Most Laboratory Testing For Cancer-Causing Gene Mutations Found Reliable Interview with:

Annette S. Kim, MD, PhD Associate Professor, Harvard Medical School Brigham & Women's Hospital Boston MA 02115

Dr. Kim

Annette S. Kim, MD, PhD
Associate Professor, Harvard Medical School
Brigham & Women’s Hospital
Boston MA 02115 What is the background for this study? What are the main findings?

Response: The recent debate on laboratory developed tests (LDTs) and FDA-approved companion diagnostics (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 that we wanted to share with the community.  We analyzed almost 7000 PT responses on three molecular oncology tests, those for BRAF, EGFR, and KRAS mutations, and found that both LDTs and FDA-CDs demonstrated excellent performance, with both test types exceeding 97% accuracy overall.

The second key finding of the study was that more than 60% of all laboratories in our study that were using an FDA-CD kit report using it with modifications from the FDA-approved protocol.  These modifications in fact render these test LDTs.  These modifications appear to be driven by the exigencies of real day-to-day clinical practice that requires 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 that those mandated by the FDA approval based upon pre-existing technologies in the laboratories.  In the clinical laboratory, we are always acutely aware that there is a patient awaiting this result.

Therefore, we validate our assays to ensure that we can provide reliable and accurate results from our laboratory under as many varied clinical situations as possible. These data support that practice. What should clinicians and patients take away from your report?

Response: The results of this study should reassure the community on the excellent performance of laboratories whether they use an LDT or an FDA-CD.   The largest contribution of patient results delivered every day is from LDTs and, of the laboratories that purchase an FDA-CD kit, more than half have modified those assays to meet the clinical needs of their patients and the infrastructural environment in their institution.  It is also important to note that performance is regularly assessed through PT administered by experts in their respective fields who keep a finger on the pulse of emerging trends in testing practices and develop PT accordingly. PT programs, as required by CMS under CLIA, provide a rigorous way to monitor the performance of laboratories, whether they are performing an LDT or an FDA-CD, to ensure reliable and accurate results for patients.

The data show that the laboratories are doing an excellent job overall and PT programs that grow with the testing environment will help ensure this success moving forward. What recommendations do you have for future research as a result of this study?

Response: It is important to recognize that this study only addresses the accuracy of results from laboratories.  Other aspects of laboratory practice are not addressed. However, where possible, these other aspects should be published as solid and vetted data through peer-reviewed venues to better inform the community.   Given the nature of the PT that our CAP Molecular Oncology Committee oversees, we plan to continue to delve further in laboratory performance data in several upcoming manuscripts. Is there anything else you would like to add?

Response: This work was performed through the CAP and the authors are either members of the CAP Molecular Oncology Committee or CAP staff members.  Individual authors had specific disclosures, none of which represented conflicts of interest with the content of the study. Thank you for your contribution to the community.


Annette S. Kim, Angela N. Bartley, Julia A. Bridge, Suzanne Kamel-Reid, Alexander J. Lazar, Neal I. Lindeman, Thomas A. Long, Jason D. Merker, Alex J. Rai, David L. Rimm, Paul G. Rothberg, Patricia Vasalos, Joel T. Moncur. Comparison of Laboratory-Developed Tests and FDA-Approved Assays for BRAF, EGFR, and KRAS Testing. JAMA Oncol. Published online December 14, 2017. doi:10.1001/jamaoncol.2017.4021

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions. 

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