This article has been corrected from a previous version because it referred to the local coverage determination on comprehensive genomic profiling for non-small cell lung cancer as a draft policy based on an earlier version of the document issued by Palmetto in error. Stakeholders can submit comments to the final LCD in the form of a "reconsideration."
NEW YORK (GenomeWeb) – Medicare contractor Palmetto GBA recently issued a final local coverage determination (LCD) asking labs performing comprehensive genomic profiling in lung cancer to submit testing and patient data through registries that are broadly accessible.
Palmetto's decision to collect such data through registries comes at a time when the National Institutes of Health, the National Cancer Institute, and the US Food and Drug Administration all have launched initiatives to encourage the life sciences community to share data in order to advance genetic testing and personalized medicine.
"The problem that we face in this arena is that we need to collect a great deal of data if we're going to figure out not only how valuable this testing is, but how we can apply it to patients in the most correct way," said Dane Dickson, CEO of the Molecular Evidence Development Consortium (MED-C), a nonprofit organization that has built a registry that appears to meet many of the criteria in the LCD. MED-C is in discussions with Palmetto to gain approval for its registry.
Palmetto's latest policy (see PDF at the end of this article) amends a version it issued last year through its MolDx program, proposing coverage for comprehensive genomic profiling for advanced non-small cell lung cancer patients who are non-smokers or light smokers and whose tumors are negative for EGFR mutations or EML4-ALK translocation based on an FDA-approved companion diagnostic.
Industry observers had said at the time that this was a good first step, but had criticized that the policy was not sufficiently attuned to the challenges of retesting cancer patients with limited tissue. Others had noted that the coverage restrictions would miss a proportion of NSCLC patients who might benefit from molecular characterization of their tumors.
Palmetto appears to have listened to this feedback, and in its final LCD said it will cover comprehensive genomic profiling for advanced NSCLC patients who have not been tested for genomic alterations or who have tested negative for EGFR mutations, EML4-ALK rearrangements, or ROS1 rearrangements. The policy no longer mentions smoking status.
When compared to an earlier version an LCD expands coverage for an intervention to more Medicare beneficiaries, contractors can finalize it without public comment. Stakeholders who want to comment on the final policy may submit them to Palmetto as a "reconsideration."
"The expanded coverage to include all Stage IIIb/IV NSCLC individuals regardless of smoking history is stepwise progress that offers significantly more individuals with lung cancer the opportunity to participate in precision medicine-based cancer care," Michael Pellini, CEO of Foundation Medicine, told GenomeWeb. The company markets FoundationOne, a next-generation sequencing test that profiles patients' solid tumors for more than 300 cancer-related genes. "We believe this expanded LCD lays the groundwork for expanded coverage beyond lung cancer, over time," Pellini added.
Palmetto amended its policy on comprehensive genomic profiling so that it reflects the latest knowledge on how genomic biomarkers impact NSCLC patients' treatment and outcomes. The LCD cites a recent study where comprehensive genomic profiling, compared to non-NGS testing, identified 7 percent more patients with EGFR mutations and 6 percent more patients with ALK translocations. Many of these patients would benefit from targeted treatment, Palmetto notes in the policy.
While next-generation sequencing is increasingly being performed in cancer, Palmetto Medical Director Elaine Jeter told GenomeWeb that there are also documented discrepancies in results between different tests and methodologies. Regulators, payors, and lawmakers are concerned about this. Senators held a hearing last week to discuss how to best regulate lab tests, including cancer genomic profiling assays, while the FDA a few days later held a workshop to encourage the NGS testing community to advance standards that can bring some consistency to the field.
"If you're a patient, you don't want to go to one lab and get one result and go to another lab and get a completely different result," Dickson said. "But that's what's happening right now because there is no cross standardization."
Palmetto attempts to address this challenge in the LCD. For coverage, labs performing comprehensive genomic profiling must demonstrate that their tests conform to Palmetto's analytical performance specifications and either submit the information directly to the Medicare contractor or to a Palmetto-approved registry. The Medicare contractor also expects labs to collect data on the comprehensive genomic profiling test and patients who received it in an approved registry that meets an extensive set of requirements.
For example, approved registries must be national in scope and independent of submitting labs. They must collect detailed information on patients' genomic markers, including raw genomic data and clinically significant variant calls, and provide reports to Palmetto on patient outcomes and other aspects every six months. When there is an FDA-approved diagnostic for a particular biomarker, the registry administrators will also have to report to Palmetto concordance between that test and the comprehensive genomic profiling test.
Importantly, Palmetto wants the registries it approves for data collection to have a strong commitment to data sharing. According to the LCD, these registries cannot have a history of data siloing, and must allow open access for research and equal commercial access. "Any registry that is considered for inclusion by Palmetto in the policy must show a detailed plan for data sharing and research access," Jeter said.
When a group decides to hold onto data from a patient for proprietary gain, this limits the ability for learning.
Encouraging data sharing
Palmetto's focus on data sharing in the LCD is in line with efforts across government agencies to encourage the same.
An expert panel recently recommended that under Vice President Joe Biden's Cancer Moonshot, the NCI should create a federated network through which patients can get their tumors molecularly profiled, share that data, and be contacted if they qualify for clinical trials. The panel also put forth the idea of creating a National Cancer Data Ecosystem to collect and share large datasets that doctors, researchers, and patients can contribute to the Cancer Moonshot.
The Genomic Data Commons (GDC), a cloud-based platform that the NCI launched in June to make genomic and clinical data from large-scale projects available to researchers, will also facilitate data sharing within the Cancer Moonshot.
Palmetto expects the registries it approves to contribute to national projects with a strong focus on data sharing, such as the GDC and the Cancer Moonshot, and regularly report on these activities.
Meanwhile, the FDA is trying to create a flexible regulatory framework for NGS tests and has issued a draft guidance outlining the process by which administrators of public genomic variant databases can apply for the agency's recognition. The FDA is hoping that test developers can use the variant classifications in recognized repositories to establish the clinical validity of their diagnostics instead of having to perform studies on the individual variants.
Similarly, Palmetto has been trying to nudge test developers into sharing data through its coverage policies. "When a group decides to hold onto data from a patient for proprietary gain, this limits the ability for learning," Jeter said. "We believe a properly designed and administered registry can provide protections for all parties, [including the] patient and test provider, while supporting the goal of broadening data collection."
In its recently outlined criteria for evaluating the analytical performance of circulating tumor DNA tests, Palmetto recommended labs submit variant interpretations to ClinVar, NIH's freely available archive of genotype and phenotype relationships. At least one national insurer, Aetna, is requiring that all newly contracted labs submit their variant interpretations to ClinVar as a condition of participation in its network for BRCA genetic testing.
To date, close to 600 submitters have contributed variant data to ClinVar. But plenty of commercial and research entities haven't, citing inaccuracies in such databases, liability risk, and the need to protect patients' privacy.
According to Dickson, academic labs and commercial companies have both held onto data they consider proprietary for competitive reasons, while many groups are "pseudo data sharing" — saying they are contributing to public repositories for the positive sound bite but really not submitting useful information. "They're sharing the crumbs off their dataset," he said. "They give away things that are old or not the most important data that people want."
Foundation Medicine's Pellini reflected that the LCD may draw stakeholder comments due to its patient consent and data sharing requirements. He added that although cancer patients are usually willing to share their data for research, "it is of paramount importance that any proposed data sharing initiative be fully transparent and at the discretion of each patient." Foundation Medicine, which has sequenced more than 90,000 patient tumors, recently committed to sharing data from 18,000 cases within NCI's GCD.
The CMS payment for the tests in question is as low as $598, and the long term costs of registry management per patient could be a substantial part of that.
Funding registries
Although Palmetto hasn't formally reviewed any registry proposals to see if they meet its criteria for approval, Jeter noted that she and her colleagues have had discussions with a number of data collection groups in recent months, including Flatiron Health, Syapse, CancerLinQ, and MED-C. Groups interested in submitting their registry for acceptance under the policy should contact MolDx, she said.
MED-C is already in discussions with Palmetto about its N1 Registry, which appears to check off many of Palmetto's requirements for approval. Dickson, who stepped away from his position as director of clinical science at Palmetto's MolDx last year to start MED-C, highlighted that the N1 Registry — which isn't only for NSCLC but can include information on a range of tumor types — already has IRB approval, a medical oversight committee, a data oversight committee that will ensure that labs submitting to the registry are performing tests according to standards issued by accrediting bodies, and a business plan for implementing the registry in a cost-effective way.
Any regulatory or reimbursement model that depends on labs, physicians, or patients submitting data to a registry or database must address the challenge of funding the operation, while maintaining broad access and limiting conflicts of interest. "MolDx has been stating in public meetings for at least a year that independent registries are favored over company-managed ones," said Bruce Quinn, Medicare expert and senior advisor at FaegreBD Consulting. He noted, however, that the Medicare contractor is "silent whether the registry would be publicly funded or supported by participating laboratories."
Diagnostic labs, even those performing NGS cancer testing, may be unable or unwilling to pay into registries in an already challenging reimbursement environment. Many NGS providers feel that Medicare payments fall far short of what it should pay for such tests, which usually have list prices of several thousand dollars. Palmetto's LCD doesn't address this difficulty, but notes that approved registries must be independent of the academic or commercial labs contributing data. "The CMS payment for the tests in question is as low as $598, and the long term costs of registry management per patient could be a substantial part of that," Quinn observed.
Last year, Thermo Fisher Scientific, Illumina, Eli Lilly, Celgene, and Roche/Genentech committed their expertise and funding to MED-C, but the Dickson's team is working to keep the registry costs down by leveraging partnerships. For example, he highlighted that MED-C is considering using genomic analysis tools that are already being used within NCI's GDC.
In the future, MED-C could consider implementing membership dues, where people interested in accessing the registry data would pay on a sliding scale based on whether the information is used for research or commercial purposes. Dickson is hopeful that companies would eventually be willing to enter into profit-sharing agreements if the data from the registry leads to marketed tests or drugs.
No one is going to get incredibly rich collecting this data.
Who benefits?
Ultimately, submitting to a registry like N1 is a much cheaper proposition for labs than building a data repository from scratch that meets Palmetto's lengthy list of requirements, Dickson estimated. He added that MED-C plans to give clinics "appropriate" remuneration, at "probably less than fair market value" for the time their staff spends putting patients' data into the registry.
"No one is going to get incredibly rich collecting this data," Dickson said, but he also acknowledged that the lack of incentives for submitting data into efforts like ClinVar has slowed broad participation.
This is a touchy area because the Office of the Inspector General considers it illegal for labs to pay doctors more than fair market value or provide free testing. Two years ago, OIG specifically called out labs paying physicians for submitting data to registries as a practice that poses "substantial risk of fraud and abuse under the anti-kickback statute."
Although OIG frowns upon direct payments from labs to clinics for data collection, the conflict might be mitigated when an independent third party is collecting the data and providing the incentives to submitters. "Working with a research organization, with appropriate oversight by independent individuals, provides some layer of protection that would not be there with direct contact," Palmetto's Jeter said. "With this said, it is incumbent on the laboratories and registries to carefully review and ensure any relationship avoids any potential conflicts."
The Agency for Healthcare Research and Quality has recognized the need for registry administrators to provide "a broad range of incentives" to submitters, such as access to useful data, continuing medical education, or certification, on top of fair market value payments. Citing AHRQ's advice, Dickson highlighted that doctors submitting to MED-C's registry will get access to high quality NGS testing, educational data on biomarkers identified by testing, aggregate patient outcomes data, and information about clinical trials that may not be available elsewhere.
Other stakeholders would benefit, too, he said. Payors could use the information in registries to figure out when comprehensive genomic profiling is useful. Patients would have access to better testing and access to clinical trials.
Meanwhile, Dickson noted that labs should also see an upside for submitting data to the registry and meeting a higher analytical standard. "We're going to say this is a higher quality of service," he said. "So, hopefully, the payors will come in with a payment rate that will be very appropriate for the testing and also the responsibility of a registry to be taken care of."