Friday, June 11, 2021

Medicare's Somewhat Confusing Path to Liquid Biopsy Coverage: A Brief Recap

There's a huge amount of news every week about liquid biopsy in cancer management - even more this week, with the bonanza of reports at ASCO.  Here, here.

Medicare's coverage is a little confusing, so I'll briefly recap here.

National Coverage

CDx and Hereditary Risk (FDA).  Medicare has a national coverage decision NCD 90.2 governing the use of FDA approved or cleared NGS tests in cancer - both companion diagnostic tests and hereditary risk management.   This NCD covers the use of NGS tests as companion diagnostic, among them CDx liquid biopsy tests, on a rolling basis as they are approved by FDA.  

Currently the FDA CDx liquid biopsy tests covered under NCD 90.2 are the Foundation and the Guardant PMA LBx NGS tests.   The FMI test is 0239U, the Guardant test 0242U.

Screening for CRC.  Separately, CMS has a national coverage decision for liquid biopsy screening tests for colorectal cancer, IF they meet sensitivity and specificity standards already set by CMS.    Several such tests for CRC screening will likely be approved by FDA in the next several years, and in essence, the CMS NCD coverage is "pre written" or "pre fab" awaiting them.  See the CRC NCD, 210.3, version 6.  See an implementation guide from CMS, here, here.

Local Coverage

MolDx: CRC Management.  In 2019, MolDx promulgated an LCD covering the use of the Natera Signatera test in colorectal cancer management.   This was proposed as DL38290, with Signatera as the name-brand test in the LCD title. It was finalized as L38290, which removed "Signatera" from the LCD title, and focuses on the Signatera test but is not specific to that test alone.  The original proposal is still online here.  The final version is here.    This is MolDx's current active LBx MRD coverage.

L38290 or an identical version with a different code number is active at three different MolDx MACs - WPS, CGS, Palmetto.   Quirkily, and in contrast, the fourth MAC, the one Natera actually bills to, Noridian, covers the test by an "article" that recapitulates the text of the MolDx LCD used elsewhere.  See article A58449.

MolDx: Pan-Cancer Management.  Since last August, MolDx has a new and broader liquid biopsy LCD under review, DL38779.   This will (A) have coverage for most all kinds of cancers (both solid tumors and hematopoietic cancers) and (B) cover two major intended uses, recurrence monitoring (such as after colectomy) and determining therapy response.  It should be finalized by August 2021.  See the "four-square" table immediately below.


click to enlarge
Pricing for MRD/LBx

Palmetto MolDx run a branded website that is separate from the main MAC website, the Diagnostics Exchange.   Here you can often find locally-set test pricing information. 

For Natera, there are three pricing levels for different configurations of Signatera.  
    • $5897
  • EXOME TEST AND PLASMA TEST (no remark on bundle, so presume 1 exome, 1 design, 1 plasma test)
    • $3878
    • $3177
    • (Patient has a previous exome test from somewhere used to design the bundle 4 test plasma test)
Running the Numbers

If you assume the values of the different components are linear  you can impute or interpolate internal values.

The MolDx public prices and descriptors translate into a table without using any new math:

From the table above, it looks like the exome is valued at $2720.   This is because exome and four plasma tests (top row) are $5897, but the four tests without the exome (bottom row) are $3177.   We can illustrate it like this:

In the box above, note from the bottom row that 4 plasma tests w/o any exome test are $3,177.  This suggests a price per test of $794.

Moving on, now let's look at the other white box.  The exome and four tests is $5897 (top row), but the exome and 1 test is $3878 (second row.)  This suggests the value of the 2nd/3rd/4th test might be $2019.   We can illustrate it like this:

So - if the MolDx pricing was linear, and we don't know that - we would end up with this table:

We know that the $2,019 represents 3 tests, so if we divide by three we get $673.

There's just one box we haven't addressed.   If we assume the first column is valued at $2720, and the third column is valued at $2019, and all three columns add up to $5897, then the middle column - what we're calling "first plasma test" - can be gapfilled at $1158 ($5897-$2019-$2720 = $1158).  Shown next:

Again, and I got a couple calls and emails, this is only doing the third-grade arithmetic with the information that we read about different test versions and different prices that MolDx has posted publicly.  MolDx gives you a price for exome and four tests; and a price for exome and one test; and a price for four tests, but no exome.   That gives you the rows and columns of the table.  Arithmetic gives you the numbers shown, but it doesn't guarantee the MolDx pricing ever thought about it this way.


For a large new paper on CRC MRD, see Chen et al. 2021 (here).