What Is Clinical Utility in a Tumor Biomarker Test? Former ASCO President Knows It When He Sees It

Daniel F. Hayes, MD, offers definitions and an algorithm for clinicians to define clinical utility.

A former president of the American Society of Clinical Oncology (ASCO) has provided a “pragmatic clinical guide” for fellow oncologists in deciding when to use tumor biomarker tests (TBTs) across an array of cancers, recognizing that the standard of “clinical utility” remains poorly defined years after payers began using it as the bar for reimbursement.

Daniel F. Hayes, MD, a breast cancer specialist from the University of Michigan who served as ASCO president in 2016-2017, recently published “Defining Clinical Utility of Tumor Biomarker Tests: A Clinician’s Viewpoint” in the Journal of Clinical Oncology, the official ASCO publication.

Hayes offers definitions and an algorithm for the circumstances when a TBT offers clinical utility, by considering factors such as intended use, various end points used to define a therapeutic strategy, who are the stakeholders, and, perhaps most critically, the risk tolerance of the various stakeholders.

“There is no strict definition of clinical utility for a TBT,” Hayes writes. “Consideration of these factors will lead to more objective conclusions.”

First, Hayes clarifies key terms involved in TBTs: analytical validity, clinical validity, and clinical utility. He writes that analytical validity refers to the performance value of the test—in other words, is it accurate—which may be complicated. A single biomarker may involve 1 or more assays to measure analytical validity. Once this is established, the same test may be used to establish clinical validity and clinical utility; the first term refers to a segment of the population, and the second asks whether decisions based on the test lead to meaningful patient outcomes.

Clinical utility has always been difficult to define. Hayes discusses this with a famous example, invoking Supreme Court Justice Potter Stewart’s 1964 decision on obscenity, which famously stated, “I know it when I see it.” Clinical utility, Hayes writes, also depends on the context, which has made the judgment calls by payers frustrating as precision oncology advances in cancer care. In too many cases, providers can point to cases where paying for a biomarker test might have guided care and saved money.

Thus, if providers are taking on risk in the era of value-based care, some say letting them make TBT decisions makes sense.

Hayes presents the TBT in light of what is known about BRCA mutations in breast, ovarian and prostate cancer, as well as KRAS in colorectal cancer and estrogen receptor (ER) in breast cancer. Results create an “opt-in” or “opt-out” scenario, in which providers should pursue additional diagnostic testing or a certain therapeutic strategy, or that such strategies will not work.

Other considerations include a patient's tolerance for the benefit gained, given the likely toxicity of a therapy for a given strategy. Knowledge gained from a TBT-selected subgroup can help drive treatment decisions, if the benefit to be gained is not deemed to be worth the toxicity, Hayes writes. Similar judgment calls can be made based on financial toxicity.

A big challenge, Hayes writes, is deciding which stakeholder’s voice matters most. Some may be more risk averse than others. “Some stakeholders might be willing to risk toxicities to gain even small benefits, whereas others might choose to forego some level of benefit to avoid toxicities,” Hayes writes. “These are difficult decisions for which there is no single answer but rather will depend much on the perceptions, preferences, and judgments of those making them—the patient, the caregiver, or society or third-party payers—and the variability in risk tolerance among each.”


Hayes DF. Defining clinical utility of tumor biomarker tests: a clinician’s viewpoint. J Clin Oncol. Published December 16, 2020. DOI: 10.1200/JCO.20.01572

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