Friday, September 20, 2019

Very Brief Blog: ACLA Sends Letter on Pharmacogenetics Policy to FDA

In 2018, FDA then-Commissioner Gottlieb made a number of remarks adverse to pharmacogenetic panel testing, and this ramped up in 2019 with actions against LDT pharmacogenetic testing reports created at the Inova health system precision medicine program.  (Open access entry point here; see also background explained within the ACLA letter below).


On September 18, 2019, the ACLA sent a 4-page letter to the FDA protesting the recent actions as unnecessary and counterproductive. 

  • See the letter here
  • See the ACLA press release here.   

The letter argues that FDA exceeds its authority, provides contradictory instructions at different timepoints or places, and in part makes assertions that "defy common sense."  ACLA also is concerned this is not a good-faith action by FDA at a time when ACLA, FDA, and Congress are working on new legislative frameworks for diagnostics (e.g. VALID act; here, here).


A few weeks ago, AMP released a best-practices statement for pharmacogenetics.  See trade press here, the 3-page AMP statement here.  This policy statement is quoted in ACLA's letter.



The MolDx program releases several PGx LCDs in August 2019 in draft form (here).  In June, MolDx held an information-gathering public meeting on PGx, here.

To my knowledge, MolDx hasn't yet posted its transcript of the June meeting, but I've put a transcript in the cloud here.


On September 18, 2019, ARUP held a webinar on pharmacogenetics, here.  I missed it, but the slides are online.


Bonus - actual word cloud of ACLA letter:

Journal Watch: Growing Businesses Aim to "Manage" Lab Claims & Reimbursement

For several years, Dark Report has published regular articles on the growth of the "Lab Benefit Management" or LBM industry.  Panels on this topic are a regular part of lab industry conferences.  Notably, in August 2019 investor call, Myriad noted that in recent quarters it had lost $50M due to LBM edits (primarily on CYP CPT codes; see also here.)

Currently, in September 2019, see a deep-dive article on test order management as a growth industry in themselves, by Adam Bonislawski at 360Dx.  Article here.  (360Dx is a sister journal to Genomeweb).

Rather than focusing on traditional LBMs, which help payers institute prior authorization, claims editing, and denials, these new companies focus on EHR-based software that review and redirect test orders right during the physician's initial ordering process.  Players include NDSC for its CareSelect Lab, and Medical Database Inc's Lab Decision System or LDS.  See a new open-access publication on the value of LDS by Leblow et al. here.   The 360Dx article also highlights a JAMA article using machine learning to cull low-value lab tests (Xu 2019, here), and discusses the Quest Lab Stewardship programs (here, here), which partner with vendor and AI company hc1 (here).

The industry also builds on platforms developed for radiology medical necessity management ("AUC" or "Appropriate Use Criteria," required in the last couple years by CMS.)

Only Here: 
Collection of Links - and a House Hearing - 
on Prior Authorization 2018/2019

In a separate "Notepad Blog," I've collected about 20 links.  Not specific to the lab industry, I've collated OIG reports, letters to Congress, the AMA Prior Auth Website, and trade journal articles on abusive prior authorization processes.

I've also provided a ZIP file that collates all the documents from a House Small Business Committee hearing this week, including a full-length transcript of that hearing which describes four viewpoints on the high burdens placed on providers by prior auth systems.

See these links here.


Actual "word cloud" of Adam Bonislawski article:

Thursday, September 19, 2019

Public Comments on NGS NCD in June 2019: All Organizations Disagreed With It

On August 26, 2019, Genomeweb's Kelsy Ketchum ran an article on the ongoing issues with the CMS NCD for next-generation sequencing, which purports to create non-coverage for diagnostic domains never reviewed in the analysis.   (Article here; subscription).  I recently argued that this seems to directly violate the statute for how exclusions in NCDs have to be created (see here).

Ketchum's August article is based on the dozens of public comments submitted to CMS at the beginning of summer, as well as additional interviews with clinicians and health policy experts. 

The Timetable for CMS

The NCD is under a slow revision process now, which began with public comment in May 2019 and will take a next step with a CMS revision proposal in October 2019 (tracking sheet here.)   Public comments are available online, but it's pretty tedious to click through one at a time.

Now!  User-Friendly Access to the Public Comment Files

I've made two different collations to dramatically speed up the process and give the clinical and diagnostic community better access to the comments.
  • I've created a 25 page PDF, which brings together some large organization comments, like American Cancer Society and National Comprehensive Cancer Network. I've also included some key documents like Cornell's WSJ op ed in 2018, and the 60-organization protest letter in January 2019.  One-stop shopping.
  • I've also created a ZIP FILE with several dozen public comments, so you can see even more of the original sources.
Letters Did Not Pull Punches

The letters can take some pretty strong positions.  The ACS letter has a header, "CMS's Previous NCD Decision Was Misguided."  Ouch!

Friends of Cancer Research pushed back because of the adverse impacts on frontline therapies, special needs for repeat testing, and value of selected germline testing.  They conclude the scope of non-coverage must be narrowed, and I argued in a separate blog that statutory language requires that too (here).   For either the 25-page view or access to all 100-plus pages of comments, see the first or second links at the bullets above.


My own comment submitted to CMS in May 2019 is here.

Policy Discovery!! Statute Prevents CMS From Issuing Blanket NonCoverage NCDs

By far the most impactful NCD for the diagnostics industry and cancer patients is the March 2018 NCD 90.2, "Next Generation Sequencing (NGS) for Medicare Beneficiaries with Advanced Cancer" - here.

In its original March 2018 form, the NCD provides coverage for FDA-approved diagnostics if they are (1) based on NGS technology, (2) used only once, and (3) used in advanced cancer patients (defined as stage 3,4, metastatic, recurrent, relapsed). 

The original analysis focused only on companion diagnostic tests (e.g. oncogenes like KRAS and ALK), and contained a statement that the scope applied NOT to all NGS tests, but ONLY to tests for prescription of targeted chemotherapies. There was also a statement that "the scope of the review" was limited only to "advanced cancer."  (In total, the phrase "outside the scope" is used 9 times!  Many things were outside scope of review.)

However, and fairly notoriously, in November 2018, CMS issued a transmittal about the NCD that added a section (inserted as ^ "C") that made all services that are not covered by the NCD, nationally non-covered.  See CR10878 (the most recent version of the November 2018 document) at link.

Statute Prevents This Switch

Note that the NCD body (which describes literature search, data review, and scope), repeatedly and explicitly limits the scope to "advanced cancer."  This matches the literature reviewed.  CMS also reviewed only single-use test scenarios.  CMS made germline testing topics entirely out of scope as its review, and the bibliography corroborates this, and the keyword search, and the absence of germline guidelines in the guideline review subsection.

You can't do that and then switch in the decisional section to voiding coverage of all topics never reviewed and not discussed.   See the statute in Section 1862, which is titled "EXCLUSIONS FROM COVERAGE".  (As in the legal rules for "how to" make exclusions from coverage.)  This section defines how and when CMS can (and can't) make exclusions from coverage through NCDs.

In particular, Congress instructs CMS (text immediately prior to 1862(b)):
"In making an NCD, [CMS] shall ensure that...[CMS] has considered applicable information with respect to the subject matter of the determination AND, in the determination, provides a CLEAR STATEMENT of the basis of the determination, AND make available to the public the data considered in the determination."
What this means is really simple.

The CMS determination of an exclusion to coverage MUST be made based on applicable information AND the data used must be public (and part of public comment). 

Since CMS didn't consider germline data in the review (it deliberately excluded it; read the body of the analysis), OR any multiple-use tests, OR any tests in less-advanced cancer (e.g. even neoadjuvant therapy with Herceptin based on Her2-neu positivity, an on-label use of the FMI NGS test, was excluded from review), the "determination" that rests atop the CMS "analysis" ... can't deal with those subjects.  Graphically as follows:

click to enlarge

The rules CMS must follow when issuing an NCD exclusion from coverage.


An analogy would be an NCD analysis that studied aortic valve repair, and reviewed the literature on aortic valve repair.  Thereupon, the determination following this analysis - to be legally compliant with statute - could cover, or non-cover, aortic valve repair technology.   But it could not non-cover all other cardiac services (for example, CABG or stents), which weren't part of the review or offered to the public as data and CMS rationale.  It's not only that this makes sense; but it's also directly written into Medicare law as shown in this article.

Similarly, for the NGS NCD, the scope of the determination must rest upon the scope of the data analysis and the clearly stated scope of the review.  The statute requires it, in black and white.

It's my understanding that CMS has said, what we say or remark in the analysis doesn't matter, the decisional part of the NCD is only the "determination" (if the two contradict in scope).  But no.  The determination MUST rest on the scope and content of the analysis, as statute requires.

Thursday, September 12, 2019

Very Brief Blog: CMS Ups Its Game on Opioid Crisis; Sets Up Town Halls and RFI's

CMS should be commended for several current actions it's taking to gather community information, best of breed practices, and new ideas for handling the opioid crisis.   The portfolio of events are related to SUPPORT Act Section 6032 - here.  See also the May 2019 HHS Action Plan, here.
  • Public Meeting.  On September 20, 2019, CMS is hosting a full day public meeting in Baltimore on the topic, agenda here.
  • Listening Session.  CMS will hold a "Listening Session" on defining and managing "outlier prescribing," here.
  • RFI.  CMS has released a very well-designed and broad-ranging "request for information" (RFI) on new ways to handle the opioid crisis.  Comments are due by October 11, 2019.  Here.

The RFI is worth reading; it's a model of its type.

Why Not an RFI on Sepsis, Antibiotics, Diagnostics?

Recently, CMS has been criticized by a low level of impactful activities on the antibiotic crisis (e.g. here and here.)   While Seema Verma, the administrator, recently wrote an article on CMS's activites in that area, it would be ideal if CMS would reach out to the community for really innovative ideas on antibiotics, diagnostics, infection, sepsis, similar to the opioid RFI above.

Very Brief Blog: BARDA Industry Day October 15-16, 2019

BARDA is the innovative and important biotech defense agency.   I've had several contacts with them in the last two years and BARDA has very impressive and proactive management.   BARDA regularly funds medical diagnostics related to sepsis and pathogen identification (see for example LexaGene here, Inflammatix here).   BARDA also supports the CARB-X industry-government partnership (here).

On October 15-16, 2019, BARDA hosts its industry days, at the Hyatt in Washington.  I attended last year and it was extremely interesting.  Registration is free; it's a big event (many hundreds of attendees) and may become fully booked as the event draws closer.  See web pages and registration here.

More About BARDA

See BARDA at Wikipedia, here.

Other Infection and Sepsis News

In other news, Friday, September 13, 2019, is World Sepsis Day, here.   For example, Thermo Fisher has a whole range of webinars and activities in September, here.     See Sepsis Alliance, here.  German Sepsis Society is currently holding its annual conference in Weimar, September 11-13, 2019, here.    ID WEEK will be held in Washington, October 2-6, 2019 - here.    Stay in DC for BARDA, October 15-16, as above.

If these topics are of interest to you, see CMS administrator Seema Verma's article in Health Affairs on CMS and antibiotic resistance, here.  (Last year, Pew Foundation called on CMS to do more, here; similar theme at APIC here.*)  Joint Commission also works in this area, here.  You may also want to track the President's Advisory Council on Antibiotic Resistance, PAC-CARB, here, and the HHS new 2020-2025 5-Year-Plan for antibiotic resistance.   See also the topic page at World Health Organization here.

DISARM Legislation in Congress

Also in Washington, this fall Congress is considering the DISARM Act, which would provide hospitals special payments for special-class antibiotics if the hospital (A) has an approved antibiotic stewardship program, and (B) contributes data to a CDC big data program on antibiotics and resistance.   Articles here and here.



* Along the theme of CMS doing something creative to push forward antibiotic management issues, I noticed that CMS just released an open-ended public request for comments and ideas on how CMS can better address opioid management.   (Here).  From my observations, it would be a good idea if CMS also did a parallel community-wide request for idea - request for information, RFI - on antibiotic management. 

Tuesday, September 10, 2019

New CMS-Funded Study Faults Cologuard Cost Effectiveness and Life-Years-Gained Effectiveness

On September 4, 2019, PLOS One published an open-access study by Naber et al. that is highly critical of the clinical effectiveness (life-years-gained, LYG) and the cost-effectiveness ("worse than any other method") for Cologuard (CPT 81528, $512).

See the paper here.  For trade news at 360DX, here.  360DX discusses potential flaws in the study; I'm not an epidemiologist and I'm discussing the study as-is.  I did notice (see also 360DX) that the costs of a Medicare colonoscopy were significantly underestimated by the authors.  See an Exact press release here; an article in MedTechDive here.

The paper is funded by HHS/CMS grant to the Mitre Corporation, but there are no Mitre authors listed.  Authors are from the Netherlands, Univ MN, Kaiser, RAND, MGH, MSK, etc.

In a key table, the authors find that a Cologuard-managed population would have 30 CRC cases and 8 deaths.   However, an FOBT poulation would have 25 cases and 6 deaths, a FIT population 27 cases and 6 deaths, and a colonoscopy population 9 cases and 2 deaths.   While the Cologuard population would have 79 life years gained per 1000, nearly all the other methods would have more LYG than that.

Authors report that Cologuard could be a dominant cost-effective strategy if cost was reduced to about $10.

CMS Asked About Cost-Effectiveness Rates

The introduction states directly that CMS requested the analysis, asking whether Cologuard was a cost-effective alternative, and if not, at what reimbursement rate or screening interval Cologuard would be cost effective.


The paper explicitly describes how the Cologuard rate was set (by crosswalking; 81315+81275+82274), a 2016 rate at circa $500 that was minimally changed by PAMA surveys in 2016 and rate setting for 2018-2020.


Note that in addition to the 20-page PDF publication, there are a number of supporting figures online, inline with the web text.

See also references to Ladabaum & Mannalithara, ref. 46, Gastroenterology 2016 151:427.


Cologuard was the highest-line-item cost in the CMS molecular payments for 2017, table:

click to enlarge

(Note in the above table, while we hear about 200,000 or 300,000 genetic tests, or 5000 new genetic tests per week, just four familiar codes captured over 50% of CMS spending.)


Lab tests for CRC in 2017 at Medicare Part B were:

click to enlarge


In Statute, at 1861(oo) and (pp)Medicare's add-on line item benefits for preventive prostate testing (which have never been used) include cost effectiveness; for colorectal preventive testing, they do not (here).  When preventive benefits are added after USPSTF approval, cost may be considered.


Over two days, Exact share price slipped about 12% (122 to 106), a market cap change of about $1.5B.


Note that there are two required levels of compliance with fecal testing.  One is whether the test kit is ever used and returned (the ick factor).   The second is, when you have a positive test, do you advance efficiently to a colonoscopy to investigate (the oh-no colon prep factor and the day-lost factor).

Monday, September 9, 2019

Brief Blog: Understanding Concert Genetics' Two New White Papers on Genetic Coding Mess

Concert Genetics, a consultancy in Nashville, is currently hosting the annual Genetic Health Information Network Summit (GHIN Summit, September 9-11, 2019) - here.  Concert Genetics is well-known for its series of white paper on the U.S. genetic testing industry, volume, test types, and code mapping.

This week, they've also released two important new white papers on genetic coding.   I'll summarize briefly.

  • For Concert Genetics home page, here.
  • For white papers, here.  
    • A prior Concert Genetics white paper cited in Congressional testimony, here.
    • For some peer-reviewed papers Concert has written or collaborated on, here.
    • Patent, Systems and method for tracking...diagnostic testing products, here. (Cited in WP#1).
  • For blog, here.
  • For Variability in Coding white paper (#1), here.
  • For Coding Solution white paper (#2), here.

White Paper #1 - Variability

Working with a database of 35M claims and 2M genetic tests, Concert categorized by test type (for example, tumor testing, cancer risk testing, carrier testing.)  
  • Within each category, there was huge variability in coding and pricing.   
  • Those categories with the highest variability in coding had highest variability in pricing.

White Paper #2 - Coding Solution

We're all familiar with correct coding principles, some (brief ones) found in the CPT handbook, some in Medicare documents (Correct Coding Edits), some unwritten, some in payer articles, etc.   What Concert proposes is to have one uniform, systematic set of rules that are always applied as algorithms.  They are commonsensical (if there is a PLA code, use PLA code.  If there is a fit to a GSP code like Hereditary Breast and Ovarian Cancer, 81432, then apply that.   If there is a Tier 2 code, then apply that; and so on).   

It's different than today's coding because, while there is a dream that all human coders will code correctly and the same, here, a computer (or a human following iron-tight rules) will always reach the same result.   
Let's apply the idea to a dictionary.  We want to categorize the words in a dictionary.  First, categorize as English vs foreign.  Then, second, categorize as A-L or M-Z.  Then, third, categorize as one syllable, or two or more syllables, etc.   You'd have a rule set that could categorize any word, even words it hasn't seen before.  Same idea here, but for genetic coding.


One is is special rules.  Medicare MACs may have special coding rules they insist be applied (although sometimes this collides with payers; Myriad 2019 case here.)   Medicare has national special coding rules (Correct Coding Edits), although sometimes CCI rules are bizarre, as the industry has complained about some 2019 genetic coding rules therein (here, here).   MolDx has a "Test Panel" coding rule, which is dead-simple to state, but public data shows that Noridian is unable to consistently apply it.  Concert plans to have one uniform set of rules, limited in number, applied in specific order.



While it is common to hear of the 100,000 or 200,000 genetic tests, in 2017 Medicare data, 72% of volume was driven by only 10 codes.  Most of this was concentrated in the top 5 codes alone. 

While the top 5 codes did include 81479 (unlisted code) at 18%, if you went inside that unlisted code, most of the 81479 volume was driven by a few tests like Myriad Assurex Genesight, which is about half the 81479 volume.   (And almost all of the 81479 billing comes through the MolDx states, zero elsewhere).   In short, CMS data shows heavily concentrated use of a few blockbuster genomic tests.

Friday, September 6, 2019

New LCD Rules 2019: A Flow Chart View

For 2019, CMS posted new rules for the Local Coverage Determination process, the first substantial update since the 1990s.

The CMS rulebook for MACs is online (called Program Integrity Manual, Chapter 13, LCDs).  Find it at CMS, here.

However, it can be confusing to understand what is the same and what is dropped or wholly new.   I've tried to show major features of the old and new process in two slides. 

The PPT slides are open-access in the cloud here.

Old Process 1990s-2018

New Process 2019 Forward

New features include:
  • Special rules for asking for an "Informal Meeting," which MAC can grant at its discretion
  • Special rules for applying for an LCD ("New LCD Request" rules) such as "stating the benefit category"
  • MAC must acknowledge it has received, validated, and queued the LCD request, but there is no timeline for further action.  MAC should NOT say if it views coverage request favorably or unfavorably.
  • CAC meeting is OPTIONAL
  • CAC meeting may be PRIOR to any LCD, as "information gathering" for the MAC
    • MAC controls agenda, speakers, etc
    • CAC must be an open audioconference with later transcript
    • CAC meeting may be multi-MAC
  • New LCDs, LCD restriction, LCD expansion must *all* go through public process
    • This is a big change in regard to LCD expansions, which were formally quick online edits.
  • Draft LCD must be killed if not finalized in 1 year

Expect the process to take a full year. 

Example:  MAC request from stakeholder in January, with publications.  MAC holds informal meeting in February.  MAC holds CAC meeting in May.  MAC writes draft LCD in June.  Draft LCD circulated to CMS in July (in case CMS has any questions).  LCD draft posted in August.  Public meeting in September.  45 day comment period to November 1.  MAC reviews comments in November, December, January.  MAC posts revised LCD in February, effective April. 


All draft and active LCDs are in an online CMS database, here.


There was a CMS press release on the changes in October 2018, but frankly, I found it more confusing than helpful and it discussed a "faster" process which I can't see in the real world.  Here.

Thursday, September 5, 2019

Very Brief Blog: AMA Publishes Detailed RUC Minutes

Here's something new.   AMA conducts elaborate meetings of its RUC (relative valuation) committee, passes those recommendations to CMS, which heavily influence the assignment of CMS values and pricing to CPT codes. 

Very lengthy minutes are left behind online.   The RUC Minutes home page is here:

This either requires no registration or an email registration.  For example, the May 2019 RUC minutes are 376 pages of detail:

Separately, through the AMA Store, AMA sells online annual subscriptions for $320 to the RUC RBRVS Database, which gets you into definitions, RUC decisions, valuation, and utilization of every CPT code.   Search AMA Store for "RBRVS Data manager Online."  (One version here.)

After CPT meetings, with a delay of a few weeks, AMA publishes a brief table whether each code agenda item was approved, disapproved, or tabled.  AMA calls this "Summary of [CPT] Panel Actions."  See here.  May 2019 is here.

Finally, if of interest, an AMA CPT confidentiality statement sample is here.  It's aimed primarily as protecting AMA CPT copyright interests.

Genomeweb Joins Crain Communications

Rare is the day I don't see the Genomeweb website twice, and that's been true for about ten years.  Today, Genomeweb's CEO, Bernadette Toner, announced that the company has been acquired by Crain Communications.   "Operations and staff will remain unchanged."   According to Wikipedia, Crain has about 30 publications and 850 staff.   They've owned Modern Healthcare (for the hospital industry) since 1976.

Genomeweb recently diversified into three websites, with some shared stories, being (1) the original Geneomeweb, (2) 360DX (focused on the clin lab industry) and (3) Precision Oncology News.

Wednesday, September 4, 2019

Very Brief Blog; AMP Holds Molecular Pathology Economics Summit, Washington, 9/20/2019

The Association for Molecular Pathology is holding a Molecular Pathology Economics Summit in Washington, DC.   It will be on Friday, September 20, 2019.

The AMP website for the conference is here.

I've clipped partial information on the conference as text below.  At bottom of this blog, I mention a few other coming precision medicine events.

AMP September 20:
Molecular diagnostics is a rapidly evolving field with frequently changing standards for care that challenge the current paradigm for coding, coverage and payment. The Association for Molecular Pathology (AMP) is bringing together stakeholders across the healthcare spectrum in a one day summit with the goal to establish shared opportunities to improve the molecular diagnostics economic landscape.  
Attendees will participate in guided discussions to identify barriers to appropriate reimbursement for molecular pathology procedures and then explore and have the opportunity to propose solutions to critical challenges that are limiting full realization of the possibilities offered by precision medicine. The Summit will connect experts across multiple industries and professional arenas harnessing the collective effort to advance the national dialogue towards improving patient access to appropriate molecular diagnostic care. 
AMP’s Molecular Pathology Economics Summit will be a highly interactive one-day gathering focused on:
  • Identifying barriers to appropriate reimbursement for molecular pathology procedures;
  • Identifying the impact of these barriers on various stakeholders and patient access to care; and
  • Identifying potential solutions and/or novel approaches to overcoming barriers, with a goal of identifying shared policy agendas for the participating stakeholders in oncology, infectious diseases, and inherited conditions
Date: September 20, 2019
Time: 8:00am - 3:30 pm Eastern
Location: Conrad Washington DC, 950 New York Ave. NW, Washington DC, District of Columbia, 20001


A few other upcoming conferences include a trendy health modernism conference called HLTH, October 27-30, 2019, at MGM Las Vegas - here

Precision Medicine Leadership Summit (I am a speaker) October 10-11, 2019 in La Jolla, here

The 25th Annual AMP Meeting is November 7-9, 2019, in Baltimore.  Here.

The 15th Annual PMC Conference at Harvard is November 13-14, 2019, here

Brief Blog; Ubiome Files for Bankrupcy

According to the WSJ and other sources, on September 4, 2019, UBIOME filed for bankruptcy, suspended operations, and put its assets up for sale.  Story here.  Business Insider  open access, here.  Forbes here.

In particular, the company had prior raised $83M from some leading investors.  For an investigative story had Business Insider (subscription), Erin Brodwin, in August 2019, here.

Some additional press.  Exconomy, "UBiome Founders May Have Misled Investors," here.  From back in September 2018, exactly a year ago, "uBiome Jumps Into Therapeutics with $84M in Series C," TechCrunch, here.

I was briefly quoted in a WSJ story on the case, back in June (here).  I had discussed my experience with consumer testing at COLOR and at UBIOME in December 2018 (here).  I also posted some redacted multi-thousand-dollar bills that UBIOME sent to my insurer, after I had paid for the DTC test by credit card originally.  (May 2019, here.).  A teledoctor I had never heard of (NPI '768 in California) had ordered my test in the background before the Ubiome bill went to the insurer.  The insurer entirely rejected the claim.