A Discussion of Several Panels at the 16th Annual Meeting of the Personalized Medicine Coalition
by John Otrompke
Although reimbursement coverage is now available for select use cases for molecular diagnostics, these use cases have been demonstrated to be too narrow. Almost 10% of colorectal cancer patients treated at Mayo Clinic Cancer Centers for the two years before the pandemic had actionable germline genetic variants that would not have been identified by contemporaneous guidelines from medical societies such as the National Comprehensive Cancer Network (NCCN), or the 20-gene sequencing panel based on those guidelines, according to a recent article. (Uson P, Riegert-Johnson D, Boardman L, et al. Germline Cancer Susceptibility Gene Testing in Unselected Patients With Colorectal Adenocarcinoma: A Multicenter Prospective Study, Clinical Gastroenterology and Hepatology 2022;20:e508–e528).
Next generation sequencing was performed on the 361 patients using the 84-gene Multi-Cancer Panel from Invitae Corp. (NVTA, San Francisco). Researchers found incrementally actionable variants in 9.4% patients that would not have been identified by the 20-gfene panel from the same company.
“We collaborated with the Mayo Clinic, and the study showed that family history and age are imperfect predictors of whether you have Lynch syndrome, so we ought to test every patient,” explained Robert Nussbaum, MD, CMO at Invitae, a co-author on the article.
The company also recently launched its personal care monitoring service, which measures minimal residual disease in the form of cell-free DNA. “Does the patient need adjuvant treatment? Will they relapse, and if so, when?” added Nussbaum, who also spoke on a panel about diagnostics at this year’s annual Personalized Medicine Conference at Dana Point, California, in May. Some payors are reimbursing for the diagnostic test, Nussbaum said.
Reimbursement for genetic diagnostics is likely to grow in the future as researchers develop more evidence about the clinical and economic benefits that such testing can provide. If genetic diagnostics are not reimbursed consistently, drugmakers may have a harder time marketing genetically guided therapeutics.
“Even in the primary care setting, virtually every patient should be assessed for hereditary risk factors,” noted Lisa Alderson, CEO and founder of Genome Medical, Inc., in South San Francisco, CA. “While 7% of the population has a single-gene variant that impacts their health, a much larger percentage, approximately 17%, have moderate risk variants that may influence treatment or preventive options.” Fully 85% of people have genetic factors that impact their response to prescribed drugs and could change dosing or therapeutic selection, particularly in the areas of pain management, oncology, and mental and behavioral health, added Alderson, who also spoke at a session at the PMC conference on precision medicine in differently-structured health systems.
“We have a full-time team of leading molecular geneticists, genetics counsellors and a pharmacist, as well as a contract network of specialists and primary care doctors whom we bring into specific patient’s cases as needed. We see patients directly and also support providers in appropriately utilizing genomics. We are simplifying the process of finding patients with need through our patient assessment and clinical support tools. Physicians just point patients to our platform, which identifies those who meet NCCN guidelines for oncology testing and hereditary cancer risk assessment,” she added.
“Genome Medical is a covered benefit for approximately 170 million people, including all beneficiaries of United Healthcare, CIGNA, and most of the Blues,” said Alderson. “Many payors are bringing Genome Medical in network to better support this complex area of medicine. Today, we have both underutilization and overutilization of genetic testing in the market. The majority of patients meeting guidelines are not identified and when testing is ordered, up to 25 percent of the time, it is the wrong test. We also support clinical decision making to ensure action is taken on the results.
“Take colon cancer as an example. If somebody is at an elevated risk for cancer because of their genetic make-up, that changes the standard of care for cancer screening. The standard of care is for the average patient to have their first colonoscopy at age 45, but if they are at higher risk, the first colonoscopy may take place when they are in their 30s. If they have a colonoscopy earlier, the cost is quite low compared to that of treatment, because removing polyps means you can prevent colon cancer from forming,” she explained.
“There is a pretty steep lag between when you demonstrate clinical utility and when you have broad-based adoption, but we’re trying to build a future model in which providers order genomics earlier and particularly for complex cases. There is a gap in knowledge which is creating a gap in clinical care, but by reducing underutilization and overutilization, we show a very immediate return-on-investment, a 5-times ROI,” Alderson said.
Speeding the Time to Clinical Acceptance
Colon cancer is far from the only example of a disease state in which genetic science is changing medicine and saving lives. “Sepsis accounts for half of all hospital deaths in the US. As it is a time-critical disease, earlier detection or prediction can help save lives. Currently, there is no single biomarker that can accurately predict sepsis. However, research has shown that the combination of a few in vitro diagnostic tests can significantly improve the prediction of sepsis,” said Okan Ekinci, MD, global head of marketing and innovation for Roche Diagnostics Information Solution in Basel, Switzerland. A recent study suggested that a combination of five biomarkers improved sepsis prediction in children compared with C-reactive protein alone, added Ekinci, who also spoke at the PMC conference panel on diagnostic tools. (Rautiainen L, Cirko A, Pavare J, et al. Biomarker combinations in predicting sepsis in hospitalized children with fever. BMC Pediatrics [2022] 22:272).
Success stories such as those of Genome Medical and Invitae come as some payors express frustration with the lack of transparency regarding some diagnostic tools, such as smaller, locally-designed tests.
“It can take 14 to 17 years for a new test to get to widespread adoption, but hopefully we can get it under 10 years, and maybe as low as 7,” agreed Jill Hagenkord, MD, CMO at Optum Genomics in Eden Prairie, Minnesota. (Optum Genomics is currently part of United Healthcare).
To help reduce the time lag, Hagenkord is leading the roll-out of the Optum Evidence Engine, a service which connects developers of diagnostic tests with market access experts who can help design studies and communicate with investors.
“There is a lack of consistent regulatory oversight due the FDA’s exercise of its enforcement discretion, so that anything can go on the market, and does, without any clear criteria. It’s impossible to determine whether the tests do or don’t work at all. Nobody even knows how many tests are on the market, because we don’t have unique identifiers for them, which could make it easier for payors to distinguish between those that do and those that don’t work. So some payors decide that they’re either just going to pay for all laboratory-designed tests, or pay for none of them.” Those at the Optum Evidence Engine have finally begun to assign unique identifiers to the locally-designed tests within the past year, added Hagenkord, who spoke on a panel about reimbursement at this year’s annual PMC conference.
While there may be a significant time lag in personalized medicine between the demonstration of clinical utility and widespread adoption, it is undeniable that broader reimbursement for genetic testing is a fait accompli. Breast cancer is one important example of a clinical area where the clinical importance of personalized medicine has perhaps been longest-established.
“Anybody who has hormone receptor-positive breast cancer, and that’s 80% of breast cancers, is getting targeted therapy,” said Kevin Hughes, MD, director of cancer genetics at the University of South Carolina in Charleston.
Genetic testing for the approximately 13 gene signatures associated with breast cancer is almost always reimbursed, added Hughes, who is also a board member for the American Society of Breast Surgeons. “We’re trying to get the NCCN to change to guidelines to match ours, because they have a very complex set of criteria that ends up with about 50% of breast cancer patients testable,” he noted.
The author is a member of the Personalized Medicine Coalition
© 2022 John J. Otrompke, JD
