The Wall Street Journal examines the FDA’s position on LDTs and looks at the pros and cons of LDT regulation by the federal agency

National news coverage over the deficiencies uncovered by Clinical Laboratory Improvement Amendments (CLIA) inspections of the clinical laboratory operated by Theranos in Newark, Calif., may have an interesting consequence that affects all medical laboratories and pathology groups.

Over the past 30 months, Theranos has regularly asserted that its laboratory-developed tests (LDTs) were under review by the Food and Drug Administration (FDA). For example, in an interview published in the December 14, 2014, issue of The New Yorker, Theranos Founder and CEO Elizabeth Holmes stated, “We believe that to realize our vision we must operate at the highest levels of excellence… And the FDA’s stamp of approval is seen as an indicator of the quality of a product.”

Thus, it would be ironic if the problems in the quality of clinical laboratory tests uncovered by federal CLIA inspectors at the Theranos lab facility in Newark was used by the FDA to justify their intent to regulate LDTs. The FDA has already released a report to the public that identified instances where laboratories running LDTs were alleged to have reported inaccurate lab test results to patients and their physicians.

In fact, this FDA report was one factor used by a Wall Street Journal (WSJ) story to label LDTs the “Wild West of Medicine.” That story intensified the spotlight on clinical laboratory testing services and was seen as strengthening the FDA’s hand as it looks to expand its regulatory reach.

Media Scrutinizes Mayo Medical Laboratory’s Million-Dollar LDT Business

In its report, the WSJ expanded the investigative focus to include the multibillion-dollar-a-year business of LDTs, zeroing in on Mayo Medical Laboratories, which generates as much as half of its annual revenue of $600 million from LDTs. The WSJ stated that half of the roughly 3,500 medical tests done each year by Mayo Medical Laboratories are LDTs—a business supported by FedEx deliveries from hospitals and doctors worldwide.

Increased Regulation of LDTs Would Negatively Impact the LDT Business

While Mayo Clinic’s total patients reached roughly 1.3 million, and its annual revenue nearly $9 billion in 2014, laboratory officials stated that increased FDA regulation would hurt their bottom line. Curtis A. Hanson, MD, of Mayo Medical Laboratories, told the WSJ that closer regulation by the FDA would result in “a serious and negative impact on our ability to provide high quality and accessible patient care.”

Irving Nachamkin, DrPH, MPH, D(ABMM), FAAM, FIDSA, Director of the William Pepper Laboratory and the Division of Laboratory Medicine at Penn Medicine, takes issue with the WSJ’s implication that clinical laboratories operate in a largely unregulated environment.

In a Penn Medicine blog, Nachamkin pointed out that the WSJ failed to mention the Clinical Laboratory Improvement Act (CLIA) regulations cover all lab tests, including LDTs.

“What is really needed is congressional action to modernize CLIA regulations to fill in the gaps to ensure LDT quality, rather than having the FDA impose new and unrealistic regulations on top of CLIA requirements,” Nachamkin wrote. “To point: the majority of commercial test kits cleared by the FDA for sale to clinical labs go through a 510(k) review, and many provide neither sensitive nor specific results, nor are they required to do so.

“FDA clearance of LDTs, therefore, will not necessarily have the desired effect and only add significant cost to an already expensive and overburdened healthcare system, and impose additional regulations on laboratories that are already covered by existing, although not perfect, government regulations,” Nachamkin added.

FDA Report Concludes Harm Has Been Committed: Increased Regulations Needed

The FDA bolstered its case for increased regulation of LDTs with the November 2015 release of a report titled, “The Public Health Evidence for FDA Oversight of Laboratory Developed Tests.” The FDA reviewed 20 case studies of LDTs for Lyme disease, ovarian cancer, whooping cough, fibromyalgia, prostate cancer, autism, breast cancer, melanoma, Vitamin D, and other conditions. The agency concluded that in many instances “patients have been demonstrably harmed or may have been harmed by tests that did not meet FDA requirements.”

The Association for Molecular Pathology (AMP) has been sharply critical of the FDA’s report, challenging its conclusion that FDA oversight would prevent the potential harm to patients outlined in the case studies.

The Association for Molecular Pathology (AMP) criticized the FDA’s 2015 report that concluded patients may have been “demonstrably harmed by tests that did not meet FDA requirements.” Roger D. Klein, MD, JD (above), Chair of the Association for Molecular Pathology’s Public Relations Committee, and Medical Director, Molecular Oncology at Cleveland Clinic, called the case studies cited by the FDA “mostly a hodgepodge of outlier assays.” (Photo copyright: Centers for Disease Control and Prevention.)

The Association for Molecular Pathology (AMP) criticized the FDA’s 2015 report that concluded patients may have been “demonstrably harmed by tests that did not meet FDA requirements.” Roger D. Klein, MD, JD (above), Chair of the Association for Molecular Pathology’s Public Relations Committee, and Medical Director, Molecular Oncology at Cleveland Clinic, called the case studies cited by the FDA “mostly a hodgepodge of outlier assays.” (Photo copyright: Centers for Disease Control and Prevention.)

Roger D. Klein, MD, JD, is AMP Professional Relations Chair, and Medical Director, Molecular Oncology at Cleveland Clinic. In an AMP statement, Klein stated that “The 20 tests described by FDA are mostly a hodgepodge of outlier assays including tests that were never offered, tests for which comparable FDA assays perform poorly, tests for poorly defined disorders with psychologic components, and use of an FDA-approved test off-label.” Klein continued, “Also included, are examples of tests that are widely regarded as major scientific breakthroughs and which are recommended in major medical guidelines… That FDA could find only these dubious examples out of the many thousands of laboratory developed procedures (LDPs) that benefit patients each day, calls into question the agency’s rationale for expanding its regulatory scope to include LDPs,” he concluded.

The FDA report, however, contends additional oversight is needed because CLIA does not:

• Ensure the safety and effectiveness of LDTs prior to marketing;

• Assess the quality of the design and manufacture of devices;

• Ensure test labeling provides adequate directions for use;

• Require truth in marketing materials and other labeling;

• Require adverse event reporting;

• Permit removal of unsafe devices from the market;

• Require informed consent for patients participating in clinical studies of LTDs;

• Establish procedures for the conduct of such studies.

“While certain LDTs have undoubtedly brought benefits to many patients, the increase in complexity and patient volume brings [an associated] risk that patients will be harmed—and, in fact, have been harmed—and highlights the need for appropriate oversight,” the report states.

The WSJ article continues the growing trend of the national news media investigating medical laboratory failures or systemic problems in medical laboratory regulation and inspection. Given this ongoing public scrutiny, it is essential pathologists and clinical laboratory executives act now to improve the quality of their laboratory testing and associated services.

—Andrea Downing Peck

Related Information:

Is Lab Testing the Wild West of Medicine?

AMP Responds to FDA Report on Oversight of Laboratory Developed Testing Procedures

The Public Health Evidence for FDA Oversight of Laboratory Developed Tests: 20 Case Studies

Laboratory Testing Services, as the Practice of Medicine, Cannot Be Regulated as Medical Devices

LDT Update: FDA and CMS Testify Before House Energy & Commerce Committee Following Year of Debate on Oversight of LDTs

Summary of CAP’s Legislative Proposal for the Regulatory Framework of Laboratory-Developed Tests (LDTs)

CAP’s Legislative Proposal for Laboratory Developed Tests

Wild West of Medicine Needs a New Sheriff

Laboratory Developed Tests (LDTs)

Draft Guidance for Industry, Food and Drug Administration Staff and Clinical Laboratories

Why the FDA Should Oversee Laboratory Developed Tests