WASHINGTON—Earlier this month, at the American Urological Association Annual Meeting (May 4-8, in San Diego), researchers from the University of California, San Francisco released the much-anticipated validation data in prostate needle biopsy specimens on the investigational Oncotype DX genetic prostate cancer test. Before that presentation, as noted here at a summit last month sponsored by the Personalized Medicine Coalition and the Biotechnology Industry Organization, Steve Shak, MD, Chief Medical Officer and Executive Vice President of Research and Development for the assay's manufacturer, Genomic Health, Inc., said the aim was to complete the work necessary to bring the new biomarker-based molecular diagnostic test to market soon—“perhaps by the end of June.” In fact, though, the company announced on May 8 that it was making the test available to physicians and patients immediately.
The multi-gene Oncotype DX prostate cancer test is designed to help physicians determine which patients need prostatectomies and which patients can safely be spared the surgery. Shak, who developed the Oncotype DX breast cancer and colon cancer assays and led the clinical team that gained approval for trastuzumab, was a panelist at the summit, which was devoted to evidence, coverage, and incentives in the development of personalized (precision) medicine, focusing on molecular diagnostic tests.
Speakers at the meeting, “Evidence, Coverage, & Incentives,” debated and discussed issues related to: reimbursement hurdles, including inadequate coding; gaps in regulatory oversight; evidence needed for payer coverage; and inclusion of molecular diagnostics into clinical guidelines, among other topics. The emphasis was on the need for more physician education on molecular diagnostics, starting in medical school and continuing on into clinical practice.
“This is the most challenging and difficult time in the history of modern medicine,” said one of the keynote speakers Reed V. Tuckson, MD, Managing Director of Tuckson Health Connections and former Executive Vice President and Chief of Medical Affairs for UnitedHealth Group.
In an environment of rapid cost escalation, all medical innovations are going to have to prove their value, he said. No longer can the United States afford a health system that is “inconsistent with the scientific evidence about half the time.” While it is logical that molecular diagnostic tests can improve precision medicine, he said, they will add costs to an already costly system, and today this field is in “a very lawless and ungoverned wild west situation.”
The majority of genetic tests don't have CPT codes, he said, since the coding and payment system was not designed for complex molecular diagnostic tests. Therefore, most new diagnostic tests are reimbursed through grouping codes that describe each step in the laboratory protocol—a process known as code-stacking.
Code stacking just adds to the confusion in the field, said Tuckson. “We want to know if the test works. We want to be able to certify the labs; there are holes in oversight.
“Our coding system and our payer system have not really caught up…that's bad,” agreed Kristin Ciriello Pothier, who leads the Diagnostics and Life Sciences Practice as a partner at Health Advances. “Payers want to give reimbursement,” she added, but they want and need the evidence to do it.
Oncology Leading the Way
“In many ways oncology is leading the way in personalized medicine,” said Jeff Allen, PhD, Executive Director of the nonprofit advocacy organization Friends of Cancer Research and a board member of the Alliance for a Stronger FDA.
In determining the value of a new diagnostic test, the focus should be first and foremost on outcomes, he added, pointing to the field of blood cancers, in which a better understanding at the cellular level led to increased survival. “I think we're seeing something similar today in solid tumors,” he said.
“There's not really a standardized model to follow in the development of molecular diagnostic tests, which adds a layer of complexity to the clinical development process.” But, he noted, “one good sign is that at least in oncology you are starting to see co-development of diagnostics and therapies.”
The co-development process, he explained, leads to more clear-cut oversight because the diagnostic test and the drug can be approved at the same time and are meant to be used together in clinical practice.
Three Criteria to Meet
To have value, a molecular diagnostic test should meet three major criteria, said Bruce Quinn, MD, PhD, Senior Health Policy Advisor at Foley Hoag, LLP, and former regional Medicare Director for the California Part B program:
* Analytical validity (test tube results);
* Clinical validity (correlation between the test tube results and the patient); and
* Clinical utility (usefulness of the test in patient care).
The latter point is critically important, he said, because to prove its value a test needs to show it is truly useful, such as improving clinical decision making and/or increasing patient survival.
Quinn recommended a “pick list” to determine the value of a molecular diagnostic test, which might ask the following questions: Who should be tested and under what circumstances? What information does the test provide? Can care providers act on the information the test provides? Will providers act on this information? Does the patient outcome change in a way that provides value to care? Is the test affordable?
Agreeing with Allen and Quinn, several speakers said that to be reimbursed by payers, a molecular diagnostic test must demonstrate that it makes a difference in patient outcomes. That is not always easy in a health system that is fragmented and variable and lacks transparency and standardization.
“I have regulatory and statutory issues,” said Tamara Syrek Jensen, JD, Deputy Director of the Coverage and Analysis Group at the Center for Medicare and Medicaid Services and a board member of the Medical Device Innovation Council. “I need to see if the diagnostic test is improving the health outcomes of beneficiaries.” CMS has a molecular diagnostic pilot project, she noted, and “right now we're getting some positive results from that.”
Payers are concerned that covering a new molecular test will add to their costs, but if it helps get the right therapy to the right patient at the right time, it is actually cost-effective, said several speakers.
Jensen said her message to industry is: “Come to us and show us the evidence [for a new molecular diagnostic]. Be very honest with us. We don't want to be in the way; it's never too early to just pick up the phone and call us.” She added, “We're working in a gray area; if it's a really good product, it's going to fly through the system.”
Jensen said she would love to see the molecular diagnostic community come together to shape an evidence-based platform for an effective new test, rather than having CMS shape the paradigm. She prefers to think of CMS as “an enabler, not a watchdog.
When it comes to reimbursement for molecular diagnostic tests, “it's much easier to deal with a therapeutic simply because of the evidentiary experience,” said Louis Jacques, MD, Director of the Coverage and Analysis Group at CMS, another keynote speaker. He stressed the importance of quality of life in making national coverage decisions.
“We inflict many things on our patients that are absolutely not benign,” he said. “I am probably the biggest proponent of quality of life in national coverage decisions. I would be thrilled to cover something that had a quality-of-life benefit even if it didn't have a reduction in mortality benefit.”
As for the incorporation of a molecular diagnostic test into clinical practice guidelines, the key is the biological activity of an actionable biomarker, said Joan S. McClure, MS, Senior Vice President of Clinical Information and Publications at the National Comprehensive Cancer Network.
The test should define a patient's risk or prognosis and point toward a specific therapy and/or patient monitoring, she said, noting that NCCN updates its guidelines up to four times a year.
“With a few notable exceptions, we haven't seen high-quality data on biomarkers,” said McClure, adding that she was shocked during a recent convalescence for influenza to see the number of direct-to-consumer advertisements for molecular diagnostic cancer tests on cable television.
At the end of the day, it's still all about treating an individual patient, and “a good diagnostic is just as important as a good drug,” Shak summed up. “We need to challenge ourselves and others to do the best work we can do.”