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By: Susan Van Meter, Executive Director, AdvaMedDx
March 6, 2018

Not All Tests Created Equal: AdvaMedDx Response to JAMA Oncology Article

Recently, researchers at Brigham and Women’s Hospital published an article in JAMA Oncology that sought to compare the performance of FDA-approved companion diagnostics (FDA-CDs) and laboratory-developed tests (LDTs). In recent years, public debate and scrutiny has intensified regarding the oversight paradigm for diagnostics as well as the highly disparate treatment of tests that are the same from the perspective of patient risk and safety.

While papers such as these represent an important contribution to an area that has come under intense scrutiny, the overall study methodology invites a number of questions that warrant further review, and extrapolation of the paper’s conclusions without acknowledging the limitations could pose serious health risks to patients.

The study presents a comparison of FDA-CDs to FDA-CD’s with some degree of modification, rather than to true LDTs that are designed and manufactured in a laboratory setting and never submitted for FDA review. While the study does not describe the types of modifications that were made – another inherent limitation in the methodology – the analysis clearly better supports the finding that FDA-approved tests are well-performing technologies that are helping to drive drug delivery and patient care in a high-risk space.

Second, the study authors selected well-established FDA-approved tests rather than novel tests – an important factor in truly assessing appropriately validated tests – thus we cannot theorize the results are applicable to other, more involved tumor tests. In fact, the increasing development of Next Generation Sequencing (NGS)-based testing—with significantly more complex workflows covering much larger numbers of genes and variants—highlights the importance of risk based framework to ensure appropriate oversight.  The inference of equivalence between LDTs and FDA-CDs should also not be extrapolated to encompass any and all higher risk tests.

Finally, the paper represents a comparison of test results, not the tests or the laboratories themselves, and not all data was reported. All FDA-CD devices must undergo a rigorous set of analytical and clinical validation studies before approval for which there is transparency regarding performance claims.  This remains a risk for tests that have not undergone FDA review.  In this study, more transparency to better understand reporting mechanisms as well as why participants omitted results is needed to truly assess the study’s value.

The introduction and expanding use of molecular diagnostic tests to detect cancer and manage cancer care mark a major milestone and herald future progress in the fight against the disease. These tests are relied upon by doctors and patients to guide critical health care decisions in cancer treatment, however, they have grown increasingly complex over the last decade. Consistent and effective oversight of all diagnostics, including those developed by both manufacturers and laboratories, under a risk-based approach with sufficient transparency about known risks and limitations for tests while still promoting public health and innovation is the only path forward.  Overly general comparisons for limited studies that make limited conclusions do not help advance patient care.