FDA-approved assays, lab-developed tests perform equally for certain cancer diagnostics

Last Updated: 2017-12-21

By Marilynn Larkin

NEW YORK (Reuters Health) - Both laboratory-developed tests (LDTs) and U.S. Food and Drug Administration-approved companion diagnostics (FDA-CDs) show a high degree of accuracy and comparable performance for three oncology analytes, researchers say.

Dr. Annette Kim of Brigham and Women's Hospital in Boston told Reuters Health by email, "The recent debate on LDTs and FDA-CDs has centered upon both the regulatory and performance aspects of LDTs and we, at the College of American Pathologists (CAP), had the data through our proficiency testing (PT) programs to address the latter point, performance, which we want to share with the community."

A total of 6,897 PT responses from laboratories participating in the College of American Pathologists' PT program were included in the analysis: 2,524 BRAF analytes in 14 PT samples; 2,216 EGFR analytes in 11 PT samples; and 2,157 analytes in 10 PT samples. LDTs and FDA-CDs were compared for both accuracy and laboratories' preanalytical practices.

"We found that both LDTs and FDA-CDs demonstrated excellent performance, with both test types exceeding 97% accuracy overall," Dr. Kim said.

The team also notes, in their December 14 JAMA Oncology online report, that more than 60% of participants using an FDA-CD modified their assays from the approved procedure.

"These modifications in fact render these tests LDTs," Dr. Kim said. "They appear to be driven by the exigencies of real day-to-day clinical practice, which require adapting the assays to meet the needs of a variety of clinical situations that may not be accommodated by the FDA-approved protocol."

"These modifications include, for example, the testing of other tumor types that may carry targetable variants; different types of input specimen preparations available in pathology, such as cytology smears or other fresh specimens rather than paraffin blocks; and availability of different methods of DNA quantification than those mandated by the FDA approval," she explained.

"It is important to recognize that this study only addresses the accuracy of results from laboratories. Other aspects of laboratory practice are not addressed," she noted. "However, where possible, these other aspects should be published as solid and vetted data through peer-reviewed venues to better inform the community."

In a joint email to Reuters Health, Dr. Rodney Rohde, chair of clinical laboratory science at Texas State University-San Marcos and Dr. Peter Hu, director of the molecular genetic technology program at MD Anderson Cancer Center in Houston, commented, "At present, there are no convincing arguments that LDTs are inferior to any other type of developed tests including companion diagnostics."

"That is because as these tests are developed in CLIA-compliant labs, the stakeholders - e.g., directors, managers, supervisors, and technologists - all have gone through extensive training with expertise in the design, development, and clinical validation for optimal use," they observe.

"In addition," they note, "there are other oversight bodies such as CAP, licensure or board certification of practitioners, to make sure these tests are effective and patient-centered, backed by the highest level of quality control and assurance on the methods and procedures."

Separately, a research letter in the same issue of the journal reports on a comparison of two platforms for targeted next-generation sequencing of cell-free (cf)DNA: Guardant360 (GuardantHealth, Inc) and PlasmaSELECT (Personal Genome Diagnostics, Inc). Investigators from Johns Hopkins University School of Medicine in Baltimore found very low congruence for paired samples from 40 volunteers with metastatic prostate cancer, raising the possibility that patients could receive different treatments depending on the cfDNA platform.

Dr. Daniel Hayes of the University of Michigan Comprehensive Cancer Center in Ann Arbor, who commented on both studies in an editorial, called the results of the second study "disturbing."

"Clinicians need to have confidence that the test they are using to guide treatment is as reliable as the drug they prescribe," he told Reuters Health by email. "We have faith that a drug is manufactured appropriately, mixed carefully, and administered appropriately, and that the high levels of evidence from well-designed, scientifically rigorous, prospective clinical trials are available for recommending its use."

"The FDA has a good track record of determining if a new drug or new indication is 'safe and effective.' However," he noted, "analysis for tumor biomarker tests is much less consistent."

"I, for one, advocate for a more consistent regulatory environment for tumor biomarker tests so that clinicians and patients can be confident that a test used to direct care is as good as the drug," Dr. Hayes concludes.

Dr. Kim and one coauthor report fees from companies involved with molecular diagnostics.

SOURCES: http://bit.ly/2CPcnqi, http://bit.ly/2BVevQA and http://bit.ly/2Bn9q41

JAMA Oncol 2017.