In mid-2019, MolDx held a public conference on pharmacogenetics, with expert panelists, and a few months later they proposed a new LCD covering Genesight and several other psychiatric panel tests, and covering pharmacogenetics in general not too much different than before.
However, in June 2020, things changed rapidly. MolDx released a brand new single LCD for PGx from summer 2020 forward, along with a 22-page comment document. (See particular links in the blog, here.) In my June 11 blog on the topic, I focused on the possible impact on Genesight and less on the general pharmacogenetics coverage. See LCD L38294 here. See Q&A document A58157 here.
Deeper Dive on the New PGx LCD
If I read the new LCD correctly, it's radically different than the LCD it replaces. It provides coverage for any gene-drug combination endorsed by the FDA or by CPIC, the pharmacogenetics consortium. (CPIC provides its A/B rated conclusions in an Excel table on its website). Note, however, the LCD is somewhat convoluted in its reference to FDA endorsed testing. [*]
See FDA here: https://www.fda.gov/medical-devices/precision-medicine/table-pharmacogenetic-associations
See CPIC here: https://cpicpgx.org/
FDA's PGx table includes 13 genes and about 50 drugs.
The CPIC table of A/B rated drug-gene pairs has 33 genes (including 12 of the 13 FDA genes) and about 120 drugs, as well as guidance to two drug classes, "antidepressants" for ABCB1 testing and "aminoglycoside antibiotics" for MT-RNR1.
(Right there you've learned something: CPIC A/B status endorses testing for ABCB1 and for MT-RNR1, two genes I had never heard of.)
The MolDx rules in LCD 38294 require that a physician is considering prescribing a drug (before ordering PGx testing), or the patient is on a PGx-affected drug and the physician is considering modifying the dosage. If so, if that drug is on the FDA/CPIC list, then the associated gene testing is covered.*
Right about now, most readers are wondering, what are the 34 genes endorsed by CPIC and/or FDA, and how many of them have CPT codes, and if they have a CPT code, what is the price?
See the chart below. Of the 34 genes, 23 have CPT codes and 11 do not. If you billed all the CPT codes (an unimaginably complex patient to merit all those gene-drug pairs), you reach $5,175.
Idea for AMP?
Since the MolDx LCD points externally to the CPIC gene list as its currently payable genes, it's a shame some of the CPIC endorsed genes have no AMA CPT codes (to my eye). Hopefully AMP or CPIC or another group will add the 11 missing CPIC genes to the AMA CPT vocabulary in the next code application cycle, which I believe is submissions due November 8.
*The LCD also states a panel is covered if a patient needs at least two genes on the panel, based on the patients drug list and the resulting drug-gene pair list. For me the math works out that a 34 gene list gives 35,904 different unique combinations for a 3-gene panel (34*33*32).
See the spreadsheet I used for this analysis in the cloud here.
Some of the CPIC drugs are common (CPIC even includes ibuprofen with a 1A rating for CYP2C9 testing), like tamoxifen (CYP2D6) or clopidogrel (CYP2C19), some seem pretty uncommon (methoxyflurane and methylene blue, the latter having a B rating for G6PD. One use of methylene blue is to treat methemoglobinemia, carbon monoxide poisoning).
|click to enlarge|
[*] References to CPIC Clear, References to FDA Not Clear
The LCD clearly refers to coverage of tests that are CPIC A/B rated, which is a lot of drugs and a lot of genes, including some I'd never heard of. OK.
Regarding FDA, the LCD language turns out to be somewhat murky. The LCD covers FDA recommendations that are "clinically actionable." That's a vague term, but I assume it is the same as the table of FDA "therapeutic management recommendations," as a "management recommendation" is surely "clinically actionable." However, then MolDx adds a parenthetical, (gene required for safe administration) which clouds the issue. Later, under the definition of "clinically actionable" MolDx defines this as CPIC A/B again, OR "based on an FDA label for a drug" which seems real broad, OR "an FDA warning or safety concern" which is more narrow. Net-net, there are a lot of different phrases with different meanings flying around as you read up and down the LCD in regard to use of FDA recommendations. PharmGKB also has a public definition of "actionable" PGx (here) but it's not explicit if MolDx recognizes it.