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

The Association for Molecular Pathology (AMP), Bethesda, Md, has issued a response to FDA’s recently released report on the oversight of laboratory-developed tests with its own detailed analysis of the case studies presented in the agency’s report.^1,2

After a thorough examination of the instances cited in the report, AMP concludes that FDA oversight would likely prevent few of the potential patient harms postulated by the agency. Instead, the association asserts, the potential problems identified by the agency would be handled more successfully by the Centers for Medicare & Medicare Services (CMS), which has statutory authority over the Clinical Laboratory Improvement Amendments (CLIA) program.

“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 psychological components, and off-label use of an FDA-approved test,” says Roger D. Klein, MD, JD, FCAP, medical director for molecular oncology at the Cleveland Clinic, and chair of AMP’s professional relations committee.

“Also included are examples of tests that are widely regarded as major scientific breakthroughs and are recommended in major medical guidelines,” says Klein. “In one case FDA appears to imply that a manufacturer invented testing for a particular mutation, although laboratories in the United States had for many years been performing more-flexible, more-practical, and in many instances arguably superior procedures for the same analyte, prior to introduction of the FDA-approved test.

“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,” Klein adds.

In its response, AMP concludes that FDA’s criticism of some assays should not have been aimed at the procedures themselves, but at a small number of treating physicians who failed to follow up a screening test with another test that would have provided a definitive diagnosis, or otherwise acted on results in a manner inconsistent with standard medical practice. Nevertheless, AMP has long maintained that the involvement of board-certified professionals is critical for the development of accurate and reliable LDPs, as well as for correct utilization, accurate interpretation, and appropriate application of molecular test results. According to the association, insistence on the involvement of appropriately trained and qualified laboratory professionals, rather than FDA regulation, will best protect patients and ensure they receive optimal testing services.

FDA’s concern about an ‘uneven playing field’ suggests that the agency may be more concerned with protecting competitors than patients. “FDA mistakenly advances the illusion that multibillion-dollar IVD kit manufacturers are competing with, and are at a competitive disadvantage to, LDP services provided by academic medical centers, hospitals, health systems, and independent laboratories across the country—and that it is the agency’s job to ‘level the playing field,’” says Klein. “However, not only is there not an uneven playing field, FDA fails to recognize that service providers and manufacturers are not on the same field at all.”

According to AMP, the agency’s report doesn’t acknowledge the improvements that many LDPs offer relative to FDA-cleared and approved tests. LDPs include tests that detect key genetic mutations critical to therapy selection under circumstances in which use of FDA-approved assays can lead to incomplete or even false negative results—and therefore failure of patients to receive potentially beneficial treatments. Often, LDPs designed and properly validated by molecular professionals are the only tests available for accurately analyzing a patient specimen and detecting the mutation of interest.

“The report released by FDA provides misleading information in an attempt to achieve a political end,” says Janina A. Longtine, MD, professor of pathology at the Icahn School of Medicine at Mount Sinai Hospital and AMP immediate past president. “Clear and accurate information is needed to avoid a misinformed and alarmed public, especially as stakeholders are working together with Congress to achieve policy changes that will truly benefit patient care.”

AMP has long held the position that requiring LDPs to undergo pre-introduction review by FDA would disrupt patient care without necessarily making patients any safer.

According to the association, LDPs that have been cleared or approved by FDA have been submitted by a few esoteric, commercial laboratories that perform a small number of sometimes proprietary tests in extremely high volume for narrow clinical indications. Some of those companies have spent millions of dollars and built separate laboratories dedicated to performing a single FDA-regulated service.

By contrast, says the association, requiring mostly nonprofit academic medical centers, hospitals, health systems, and cancer center laboratories to submit their LDPs for pre- introduction approval by FDA would be both financially and administratively infeasible. Services for which FDA clearance or approval is required will very likely cease to be offered, and patients will lose access to innovative and accurate laboratory testing procedures.

“AMP believes that the most reasonable and effective path forward is for Congress to insist that the CLIA program modernize, expand its current network of third-party medical experts, and utilize scientific expertise from FDA and CDC—rather than relinquishing its duties regarding the accuracy and reliability of LDPs,” says Charles E. Hill, MD, PhD, associate professor of pathology and laboratory medicine at Emory University and AMP president.

“AMP strongly urges the Department of Health and Human Services and the Office of Management and Budget to perform a thorough, scientifically unbiased analysis of potential harms and benefits of FDA regulation of LDPs prior to embarking on a massive new regulatory program that would be enormously disruptive to healthcare and would likely have profound adverse consequences for patients across the country.”

For further information, visit the Association for Molecular Pathology.

REFERENCES

1. The public health evidence for FDA oversight of laboratory-developed tests: 20 case studies. Silver Spring, Md: FDA, 2015. Available at: www.fda.gov/AboutFDA/ReportsManualsForms/Reports/ucm472773.htm. Accessed December 16, 2015.

2. Facts FDA ignored: an analysis of the FDA report, “The public health evidence for FDA oversight of laboratory-developed tests: 20 case studies.” Bethesda, Md: Association for Molecular Pathology, 2015. Available at: http://amp.org/emailads/documents/ampresponsefdacasereportfinal.pdf. Accessed December 16, 2015.