NEW YORK – When the US Food and Drug Administration (FDA) called for public comments on its proposed rule regulating laboratory-developed tests, medical provider groups and professional organizations were broadly opposed.
The American Medical Association registered its discontent with the rule as did a wide range of specialist organizations. One notable exception to this trend was oncologists, as a number of prominent cancer groups, including the Association for Clinical Oncology (ASCO), the American Cancer Society’s Cancer Action Network, the Cancer Leadership Council, the National Brain Tumor Society, and Friends of Cancer Research, issued comments in favor of the rule.
Some 18 months later, the FDA rule is officially dead, the federal government having this month declined to appeal the federal court decision vacating the rule. This development came as a relief to the many clinical laboratory and provider organizations that opposed the rule, but it has left oncologists still confronting challenges around the use of LDTs that some had hoped FDA oversight could help address.
Julie Gralow, executive VP and chief medical officer at ASCO, suggested that the oncology community’s openness to FDA oversight of LDTs was in part a reflection of the challenges the field has faced in grappling with an explosion of new tests — both LDTs and FDA-regulated assays — in recent years.
She cited the case of companion diagnostics used for guiding targeted therapies, where, as ASCO noted in its letter of support for the FDA rule, the FDA has approved more than 180 drugs across more than 300 types of cancer that require assessment of a cancer biomarker via a companion diagnostic. While such companion diagnostics are typically FDA-cleared, clinical labs frequently develop LDTs that can also be used to assess these biomarkers.
“In oncology over the past five to 10 years, we have just had such a proliferation of these tests,” Gralow said. “We were overwhelmed with the mess … and we were looking for more consistent regulation of how these [tests] came about.”
Jeff Allen, president and CEO of Friends of Cancer Research (FOCR), similarly highlighted the wide use of companion diagnostics and biomarker testing within oncology as driving the space’s relatively supportive position regarding the FDA rule.
“By some estimates, well over 30 percent of all new oncology [therapeutic] products will have some sort of biomarker selection associated with their use,” he said. “So, there’s a degree of experience with that and a recognition of the importance of accurate testing.”
Allen said that the emergence of multiple tests — both LDTs and FDA-regulated tests — for the same intended uses raised questions among oncologists about their equivalence. He added that pilot projects conducted by FOCR had found variability between different tests that targeted the same biomarker, and in some cases, these cross-comparisons involved as many as 17 different laboratories and test developers that had assays to the same marker being measured.
“That was one of the reasons we were interested in [FDA oversight of LDTs], because there are so many different tests for the same biomarkers that we want to ensure the results are consistent and accurate,” Allen said.
In the absence of FDA oversight of LDTs, the oncology community is looking to other approaches to ensuring test consistency and accuracy.
One tack, Gralow said, is expanding the use of molecular tumor boards, both in the academic and community settings. Such boards can bring together not only oncologists but also the pathologists and laboratory medicine providers who may have a deeper understanding of the available tests, in what situations they are useful, and the assumptions and interpretations underlying their results.
“We have not just experts in knowing what targeted therapies are available but also what are the assays that lead us to that targeted therapy,” Gralow said. “At the molecular tumor board level, it’s very transparent what you call the cut point for amplification [of a biomarker], for example. And it becomes apparent how complicated interpreting if something is positive or negative can be in many cases.”
Use of molecular tumor boards “is expanding,” Gralow said, adding that large academic centers with the resources and personnel to put together these boards are increasingly inviting oncologists from the community setting to present cases.
Gralow also highlighted the emergence of “biomarker navigation,” in which cancer centers have created roles for “biomarker navigators” (also known in some cases as precision medicine stewards) to help coordinate and streamline the biomarker testing process, serving as a liaison between oncologists, patients, internal and external laboratories, and other stakeholders.
In 2022, the Association of Community Cancer Centers launched a series of focus groups to study the implementation of such programs in both the academic and community settings. Last year, the American Society for Clinical Pathology launched a pilot study to examine the feasibility of incorporating what it termed Cancer Biomarker Testing Navigators into oncology testing workflows.
Gralow said she is now working within ASCO to explore whether the organization could help interested members implement biomarker navigation at their centers.
Allen noted that New York state’s Clinical Laboratory Evaluation Program (CLEP) continues to perform test performance evaluations for assays offered in the state.
Insurers might also move to require more in-depth data on test performance. In 2022, for instance, Highmark asked in-network labs to provide test accuracy data for certain genetic cancer tests beyond that required for CLIA certification and accreditation by the College of American Pathologists (CAP). Allen said, however, that he has seen little in the way of new payor initiatives to require additional performance metrics for cancer tests.
Despite ASCO’s support for the FDA’s LDT rule, Gralow said that given there is “so much else going on in the current environment,” a renewed push for legislative or regulatory action on LDTs “is not a high priority” for the organization or its members.
“I would say we are in a listening mode,” she said.
Allen said that FOCR remains focused on the goal of maintaining access to testing while also ensuring transparency, consistency, and accuracy in results but that new approaches will likely be necessary. Last year, FOCR joined with CAP, Mayo Clinic, Roche, Thermo Fisher Scientific, and Alexion to form a new organization, the Coalition for Effective Diagnostics, that called on lawmakers to pass legislation revamping diagnostics regulation, including the oversight of LDTs. Allen said, though, that he sees little chance of Congress passing a bill like the Verifying Accurate Leading-edge IVCT Development (VALID) Act, which was in recent years the primary legislative vehicle for diagnostics reform.
CLIA reform is another possible route for strengthening LDT oversight, and one that many lab stakeholders have highlighted as a preferable alternative to FDA oversight. Gralow said ASCO is open to CLIA reform but noted that the organization has not put out any statements or heard concrete recommendations on how reform might address LDTs.
“I’m not sure this Congress is ready to take that up any time soon,” she added.
“We’d be happy to look at” CLIA reform, Allen said. “For us, it’s not so much the agency, the avenue, or the process that is motivating our position. It’s really looking at what agencies have the capability and capacity and to help resolve some of these problems and what processes can be put into place.”