Saturday, March 28, 2020

Article in SCIENCE Highlights Precision Medicine Aspects of COVID-19

Most discussion of COVID-19 highlights increasing severity with age and comorbid conditions (see article in WSJ currently, here. Which is true, but may not be the whole story.  Consider, for example, your risk of heart attack always rises from 40 to 50 to 60, but a lot more if you have familial hypercholesterolemia.

We should also look for risk factors that pile on top of age and comorbidity, risk facts like immune system genetics, that might raise the odds of a cytokine storm caused by COVID. 

  • Jocelyn Kaiser at SCIENCE provides an article, dateline March 27, on this theme, here.    

The journalist includes quotes from CEO Kari Stefansson of Icelandic "DeCode Genetics," from the Finnish FinnGen initiative, the UK Biobank effort, and others.   Targets include scanning the whole genome for currently unguessable risk factors, balanced by looking at obvious genomic candidates, like variations in the ACE2 receptor (angiotensin converting enzyme receptor) that COVID must bind to before entering a cell.

Searching for co-pathogens that spike the risk of a patient's deterioration could also be fruitful and could be undertaken by NGS pathogen metagenomics, given that end stage patients are often on high dose antibiotics that can interfere with culture (e.g. Karius and others).   There's some preliminary journal publications that a patient's early procalcitonin bioresponse to infection (more commonly tested in US and Asia than USA) may flag early cases that are likely to deteriorate (Pubmed here).  The point is that answers could come from many different directions and help us better than "aging or comorbidity."

Adaptive Biotechnologies in Seattle, partnering with Microsoft's massive data systems,  has started an open call for samples in an initiative to seek immune system variations that develop during, or predispose to, the COVID response (entry point here).

I had an early blog on this theme March 1 - here.

Tuesday, March 24, 2020

Reminder: CMS Accepting Comments on Colorectal Screening NCD til March 29, 2020

February 28 seems like a long time ago - four weeks in the COVID era seems like four years in regular time.

Recall that on February 28, 2020, CMS announced it would be undertaking an NCD this year on the Epigenomics Epi proColon blood-based colon cancer screening test.   The test was FDA PMA approved in 2016, and the NCD opening request letter was filed by Epigenomics in April 2019.  (However, investor calls of the publicly-held company show it was negotiating with CMS well before 2019). 

The NCD opening followed fairly quickly after a favorable health economics study in December 2020 - press here, article by D'Andrea et al. here.

My original blog is here.   The CMS webpage is here.  The CMS comments page is here - see the orange box that says, "COMMENT."   There were 38 comments through March 24.   Often, commenters show up on the last day - submit your comment by March 29.

Epigenomics has the first FDA-approved blood test for colorectal cancer screening.  Multiple other companies have announced they are developing tests in this category.

Note that CMS views colorectal cancer screen by stool or blood as an intermediate test is is concerned whether the patient is "lost to followup" when positive and never gets a colonoscopy.   (An earlier lost-to-followup step is never turning in the blood or fecal test material itself).    The D'Andrea modeling study focuses on this.   

In other news, in 2019, recall a CMS-sponsored study was highly critical of the covered stool nucleic acid test Cologuard, which is circa $500 per test (Naber et al., PLOS, 2019).   Exact Sciences has market cap of about $9B, 2019 revenue around $800M,  2019 operating loss around $200M.  In 2018, The Exact Sciences Cologuard test was about 20% of Medicare's $1B in molecular spending, the highest paid single test.



Monday, March 23, 2020

MolDx Medical Director Dr Paul Gerrard Joins Consulting Group

Catching up on March news, on March 4, 2020, it was announced that Dr. Paul Gerrard of Palmetto MolDx had taken a new position as Vice President at McDermott Plus Consulting.

See his corporate web page here.  See his Linked-In here.   According to his Linked-In page, he was a medical director and MolDx Director of Clinical Science from February 2018 to February 2020.   Previosuly, he had been associate medical director at the New England Rehabiliation Center in Portland, ME.   He holds a BS in economics and an MD from the University of South Carolina; his residency was in the Harvard system.

I noted that a few weeks ago on the AMP listserv, MolDx circulated an open position for a molecular pathologist Palmetto MAC medical director, via the BCBS South Carolina job openings website.


AMA Makes May 2020 CPT Meeting Virtual - And Posts Full Code Agenda for Comment

Recall that AMA posts lab codes for public comment during a very brief window a couple weeks after the code applications are due, and months before the relevant CPT Editorial Meeting.  See lab codes for comment in February 2020 for the May 2020 meeting (here).

New news.   AMA has announced the May 14-16 CPT Editorial Panel Meeting will be virtual, so your trip to Chicago can be cancelled.   AMA page here.

Separately, AMA has posted all the CPT codes proposed for the May meeting.  See PDF online here. 

There are 54 agenda items, including a number of lab codes that had been rapidly posted for early comment in February.   To comment on a non-pathology code, submit a request-to-comment by April 23 and comment back to AMA by April 30.


Friday, March 20, 2020

Adaptive Biotech, Microsoft Commit to Rapid Deep Dive Research on Coronavirus Immune Response

On March 1, I wrote a blog that the erratic, unpredictably lethal attack of COVID-19 on the body shouldn't be attributed to random chance nor aging except as a last resort.   Before that, triggering factors must be searched with molecular methods - maybe it is something with HLA type, maybe it is the inflammatory response profile of cytokines driven by host genetics, maybe it is a co-pathogen. 

Other than age and comorbid frailty, we don't know much yet.  Maybe ibruprofen contributes.  Maybe blood type A vs O contributes.  We need to be learning fast. 

In an announcement March 20, Adaptive Technologies and Microsoft commit to rapid research and investments in the host immune signature among COVID patients.   They also commit to an open access portal for the bioinformatics.

See the full press release here and clipped in this blog below the break.  Labcorp participates.

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Tuesday, March 17, 2020

AMA Creates COVID Code; AMP Warns about Legislative Error; CMS Prices Its Two COVID Codes; More

In brief updates, AMA creates a COVID code (CMS had already rushed out a pair of COVID codes).   AMP warns on March 16 about a "legislative error" relative to legislation about COVID test coverage.   CMS issued pricing for its two "U-codes" for COVID.

1  AMA Creates COVID Code 
2. CMS Prices its own COVID Codes $36, $53
3. AMP and COVID Payment Legislation
4. Congress Introduces VALID Act for Lab Reform

5. Sidebar:  Economist article on COVID biology and virology
6. Sidebar: Trump's Remark re Obama Rules 


1. AMA CREATES COVID CODE 86735

AMA rapidly drafted a new single code for COVID-19 testing and made it immediately available for us, if payers can load it that fast.

See the AMA CPT COVID webpage here.  AMA also popped out a 4 page fact guide for the code, PDF here.  For example AMA coding advice states that if separate samples for nasal and pharyx are run, and reported separately, bill 87635 on two lines with modifier 59 on the second line.

This is a standard CPT Category I code in the molecular microbiology section, at code 87635.  The text is:

Infectious agent detection by nucleic acid (DNA or  RNA);severe acute respiratory syndrome coronavirus  2 (SARS-CoV-2) (Coronavirus disease [COVID-19]), amplified probe technique

AMA does not set fee schedule prices.

2. CMS PRICES ITS COVID CODES 0001U, 0002U, $36, $53

On around March 6, CMS released two new CPT codes 0001U and 0002U for use by Medicare or other payers effective April 1 (but dates of service retroactive to February). 

CMS did not set a national price but asked each MAC to set a price and tell CMS.  MACs set prices of $36 for CDC Test Kit Based Test, and $53 for other tests.   I believe the rationale is that CMS assumes labs running CDC Test Kit get it for free and only incur additional operating costs.   See the CMS pricing PDF here.  Or equivalently, CMS MACs think the cost of running the tests are $36 and the costs of COVID reagents is $17 ($53-36).   I saw a notice today that California Medicaid (Medi-Cal) adopted the same pricing as Medicare. 

CMS has a consolidated webpage for transcripts of its COVID calls here.  See transmittal on COVID pricing CR11681 here.

NERD NOTE:  PAYABLE IN MEDICARE OUTPATIENT SETTING

In the vast, vast majority of cases*, CMS bundles hospital clinic outpatient microbiology tests (like clinical chemistry) to underlying ER or clinic visit fees.  This is called Status Q4 for hospital outpatient billing.   Human genetic tests are billed separate (called Status A).   CMS classed U0001 and U0002 as Status A, meaning they are separately payable (unless patient is admitted). 


3. AMP CONCERNED ABOUT LEGISLATIVE FLAW

Congress is in the midst of passing legislation mandating payment for COVID testing but AMP believes there is a technical flaw in the legislation.  The concern hinges on the placement of wording about FDA emergency use approval (EUA), which some labs have and some labs don't (for example, it might be pending).   Also, requirements for EUA may change rapidly.

See the AMP press release online here.

4. VALID ACT ON THE HILL

Lost in the pandemic news, on March 5, 2020, House and Senate introduced matching versions of the VALID ACT, which would heavily reform and change the entire FDA process around diagnostic lab tests (see open access article at 360DX here.) 

Sen. Rand Paul introduced A DIFFERENT BILL (!!) on March 18, AMP press release here.

See lengthy, and I believe open access, article by Turna Ray at Genomeweb on March 16, here.  She weaves together a deep dive on VALID with a deep dive on COVID.

5. SIDEBAR: 
Economist Open Access Article on Science of COVID

The ECONOMIST published a nice Scientific-American level  article on COVID biology and virology - email registration - here.

6. SIDEBAR:
President Trump's Remark about Obama Rule Delaying COVID Testing


A few days ago, there was a spat that involved President Trump remarking on March 4 than "an Obama rule" had delayed COVID testing.  There were responses that this was not true (or stronger language).   Molecular pathologist and policy expert Roger Klein MD PhD was featured in an article on the topic in the conservative paper Epoch Times March 12 (readable with email registration, here.)

Propublica wrote a detailed article on the FDA policy steps here.

? RNA Extraction Supplies

Around March 12, there were a flurry of stories that US would run out of RNA extraction kits, which are more difficult and constrained to manufacture than any particular set of viral test probes (see e.g. here).    My MBA-school math was that you could bravely or even heroically ramp up RNA kit production 24/7 (e.g. 3-fold) but maybe demand was going up 100X or 1000X, a different order of magnitude.  We haven't particularly heard more about this

I've read that typical tests use 4 wells in a 96 well plate (about 24 patients per plate), and that some forms of test run in 3-4 hours.   Running 1M tests at 24 per plate at 4 hours turnaround per set would be about 7000 days of 24/7 plate time (for one plate reader).  If 1M tests took 2 minutes of tech time each (handling, records, etc) that would be 2,000,000 minutes of tech time or 33,000 hours of tech time or about 16 2000-hour work-years of tech time.  To do the 1M tests and 2M minutes of labor in one month would require 208 160-hour work-months or 208 techs for a month.


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* I discovered scattered molecular microbiology codes that are Status A payable, while nearly identical codes are always Status Q4 not payable separately.   As far as I could tell, the rare erratic assignment of a few molecular microbiology codes as "A" amongst the long CPT code lists of molecular microbiology codes was simply erratic.
 


Friday, March 6, 2020

CMS Announces Special New Codes for Coronavirus Testing


On March 13, CMS announced national pricing for COVID at $36 for the CDC kit test (which doesn't require internal development and might even start with a free CDC kit - not positive) and $51 for the local LDT test of various types.  PDF here.   

This is comparable to my forecast March 1, when I noted the general price for multiplex viral pathogen is $43.    To avoid federal rulemaking, CMS lists the price in the above PDF as being a reflection of the price that was set by each individual contractor (MAC).

###

CMS has announced two special codes for Coronavirus testing, both effective April 1, 2020.   U0001 will represent CDC-kit testing, and U0002 will represent other testing.

See the March 5, 2020 CMS press release here:

https://www.cms.gov/newsroom/press-releases/cms-develops-additional-code-coronavirus-lab-tests

"CMS developed the first HCPCS code (U0001) to bill for tests and track new cases of the virus. This code is used specifically for CDC testing laboratories to test patients for SARS-CoV-2. The second HCPCS billing code (U0002) announced today allows laboratories to bill for non-CDC laboratory tests for SARS-CoV-2/2019-nCoV (COVID-19)."

In transmittals on the Clin Lab Fee Schedule here and outpatient fee schedule here:

Code: U0001
Short Descriptor: 2019 –nCoV diagnostic P
Long Descriptor: CDC 2019 Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel

Code: U0002
Short Descriptor: COVID-19 lab test non-CDC
Long Descriptor: 2019-nCoV Coronavirus, SARS-CoV-2/2019-nCoV (COVID-19), any technique, multiple types or subtypes (includes all targets), non-CDC

Codes Not Priced

CMS adds, "Local Medicare Administrative Contractors (MACs) are responsible for developing the payment amount for claims they receive for these newly created HCPCS codes in their respective jurisdictions until Medicare establishes national payment rates. Laboratories may seek guidance from their MAC on payment for these tests prior to billing for them."

Medicare MACs will simply set a price they pay, reagardless of the inbound charge.  Options may include Options include 87797 (direct probe, per organism), 87798 (amplified probe, per organism), and 87799 (quantitative DNA/RNA probe, per organism.)  CMS pays $30, $35, and $43 respectively.

Retroactive

The codes can be billed retroactive to February 4, but do not submit the claim until April 1 or later.

Hospital Outpatient Bundling?

In general, virology tests are "bundled" in the ER or hospital clinic outpatient setting

In Transmittal T4544, CR11691, CMS states that the new U-codes for coronavirus are NOT BUNDLED but are PAID SEPARATELY (status "A").   This is an exception to the usually bundling of hospital outpatient chemistry and virology codes.   (Actually, if you look at outpatient virology codes/pathogen codes, most molecular ones are bundled "Q4" but very erratically and scattershot, some are "A" not bundled.  That's a topic for another day.)

Would CPT Panel Codes Override Special U Codes?  And Re-trigger Bundling?

I don't think CMS has addressed whether coronavirus on the same day as several other molecular viruses triggers the multi layer Respiratory Panel code set (which starts at n=3), which are ER- and clinic-bundled (Q4) and paid at fixed rates.   I suspect CMS wants coronavirus coded separately, but it's not in print.  Those panels do allow for DNA and RNA viruses and do mention coronavirus in parentheticals; recall it's also a long-familiar regular cold virus.   These are 3-5 respiratory viruses, any combo (87631 $142), (98632, 5-11 $128), (87633, 12+ $417).  These apply when multiplex probe techniques are used and while technically COVID assays are. well, multiplex, it's unlikely the whole set of a half dozen or more pathogens are "one multiplex" at this point.

CDC Issues ICD-10 Coding

CDC issued a news release March 5 on Coronavirus COVID-19 coding.  Frankly, it's exactly what I think any coding expert would come up with.  There is a code for coronavirus with another disease classification (B97.29).   This is the usual correct coding, J12.89 viral pneumonia + B97.29, a coronavirus.    CDC says do not use B34.2, coronavirus infection unspecificed, since you know it's respiratory, not unspecified.   See press release at CDC here.

Very Brief Blog: No, Virginia, Medicare Might Not Pay for COVID-19 Testing Separately (See Outpatient Billing/Bundling Rules)

Note, Update March 6:  CMS announced on March 5 it would pay for new U-codes U-0001, U-0002, separately in the hospital outpatient setting details here.


In a March 1 blog, I reviewed existing Medicare LCDs and coding rules for viral testing (here).  On March 5, Vice President Pence defined COVID-19 tests as an "essential health benefit" paid under Medicaid, Medicare, and private plans (here).

Here's the conventional coding for services that don't have a CMS or AMA code yet.   Infectious agent DNA/RNA probe detection runs generally from 87471 forward.  In a nutshell, for tests for viruses not yet codified by name, payment per test is low and inadequate.

  • Options include 87797 (direct probe, per organism), 87798 (amplified probe, per organism), and 87799 (quantitative DNA/RNA probe, per organism.) 
  • CMS pays $30, $35, and $43 respectively.   

All three of these codes are BUNDLED in the hospital outpatient setting such as hospital outpatient clinics and emergency rooms.  (They are also bundled if they are tested by a hospital within 3 days before an inpatient admission).   So in most settings, for Medicare patients being seen in an ER or hospital outpatient clinic, there is no separate or add-on payment for COVID-19 testing (under a simple reading of existing rules).  The hospital eats the testing cost.

CMS represents this "bundled" status by giving the infectious disease codes classification "Q4" in the hospital outpatient coding system:

Hospital outpatient codes: Q4 = bundled
2017 Utilization of 87797, '98, '99 in CY2017 Part B Data

In a cloud database, CMS provides information on all labs and physicians paid in Part B for these codes in CY2017 (here).  Searching for 87797, 98, 99, yields 467 data lines.

For all these codes together, there were 844,400 services for $35,069,906. 

For 87797, there were 3,549 services for $96,556.
For 87798, amplified probe, there were 683,151 services for $25,822,643.
For 87799, quantitative, there were 157,710 services for $9,150,707.

To Amplify on Payments for 87798 (ha ha inside joke)

Interestingly, the the highest paid labs for 87798 (amplified probe)  in Part Bwere not the top several highest-paid labs overall.  The highest-volume labs for 87798 were CAP Dx (Irvine, CA) at 26%, Bakotic Pathology (Alpharetta, CA) at 13%; Genova Dx ((Duluth GA) at 9%, and Labcorp (Burlington NC) at 6%.   Excel in cloud here.


click to enlarge

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Nerd note.  In the first chart, where most virology codes are "bundled, Q4," I have no idea why code 87800 is not bundled (is status A) and I've asked different staff at CMS if there is any explanation.


Source Documentation: $8B Coronavirus Budget Documentation Here

Numerous headlines have flagged that House and Senate passed an $8.4B coronavirus emergency funding bill.   President Trump signed the bill on March 6 in DC, canceling an announced trip to CDC.

Not many link to the source documents.  Find them here:
  • House.gov press release on passage, here.
  • Full text of H.R. 6074 (28pp) here.
  • Official summary of H.R. 6074 4pp) here.
  • Law firm summary at Faegre Drinker here.
Via the CDC, $2.2B "to support federal, state, local health agencies."  Mostly via BARDA and in part NIH, $3B for research and development of diagnostics, therapeutics, and vaccines.  $1B goes for stockpiling emergency supplies of different types.  

Division B, Section 102, provides the Secretary of HHS the authority to waive or modify Medicare restrictions on telemedicine services.  This applies in "emergency areas" as declared by the President or the Secretary.  This budget item is stated as exempt from pay-as-you-go standards.  

Thursday, March 5, 2020

Very Brief Blog: VALID ACT to be unveiled soon on Hill

Brief reports in Bloomberg Law News and Politico Pulse state that the long-debated VALID ACT, for regulatory reform of FDA vis-a-vis lab tests, will be unveiled soon.

Politico Pulse here.
Bloomberg Law here.

Sponsors include Rep. Bucshon (R-IN) and DeGette (D-CO) and Sen. Burr (R-NC) and Bennet (D-CO). 

Politico writes in part:

BIPARTISAN BILL WOULD OVERHAUL LAB TESTS — A bipartisan, bicameral group will soon unveil legislation to overhaul how the FDA regulates laboratory developed tests and in vitro diagnostics, putting them under one framework as "in vitro clinical tests," POLITICO's David Lim scoops.... major revamp of an FDA proposal for a precertification program — now deemed "technology certification." It also creates a breakthrough program similar to medical devices to speed development and prioritize review of certain tests, as well as a user fee program to support test review.

It's an armful: a 245-page version of the bill has begun circulating.

Very Brief Blog: AdvaMed Digital Health Conference Comes to Los Angeles (May 19-20, 2020)

Last spring, I was sorry to miss the AdvaMed Digital Health Conference, held in 2019 in San Francisco.

This year, I'm tracking the 2020 conference.  It's called "The Digital Medtech Conference / Digital Health Revolution," and is jointly sponsored by AdvaMed and Biocom.  Look for it Tuesday/Wednesday, May 19-20, 2020 at the Millenium Biltmore hotel in downtown Los Angeles (DTLA).

  • See the AdvaMed "Center for Digital Health" here.
  • See the conference website here.
Registration is $550 for non-members ($500 before 4/17).  For more about the booming districts that comprise DTLA, here.   


Very Brief Blog: VP Pence Defines Coronavirus test as "Essential Health Benefit"

On March 4, 2020, Vice President Pence defined coronavirus testing as an "essential health benefit."  Essential health benefit is a term of art that applies to health plans in the U.S. under the Affordable Care Act.
  • CNBC here.
  • Fox News here.
  • At WhiteHouse.gov, see transcript of Pence speech to Diagnostics CEO's - here.
Separately, CMS issued a press release on how coronavirus prioritization would affect other issues, like hospital and nursing home inspections (here).

My earlier blog on how coronavirus fit into existing LCDs for molecular virus testing is here.  My earlier blog on precision-medicine frameworks for understanding vulnerability to coronavirus is here.

From WhiteHouse.gov:
"HHS has already denominated a test for coronavirus to be an essential health benefit, which — which is a — which ensures that it will be covered by people’s private health insurance.  It’ll be covered by Medicare and Medicaid.  And we’ll — we’ll continue to work in that way."


___

Nerd note.

Experts discuss what Pence meant - at AP, here.

See the HHS page for Essential Health Benefits at CCIIO here.   CCIIO is, " Center for Consumer Information & Insurance Oversight."

 The main categories are very broad - "ambulatory healthcare, emergency services, hospitalization, maternal care," etc.  

Wednesday, March 4, 2020

Very Brief Blog: CMS Faces Coronavirus (Press Release Here)


https://www.cms.gov/newsroom/press-releases/cms-announces-actions-address-spread-coronavirus


Coverage of this press release, at The Hill, here.

For Bill Gates' op ed on coronavirus in the NEJM - here.

In a news article today, Scott Gottlieb urges widespread coronavirus testing, naming Labcorp and Quest - here.

MedCityNews has an interesting article about innovative ways of handling coronavirus patients or using technology to management them at home - here.

##


CMS Announces Actions to Address Spread of Coronavirus

CMS calls on all health care providers to activate infection control practices and issues guidance to inspectors as they inspect facilities affected by Coronavirus

Today, the Centers for Medicare & Medicaid Services (CMS) is announcing several actions aimed at limiting the spread of the Novel Coronavirus 2019 (COVID-19). 

Specifically, CMS is issuing a call to action to health care providers across the country to ensure they are implementing their infection control procedures, which they are required to maintain at all times. 

Additionally, CMS is announcing that, effective immediately and, until further notice, State Survey Agencies and Accrediting Organizations will focus their facility inspections exclusively on issues related to infection control and other serious health and safety threats, like allegations of abuse – beginning with nursing homes and hospitals. 

Critically, this shift in approach, first announced yesterday by Vice President Pence, will allow inspectors to focus their energies on addressing the spread of COVID-19.

As the agency responsible for Medicare and Medicaid, CMS requires facilities to maintain infection control and prevention policies as a condition for participation in the programs. CMS is also issuing three memoranda to State Survey Agencies, State Survey Agency directors and Accrediting Organizations – to inspect thousands of Medicare-participating health care providers across the country, including nursing homes and hospitals.

“Today’s actions, taken together, represent a call to action across the health care system,” said CMS Administrator Seema Verma. “All health care providers must immediately review their procedures to ensure compliance with CMS’ infection control requirements, as well as the guidelines from the Centers for Disease Control and Prevention (CDC). We sincerely appreciate the proactive efforts of the nursing home and hospital associations that have already galvanized to provide up-to-the-minute information to their members. We must continue working together to keep American patients and residents safe and healthy and prevent the spread of COVID-19.”

The first memorandum released today provides important detail with respect to the temporary focus of surveys on infection control and other emergent issues. Importantly, it notes that, in addition to the focused inspections, statutorily-required inspections will also continue in the 15,000 nursing homes across the country using the approximately 8,200 state survey agency surveyors. Surveys will be conducted according to the following regime:
  • All immediate jeopardy complaints (a situation in which entity noncompliance has placed the health and safety of recipients in its care at risk for serious injury, serious harm, serious impairment or death or harm) and allegations of abuse and neglect;
  • Complaints alleging infection control concerns, including facilities with potential COVID-19 or other respiratory illnesses;
  • Statutorily required recertification surveys (Nursing Home, Home Health, Hospice, and ICF/IID facilities);
  • Any re-visits necessary to resolve current enforcement actions;
  • Initial certifications;
  • Surveys of facilities/hospitals that have a history of infection control deficiencies at the immediate jeopardy level in the last three years;
  • Surveys of facilities/hospitals/dialysis centers that have a history of infection control deficiencies at lower levels than immediate jeopardy.
The memorandum also includes protocols for the inspection process in situations in which COVID-19 is identified or suspected. These protocols include working closely with CMS regional offices, coordinating with CDC, and other relevant agencies at all levels of government. The agency is also providing key guidance related to inspectors’ usage of adequate personal protective equipment.

The other two memoranda provide critical answers to common questions that nursing homes and hospitals may have with respect to addressing cases of COVID-19.
For example, the memoranda discuss concerns like screening staff and visitors with questions about recent travel to countries with known cases and the severity of infection that would warrant hospitalization instead of self-isolation. 

They detail the process for transferring patients between nursing homes and hospitals in cases for which COVID-19 is suspected or diagnosed. They also describe the circumstances under which providers should take precautionary measures (like isolation and mask wearing) for patients and residents diagnosed with COVID-19, or showing signs and symptoms of COVID-19.

Finally, the agency is announcing that it has deployed an infection prevention specialist to CDC’s Atlanta headquarters to assist with real-time in guidance development.

Today’s actions from CMS are focused on protecting American patients and residents by ensuring health care facilities have up-to-date information to adequately respond to COVID-19 concerns while also making it clear to providers that as always, CMS will hold them accountable for effective infection control standards. The agency is also supplying inspectors with necessary and timely information to safely and accurately inspect facilities.

To view each memo, please visit the below links:


Guidance for Infection Control and Prevention Concerning Coronavirus Disease (COVID-19): FAQs and Considerations for Patient Triage, Placement and Hospital Discharge: https://www.cms.gov/medicareprovider-enrollment-and-certificationsurveycertificationgeninfopolicy-and/guidance-infection-control-and-prevention-concerning-coronavirus-disease-covid-19-faqs-and

Tuesday, March 3, 2020

Very Brief Blog: Decibio updates trends in immuno-oncology biomarkers

Los Angeles-based consultancy Decibio (here) maintains and constantly updates a large database for immuno-onology (their "I/O BioMAP;" here).

See an open-access update from Decibio on three new trends in the I/O biomarker field - online here, released March 2, 2020.  They review data on trends beyond PD-L1, like gene expression profiling and NGS.









Sunday, March 1, 2020

February 29: FDA Emergency Guidance on COVID-19 Testing under CLIA

On February 29, 2019, FDA issued an emergency bulletin allowing high complexity CLIA labs to performed locally developed testing for COVID-19.    The bulletin is here; open access coverage at Genomeweb is here.   See also coverage at MedTechDive, here.  For rapid FDA clearance of a New York State test, Genomeweb here.  For an update at WSJ through March 3, here.

For a March 4 update at Genomeweb, here; for a March 5 update at Genomeweb, here.

Large amounts of LDT high complexity CLIA lab testing is already routine in microbiology, and nationwide, without special permission.  With this bulletin the FDA, I think, is being sure to stay ahead of the policy skirmishes on this one.  AACC provides some backstory.

AACC has a webpage dedicated to coronavirus issues, here.   AACC specifically notes in a February 28 open letter to the FDA that an FDA Emergency Edict had not only allowed certain urgent new rules for approved emergency use [good], but proactively barred any other labs from doing tests outside that rule (here) [bad].  I believe AACC wanted CLIA-regulated LDTs and FDA emergency use tests to proceed in parallel in this urgent period.



____

On Genomeweb, I noted a COVID-19 qPCR webinar scheduled for March 23, sponsored by Co-Diagnostics (Featherstone & Satterfield), here.

Brief Blog: Discordant Ratio of Private and Medicare Payments, for Hospital versus Lab Services

The March 2, 2020, issue of Business Week has an article by John Tozzi and Emma Court that compares statewide hospital prices for commercial payers versus the benchmark of Medicare prices for the same inpatient or outpatient services.

For example, in Michigan, commercial inpatient and outpatient prices are about the same as CMS prices.  Everywhere else, they're higher.  They're 80% higher in NY, but they're more like 300% higher in Indiana.  See graphic (attributed to Rand).

Why?  Well, from an armchair, you might guess that in Michigan, hospitals are fragmented and their is one highly consolidated payer, so the payer gets hospitals to bend to low prices.  You might think that in Indiana, hospitals are highly consolidated, and payers are fragmented, so hospitals can contract to high prices and make it stick.   Of course, any real-world conclusions would require a lot of analysis.

Labs and PAMA

The interesting for labs, under PAMA surveys of commercial payer prices, at least for freestanding labs, often commercial prices were lower than CMS prices, at least in CY2017.

That is, the PAMA data points would be displaced off the left-hand side of the graphic and below the 100% line which is the bottom of the chart.

Suggesting the payer-provider dynamics were very different for labs than for hospitals in most states, vis-a-vis the payer industry segment.

___

From the March 2, 2020, paper issue.  The online version has the same text but not the same graphic I've shown above.  Here. I suspect the underlying source is RAND, 2019, here.

CMS Opens NCD on First FDA-Approved Blood-Based Screening Test for Colorectal Cancer

CMS covers a range of services for screening for colorectal cancer - colonoscopy, fecal occult blood testing by immunoassay, and most recently, the Cologuard FDA-approved oncogene detection test which is stool-based.

2018 payments for Cologuard (CPT 85128) were $170M, about 15% of all Medicare genomic payments [excluding virology; this blog, here.]  However, Cologuard has recently been faulted in terms of cost-effectiveness (here).

On Friday, January 28, 2020, CMS announced it was opening a review of another FDA-approved colon cancer screening test, the Epi proColon test.
  • See the CMS tracking sheet here.  CMS will take public comment on the proposal to review Epi proColon from 2/28/2020 to 3/29/2020.
  • CMS expected to release a draft NCD by August 28, 2020 and a final NCD by November 26, 2020.
    • Epigenomics, the parent company, requested the NCD in April 2019 (here).  
    • This means the duration from from request to final NCD will be about 16 months.
    • BUT: I think it's clear from Epigenomics quarterly investor calls that discussions with CMS began much earlier, closer to its FDA approval in June 2016 and thus through CY2017 and CY2018.
  • See Genomeweb open access summary here.
A substantial proportion of US beneficiaries get no colorectal cancer screening by any method.  A blood test could provide access to screening for those who are not performing the stool tests nor undergoing outpatient colonoscopy.

Other companies are putting blood-based CRC screening tests into large clinical trials, e.g. Guardant Health (here).   Typically, the screening studies survey circa 10,000 patients to have a 1% hit rate (100 patients) with actual colorectal cancer, to allow good statistics around that subpopulation of n=100 who are true positives.

A recent publication, supported in part by Epigenomics, found that while colonoscopy has very high theoretical health impact, at real-world reported adherence rates, other tests such as Epi proColon (methylated Sept9) may have equal or better health impacts.  See D'Andrea et al. 2019 here.




Medicare (Dys)Regulation and COVID-19 Coronavirus testing

Update March 4, 2020:  Pence announces coronavirus is a required essential health benefit under private plans, Medicare, Medicaid: here.

Update March 6:  CMS announced on March 5 it would pay for new U-codes U-0001, U-0002, separately in the hospital outpatient setting details here.

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With a rapidly emerging public health crisis emerging around COVID-19, how does molecular testing engage with CMS policy?    At least some CMS policies appear to be clearly non-helpful.

  • See also a prior blog in which I discussed the promise of genomic approaches to COVID-19 - here.

CMS Bundles All Molecular Infectious Disease Testing in Most Settings!

In hospitals, molecular testing for infectious disease is bundled to the hospital's overhead costs for each patient (e.g. bundled under a Diagnosis Related Group or DRG).   Few people outside of the lab industry or Medicare policy specialists understand the further extensions of this bundling concept, however. 

Dating back many years, CMS also bundles tests performed by the hospital within three days prior to admission, even if the tests were otherwise payable.   Beginning in 2014, CMS bundles all microbiology tests performed in emergency rooms and other hospital-based outpatient encounters (e.g. an on-site or off-site hospital clinic).   The hospital gets a payment for an encounter or office visit, but any lab tests ordered and performed by the hospital get no additional payment.  (The office payments were raised a bit in 2014 to cover average lab costs.)   The only exception is human genetic tests, and a COVID-19 PCR test is not a human DNA or RNA test.

In short, hospitals are on the hook for testing for  COVID-19 and are even incented not to do so, unless absolutely necessary.   Outpatient visit G0463 (hospital outpatient clinic visit) pays about $115 (APC 5012), so ordering multiple $30 to $120 molecular virology tests could exceed CMS's payment for the whole visit, including time, nursing staff, and overhead.  Doctors would be highly disincented from ordering a viral pathogen screen for $142 (87631) if the whole payment from CMS is only $115 all-inclusive.

MolDx Policy L37713 Provides Very Limited Coverage for 
Office-Based Molecular Virology

About 30 states participate in the MOLDX policy system for molecular testing.  Policy L37713 covers molecular virology for respiratory disease, but only in the "free-standing" setting - not in the hospital inpatient setting, or emergency room, or hospital outpatient clinic (due to bundling as just explained).

Policy L37713 has very narrow coverage for any molecular testing of respiratory illness in Medicare outpatients, a position that drew stormy comments from a range of US associations, including American Society for Microbiology, Infectious Disease Society of America, and other leading organizations.   The policy and the range of association disagreements are placed in a cloud zip file here.  Net-net, when multiple pathogen and multiple pathogen testing is required, it's generally not paid for by CMS.

In L37713, CMS focuses on identifying viral illness only when a specific antiviral drug is available.  When a specific antiviral drug is not available, CMS states that the need for identify the causative organism is minimal ("viruses cause most respiratory infections, so the diagnostic role of laboratory investigation is limited.")  Specifically, monitoring outbreaks to identify the cause of the viral pneumonia and improve early detection is "not a Medicare benefit."

It appears that if or when adding coronavirus drives a test order from 5 to 6 viral pathogens, it becames unpayable (payment falls from $142 under code 87631 to $0 under code 87632).

AMA CPT Coding

Infectious agent DNA/RNA probe detection runs generally from 87471 forward.  In a nutshell, for tests for viruses not yet codified by name, payment per test is low and inadequate.  Options include 87797 (direct probe, per organism), 87798 (amplified probe, per organism), and 87799 (quantitative DNA/RNA probe, per organism.) CMS pays $30, $35, and $43 respectively.   There are test codes for multiple unique concurrent respiratory viral tests (87631 3-5 targets, 87632, 6-11 targets, and 87633 12-25 targets) which pay $142, $218, and $416, but these are generally not paid by CMS (except for 87631; for rules, see LCD zip file listed above). 






Coronavirus COVID-19: Urgent need to explore the precision medicine component?

In cancer, we take it for granted that as few as 1-2 percent of patients may have distinct responses because of distinctive genomic patterns - such as lung cancer patients with ALK or ROS-1 driver mutations.

In SARS, we read that the mortality rate is around 1-2%.   The press is attributing this to generic cofactors - age, concurrent illness - but there is some risk this may be "satisficing" - stopping when we hear the first  reasonable explanation so we can move on to another question.  The first possible or even probable explanation isn't always right, however (for data on COVID-19 and age, here, here.)

According to Chen et al. in Lancet - who studied a hospital population, pre-selected for severity - of 99 patients observed for a month, 11 developed multi-organ failure and death (here).   WHO guidelines emphasize that terminal care may shift to the management of sepsis and septic shock (here).   In the earlier SARS crisis, reports of coinfections appeared (e.g. Gu & Korteweg, Am J Pathol 2007, 170:1136, here.)

It's been known since 2005 that respiratory coronaviruses can induce "hyperattack" immune responses which may be fatal - e.g. Perlman & Dandekar in Nature Rev Immun 5:917 (here).  Popular sources summarize this in 2020 as, "coronaviruses can spark a viral-induced fire through many of a person's organs" e.g. here.  An academic journal in 2020 remarks, "immunopathogenesis [in coronavirus] is associated with an immune response that is out of control" (e.g. Li et al., J Med Virol epub here.)

The facts that children are unlikely to get severe COVID-19 disease and men are more likely to die than women also suggests that subtleties of immune regulation and dysregulation are important.

Possible Precision Medicine Aspects of COVID-19: Things We Can Do Now

Molecular pathology can make many contributions to understanding the mortality pathways of the COVID-19 virus, besides access to rapid viral identification.

Do HLA or Other Innate Genomic Factors Raise the Odds of a Crisis Response?

Possibly.  Some review literature points in SARS to some reported high odds ratios (4 and higher) with some HLA genotypes (see Sun & Xi, 2014, book chapter, here).   An HLA receptor class 1 antigen can service as a receptor for some coronaviruses (Gralinski & Baric, J Pathol 2015 235:185, here.) although COVID-19 is thought to bind to the same angiotensin (ACE2) receptor as SARS-CoV (del Rio, JAMA 2/28, here).   In any case, we should also look beyond the main HLA associations and look at other genomic factors contributing to the dysfunctional immune response - we may find something much more specific than generic contributing factors like age or heart failure.

Genomics of Host Response

See an excellent open access paper by Gunsolus, Sweeney, et al., in J Clin Microbiol 2019 (here).   In a prior article (Sweeney et al., Crit Care Med 46:915, 2018, here), Sweeney and colleagues discovered and categorized three distinct molecular categories of host response to sepsis.  Each has different implications for etiology and novel immumodulatory interventions.   Potentially, patients developed a septic shock pattern after COVID-19 fall disproportionately into one of these categories, in a way that will be important to identify.

Do Coexisting Passive Infections Raise the Odds of a Crisis Response?

Another factor could be coexisting and otherwise passive infections.  (See assertions that healthcare workers do worse; here.)   One approach would be to sample the blood microbiome of patients with mild cases of SARS and looking for distinguishing associations with those who develop a fulminant COVID-19 syndrome with multiorgan failure and sepsis.   The blood microbiome can now be screened in non-selective (broad-band) ways by next-generation sequencing (e.g. one example is the commercialized Karius Test, Blauwkamp et al., 2019, here.)

Another approach would be to take patients already in multi-organ failure and sepsis and use blood microbiome screening to look for co-infections associated with death.   This lacks the predictive element but is more focused and still informative.


Funding

In a separate article, I discuss the severity of CMS policies for underfunding molecular virology (here).   CMS policies have to change quickly to meet the crisis.

However, venture capital and federal funding is flowing into this space.  Karius raised $165M in February 2020 (here), and Inflammatix (of which Sweeney is CEO; cited above) recently raised $32M (here) plus BARDA funding.