The original NCD, released in March 2018, was criticized for being liable to ambiguity but potentially adverse to NGS testing in Stage 1/Stage 2 cancer patients or those who require repeat testing. This criticism accelerated after some restrictive additional interpretative statements released by CMS in November 2018. CMS held a comment period in May 2019, and received uniformly negative comments (here).
- The tracking sheet for the NCD revision is here.
- The revised NCD, for new cycle of public comment, is here.
- I've put a PDF version in the cloud, here.
Comments are during on Thanksgiving, Thursday, November 28, so many stakeholders may want to view Friday November 22 as an effective corporate pseudo-deadline. The final NCD is due about 60 days from November 28, e.g. January 28.
Coverage at Genomeweb here.
What Happened in Brief
Warning - these are my first-pass interpretations; it could be that other readers will find textual ambiguities or problems I haven't noticed.
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NCD Coverage. Previously, CMS nationally guaranteed coverage for NGS testing for NGS tests approved as CDx, if the patient had advanced cancer (metastatic, stage 3/4, etc). For example, the FMI F1 CDx test was covered per its FDA labeling in such patients.
>>> Now, CMS also proposes to nationally guarantee coverage for FDA approved or cleared tests (NOT necessarily CDx) in patients with ovarian or breast cancer, indications for germline testing, risk factors for inherited cancer. Such patients have no stage restrictions like Stage 3/4.
In short, the areas of the NCD which nationally guarantee coverage pivot on being an FDA CDx test, and now it adds coverage for FDA tests that are not CDx for any indicated genes (per FDA) in breast and ovarian cancer.
LCD Flexibility. Previously, CMS gave MACs discretion to cover non-FDA-approved (LDT) NGS tests, or FDA tests off-label, as long as it was ONLY for one test and ONLY in advanced cancer patients.
>>> Now, CMS will let MACs allow coverage for NGS testing with LDT tests in patients with diagnoses other than breast and ovarian cancer (e.g. colon cancer), as long as they have inherited cancer risk factors and not prior tested with NGS. There are no stage restrictions.
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- HBOC patients get only FDA tests that don't exist. Breast and ovarian cancer patients can only get germline (inherited) testing for FDA cleared or approved tesst. The only ones are for BRCA, and in fact, the Myriad germline BRCA test is not NGS (it's Sanger) and the Foundation BRCA test and Myriad MyChoice BRCA test are NGS but are somatic tumor tests. Oops.
- The standard of care is almost certainly more than BRCA gene testing alone, it's panel testing, while only BRCA has FDA approvals (albeit defective ones relative to the NCD, as just stated).
- Myriad CEO Marc Capone also remarked that the NCD text here was very important and that the NCD points to FDA tests that don't exist, in a November 4 investor call (here).
- Still a one test per patient rule. Only one test per patient, so not obviously helpful yet to recurrent disease detection.
- Glitch re types and classes of testing. The new passages about germline testing preclude any prior NGS method testing, but, for example, you might have to use one somatic FDA test for genes like EGFR and KRAS, and a different germline FDA test for BRCA. The NCD doesn't seem to contemplate this problem. For sure, there isn't any one FDA test today that covers both somatic CDx mutations and germline management mutations. The NCD would cover both, as long as you don't do more than one. Oops.
- The new parts of the NCD allow germline testing as long as "patient has not had a prior NGS test." Really? Any prior NGS test? FDA has approved an NGS HIV test - if you've had that, it's a prior NGS test, so you can't have BRCA testing? Here.
CMS distinguishes breast and ovarian cancer patients because they found the best germline literature in these groups. Throughout the NCD, they are cautious to refer only to published NGS literature for outcomes, which is a little daffy, since a particular mutation sequenced by Sanger or by NGS gives the same outcomes.
There's also still a barrier to technology modernization that I dislike. Many women with breast cancer get the Oncotype Dx or similar tests, which aren't NGS so they aren't under this NCD. But if they were migrated to NGS platforms (and Mammaprint had been able to do this), they would be under the NCD but in very limiting or counterproductive ways.
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Nerd Points.
The prior NCD covered certain tests, if that test hadn't been used in that patient before. The new language covers certain germline testing, if the patient hasn't recent [any] NGS test before. This is confusing. Although it's now rare, someday, a patient might have e.g. NGS microbiology testing, which would be "a prior NGS test." Who would track that? Obviously an unintended issue. Or a patient might have an NGS epilepsy panel as a child, but need NGS testing for cancer as an adult. The NCD doesn't seem to contemplate that, since it blocks testing if the patient had "a prior NGS test." This will hopefully be fixed in the final revision.
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APPENDIX B
Medicare National Coverage Determinations Manual
DraftMedicare National Coverage Determinations Manual
We are seeking public comments on the proposed language that we would include in the Medicare National Coverage Determinations Manual. This proposed language does not reflect public comments that will be received on the proposed decision memorandum, and which may be revised in response to those comments.
Table of Contents
(Rev. in Redline)
(Rev. in Redline)
90.2 Next Generation Sequencing (NGS) for Patients with Advanced Cancer
A. General
Clinical laboratory diagnostic tests can include tests that, for example, predict the risk associated with one or more genetic variations. In addition, in vitro companion diagnostic laboratory tests provide a report of test results of genetic variations and are essential for the safe and effective use of a corresponding therapeutic product. Next Generation Sequencing (NGS) is one technique that can measure one or more genetic variations as a laboratory diagnostic test, such as when used as a companion in vitro diagnostic test.
Patients with cancer can have recurrent, relapsed, refractory, metastatic, and/or advanced stages III or IV of cancer. Clinical studies show that genetic variations in a patient’s cancer can, in concert with clinical factors, predict how each individual responds to specific treatments.
In application, a report of results of a diagnostic laboratory test using NGS (i.e., information on the cancer’s genetic variations) can contribute to predicting a patient’s response to a given drug: good, bad, or none at all. Applications of NGS to predict a patient’s response to treatment occurs ideally prior to initiation of such treatment.
B. Nationally Covered Indications
Effective for services performed on or after March 16, 2018, the Centers for Medicare & Medicaid Services (CMS) has determined that Next Generation Sequencing (NGS) as a diagnostic laboratory test is reasonable and necessary and covered nationally, when performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, when ordered by a treating physician, and when all of the following requirements are met:
1. Patient has:
- either recurrent, relapsed, refractory, metastatic, or advanced stage III or IV cancer; and,
- either not been previously tested using the same NGS test for the same primary diagnosis of cancer, or repeat testing using the same NGS test only when a new primary cancer diagnosis is made by the treating physician; and,
- decided to seek further cancer treatment (e.g., therapeutic chemotherapy).
2. The diagnostic laboratory test using NGS must have:
- Food & Drug Administration (FDA) approval or clearance as a companion in vitro diagnostic; and,
- an FDA-approved or -cleared indication for use in that patient’s cancer; and,
- results provided to the treating physician for management of the patient using a report template to specify treatment options.
^ Effective for services performed on or after [Month/XX] [Day/XX], [20XX], the CMS, proposes that NGS as a diagnostic laboratory test when performed in a CLIA-certified laboratory, when ordered by a treating physician and when all of the following requirements are met:
The patient has:
- ovarian or breast cancer;
- clinical indications for germline (inherited) testing,
- risk factors for germline (inherited) cancer breast or ovarian cancer; and
- not been previously tested using NGS.
The diagnostic laboratory test using NGS must have all of the following:
- FDA approval or clearance;
- an FDA approved or cleared indication for use in that patient’s cancer; and
- results provided to the treating physician for management of the patient using a report template to specify treatment options.
C. Nationally Non-Covered
Effective for services performed on or after March 16, 2018, NGS as a diagnostic laboratory test for patients with cancer are non-covered if the cancer patient does not meet the criteria noted in section B.1. above.
D. Other [aka local coverage section]
Effective for services performed on or after March 16, 2018, Medicare Administrative Contractors (MACs) may determine coverage of other NGS as a diagnostic laboratory test for patients with cancer only when the test is performed in a CLIA-certified laboratory, ordered by a treating physician, and the patient has:
- either recurrent, relapsed, refractory, metastatic, or advanced stages III or IV cancer; and,
- either not been previously tested using the same NGS test for the same primary diagnosis of cancer or repeat testing using the same NGS test was performed only when a new primary cancer diagnosis is made by the treating physician; and,
- decided to seek further cancer treatment (e.g., therapeutic chemotherapy).
^ Effective for services performed on or after [Month/XX] [Day/XX], [20XX], Medicare Administrative Contractors (MACs) may determine coverage of other Next Generation Sequencing (NGS) as a diagnostic laboratory test when performed in a CLIA-certified laboratory, when ordered by a treating physician, when results are provided to the treating physician for management of the patient and when all the following conditions are met:
The patient has:
The patient has:
- a cancer diagnosis other than breast or ovarian cancer,
- clinical indications for germline (inherited) testing,
- risk factors for germline (inherited) cancer other than inherited breast or ovarian cancer, and
- not been previously tested using NGS.
