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Many Challenges Loom in Ensuring Validity and Utility of Diagnostic Tests

Surabhi Dangi-Garimella, PhD
Published: Tuesday, May 12, 2015
Dr. Daniel F. Hayes

Daniel F. Hayes, MD

Precision medicine has affected every aspect of healthcare today, and—as is evident from President Obama’s State of the Union speech in January—is front of mind with the federal government, which has plans to increase basic research funding for the National Institutes of Health and boost the regulatory role of the FDA. However, while diagnostic tests play a critical role in physician decision making—particularly in oncology—questions remain regarding the clinical utility of some of these tests, as well as the validity of laboratory-developed tests (LDTs). While next-generation sequencing is on the horizon for the FDA’s regulatory purview, assessing the validity and utility of existing FDA-approved tests and LDTs, and deciding who pays for the tests, are important issues that remain unaddressed.

The American Journal of Managed Care convened an expert panel to discuss these and other issues regarding diagnostic testing.

Perspectives on the topic were contributed by Francisco J. Esteva, MD, PhD, director of Breast Medical Oncology and associate director of Clinical Investigation, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center; Daniel F. Hayes, MD, Division of Hematology/ Oncology, Department of Internal Medicine, University of Michigan Medical School; John L. Fox, MD, MHA, associate vice president, Medical Affairs, Priority Health; and Bryan Loy, MD, MBA, vice president of Oncology, Laboratory and Personalized Medicine at Humana. Surabhi Dangi-Garimella, PhD, managing editor of Evidence-Based Oncology, served as moderator.

Factors in Determining Value

The discussion started with Dangi-Garimella asking the panelists how they scrutinize the “value” of a diagnostic test beyond its analytical performance: “Between outcomes for a particular patient population, improved healthcare quality, the cost of a test, and how complex the procedure is for conducting a particular test, what are the different parameters that clinicians and payers consider?”

For a long time, biomarkers included in these diagnostic tests had not been validated, answered Esteva, resulting in smaller retrospective—not prospective— trials being conducted to evaluate the tests. Referring to biomarkers identified in breast cancer, he added that the estrogen receptor (ER), the progesterone receptor, and HER2—the standard of care—had not been validated via a prospective trial. He believes that despite the lack of prospective data, there is value in some of the new diagnostic tests used in breast cancer, such as Oncotype Dx, Mammaprint, and Prosigna. However, he sees a problem with the lack of clinical or outcomes data of some of the genomic/next-generation sequencing tests now in use.

Francisco J. Esteva, MD, PhD

Francisco J. Esteva, MD, PhD

According to Hayes, we critically need to take three actions: (1) modify the regulatory environment; (2) discuss the analytical validity of a diagnostic test; (3) and identify who really decides the utility of LDTs.

Unlike drug manufacturers, whose products face rigorous evaluation through clinical trials, manufacturers of diagnostic tests have the option of gaining FDA approval through a Premarket Approval process, or 510(k) clearance, or through an FDA-independent process that requires approval through the CMS-initiated Clinical and Laboratory Improvement Amendments (CLIAs).

LDTs, developed by individual laboratories, can escape FDA evaluation as long as they have CLIA approval, which “really means that the laboratory adheres to good laboratory practices, but has nothing to do with the value of that test to take care of an individual patient,” Hayes emphasized.

The “clinical utility” of a diagnostic test needs attention, said Hayes, because it indicates whether analyzing for the particular biomarker on the diagnostic test improves patient outcomes. However, he pointed out that the FDA approval process does not require the manufacturer to establish clinical utility—analytical and clinical validity suffice. So the FDA-approved tests, in his opinion, may not be valuable in terms of patient care, and even if they are, there are no studies to prove so.


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