Emerging genetic testing technologies must have performance standards, limber FDA oversight, and dependable insurance coverage to advance the burgeoning field of tailored medical treatment, cancer-advocacy and industry representatives said.
Next Generation Sequencing (NGS) testing is the foundation of precision medicine, an innovative approach that narrowly tailors disease prevention and treatment based on an individual’s own genes, environment, and lifestyle, according to the Food and Drug Administration. The FDA’s Precision Medicine Initiative describes it as an improvement on the “one-size-fits-all” approach to treatment. As part of the initiative, the National Institutes of Health has launched its massive All of Us Research Program, which aims to build a research cohort of at least 1 million participants.
Cohort of 1 Million
“This is an incredibly ambitious project,” Carrie Wolinetz, NIH associate director for science policy and chief of staff for NIH Director Francis Collins, said at an Sept. 18 forum held by Arent Fox LLP. “[W]e will have a large enough cohort to begin to really understand and drill down into the differences between individuals,” allowing researchers to understand how different people respond to specific therapies, she said.
NGS tests are capable of detecting hundreds of genetic variants in a person that could help physicians identify that person’s best treatment options. NGS testing specifically has given researchers and physicians a deeper understanding of tumor biology, the Friends of Cancer Research (FOCR) said in a draft white paper it released at a Sept. 13 forum. The draft document, “Charting the Course for Precision Medicine,” said uniform NGS assessment standards and rapid FDA approval of test modifications are needed to make the tests more useful.
Set Standards
FOCR’s draft white paper said baseline standards are needed if NGS testing and precision medicine are going to advance. “Consensus should be established on the minimal analytical performance characteristics that every NGS diagnostic used in clinical care should meet,” the documents said, “and these performance characteristics should be utilized uniformly.”
“This is really about trying to set a playing field so that everybody is reading from the same book,” University of Colorado School of Medicine associate professor Dara Aisner said at the FOCR event.
Using carrots and sticks may be the best approach to getting labs to adhere to standards, said Erasmus Schneider, associate director of research and technology with the New York State Department of Health’s Wadsworth Center. The center provides laboratory certification and education programs. Labs could proudly claim adherence to them, and insurance companies might refuse to reimburse them if they don’t, he said at the FOCR event.
Mere minimum standards should be enough to incentivize labs, said Rasika Kalamegham, group director of U.S. regulatory policy at Genetech Inc.
“What we’re saying is, ‘Let’s agree on a minimum standard. It doesn’t mean you can’t exceed it,’” she said. “It’s sort of like fuel efficiency in cars. There’s a consensus that if you’re a sedan you have to meet this, if you’re an SUV you have to meet this. When you do exceed it, it becomes a badge of honor.”
FDA procedures for approving proposed changes to in vitro diagnostics also need to change if NGS testing is going to be as effective as possible, the FOCR draft white paper said. Modifications are subject to the FDA’s premarket approval (PMA) process, which can take up to 180 days, the document noted. That’s too long for a technology such as NGS, which can produce vast amounts of data that might be immediately put to use in patient care, the paper argued.
“To deliver the best patient care, tests should evolve with technology and clinical science in a near simultaneous manner,” the paper said.
A “pre-specified modification plan” established between an NGS sponsor and the FDA should be set before or at the time of a PMA submission, FOCR recommended. Subsequent modifications to the plan would not need to be submitted as a PMA.
The Payment Problem
Of all the obstacles to making genetic testing routine, “there’s no question the largest obstacle … is reimbursement,” said Troy Cox, chief executive officer of Foundation Medicine Inc., based in Cambridge, Mass.
“If payers don’t pay for the diagnostic test, then obviously we’re going to have a hard time realizing our precision medicine goal,” he said at the Arent Fox event.
While acknowledging insurers have genuine concerns, genetic testing costs are “quite manageable in the scheme of things,” he said, noting that his company’s comprehensive genetic tests cost an average of $3,000 to $5,000.
“Of everything you could purchase for a cancer patient, we think this is the best investment you could make,” he said.
“Cancer definitively is a disease of the genome,” he said. “We’ve known that for a long time.”
Payers are concerned about affordability and ensuring patients receive therapy that is safe and effective, said Richard Bankowitz, executive vice president for clinical affairs for America’s Health Insurance Plans, an insurer trade association.
Most important to insurers is whether a test has clinical utility—whether it’s the right test, conducted on the right population, and leads to a proper therapy, Bankowitz said. Insurers will likely draw a line between medically necessary tests and experimental ones, he said. Test results should produce clinically important information that demonstrates effectiveness in improving outcomes, he said.
“[W]e don’t want to pay for things unless we know that they actually are required,” he said. “In my mind it’s really not any different from the introduction of any new therapy. We want to have evidence that the technology actually results in better outcomes.”
