After years of back-and-forth on the issue, the debate over which federal agency will regulate laboratory-developed tests (LDT) going forward is far from settled. The Food and Drug Administration (FDA) says it has the statutory authority to regulate LDTs and will release a final guidance on LDT oversight this year. Meanwhile, some lawmakers and industry groups are circulating alternative proposals that would either give FDA more authority over LDTs or give the authority to the Centers for Medicare and Medicaid Services (CMS) under an expanded CLIA program. Other groups are threatening litigation once the final guidance is released unless there are significant changes that make the new framework more palatable.

“I think at this point, everything is pretty much up in the air,” said James Nichols, PhD, professor of pathology, microbiology, and immunology, and medical director for clinical chemistry and point-of-care testing at Vanderbilt University School of Medicine in Nashville. Nichols also is chair of the AACC Government Affairs Committee. AACC recently released a position statement on CLIA calling for CMS, not FDA, to be responsible for LDT oversight. Vanderbilt has developed hundreds of LDTs and would be significantly impacted by a requirement that it file a premarket submission for each one, Nichols noted.

FDA Plowing Ahead

Even as legislative drafts dealing with LDTs circulate in Congress, FDA is moving ahead with plans to issue a final guidance in 2016, said Eric Pahon, an FDA spokesperson. The agency in 2014 issued a draft guidance under which it would implement a risk-based, phased-in approach for oversight of high- and moderate-risk LDTs. It would continue to use enforcement discretion for low-risk LDTs, as well as certain categories of moderate- and high-risk LDTs. “We are in the final drafting phase of the final guidance,” Pahon told CLN. “We have carefully considered the comments and concerns that have been brought up. We take the comments very seriously. The FDA doesn’t want to stifle innovation or stifle access, but we do want to make sure that the public is safe.” Once the agency finishes drafting the guidance, it will have to go through an additional review with the Department of Health and Human Services and the Office of Management and Budget before being announced.

At the heart of the debate over LDTs is the question of whether these tests actually pose a risk to patients. FDA argues that many do, and in a report issued in November 2015 it presented 20 case studies of LDTs that it believes may have caused or could cause harm to patients.  “I question the premise that there is a problem with LDTs,” Nichols said. “I don’t think the issue is with the tests themselves, but perhaps with communication and interpretations of the test results. That’s not something the FDA guidance would solve.”

Expanding CLIA

AACC and several other laboratory industry groups, including the Association for Molecular Pathology (AMP) and the College of American Pathologists (CAP), are advocating an alternate approach to oversight of LDTs that would build on the existing CLIA framework. In its recent position statement, AACC recommends that CLIA remain the primary mechanism for overseeing clinical laboratories and supports modernizing the regulations to ensure that they continue to meet the changing needs of the healthcare community.

“Revisions to the regulations should particularly address the laboratory inspection process, quality control recommendations, proficiency testing requirements, and the definition of what constitutes an LDT,” the position paper says.

In response to concerns that CLIA does not require clinical validation of tests, AACC notes that more than 8,000 labs are accredited by CAP or the Joint Commission, both of which require clinical validation of any claims relating to the use of LDTs for patient care. The New York State Department of Health also requires such validation.

“Expanding clinical validity to all LDTs under CLIA appears to be a viable regulatory option that would achieve the goal of ensuring clinical validity without the prohibitive administrative burden of dual oversight by FDA and CMS,” notes AACC in its position statement. To implement this requirement, CMS could either hire additional staff to review the laboratory validation data, use the existing processes already in place at CAP, Joint Commission, and New York State, and/or contract with third parties to conduct the reviews.

The issue of resources needed to ensure clinical validity is a critical one that would need to be addressed by whichever agency ends up with LDT oversight authority. During a November 17 hearing before the House Energy and Commerce Committee, Patrick Conway, the CMS deputy administrator for innovation and quality and chief medical director in the office of the administrator, said repeatedly that CMS does not have the resources or expertise to conduct premarket review of LDTs and that giving CMS that responsibility could cause a backlog that would stifle innovation.

FDA would also need additional staff to conduct premarket reviews if it moves forward with oversight of LDTs. FDA estimates there are about 11,000 LDTs nationwide, but industry stakeholders believe the number is substantially larger. “It’s hard to know how many LDTs there are without defining them,” said Jeff Gibbs, an attorney with Hyman, Phelps and McNamara, PC in Washington, D.C. and a contributor to the FDA Law Blog. If a premarket submission was required every time an existing test was modified by a laboratory as FDA seemed to propose, the numbers could be staggering, he noted. It its position statement, AACC recommends defining LDTs based on clinical claims—excluding routine modifications to FDA cleared or approved tests, as well as off-label use of tests by physicians.

Alternate Proposals

Currently there are several alternate proposals being floated around Capitol Hill. Two, put forth by AMP and CAP, are similar in many ways, with both exempting low-risk tests from premarket reviews and giving CMS or third-party reviewers the sole authority to review moderate-risk tests. FDA would only be involved in review of high-risk tests.

A third proposal, put forth by the House Energy and Commerce Committee, is based on an alternate framework drafted by the Diagnostic Test Working Group, a coalition of IVD companies and laboratories. This draft legislation would create a new FDA center for in vitro clinical tests, which would use a new standard—reasonable assurance of analytical validity and clinical validity—in reviewing all high-risk in vitro clinical tests, regardless of whether the test is offered by a laboratory or as a distributed product. FDA would handle premarket review of LDTs while CMS would continue oversight of laboratory operations.

FDA was asked to provide input on the Energy and Commerce draft legislation and said it will continue to engage with lawmakers and other stakeholders on the issue. “We continue to communicate our concerns that patients are making critical health decisions based on laboratory-developed tests without the assurances that these tests are entirely accurate or effective,” Pahon said. “Without premarket review by the FDA—neither patients, their healthcare providers, nor FDA itself can be assured these tests are accurate and effective.”

Legal Challenge Likely

With so many competing proposals and final guidance reportedly on the way, what is the most likely outcome? According to Gibbs, there are several possible scenarios. In one, the final guidance would be modified enough to be palatable to the laboratory industry. Another possibility is that the guidance would be held up at the Office of Management and Budget and not released this year. Under the third scenario, the final guidance would be issued and a legal challenge brought before the guidance goes into effect. Finally, Congress could enact legislation. Gibbs believes the third scenario is the most probable.

“The single most likely outcome in my view is that FDA will issue a final guidance this year, and there will be litigation,” Gibbs said, noting that the American Clinical Laboratory Association has retained two high-powered attorneys and has indicated a willingness to take FDA to court over this issue. “I think the FDA would lose if there is a challenge under the Administrative Procedure Act,” Gibbs added. “The argument is that the FDA cannot make these kinds of changes through a guidance document, but instead needs to go through a rulemaking process.”

If that were to occur, it could be some time before any kind of rulemaking is finalized, Gibbs predicted, noting that the outcome of this year’s presidential election could also influence the outcome. “If a Republican is elected President, there’s a possibility that the guidance will be rescinded,” he said. “Because it is a guidance, it could be more easily undone than if it were a rule. Anything could happen.”

Kimberly Scott is a freelance writer who lives in Lewes, Delaware.+Email: [email protected]