The Center for Medical Technology Policy's Green Park Collaborative has embarked on a project to develop guidelines for generating evidence for the clinical utility of next-gen sequencing-based cancer diagnostics.
Over the next year or so, GPC, in collaboration with a broad array of stakeholders, plans to develop a so-called Effectiveness Guidance Document with recommendations for how to design studies to gather evidence of clinical utility. The goal is to help payors make coverage and reimbursement decisions for NGS-based diagnostic oncology tests.
There has been a rapid influx of new oncology NGS tests onto the market, and no regulatory authorities currently require proof of their clinical utility, according to Patricia Deverka, senior research director at the CMTP, a non-profit organization that focuses on healthcare comparative-effectiveness research. "Yet payors require evidence of clinical utility when making coverage determinations, [so] there is a real need," she said.
Next-gen sequencing generates large amounts of complex information that "redefines our approach to cancer" as a molecularly defined disease, she said, and the new tests might require different standards for clinical utility. "Do we need to rethink our definition of clinical utility, and how one would actually design a study to demonstrate clinical utility? What is the evidentiary framework for evaluating clinical utility?" Deverka said.
While clinical utility has already been examined for NGS-based non-invasive prenatal tests, she said, this has not been the case yet for oncology tests. The new initiative will focus on NGS tests used to manage the care of cancer patients, not tests to predict the risk of developing cancer in the future.
The target audience for the new guidelines will be NGS test developers – both in industry and academia – designing studies to show clinical utility for their tests. "We're not attempting to be prescriptive about who conducts the studies," said Elisabeth Houtsmuller, a senior program director at GPC, who spearheads the initiative. "We're providing recommendations about key characteristics of the studies, so that the unanswered questions will be answered."
Last year, the CMTP, which GPC is part of, released guidelines for the types of evidence required to show clinical validity and clinical utility for oncology molecular diagnostics.
Those guidelines focused on "first-generation technologies," Deverka said, and the new NGS-focused guidelines will build on them. Like the existing guidelines, the new ones might include standards for clinical validity as well as clinical utility.
While the existing guidelines were supposed to be platform-agnostic, "feedback we got under further review of those guidelines is that we needed to do a deeper dive, given the rapid evolution in the next-gen sequencing world, and build on that and customize a new [Effectiveness Guidance Document] specifically for next-gen sequencing," she said.
The new guidelines will be developed with the GPC's Oncology Consortium, which consists of public and private payors, regulatory agencies such as the FDA, other federal agencies, patient advocates, test providers, researchers, and funding agencies.
The process of their development "brings together all the stakeholders involved in the healthcare field, gets their input, and does an extensive literature review … to generate very condition-specific study design recommendations," said Houtsmuller.
GPC is in the process of recruiting up to a dozen or so members for a technical working group that will include clinical oncologists, representatives of next-gen sequencing tests developers, health plans, the FDA, patient groups, oncology guideline organizations, drug companies, and bioinformatics experts.
Over the next nine to 12 months, that group, in consultation with the larger Oncology Consortium, will develop draft recommendations, which will then be published by the CMTP and disseminated through presentations at scientific meetings, publications, and promotion by thought leaders in the field.
The hope is that the new guidelines will facilitate more clinical utility studies for NGS-based cancer diagnostics. "What we're trying to do here at CMTP through the design of studies in a stakeholder-driven process is recognize that traditional clinical trials, conducted in academic centers, represent a real barrier to the diagnostics industry – and that's why a lot of clinical utilities studies have not been done in the past," Deverka said.
"We're trying to find a middle ground, if you will, where we balance issues like internal validity, feasibility, cost, timeliness, [and] relevance," she said. "And we're hoping that the recommendations … will result in more clinical utilities studies being designed. I can't promise that they will be all short and easy, but everybody is hoping that we will get more and better evidence of clinical utility" for NGS-based cancer tests.