Thursday, January 31, 2019

Very Brief Blog: Reviewing ACA Rules on Voluntary Overpayments from Medicare Part A & B

From time to time I get questions about Medicare's voluntary overpayments rule.  

If you think you have such a situation, you want to talk to compliance experts or e.g. a Medicare/healthcare attorney.  I can give some general layman's background to where the policies are.

Section 1128J of the Social Security Act was added by the Affordable Care Act of 2010 (ACA).   Online here.  (See also 42 CFR 401.305 here).  Stating in part,
In general.—If a person has received an overpayment, the person shall—
(A) report and return the overpayment to the Secretary, the State, an intermediary, a carrier, or a contractor, as appropriate, at the correct address; and
(B) notify the Secretary, State, intermediary, carrier, or contractor to whom the overpayment was returned in writing of the reason for the overpayment.
(2) Deadline for reporting and returning overpayments.—An overpayment must be reported and returned under paragraph (1) by the later of—
(A) the date which is 60 days after the date on which the overpayment was identified; or
(B) the date any corresponding cost report is due, if applicable.
CMS has a fact sheet about this from 2016, here.   The full February 12, 2016 rule is here (81 FR 7654, 32pp).  A law firm 3-page white paper is here.  The section referring to MAC edits of LCDs, NCDs, is here.

Good Cop, Bad Cop

Q&A during policymaking asked if some types of overpayments "not caused by the provider" should be excluded, such as "if the Medicare contractor pays for a non-covered service due to a contractor system edit problem" or "fails to implement a national or local coverage decision correctly."  CMS answered that "we disagree" that any of those factors would override the repayment requirement.  81 FR 7657.

Very Brief Blog: Noridian Updates Germline BRCA NCD to Incorporate Restrictions under CMS NGS NCD

On January 22, 2019, Genomeweb published an article that Palmetto MolDx germline BRCA testing LCDs were being updated to include references to CMS NCD 90.2, on NGS testing in cancer, which could be interpreted to block germline testing in Stage 1/2 cancer patients.   I had pointed out this issue related to a Palmetto MolDx LCD revision on January 1, 2019 (here).

This week, the Noridian MAC contractor, which handles Mountain and West Coast states, published the same revision to a mirror LCD.   See revision to LCD L36163 here.

The revision includes a header section reference to the NCD ( ^ "National Coverage Determination (NCD90.2): Next Generation Sequencing (NGS), which describes the criteria under which contractors may cover NGS laboratory tests for patients with cancer."   Under panel testing, there are some new sentences of text that say that in addition to LCD criteria (e.g. a personal history of cancer), all NCD criteria apply as well.  The NCD directed coverage to advanced (e.g. stage 3/4 cancer) when NGS method testing is used.

Personally, I think the NCD is materially ambiguous as to whether, taken as a whole, germline tested is described as out of scope (here). 

Tuesday, January 29, 2019

Very Brief Blog: AMA Launches 100-page Digital Health Innovation Playbook

For several years, AMA has had committees and workgroups closely involved with digital health issues.   AMA now has released a 102-page "Playbook" as a magazine-style white paper, presenting key questions and choices for bringing digital health technologies to patient care.

See the home page here.   Register with email to get a link to the 102-page PDF.

Less visionary than the 100 page Playbook, see also an AMA 28 page 2018 deck on updates in coding, etc., here.

FDA, Real World Evidence Often Reflects Data from DHealth

On Monday, January 28, 2019, FDA commissioner Scott Gottlieb gave a speech at the Bipartisan Policy Center in DC on FDA's next moves in real world data, real world evidence, much of which may involve mobile health data collection. 

See review at Endpoints, here.  The speech extends the FDA viewpoint for a RWE framework as released in December.

Monday, January 28, 2019

Nerd Note: Medicare NCDs and Effective Date vs Implementation Date

CMS transmittals about new regulations and policies often include both an "Effective Date" and an "Implementation Date."  What's the difference?

If you work long enough on Medicare policy, you'll hear what the difference is, but it's hard to find it written down anywhere.

With a new regulation, "Effective Date" is the date a policy is "effective" and "can be enforced."   "Implementation Date" is a term of art that refers to the date by which CMS Part A, Part B contractors must have edits in place to enforce the policy. 

Where is this written down?   One place is the annual CMS report to Congress about its NCDs for the past year.   Find the 2016 report here


For an example of the terms in use, see CMS Change Release 10878, which was (wait for it) issued on November 30, 2018, describing an NCD policy "effective" on March 16, 2018, and providing an "implementation date" of March 8, 2019.

Click to enlarge:

Thursday, January 24, 2019

Very Brief Blog: Book List CY2018

My fourth annual book list is out, for CY2018.


Discussed are:

Society and Politics
Dreamland. (Opioids in America).
Then They Came for Me: Martin Niemöller.  (German pastor, 1930s).
Hitler's American Friends.  (Pro-German politics in the US, 1930s).
The 2020 Commission.   (Look back on the nuclear war of 2020).
God's Bankers.  (Vatican finance, 1700s to 2000s).

Business, Medicine, Strategy
The Alchemy of Air.   (Discovery of nitrogen fixation; impact on war and agriculture)
The Tangled Field.  (Scientific sociology centered around geneticist Barbara McClintock).
Never Split the Difference.  (Negotiation from an FBI hostage expert).

Memoir and Fiction
Nothing to Be Afraid Of.  (Memoir, Julian Barnes).
Dear Los Angeles.  (Diaries and Letters about LA, 1700s-2010).
Living With Monks.   (Young business entrepreneur goes off the grid for a month)
Dear Committee Members.   (Parody of academics).

Brief Mention
   Farsighted (science author Steven Johnson).  
   The Judge Hunter (light novelist Christopher Buckley).
   Avoid Boring People (James Watson).
   The Square and the Tower.  (Vertical vs flat organization and management in business and society)

Also some off beat film tips for 2018.

Wednesday, January 23, 2019

Very Brief Blog: We Cross 400,000 Hits; My 2nd Adventure with DTC Genetics

This Blog: 1,000 Posts Reached

In the past couple weeks this blog, which started in Febuary 2014, reached 400,000 hits.  (Some readers primary follow by email feeds or readers, which don't count as hits).   The blog also crossed 1000 total posts.

Today: My Second Encounter with DTC Genetics

In November 2018, I wrote a blog about my encounters with COLOR and UBIOME DTC genetics - here.  Mostly, it was a lot of confirmed negatives - my gut flora was "normal" and "had no pathogens;" I had no unusual genes for cardiac and other disorders like potassium channel mutations.

Over the holidays, I sent in a saliva sample for Ancestry and Health & Wellness reports from 23andMe.  Turnaround was  about 14 days.


My known familial history is 50% Irish (all of my dad's four grandparents) and 50% German (or French-German/Alsace-Lorraine; all my mom's four grandparents), all of whom settled in Iowa farmland around the 1880s.

23andMe came up with 80% British-Irish and 20% either French/German or Northwestern European (10% each)

Update March 2019: classed me as: 60% Irish/Scottish and 40% Britain/Northern Europe. 

23andMe classed my maternal haplogroup as J2a1a1 and my paternal haplogroup as R-CTS241, something I'll need to read up on to understand (they provide the reading).   23andMe tells me there are 1,038 potential relatives in their data.


There are 8 parameters: alcohol flush, caffeine consumption, deep sleep, sleep movement, lactose intolerance, genetic weight, muscle composition, genetic weight, "saturate fat and weight."  Most of these flit about "average" with a few "more likely" or "less likely." 

My muscle composition is "common in elite power athletes," but maybe they tell that to everyone.


Of 9 parameters, other than "slight increased risk" for macular degeneration, I had no variants for late onset Alzheimer's, Parkinson's, celiac disease, G6PD deficiency, [common] BRCA variants, or several others.

Since I had one grandparent of 4 with Alzheimer's, I had some concerns.  My academic career was in Alzheimer's research (1994-2001), so I was very familiar with the ApoE4 risk gene and the pro's/con's of test results, as discussed now for several decades.  When the test was actually available in this 23andMe report, I spent about 30 seconds deciding on the click-through to see it.

Other News

For some January 2019 press about 23andMe, usefulness, etc, see here.

Around the time this blog was published, Ubiome laid off 50 of 300 employees to concentrate on "pharma, retailers, and payers" (I guess that's the range of options, leaving out the original DTC business itself.)  UBiome raised $83M in October 2018.

Robust Agenda of 23 PLA Codes for February 2019

AMA is well into its winter quarter cycle for new PLA codes.  Applications were due January 12.  Code proposals are posted for public comment now, January 19-26

The PLA subcommittee will meet privately on the evenings of January 29 and 30 and, if you submitted a code, they ask applicants to be available by phone in case the committee has questions for them. 

In most quarters, the CPT Editorial Panel as a whole convenes very briefly by teleconference to confirm the PLA codes as finalized by the PLA committee.   However, this quarter, that editorial board action is folded into the next AMA CPT meeting, which is February 7-8-9 in Phoenix.

The next PLA deadline for applications will be April 3, then July 11.

See The Names of New Proposed PLA Codes

Read all of the current crop of applicants online at AMA, here.   This form shows the submitted names; some of which conform to the ultimate PLA name rules and some don't.  The committee at AMA will re-write lengthy or non-conforming code names.

Among the 23 applications, there's one for the Accelerate Pheno Test (agenda item 100241).  Accelerate Diagnostics has a market cap of about $900M, although share price is down from $28 to $16 over the past year. 

There are also several proposed PLA codes for FilmArray (BioFire).

Hints for PLA Code Application

The committee prefers concise code descriptors closely matched to the AMA model formats provided (in the application process).   The committee will rewrite an overly detailed Patient Vignette or Procedure Description to be concise (e.g. two sentences each).

Busy July 2019 Crosswalk Meeting at CMS

By my count, before this, there were already 22 new PLA codes (created since August 2018) entering the July 2019 CMS Crosswalk meeting, and this round in February 2019 will bring that number over 40.   Since the future codes from the April 2019 application will be completed by June, there could be over 50, even over 60, new PLA codes for CMS review in July 2019.

Tuesday, January 22, 2019

Genomeweb Publishes Article on CMS's New NGS NCD Interpretation

At Genomeweb, journalist Turna Ray publishes a long-form article on the CMS NCD for NGS testing in advanced cancer, January 22, 2019 - subscription, here

As revealed in January 1 edits to a MolDx LCD for hereditary breast cancer testing in patients with a personal history of cancer, the NCD is being applied to non-tumor testing based on a sentence in a November 2018 CMS transmittal to its contractors.  That transmittal remarks, "A diagnostic laboratory test using NGS is non-covered when cancer patients do not have the above-noted indications for cancer under either national or local coverage criteria."

Read literally, this ropes in NGS tests that are otherwise entirely outside the scope of the NCD, such as infectious disease or hereditary testing - any medical test utilizing a step that involves NGS.   


What Happened?

In November 2017, CMS proposed coverage of the Foundation Medicine F1 CDx test on-label, with off-label indications covered under CED that compared outcomes to on-label combination diagnostics.  The NCD proposal was clearly about CDx testing; the only way you could get coverage, even under CED, was as a CDx tumor test.  In CED, tests like RECIST testing for tumor size response to a targeted drug were required.

In March 2018, CMS provided final coverage to the F1 CDx test, and allowed LDT NGS tumor tests to be covered in advanced (stage 3-4) cancers.   The NCD's didn't discuss infectious disease testing with NGS or hereditary testing with NGS, except for a remark that hereditary testing (e.g. NCCN guidelines Daly et al., on which all LCDs are based) were out of scope of the discussion.

Procedural History

The procedural history actually goes back to 2004-2006.  For a short period the CMS contractor for Utah covered BRCA testing in high-risk women with a heavily loaded family history as well as women with a personal history of breast cancer.  In June 2006, working with the CMS coverage group, a new LCD was designed that covered BRCA testing only in women with  personal history of cancer - e.g. management of their ongoing disease.   (I was working for a carrier at the time, so I knew the story at the time.  Dr. Alton Wagnon was the Utah medical director.  A public article at FORCE from the period is here.  The resulting LCD is here in its 2008 version.)

So CMS Coverage Group specifically endorsed criteria (quite similar to today's NCCN criteria Daly et al.) for BRCA testing in women with a personal history of cancer

The New NCD

There's no question that the new NCD - looking at both the draft and final versions - were intended to focus on NGS somatic (tumor) testing for CDx-type genes and drugs.   As mentioned above, the draft coverage section - which the public was able to comment on - focused on CDx genes and drugs, and required comparison to prior CDx tests, and required CED methods like RECIST tumor size measurement for CDx drug response.   There was no discussion of germline testing in the draft NCD, although the final NCD was edited to state that NCCN germline guidelines were, quote, "out of scope" and to state to the reader that "This NCD does not apply to all types of NGS testing." 

For a painfully detailed discussion of the policy issues, see my January 2, 2019 blog here, shortly after the MolDx LCD was revised.

CMS Covers Same Patient, Same Gene, Same Exon, Same Mutation by Sanger, not by NGS

The most unusual result of the MolDx LCD, as revised, is that it happily covers the same patient, same gene, same exon, same mutation, same purpose, same result, same report, if it is done by Sanger testing but not if it is done by NGS testing. 

As I've been saying since April 2018, this doesn't make sense based on Medicare's legal definition of when services are "reasonable and necessary."   Or, it just doesn't make any sense at all to oncologists, patient groups, lab groups, etc.   There's no price or coding difference.  CMS pays for BRCA 1-2 sequencing under one general code 81162 at the same price regardless of method.

The result also puts Medicare patients out of sync with the conservative but recent 2018 guidelines of the UK NHS genetic services for cancer risk (here).  They treat Sanger and NGS sequencing mutation reports similarly.

When Are You A Patient "With" Stage 1 Cancer?

The NCD is directed to tests "for patients with cancer."   Most women eligible for BRCA testing have stage 1 or 2 cancer, a cancer that is completely removed by lumpectomy or mastectomy.  So after that she no longer has demonstrable "cancer" - no imaging, signs, or symptoms of "cancer." 

So perhaps a post lumpectomy women is being managed for being status post Stage 1 lumpectomy, but she is not, in the literal sense, a patient "with a cancer" that you can point to.   In that case, the NCD doesn't apply to her at all. 

Another scenario would be a patient who had a lumpectomy 30 years ago - is she still a "patient with cancer" for the purpose of the NCD?  Could she have an NGS test for infectious disease, for example?   (Sepsis is a major cause of death in cancer patients, and commercial NGS tests are available, e.g. Karius; another NGS microbiology entrant is Ares.)  At what point does the NCD say such a patient is "a patient with cancer" or when does she stop being a patient "with" cancer?  What dose "with cancer" mean?

Do Small Cancers Block Unrelated NGS Tests Approved under LCDs?

MACs already cover some innovative molecular tests on NGS platforms such as the CareDx Allosure test, testing donor DNA as a sign of graft rejection, and the Veracyte Percepta test for work-up of suspicious lung lesions.

What if a patient eligible for either test also has (or has had) a small skin cancer, or in situ cervical cancer?  Are they disqualified from these two NGS-based tests?  If not, then CMS has stopped reading the NCD literally?  If yes, for how long are such patients "a patient with cancer"? 

Another twist is that when hereditary panels in Stage 1-2 patients are positive, about 5-10% of the time, the mutation may be confirmed with Sanger sequencing before reporting.  In this case, is what is being reported the Sanger confirmation?  Then it's outside the NCD, which only affects NGS reports.


CMS Might Say, NCD Text Drives This Interpretation

CMS might say, the most close reading of the NCD text drives this interpretation and leaves policymarkers no other choice.

I don't agree at all.

There is a body of law and policy going back well over a century to avoid interpretations of policy that don't make sense (to avoid absurdity).   This situation falls well within the scope of "avoid absurdity" doctrine, which I discussed in detail in an earlier blog.   One escape would be to read the internal text of the NCD ("Does not apply to all types of NGS tests" and "Daly et al out of scope") to modify the "header" section of the NCD.

This use of modifying text to implement unclear (or otherwise nonsensical) terms is normal in regulatory interpretation.  For example (discussed in same blog), the CMS regulation about Date of Service (42 CFR 414.500) has special rules for "molecular pathology tests" ...but doesn't define them.   Other CMS sources written later define this to mean only human gene tests, and not microbiology molecular pathology tests.  That is, the later CMS sources modify the words of the regulation.  Definitions inside NCDs can modify the header sections by the same token, especially when needed to avoid absurd outcomes.  We discover a cervical cancer NCD is about gynecologic cancers - not cancers in the "neck," the first dictionary meaning of "cervical" - by reading the body of the NCD or definitions therein.  It would be ridiculous to view such an NCD as applying to cancers in the neck because one was limited to reading only the title or header of the NCD and not the body.

For an Easter egg quirk in the 2008 LCD I mentioned, here.

Monday, January 21, 2019

Very Brief Blog: Two New Articles on Directions for CMMI in 2019

The Center for Innovation at CMS (CMMI) received some blistering criticism from Republicans before the 2016 election (here), underwent a freeze and reboot effort in 2017 (here), and is the centerpiece of Trump's proposal to peg US drug prices to European prices (here).*   Except, maybe, for being struck down with the whole of the ACA by  judge in Texas in December 2018 (here).  And GAO released a critical report, at least regarding CMMI's Obama era projects, in April 2018, here.

The new 2018 director of CMMI, Adam Boehler, had a pretty low profile until a few speeches around August 2018 (here).   

Two New Articles on CMMI

The trade journal Healthcare Informatics opens 2019 with two articles on potential directions for CMMI in CY2019, by Heather Landi, January 11, here, and by Mark Hagland, editor in chief, January 20, here.


* The Trump euro drug pricing idea is tied to the CMMI because CMMI allows the executive branch to waive any portion of CMS law for the purpose of a demonstration program, but doesn't place any restrictions on the size and duration of the demo program (e.g. it could be in 50 states for 100 years...)

Brief Blog: NYT on Whether CMS Readmissions Policy Raises Mortality

When I was working as a physician executive for Accenture about 15 years ago, business operations dashboards, metrics, and key performance indicators were all the rage.   In healthcare, it's outcome measures and process measures.   They can also have unintended consequences.

For several years, there has been debate whether CMS's readmissions penalties improve or hurt healthcare.  The top line purpose is obvious:  to discourage arbitrary readmissions ($15,000,ka-ching!), and to encourage effort in thoughtful aftercare to improve health and make readmissions recidivism lower. 

The downside is discouraging medically necessary readmissions of complex and unstable patients.

This story is featured in a long article today in New York Times by Paul Span (here).  NYT even notes the issue is not "new news" but pulls the issue together for readers. 

JAMA December 2018, Wadhera et al.

The entry point is the Wadhera et al. studied, published in JAMA on December 25, 2018, associating readmissions reduction with increased mortality (here).    An earlier article in JAMA had proposed that 60% of the change in readmissions figures were due to coding-of-severity changes (here). 

In contrast, a June 2018 government MedPAC report (summarized in Circulation by Khera & Krumholz) didn't find an adverse effect of the readmissions policy (here in summary, here in original which is 32 pages of literature summary plus new analyses.) 

Some additional articles on readmissions and unintended consequences here, here, here.  For CMS Hospital Compare, where readmissions rates can be looked up, here.

Friday, January 18, 2019

Medicare's Decision on CAR-T Coverage: No More Than 30 Days Away

It seems like old news, but CMS announced a pending coverage decision on CAR-T therapy on May 16, 2018.  The request to do so came from the Chief Medical Officer at UnitedHealthcare.

Because CMS held a MedCAC - a public advisory meeting - on the topic, they have up to 9 months to issue a preliminary decision.  That decision is due in a month, no later than February 16, 2019.

  • Tracking sheet here.
  • UnitedHealthcare initiation letter here.
  • MedCAC public records, here.
Although the public meeting was webcast (and could have been screen-captured or recorded), CMS doesn't seem to archive the video any more.  However, a 332-page MedCAC transcript appeared about four months after the meeting, in mid December (here).  (The MedCAC turned to patient reported outcomes rather than on the CAR-T therapies themselves; although the NCD request letter was solely focused on coverage issues.  An interesting pivot on the part of CMS planners.)

What will the decision be?  It could be anything from declining to issue an NCD, to issuing an NCD that largely leaves decisions on this evolving topic to MACs, to a granular and specific statement of coverage conditions. 

Dr. Gottlieb at FDA recently predicted a coming boom in the number of cellular and gene therapies, here.   UK NHS approved use of CAR-T Kymriah in adults with in diffuse large B cell lymphoma in adults who did not respond to 2 or more prior treatments (here).  

CAR-T therapies like Kymriah and Yescarta in the $400,000 range are not the most expensive CMS drugs, that may be Luxturna at $900,000 (here).  As a recent article headlines, "reimbursement is complicated," here.

Thursday, January 17, 2019

Very Brief Blog: MolDx Covers Adaptive Biotechnologies ClonoSEQ Assay


MolDx has released a article providing coverage to the Adaptive Biotechnologies ClonoSEQ test.


On January 16, 2019, Monica Heger of Genomeweb published a long-form trade journal review article on the rapid rise of NGS methods for minimal residual disease testing (here).   FDA has a recent draft guidance document for this class of molecular tests (here).  FDA approved the first NGS based test on September 28, 2018, ClonoSEQ.

Article Released Today

CMS generally releases new articles and LCDs on Thursdays, and there's an important one today.  MolDx article A56270 gives coverage for the ClonoSEQ assay.  The article states:
Effective 03/16/2018, molDX has determined that clonoSEQ Assay testing is reasonable and necessary when performed on bone marrow specimens in patients with B-Cell acute lymphoblastic leukemia (ALL) or multiple myeloma. Medicare will pay for a single episode of testing using clonoSEQ in these patients. For a patient with ALL or multiple myeloma in whom clonoSEQ is being used according to its FDA cleared indications and clinical guidelines, it is anticipated that an episode of testing will typically require a baseline assay and 3 follow-up assays. This service should be billed at the start of the episode of testing.
The Article quotes the overlying NGS NCD text that " Contractors may cover up to one test per beneficiary per cancer diagnosis" and thus defines ClonoSEQ utlization as an episode of care (a baseline assay and 3 follow-up assays) that involves internal assays that are parts of one episode test.

Coverage at Genomeweb here.

Additional Sources

The CMS copy of the article is here and a cloud copy here.   ICD-10 codes listed in the article are in the C90.0X series for multiple myeloma and the C91.00 series for ALL.

See a 2018 press release about ClonoSEQ and the Amgen drug Blincynto (blinatumomab) here.  For an early (2016) but open access article on ClonoSEQ applied in B-cell ALL, here.  See the FDA classification order DEN170080 here.  (ClonoSEQ is a sole-source FDA authorized test.)  FDA Technical Summary here.  ClonoSEQ website here. Adaptive's website here.


Nerd notes.

ClonoSEQ is approved for B-cell ALL; despite the recent upgrade to ICD-10 and its "millions" of codes, there is one code for ALL...not specific to B or T cell.  There were almost no differences in ICD-9 and ICD-10 for cancers.

The CMS NGS NCD would cover ClonoSEQ automatically if it were a combination diagnostic.  Although its use is very similar to a combination diagnostic (it's for treating or not treating with a chemotherapy drug), it is not, technically, approved by FDA as combination diagnostic, so its coverage flows through the MolDx decision, not the NCD.

Super nerd note.

The NCD covers testing in "advanced cancer" (and disallows testing otherwise).  There was some question whether a hyper literal interpretation would be difficult for some cancers like leukemia and glioblastoma.  NCD defines "advanced cancer" as Stage III/IV, metastatic (usually a synonym), or recurrent/relapsed.   A new bad leukemia or glioblastoma is not stage III/VI (they don't metastasize, if GBM, and we don't use Stage in that sense for leukemia), and a new case would not be recurrent or relapsed.   Fortunately, CMS has avoided that rabbit hole and simply views leukemia and lymphoma as advanced cancers, per this article.

Wednesday, January 16, 2019

Yes, Virginia, Medicare Would Pay $900,000 For Luxturna (Retinal Dystrophy)

Today, Dr. Gottleib at FDA had a major policy announcement about the coming boom in biotech drugs based on gene and cell therapies (here).  How much staff do we need to approve them all?  How much money do we need to pay for them all?

For its part, how is Medicare handling the pricing of these biologicals?   For two early CAR-T drugs, which are for inpatients, CMS arrived at a decision to classify them as "New Technology Add On Payments" - which means hospitals get paid about 50% of the added cost.  In round numbers, hospitals would buy a $400,000 drug and get extra $200,000 in payment, thus, on paper, losing $200,000 per patient (here, here, here.)

Less notice to gene therapy Luxturna, which has a cost of around $900,000 for two eyes.   You can scout out the CMS payment trail as below.

January 2019 article on Luxturna business model here.   February 2019 article, Roche plans to be Spark/Luxturna, here.

Original article continues:

Luxturna Labeling and Dosage

Luxturna (voretigene neparvovec-rzyl) is a vector-delivered gene therapy approved by FDA in December 2017 to treat RPE65-driven retinal dystrophy (here).   FDA indications for use are here.  It's an ultra-orphan, with 2000 cases in the US.  In clinical trials, no patients were over 65, bt patients might get Medicare coverage below age 65 for legal blindness as a disability.

FDA labeling gives the dose as 1.5 x 10^11 vector genomes, per eye.  That 1.5 x 100 billion, or 150 billion, per eye.

CMS Coding and Pricing

OK.  CMS coded this as "voretigene neparvovec, 1 billion vector genome" as C9032 before December 31, 2018, and as J3398 beginning January 1, 2019.   (In May 2018, the manufacturer asked CMS to amend the text to "per treatment," but CMS left it at "per billion.")

Interestingly, I couldn't find J3398 in CMS average sales price tables for Q1-2019 (I was surprised since it's approved four quarters ago and it's injectable).  However, in the tables for pricing that accompany the CMS November 2018 final outpatient rule for CY2019, J3398 is listed as paid in Ambulatory Payment Category 9070, which pays exactly $2963.289.

Putting It All Together

So we're down to simple math.  150 units x $2963.289 = $444,493.35 per eye, or $888,986.70 for two eyes.  (Note that the copay would be about $178,000.)

For ocular drug injection CPT code 67028, the physician also gets $101.99 per eye.


I don't have a position on the pricing; just sharing the information. ICER, the health pricing think tank, has a page for its voretigene valuation (here, Reuters here).

As of January 16, 2019, the Medicare Coverage Database didn't list any LCDs or articles on correct coding or usage of J3398.  However, a draft LCD (Palmetto, DL37862) was proposed last fall, here and here.


J3398 is not on Q1-2019 injectable drug ASP tables.  Web source here.  Below, note that J3398 is missing.

New Code for 2019:

As of January 16, 2019, the Medicare Coverage Database didn't list any LCDs or articles on correct coding or usage of J3398.

Spark's One Year Share Price:  $50 to $90 to $50.

Nerd Note.

Normally, prices in the physician office are set by ASP (average sales price + 6%).  If I recall Medicare policy, when an ASP is not published by CMS (and I couldn't find it for J3398, for Q1, as described above), the MAC price in the office, the Part B price, is AWP until ASP is set.   But AWP could be 50% or 100% more than ASP.   Hmmm.

Tuesday, January 15, 2019

Very Brief Blog: CMS Slightly Updates Its New 2019 Rules for LCDs

On October 3, 2018, CMS released a major update of its rules for new LCDs and for LCD reconsiderations.  This was a major change (including large deletions) in the longstanding processes found in Program Integrity Manual, Chapter 13, LCDs.  My original article here.

On January 11, 2019, CMS released a minor revision or tweak to this large update.  The new January updates seem minor, but are hard to discern, because all the new pages of text are in "red" (including this week's tweaks).   The new document is Changer Request 10901, Transmittal 854, Released January 11, 2019, with effective date of September 26, 2018 and implementation date of January 8, 2019. 

Find the change document here.

Find the changes in context in PIM Chapter 13 as a whole, here.

The NGS MAC, for example, has updated its websites with rules for the new "LCD Request" process, A56198, here.  A different page of rules is for the "Reconsideration" of an existing LCD, A52842, here.

Some think that with the new instructions, LCDs won't contain any coding references as all (no CPT codes.)  This seems confusing, since most people start with a CPT code, and search on that to see whether there are any LCDs on it.  I'm not sure if I've gotten that correct or not.

Nerd Note!

I found at least one typo.  In the online full chapter (here),  refers the reader to the listing of specialties in a Contractor Advisory Committee/CAC in Exhibit 3. And in the Transmittal, 10901, Business requirement 7.1 states that MACs shall endeavor to have full CAC specialist panels in every state.   But if you go to the separate PDF for all exhibits, Exhibit 3 (which should be a specialties list, like surgeon, psychiatrist, internist, etc) is simply missing.

Very Brief Blog: MSK Paper Highlights Clinical Impact of TMB, Clinical Differences Among Cancer Types

Total mutation burden (TMB) has an increasingly high profile among cancer biomarkers and can be calculated several different ways. 

A new paper by Samstein et al. (Memorial Sloan Kettering) reports findings in 1600 patients over a range of cancer types. 

Key findings include high overall value of TMB as a predictive biomarker of response, but also, substantial differences among cancer types.  Expressing TMB as mutations per megabase, the threshold for decisions may vary considerably among cancers.  They recommend setting different cutoffs based on quintiles for different cancer types.   In addition, Samstein et al. found that above a certain level, TMB's predictive impact asymptotes.
  • Samstein et al. here (Nature Genetics).
  • Coverage at STAT PLUS (subscription), here.  Also Genomeweb (subscription), here.
  • It got coverage at Forbes also, open access, here.
  • Prior landmark paper by Chalmers et al. with 100,000 patients, here.
Harmonization.  A TMB harmonization project is at Friends of Cancer Research, FOCR, here.  Somewhat comically, Genomeweb notes there are multiple different harmonization committees at work in different places, here.  I think my first blog on TMB was about two years ago, here.

Tidbit.  Regarding FDA's position in November 2017, in FMI F1 CDx test paperwork, P170019C, statement that "the clinical validity of TMB defined by this panel has not been established." Here.

Top, Kaplan Meier, TMB levels set "within histology" then recombined.
Bottom, TMB impact flattens out (as hazard ratio) above 15-20.

Forest Plots for whole cohort (top line) and subgroups

Thursday, January 10, 2019

Very Brief Blog: CMS Offers PAMA Tutorial Call on January 22, 2019

CMS has announced a one-hour PAMA Private Payor Rates Call, Tuesday, January 22, 2019, at 2-3 ET.

See the CMS outreach page here.  See the registration page here.  See the registration for THIS call on that webpage, for January 22.

Register for this Medicare Learning Network (MLN) event:

Clinical Diagnostic Laboratories to Collect and Report Private Payor Rates Call
Tuesday, January 22, 2019
2:00 - 3:00 PM Eastern Time

Do you need to submit data required by the Clinical Diagnostic Test Payment System final rule? Laboratories, including physician offices laboratories and hospital outreach laboratories that bill using a 14X TOB are required to report laboratory test HCPCS codes, associated private payor rates, and volume data if they:

  • Have more than $12,500 in Medicare revenues from laboratory services on the Clinical Laboratory Fee Schedule (CLFS), and
  • Receive more than 50 percent of their Medicare revenues from CLFS and physician fee schedule services during a data collection period

This call provides a refresher on how to collect and submit required data. CMS will use this data to set Medicare payment rates effective January 1, 2021.

Email Questions in Advance
A question and answer session follows the presentation; however, you may email questions in advance to with “January 22 Call” in the subject line. These questions may be addressed during the call or used for other materials following the call. For more information, visit the PAMA Regulations webpage.

Target Audience
Clinical diagnostic laboratories, including physician offices and hospital outreach laboratories

Presentation: Available prior to the event
Audio recording and transcript: Available approximately 2 weeks after the event

Very Brief Blog: FDA Issues Recall for Some Foundation One CDx Test Reports re TMB

Update:  This blog appeared 7 am on January 10.  

A day later, on January 11, Genomeweb reported that FMI had resolved the issue (here).  The FMI announcement clarified the error described on the FDA website was related to total mutational burden (TMB) reporting.   


FDA issues innumerable notices on device recalls.   FDA current shows an open recall notice on certain FMI FoundationOne CDx test reports.

Date Initiated by FirmOctober 31, 2018
Create DateDecember 20, 2018
Recall Status1Open3, Classified
Recall NumberZ-0649-2019
Recall Event ID81614
PMA NumberP170019 
Product ClassificationNext generation sequencing oncology panel, somatic or germline variant detection system - Product Code PQP
ProductFoundationOne CDx, Model TG-HS4000 Seq Kit Test  
Recalling Firm/
Foundation Medicine, Inc.
150 2nd St
Cambridge MA 02141-2115
For Additional Information ContactNicole Green
617-418-2200 Ext. 7337
Manufacturer Reason
for Recall
An incorrect test result for a single analyte may have been reported for up to 800 physician reports
FDA Determined
Cause 2
ActionOn October 31, 2108, an outreach program was implemented by Foundation Medicine's Medical Affairs team to advise ordering physicians who received reports of possibility that the relevant reports could contain an incorrect test result.
Quantity in Commerce800 reports
DistributionUS nationwide

Wednesday, January 9, 2019

Very Brief Blog: CardioDx Shuts Down

In a short item written based on SF Chronicle, Genomeweb reports:
CardioDx, a medical diagnostic company that makes a blood test for heart disease, is shutting down, the San Francisco Chronicle reports....Chronicle adds that though the firm's closing appears sudden, it comes after Medicare stopped paying for the firm's test, Corus CAD, in November. One notice posted by the US Centers for Medicare and Medicaid Services argued that the test, which gauges whether patient with chest pain might need additional testing to rule out coronary artery disease, is not medically necessary. "Data regarding its clinical usefulness in elderly (Medicare-aged) patients, particularly males, is significantly lacking in all scientific articles," it said, according to the Chronicle.
The Chronicle newspaper also refers to whistleblower lawsuits.  Article here.

CMS 2016 data for labs and doctors shows CardioDx was paid $1050 for 22,451 tests, or about $23M.  Chronicle states that CardioDx raised in total $297M, including $22M in January 2017, with platinum investors like Kleiner Perkins and GE and Intel.

Medicare had reversed a previous favorable decision after Medicare had been one of the few or major coverers of the test, private insurers generally and major guidelines did not follow suit. As the LCD states, "The Corus CAD test is not included in any professional society management or treatment guidelines."  The LCD also notes the predominance of company-funded, company-authored studies.

Since the company is gone, the LCD L37673, may not be permanent, so I have put a PDF cloud copy here.

Tuesday, January 8, 2019

Very Brief Blog: Decibio Issues Market Report on Liquid Biopsy

With my offices being based in SF and Los Angeles, I frequently have a chance to work with Decibio, a Santa Monica-based life sciences consultancy.  I had a chance to contribute to their new report on liquid biopsy markets both US and world wide, and covering both cfDNA and other modalities like circulating tumor cells.  

Read more about the offering here.

Very Brief Blog: Suzanne Belinson's Shift from BCBS Evidence Street to TEMPUS Commercial Markets

While this is not new-news, last fall Suzanne Belison PhD, the founding director of the BCBS Evidence Street tech assessment program, shift to a commercial Vice President role at TEMPUS, the relatively new Chicago-based genomics lab valued at two billion dollars during a recent $110M round.  Linked-In gives her transfer date to Tempus as September, 2018.

TEMPUS particularly emphasizes its genomic big data and analytics capabilities.   This has been an exceptionally active area in the past week, with Sophia Genetics raising $77M, Qiagen buying N-of-1, and Illumina partnering with PierianDx.

Evidence Street was launched by BCBS in December 2016, just two years ago, as a replacement for the prior TEC (technology evaluation center).*   While TEC generally had assessments available open access, Evidence Street is using a subscription model.   See a Summer 2018 interview with Belinson about her goals for Evidence Street here.

In early 2017, there were published rumors, or announcements, or claims, (which I was always skeptical of) that Evidence Street would formally and contractually assist MolDx with evidence evaluations.  That was never finalized.

Belinson will be a speaker at the Precision Medicine World Conference in Santa Clara, January 20-23, 2019.


* Evidence Street was announced in December 2016, but BCBS filed for the trademark in May 2015.

In digital genomics, above I cited Tempus's fund-raising and new deals concerning Qiagen/Nof1, Illumina/PierianDx, and Sophia Genetics.  Another example is Mayo's collaboration with Nference (the collaboration titled Qrative), announced in late 2017.

Archive of quoted sources here.