Question
“Of course, the clinical laboratory industry generally will favor Gottlieb’s approach, which is, essentially, self-regulation,” the reader wrote. “In and of itself, self-regulation is not a problem, but doing it well and effectively would depend on the industry’s willingness to be transparent and self-correcting.
“I would be hard pressed to name any for-profit industry in which self-regulation has worked well,” he added. “Consider, for example, the oil and gas, tobacco, compounded drugs, and mortgage banking industries, among others. Clinical laboratories might be different, but, to date, we have no such evidence.”
Devil in the Details
On the issue of exempting from pre-market review tests that meet certain standards when the FDA has confidence in the labs’ underlying standards, our reader commented: “Regarding this proposal, as with many Gottlieb put forth, the devil is in the details.
“But, let’s assume the FDA’s proposal would be different from the same basic approach that the College of American Pathologists uses for its checklist,” he added. “Even if it is different from that, how would the FDA assess and enforce compliance with such standards? Also, how would such standards actually be applied to individual tests?
“As CAP and CLIA demonstrate all too well, assessing the quality of a lab and its practices is certainly not the same as assessing the quality of a specific test from that lab,” he wrote.
FDA and LDTs
Another concern involves having third-parties review LDTs. The FDA is considering qualifying the New York State Department of Health as a third-party reviewer, and the agency is seeking to develop what Gottlieb called a “flexible, modern approach to how it reviews next-generation sequencing.”
Given that health insurers already struggle to approve many genetic and molecular tests for payment, they are likely to balk at both the idea for third-party review and a more flexible approach to approving NGS tests, our reader commented.
In addition, our reader added, the New York State Department of Health has approved tests that some observers say should not have been approved for analytical or clinical validity and would not have passed FDA’s stringent review standards. But, even if the NYSDOH approves a test, such an approval does not guarantee health insurance coverage and payment, he added.
In his comments, Gottlieb frequently described the FDA review and approval process as a burden for lab-test developers. Of course, such review is not designed to be burdensome but rather is a necessary part of ensuring that patient care is not harmed, our reader commented.
The Regulatory ‘Burden’
“It’s amazing how frequently Gottlieb uses the word ‘burden,’” our commenter wrote. “Calling out FDA review as being burdensome is almost counterintuitive. A significant part of the FDA’s job is to ensure that tests do what they are designed to do, that they do not harm patients, and that they are analytically and clinically valid.
“How would the commissioner—or anyone—feel if we did away with the agency’s review for a lab test that would be used on him or on a family member?” he asked.
In one final point, our reader added that it would be worthwhile to ask the FDA if it has ever retracted marketing authorization for a test once it was on the market.
“I say that because Gottlieb offered this idea about pre-market review but never discussed the need for post-market review,” our reader concluded. “Post-market review would work only if the agency is willing and able to remove what might be called ‘bad tests’ after they have been on the market. Personally, I have little faith that the FDA has done or will do this.”
THE DARK REPORT welcomes other opinions and comments on the subject of the FDA’s proposals to regulate clinical laboratory tests.