Sunday, May 15, 2022

Very Brief Blog: MolDx Updates Billing Article for Pathogen-Testing Policy

On May 1, 2022, we noted some updates and delays regarding the MolDx pathogen testing policy - here.

Now MolDx has issued more updates to the MolDx pathogen testing "billing article," or A58710.  These are the "R2" or second round of revisions, and will be effective May 17.

Find the updated A58710 here:

The revision notice is 535 words long.   The billing article being amended is about 11,500 words long (including tables of IC10 codes).   For comparison, the US Constitution is 4400 words long.

I've put a cloud copy of the newest May 17 version (R2) over the original version (which I'm calling R0) - here.

Take a deep breath, and these are the revisions in this release:

Thursday, May 12, 2022

Brief Blog: Noridian Proposes to Delete MolDx LCD (4KScore); Palmetto Issues Update of Same

Noridian proposes a draft LCD for Opko 4KScore, seemingly only for the purpose of deleting the LCD.  Last month, Palmetto MolDx reviewed and reissued the same LCD with typos corrected. 


Since 2016, Palmetto MolDx has had a non-coverage policy for the Opko 4KScore test (L36763, here.)   This has always been an unusual policy, since the 4KScore test is a sole-source test billed to the Novitas MAC from New Jersey, and the Novitas MAC covers 4KScore.   See L37792.   In 2020, 4KScore code 81539 had 12,734 uses paying $9.7M in Medicare Part B.  

Palmetto: Revise.  Noridian: Nix.

Here's a little oddity.  Currently, in the Medicare Coverage Database, the Palmetto LCD L36763 for the 4KScore test is listed as newly revised, with Revision 8 described as a revised title, bibliography format changes, and typos corrected.   OK.   Here.   I don't recall seeing it listed as "draft under revision," so maybe typos can be corrected without public comment.

But there is a version of the same LCD proposed as "DL37120," a draft LCD, on the Noridian website.   Here, the LCD is presented with the comment, "This LCD is being retired because this lab or test is no longer available and Noridian does not anticipate any claims for this service."   This isn't exactly correct, the test is very available, but not in Noridian's territory, so it's true, Noridian won't see any claims. [*]  The CMS database website lists this LCD version as "draft in comment" April 28 to June 11, but the D-LCD itself doesn't list any comment period nor does it list a public comment meeting.    

Before procedural revisions in 2019, attributed to "21st Century Cures Act," LCDs could be expanded at any time (without notice) and deleted at any time (without notice).  This Noridian maneuver suggests that an LCD deletion gets a comment period for 45 days.


81539, 4KScore, is $760.  This is a common price for specialty tests, the price for 81539 plus (0005U, 0011M, 0012M, 0013M, 0021U, 0089U, 0113U, 0203U).  

I think that 81539,  4KScore, was the originally priced test at $760, so all the others are "crosswalked" to it, but I haven't confirmed that.   


Nerd note: 30% Rule 

There is an exceptional case where Noridian might see an 81539 claim: if a lab gets an order for the test in a Noridian state, and sends it out as a reference test to Opko, in which case either lab can bill the test (as long as only one does), or, the Opko lab actually has to bill the test if the referring lab (that got the specimen) sends out more than 30% of its tests annually.  This is the Medicare rule about the 30% line and lab-to-lab billing.   It's a statutory rule to avoid the creation of shell labs that only bill tests that are actually performed in other wet labs, the latter of which would be evading the visibility of direct Medicare billing. But, if a lab gets an order for 10 tests, and sends out just 1, it can still bill for all 10 tests.


Generally, the 4 MolDx MACs have had uniform LCDs.   The fact that a service wasn't offered in some states (e.g. not offered in CGS MAC or WPS MAC) hasn't been a factor in whether the LCD would be issued across all MolDx MACs.   Here, Noridian proposes to delete an LCD because it doesn't expect claims, but if that were the general rule and applied uniformly at MolDx, a number of MolDx LCDs could be deleted in places like Iowa (the WPS MAC).

Guidelines for Prostate Genomics

Although not directly tied to 4KScore (which is used for "biopsy decision management," not active cancer management), the AUA recently updated its guideline for genomic (RNA expression) tests in prostate cancer management - here.

Opko History

Opko acquired BioReference Laboratories in 2015 for around $1.5B. The genetic division, GeneDx, was sold to SEMA4 in early 2022 for around $650M.   At $9.7M revenue (Part B) in 2020, 4KScore (Part B) was 0.7% of OPKO's $1.4B in revenue.

OPKO stock peaked at $17 in 2015, currently $2.85.  

SEMA4 stock peaked at $20 in December 2020, currently $1.66. 

Tuesday, May 10, 2022

FDA Approves CSF Alzheimer Test. "14 Day Rule" Rears Its Head.

On May 5, 2022, we had an article in ONCLIVE on testing challenges in cancer patients (here), and on May 4, FDA announces approval of the second-ever biomarker test for Alzheimer's disease, a CSF test (here, here).  

What connects these?   Remarkably, the "14 day rule" for Medicare hospital inpatient and outpatient services.

The 14 Day Rule

The 14 Day Rule is actually an interaction between two different regulations.  All hospital inpatient biopsies and tests are bundled to the DRG, unless ordered 14 days after discharge.  All hospital outpatient biopsies and tests are also bundled to the hospital outpatient payment, per regulation 42 CFR 419.2(b)(17), unless there is an exception.  Exceptions are created not at 419.2, but at an entirely different regulation, 42 CFR 414.510, the date of service rule.  The main exception is for human DNA-RNA tests.    

Tests on biospecimens that are not hospital-related (from physician office or a lab draw center) are always paid fee for service and not bundled.


The ONCLIVE article discusses the 14 day rule as a barrier for cancer testing.  This is especially true for inpatient biopsies (such as tissue from a lung lobectomy, or a colectomy, or nephrectomy).  Payment for genomics may be delayed more than 14 days - for example, 5 days while the patient recovers in the hospital, plus 14 days after discharge, = 19 days, and that's for ordering the test, allow more time for running the test and delivering it.  

For a hospital outpatient biopsy (e.g. melanoma tissue), for most cancer tests the DNA-RNA rule applies and the biopsy can now be tested and paid separately right away.  

CSF - Alzheimer Proteomics Test

The Alzheimer CSF test also bumps up into this rule, as I read it.  

The Fujirebio "Lumipulse" Alzheimer test is a proteomic test, an ABeta 42/40 ratio, so it's not a DNA-RNA test.  The main CSF lumbar puncture code is 62270, which ran about 80,000 services per year 2015-2019 (pre COVID).   But, 44% of these tests are inpatient, and 35% are E.R. and another 10% are hospital outpatient.  (That tallies about 90%).   For proteomic tests, all of these hospital-associated CSF biospecimens collide with the 14 day rule.   Only 10% of the 80,000 tests, or 8000 tests, were in a physician office which doesn't collide with the 14 day rule, and where the test can be billed immediately.

To my knowledge, there isn't yet a specific CPT code for "amyloid biomarker lab test," nor a PLA code for this test. 



In 2020, coding was changed.  62270 continues, but over half of services now bill under the new code 62328, which is lumbar puncture including imaging guidance.  The coding complexifies, but the 14 day rule applies the same.


The Fujirebio test had Breakthrough review at FDA, granted in February 2019.


Per FDA, "97% of individuals with Lumipulse G β-amyloid Ratio (1-42/1-40) positive results had the presence of amyloid plaques by PET scan and 84% of individuals with negative results had a negative amyloid PET scan."  Detailed FDA summary-of-effectiveness usually appears weeks or even a few months after approval (clearance).  This product went through De Novo review.

ADLT Not Possible

The test isn't eligible for ADLT status, since it's not a sole source test.  Even if it got ADLT status as an FDA-cleared test, FDA-cleared ADLTs don't get exemption from 14 day rule, only MAAA-type ADLTs (see 414.510).   

Amyvid PET History

FDA previously approved the Lilly Amyvid PET Amyloid biomarker (and later several other brands) in 2012 (and as a PMA approval as a drug), but CMS has "non-covered" it since 2013.  (There's are some paid claims for approved clinical studies - here.) 


So in summary, if you have Alzheimer's disease, you can't get a PET scan, you can't get an amyloid drug (Aduhelm), and it's darn hard to get a proteomic CSF test due to bundling.

I mentioned effects of this type of bundling on innovation in a recent article.   This aspect of bundling is usually left out of articles on bundling (JAMA 2022 here).

Very Brief Blog: CMS Posts CLFS Update, New Codes, Reprises PAMA Years

CMS issues the Clin Lab Fee Schedule (CLFS) update for July 1, 2022, with cover date May 4, 2022.

CMS adds 9 new PLA Codes for July 1, 0323U-0331U.  These are codes that were announced by AMA CPT on about April 1.   (CMS also mentions deletions of 0139U, 0168U).  Note that the newest batch of PLA codes are voted on this week at AMA CPT and will be released by AMA on July 1, but, will probably also be released by CMS by early June to be part of the June annual pricing meeting.    

CMS also reprises info on PAMA timelines.

The next data reporting will be 1Q2023, reporting claims data from 1H2019.  This will result in a new fee schedule CY2024 2025 2026.   Labs will report 2025 data in 2026 to make a new three year fee schedule CY2027 2028 2029.

CMS notes there is 0 price reduction in 2021 2022, and a max price reduction per year of 15% in CY2023-2024-2025.   

After that (e.g. 2026 or for the new years 27-28-29) there is no annual cap on the price reduction, it is based only on survey data with an immediate price reset.  

Monday, May 9, 2022

Has the Famous "HHS Directory" Suddenly Dropped Email for Staff?

Update May 11.

Yes, HHS dropped emails from the cross-HHS directory (FDA, NIH, CMS, etc).  Reported on this blog May 9, and confirmed by POLITICO on May 11.

Original May 9 Blog Follows

For at least 15 years, there's been an HHS Online Directory of all staff (HHS, CMS, FDA, etc), providing name, agency, department, phone, and email.   

Someone asked me for staff emails just a few days ago, and I looked the person up, got their email, but also provided the main directory link.

As of this morning, May 9, 2022, the directory is returning only name, agency, and department.  No actual contact information!  New to me.

There are a lot of implications.  

  • Recently, a FOIA request from me to a MAC was badly mishandled.  (Helpfully to itself, the MAC provided no appeals contacts or information in its reply).   I can no longer look up the next-level-up FOIA person at CMS to address the error.
  • Academics at universities will find it much harder to reach their colleagues at NIH.
  • What if you have an issue for a mid-level person at CMS?  You can no longer access their email or any other contact info.  Are you supposed to send your correction or issue to the head of the agency (Chiquita Brooks-LaSure) and hope it gets filtered down through multiple departments and divisions to the person you know is supposed to handle it?



HHS DIRECTORY was not the only place to get government staff emails, but it was a very convenient one.   Here are some examples.

FDA - FDA lists lots of management email contacts, such as here at the CDRH (devices) website:

CMS - CMS regularly lists some staff emails, for example, every MAC instruction or transmittal is public and has staff contact emails for that particular document.   CMS publishes elaborate annual rulemaking in numerous areas (hospital outpatient, hospital inpatient, etc) and each one lists 20 or more staff contacts & emails for each subsection.  

NIH - I would think academics at universities would regularly want to get in touch with their comrades at NIH.  HHS DIRECTORY was one stop shopping for those emails.   Usually you can get university emails from the university directories, but now it's gotten harder to find an NIH faculty email.   

Tuesday, May 3, 2022

CMS Renews MAC Awards for NGS MAC and for FCSO MAC

In December 2021, CMS renewed the contract for the NGS MAC for "Jurisdiction K," New York and New England.  This MAC, which is related to Anthem, also has a midwestern MAC with MN, WI, IL aka J6.

On May 1, 2022, CMS renewed the contract for FCSO MAC for "Jurisdiction N," which is Florida and Puerto Rico.  Like the Novitas MAC, FCSO MAC is related to Florida BCBS.  In the last couple years, to my observation, Novitas MAC and FCSO MAC have had more policies in closer (or identical) alignment, which wasn't always the case.

See the MAC page at CMS here:

In older news, Novitas was re-awarded JL in July 2021, and back in 2020, Noridian was re-awarded JE, and NGS MAC was re-awarded J6.

National Quality Forum Dismisses "SEP-1" Appeal Process

In this blog, I covered trade journal articles and NQF website announcements regarding the five year review, and an appeal from IDSA and others, regarding the SEP-1 quality measure (NQF 500).

Original blog and links here, March 8, 2022.  See March 2022 MedPageToday here.

On April 29, 2022, SEPSIS ALLIANCE issued a press release that NQF had dismissed the appeal of IDSA and other organizations.  If I read this correctly the Sepsis Alliance announcement on April 29 matched the closing date on the NQF website of an appeal-triggered comment period.

See: Medpage Today, May 2022 here.

See:  NQF Press Release, May 2022 here.

The SEPSIS ALLIANCE statement is here:

APRIL 29, 2022

Sepsis Alliance commends the National Quality Forum (NQF) Appeals Board for dismissing the submitted appeal of NQF #0500: The Severe Sepsis and Septic Shock Early Management Bundle, also known as “SEP-1.”  Since its initial endorsement by NQF, SEP-1 has been saving lives and limbs, in large part due to its evidence-based focus on timely recognition and early therapeutic intervention. Because SEP-1 offers a standardized process for every patient with sepsis or suspected sepsis, it encourages closing gaps in sepsis outcomes across race, socioeconomic status, geography, and insurance type, and it supports hospital leadership in retaining focus on the possibility of sepsis in every case. Today’s decision by the Appeals Board will keep sepsis—the leading cost of care and cause of death in U.S. hospitals—at the forefront of clinical discourse, where it belongs. 

We thank NQF for its work making evidence-based determinations to improve care quality for all patients, and we support the ongoing efforts to modify SEP-1 in response to updated evidence. 

There is certainly still work to be done. We will continue to pursue quality improvement initiatives that benefit sepsis patients, as well as better public and provider sepsis education and policy solutions. Today’s decision paves the way for continued improvement. 

Monday, May 2, 2022

FDA Posts Draft Guidance: ctDNA in Clinical Cancer Trials

In January 2020, FDA released final guidance on use of minimal residual disease tests in clinical trials for hematologic malignancies (MRD; here).

Fast forward to May 2022.  FDA releases a draft guidance for use of circulating tumor DNA (ctDNA) in clinical trials for solid cancers.  11 pages, find it here.   The LCD covers three use cases, ctDNA for patient selection, ctDNA for patient enrichment, and ctDNA as a measure of response.   They note (page 8) that tests might be bespoke (tumor-informed such as post tumor exome sequencing) or tumor-naive.  They note that tumor naive panels could like at epigenomic methylation or fragmentomics.

The Federal Register comment period notice will be in the Fed Reg on May 3.  Here.  The comment period will run 60 days (about July 1).

Draft Guidance

MIni Update: CMS Provides Partial New Codes List for Summer Lab Pricing Meeting

 In mid-April, CMS announced dates for its June and July clinical lab fee schedule public meetings for pricing new codes.  Here:

On that page, they have posted a first-draft agenda for the meeting (see Zip file for Excel spreadsheet):

The current version of the Excel code agenda list has 70 items, nearly all PLA codes.  I assume they will update with the several regular 80,000-series new codes before long.   Also, in recent years, CMS has also updated the list circa June 1 to include codes ratified at the mid-May AMA CPT meeting.  

Items 39-58 are reconsideration codes, almost 20, instead of the usual two or three.  While the majority of all codes are PLA codes, nearly all the reconsideration codes are 80,000-series codes.

Sunday, May 1, 2022

Very Brief Blog: MolDx Delays Infectious Disease Panel LCD, Issues "FAQ"

This was published May 1, see another update May 15.

In early March 2022, MolDx released a wide-ranging new LCD for infectious disease molecular testing, and a week later, released a technology assessment template for it (here).  Thetech assessment template is in a different, and to my eye, more helpful format than they'd used previously.  (Helpful, but also, pretty long and detailed).  

On April 22, MolDx announced a delay in the implementation of the LCD, to May 17.  Here, and screen shot below.

MolDx also released an FAQ, web page here, PDF here.  Cloud copy here.

Friday, April 29, 2022

Very Brief Blog: 3 Articles Critical of Quality System Campaigns

 A couple weeks ago, I highlighted a Rosenbaum article in NEJM on "Metric Myopia" (do metrics pull attention to a few things while other issues go unattended).  Blog here.

Let me quickly tie three articles together, from the last couple weeks.

  • In NEJM April 20, Lisa Rosenbaum writes, "Metric Myopia - Trading Away our Clinical Judgement."  Here.
  • Pair that this week with an NEJM April 28 article, also by Lisa Rosenbaum, "Reassessing Quality Assessment - A Flawed System for Fixing a Flawed System."  Here.
  • And I'd make this a triple play, yet again in NEJM, by adding in Elizabeth Rourke's April 7 article, "Ten Years of Choosing Wisely to Reduce Low-Value Care," which in part argues that nominated topics are too often figureheads that are either low cost or rare or practiced by somebody else.  Here.
    • See similarly a January 6 article in HEALIO, here.
    • HEALIO pivots off a December 2021 article in JAMA IM by Ganguli et al. here.
Regarding "Reassessing Quality Assessment," see complaints by major organizations like IDSA (Infectious Disease Society of America) that review of a quality measure, SEP1 or NQF-500, was poorly handled by NQF - here.  Coverage also at MedPageToday, here

Regarding the Rosenbaum series, see part 3 also, "Peers and Professionalism," here.

Thursday, April 28, 2022

More Data on Medicare Advantage Denials: OIG Weighs In with 2022 Report

Direct instructions from CMS require that Medicare Advantage cover all services covered by traditional Medicare.   So the simple rule is, if the service gets coverage from Traditional Medicare, you get Medicare Advantage coverage for that service, also.   

(And, normally, that Medicare Advantage payment rate should be the same as traditional Medicare, unless you have negotiated a lower-fee contract - details here).

However, as a consultant, I also warn people that getting that coverage and payment from Medicare Advantage may take a lot of hand-holding or appeals.  And it seems to be focused on labs.  A Health Affairs report earlier this year by Schwartz et al. (here) found that MA plans just denied 1.4% of all claims, but hidden deep in the paper, a huge proportion, like 80-90%, of those denials were lab claims.

Now we have a new 61-page OIG report on MA denials of medically necessary care, as adjucated by physicians hired by OIG.  See the OIG report here, and see coverage at New York Times here.

OIG had 3 recommendations to which CMS concurred.

  1. Issue guidance on the use of medical appropriate use criteria for MA plans,
  2. Update audits to quantify and enforce action on this problem,
  3. Direct MA plans to address their "vulnerabilities" that lead to the excess denials.


Below, from Schwartz et al 2022, Lab denials (either under MA specific rules (yellow) or under LCD rules enforced by MA plan(blue)) were the vast majority of all types of denials.


For labs, MolDx has announced it is contracting to share edit protocols with MA plans, which should tighten the linkage between what FFS Medicare covers and what a MA plan covers.

ASCO Updates Guidance for Breast Cancer Prognostics (Adjuvant Chemotherapy)

 One of the early landmark tests in precision medicine was the Oncotype DX test for breast cancer prognosis, first published in the NEJM in 2004.   Today, there are a half-dozen tests recommended with a few variations in society guidelines.   

ASCO has updated its guidance and published it April 19, 2022, as Andre et al., "Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer" (30 pp).  Tests include Oncotype, Mammaprint (FDA), Breast Cancer Index, Endopredict, Prosigna (FDA), IHC-4.  When access to these is not available, they recommend Ki67 (a single immunostain).   Find Andre' et al here, open access:

The prior version was Harris et al. 2016.

Flow chart from Andre' 2022

See coverage at Genomeweb here.

The Andre' guidance  has a significant section on ctDNA as a biomarker for the need for adjuvant therapy, however, falls back to a 2018 ASCO/CAP guidance (Merker et al) that stated this approach was not ready for routine clinical use as of yet.  

History Lesson

Today, MolDx has several LCDs that are keyed directly to relevant extramural guidelines, such as tying PGx coverage to CPIC and FDA PGx recommendations.   

Tidbit:  In May 2016, MolDx briefly proposed, then withdrew, a plan to directly lock Medicare coverage directly to current ASCO recommendations.  (My blog here).    (One community objection, at the time, was that guidelines are only updated every 5-6 years, as we see here with Harris et al. versus Andre' et al, 2016, 2022).

The Brief Noisy History of "CDD" and CED

Not directly related, but my search for the above link led me first to a December 2016 blog where MolDx proposed withdrawing coverage for the Vectra test (here).  That blog also talks about how MolDx seemed to be canceling or withdrawing references to its short-lived local "coverage with data development" or CDD effort.  MolDx later dropped CDD paragraphs from the MolDx handbook in 2018, here.  

A 2022 article on Medicare and risk sharing arrangements including CMS CED  by Chen & Carlson tallied up a large number of those long-defunct MolDx local CDD policies (here).   Not touching on MolDx CDD, but taking a deep dive into CMS NCD CED, see Zeitler et al. (entry point here).

Next: AI for Breast Cancer Prognostics

By keyword search, artificial intelligence and machine learning are not mentioned in Andre' et al.  However, there are already not just original studies but quite extensive review articles on using machine learning for breast cancer prognostics (see review by Li et al, PLOS ONE, 2021, here; see also Yousif 2022 here, Wang  2021 here, Fitzgerald 2021 here.)

A Sociologist's View

See a book on precision medicine from the sociology and anthropology viewpoint, with a chapter on the adoption and changing viewpoints of the Oncotype Dx test.  Chapter 2, Genomic techniques in standard care: Gene-expression profiling in early-stage breast cancer, in book: Personalized Cancer Medicine, Kerr et al., Manchester Univ Press, 2021.  (Hardcover only).

Wednesday, April 27, 2022

Case Study: When Do Evaluators Think a Test's Incremental Accuracy is Too Small?

When do evaluators, like tech assessment committees, think an increase in test accuracy is "too small" to be impactful?  This is something modern molecular diagnostics run into all the time.   Does a molecular expression test in breast cancer or prostate cancer provide enough added value, over pathology grade and tumor size?    

We have a case study, although from radiology not pathology, this week in JAMA Internal Medicine. 

Ominously, the research article and the op ed run under a banner, "LESS IS MORE," see also the home page for this series here.   If your new technology is reviewed under a logo "LESS IS MORE," it's probably never a good sign.

The two articles are Bell et al., a systematic review and meta-analysis of adding Coronary Artery Calcium Score to a "traditional CV risk assessment' e.g. things like BP and cholesterol.   There is an op ed Gallo & Brown.  Note, the op ed banner title includes "PRIMUM NON NOCERE" (first do no harm), which is probably never a good sign in an article about your product.

I think the key point is summarized by Gallo & Brown.  Existing predictors have C statistic of .70 to .80, and CACS adds .03  (e.g. 0.73 to 0.83).   They find this unimpressive and give some reasons why.


BELL (Article) here

GALLO (Op Ed) here


Usually, the popular statistic "area under the curve" is a hard way to show "added clinical value."  If the AUC of the standard of care is .75, and the AUC of your molecular test is .79, what does that mean for outcomes and care?   First, AUC is an abstract concept, and second, AUC (or ROC) assume binary tests without a middle ground, and are based on pure sensitivity (in 100 known patients) and pure specificity (in 100 negative patients), so base rates are hard to extrapolate.   AUC means very different things clinically if there are 10 patients per 20 tests given, or 5 patients per 100 tests given.  

Usually it's better to translate to terms like "Current standard has 20 false positives per 100 patients, but our test cuts that in half.  This means 10 less patients per 100 get a needless biopsy." 

Friday, April 22, 2022

Very Brief Blog: CMS Publishes Notice, Annual Lab Pricing Meeting

CMS holds public meetings each summer for pricing new lab codes.

CMS has published the announcement for this year's annual public meeting, "For CY2023 Codes," which will be June 23, 2023.  See 87 Fed Reg 22897, April 18, 2022, here:

CMS will publish the code list about 30 days before the meeting.  In past years, new codes approved at the early May 2022 AMA CPT meeting are included in the June CMS meeting.  Also, the meeting "rolls up" and includes all PLA codes from the prior 3  quarters, meaning PLA codes applied-for on July 1, 2021 or later.

Presentations: June 2

Presentations must be submitted by June 2.  

Expert Panel: July 18-19

The Medicare Advisory Panel (of about 12 experts) will meet on July 18-19, 2022.  It has its own announcement, at 87 FR 22895, here: