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Comparative Study
. 2018 Jun 1;4(6):838-841.
doi: 10.1001/jamaoncol.2017.4021.

Comparison of Laboratory-Developed Tests and FDA-Approved Assays for BRAF, EGFR, and KRAS Testing

Annette S Kim  1 , Angela N Bartley  2 , Julia A Bridge  3 , Suzanne Kamel-Reid  4 , Alexander J Lazar  5 , Neal I Lindeman  1 , Thomas A Long  6 , Jason D Merker  7 , Alex J Rai  8 , David L Rimm  9 , Paul G Rothberg  10 , Patricia Vasalos  6 , Joel T Moncur  11
Affiliations
Comparative Study

Comparison of Laboratory-Developed Tests and FDA-Approved Assays for BRAF, EGFR, and KRAS Testing

Annette S Kim et al. JAMA Oncol. .

Abstract

Importance: The debate about the role of the Food and Drug Administration (FDA) in the regulation of laboratory-developed tests (LDTs) has focused attention on the analytical performance of all clinical laboratory testing. This study provides data comparing the performance of LDTs and FDA-approved companion diagnostics (FDA-CDs) in proficiency testing (PT) provided by the College of American Pathologists Molecular Oncology Committee.

Objective: To compare the analytical performance of LDTs and FDA-CDs on well-characterized PT samples and to compare the practice characteristics of laboratories using these assays.

Design, setting, and participants: This comparison of PT responses examines the performance of laboratories participating in the College of American Pathologists PT for 3 oncology analytes for which both FDA-CDs and LDTs are used: BRAF, EGFR, and KRAS. A total of 6897 PT responses were included: BRAF (n = 2524; 14 PT samples), EGFR (n = 2216; 11 PT samples), and KRAS (n = 2157, 10 PT samples). US Food and Drug Administration companion diagnostics and LDTs are compared for both accuracy and preanalytic practices of the laboratories.

Main outcomes and measures: As per the College of American Pathologists PT standards, results were scored and the percentages of acceptable responses for each analyte were compared. These were also broken down by the specific variants tested, by kit manufacturer for laboratories using commercial reagents, and by preanalytic practices.

Results: From analysis of 6897 PT responses, this study demonstrates that both LDTs and FDA-CDs have excellent performance overall, with both test types exceeding 97% accuracy for all 3 genes (BRAF, EGFR, and KRAS) combined. Rare variant-specific differences did not consistently favor LDTs or FDA-CDs. Additionally, more than 60% of participants using an FDA-CD reported adapting their assay from the approved procedure to allow for a greater breadth of sample types, minimum tumor content, and instrumentation, changing the classification of their assay from FDA-CD to LDT.

Conclusions: This study demonstrates the high degree of accuracy and comparable performance of both LDTs and FDA-CDs for 3 oncology analytes. More significantly, the majority of laboratories using FDA-CDs have modified the scope of their assay to allow for more clinical practice variety, rendering them LDTs. These findings support both the excellent and equivalent performance of both LDTs and FDA-CDs in clinical diagnostic testing.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kim works or has worked as a consultant to Aushon Biosciences. Dr Rimm works or has worked as a consultant or advisor to Astra Zeneca, Agendia, Bethyl Labs, Biocept, BMS, Cell Signaling Technology, Merck, OptraScan, Perkin Elmer, and Ultivue; has equity in Metamark Genetics and PixelGear; and receives research funding from Astra Zeneca, Cepheid, Navigate/Novartis, Gilead Sciences, Pierre Fabre, and Perkin Elmer. Dr Rai is the American Association for Clinical Chemistry liaison to the College of American Pathologists Molecular Oncology Committee. Dr Rothberg is the Association for Molecular Pathology liaison to the College of American Pathologists Molecular Oncology Committee. Dr Moncur is employed at Walter Reed National Military Medical Center. The identification of specific products or scientific instrumentation is considered an integral part of the scientific endeavor and does not constitute endorsement or implied endorsement on the part of the authors, the Department of Defense, or any component agency.

Figures

Figure.
Figure.. Methods of Performing Assays by Laboratories Based on Tissue Preparation and Tumor Type
A, Percentage of laboratories performing their assays on FFPE tissue preparations exclusively vs laboratories that are inclusive of other types of tissue preparations. B, Percentage of laboratories performing their assays on FDA-approved tumor type (melanoma for BRAF) exclusively vs laboratories that are inclusive of other types of tumors. FDA indicates US Food and Drug Administration; FFPE, formalin-fixed paraffin-embedded; LDT, laboratory-developed tests.
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