Sunday, April 30, 2017

Brief Blog: Three New Popular Books on Genetics

The last several weeks have seen publication of three popular books on genetics and the genetics industry.

In The Gene Machine, Bonnie Rochman surveys how genomics - such as Ashkenazi and expanded carrier screening (here, here) and NIPT - are influencing family planning decisions.   Companies like Counsyl are profiled.   In Mercies in Disguise, experienced science journalist Gina Kolata profiles a family with the rare, fatal adult onset neurological disease Gerstmann Straussler Sheinker Syndrome.  In The Family Gene, Joselin Linder describes her family's battle with an N of 1 genetic disorder causing liver failure - known as a "private mutation."  

  • Amazon hotlinks to Gene Machine, Mercies in Disguise, and The Family Gene.
    • All are available as books and ebooks; Mercies and Family Gene as audiobooks too.
  • NYT review of Mercies in Disguise and Family Gene, here.  Gene Machine reviewed here.
  • Gina Kolata describes how she wrote her book, here.

Friday, April 28, 2017

Brief Blog: Cost Effectiveness of Gene Panels in Familial Breast Cancer

In women who have an elevated risk of breast cancer, USPSTF recommends genetic counseling to consider testing for the BRCA1-BRCA2 genes.  (And HHS guidance views the genetic testing as a USPSTF-endorsed and copay-free preventive benefit).  That's the solid ground.

Two additional topics are: 
  1. Whether to extend genetic screening to women without a high-risk family history.  
  2. Use and cost-effectiveness of gene panels for a range of breast cancer risk genes.
The second topic is addressed in a new study.

In a study in Value in Health,  Li, Devlin and colleagues report that gene panel screening is cost effectiven, with costs/QALY well in the $20,000-70,000 range used for other therapies.  See Li et al. here.  The costs/QALY for gene panels were also well in the range used for screening mammography (e.g. see Pataky et al., 2014, here).   Coverage of Li et al. at Genomeweb, here.

Devil in the Details - Turning Devlin's Analysis Upside-Down

The authors state that they took costs for BRCA testing (and mammography) from the 2015 CMS fee schedules.  The cost "for the seven gene test was provided by Quest diagnostics."  The BRCA test was scored at $2178 ... and the cost of the seven gene panel as $2178 +$210 (see Devlin's Table 1, Costs [2015 US Dollars].  

However, if you use 2017 Medicare fee schedules, Medicare prices BRCA panel testing at only $932, or alternately about $1400 in states that pay for extra dup-del coding (MolDX states block payment for extra dup-del coding).   

Therefore, if you used actual Medicare panel pricing approaches, potentially the panel testing would be a savings of about $1200, literally the opposite direction than the add-on cost of +$210 over BRCA alone, carefully modeled by Li & Devlin.

Alternately, one could argue that open market available panel prices for breast cancer panels are advertised at $1500 or less, not at prices greater than $2100 for BRCA alone.   I wrote a blog about this earlier this spring.

Wednesday, April 26, 2017

Duration Required to Release an LCD After Its Comment Period

CMS requires MACs to provides links to CMS databases for current LCDs, for draft LCD under review, and for future effective LCDs.

I pulled data for Jurisdiction F.  Currently 6 LCDs are in "released to final" status, meaning edits have been completed following a comment period.   The interval from comment period closure to release was 92 days (four out of six LCDs), with outliers at 77 and 221 days.

Jurisdiction 6 also has 22 LCDs in draft status for which the comment period has closed.  For 14 LCDs, the comment period closed very recently (usually April 10).

Eight LCDs are now in "comment review limbo," with 8 under review for 132 days (about four and a half months) and three under review for about 250-400 days (about a year).

Eleven of all the LCDs are MOLDX LCDs.

Excel here.  Raw data online here.   Picture, click to enlarge:

In the picture, NRTF = Not Released to Final.
The meaning of RTF is left as an exercise for the reader.

The Impact of PAMA on Molecular Codes Currently Unpriced by CMS

Since the new molecular coding system was introduced in 2013, CMS has priced each year's new codes by the crosswalk or gapfill method.  However, until 2016, CMS left many of the molecular codes unpriced.

Beginning in 2016, CMS began a new policy of pricing every new molecular CPT code, whether it was used by Medicare or not.  For example, the genetic code for Ashkenazi carrier screening was priced by CMS at about $600 (81412) in 2016.  What data CMS used to set this price is unknown (it was gapfilled, so only a gapfill price result exists).

PAMA requires labs to submit commercial pricing data to CMS in 1H2017 (for tests performed in 1H2016), and CMS is to calculate median prices per test to reset its national fee schedule in 2018.  While this process is running late, and might stall-out altogether, it's interesting to note that it would convert a bevy of legacy unpriced codes to priced codes.

Details after the break.

Monday, April 24, 2017

MolDx announces new Medical Director, Dr James Almas

On April 20, 2017, the MolDX program announced Dr. James Almas has joined as a Medical Director.   Dr. Almas is a board-certified pathologist who has also served as a medical officer with the CMS coverage group in Baltimore.

The MolDx announcement is here.  Dr. Almas' Linked-In is here.

Very Brief Blog: When will the July 2017 CLFS Meeting Be?

Each July, CMS holds a public meeting for discussion of pricing issues for new CLFS codes.  For the past two years, the meeting has also included a public session of the PAMA Clinical Laboratory Advisory Panel (which also discusses new code pricing recommendations.)  Webpage for these meetings is here.

Occasionally, CMS has locked and announced the July date as early as the first quarter.  This year, it's almost May and we don't know yet.

Here's for the betting person:

2016: July 18, 3rd Monday
2015: July 16, 3rd Thursday
2014: July 14, 2nd Monday
2013: July 10, 2nd Wednesday

With that landscape, looks like the 2017 date will fall between Monday July 10 at the earliest and Thursday July 20 at the latest.  ...When it is announced.

Friday, April 21, 2017

Brief Blog: S. 794: Legislation for LCD Process Clarity

LCD Legislation Re-Introduced in New Congress

"Local Coverage Determinations Clarity Act of 2017"

In both 2016 and 2017, legislation supported by AdvaMed has been introduced which would improve the clarity and independence of MAC LCD policymaking.

For the text of 2017's S.794 bill, see here.  For a 2017 press release, here.  For 2016 trade press, here.

Introduction was by Sen. Isakson of Georgia.  Full text of the legislation is also cut/pasted below the break.  The bill would largely implement in statute guidelines that are already on the CMS website, but would carry "force of law."  There are currently 8 MAC companies making policies for 12 different CMS Medicare geographies or jurisdictions (here).

S. 794 requires:
  • Publish LCD proposal, PLUS a written rational and description of all evidence relied upon.
  • Within 60 days, convene a public meeting, receive public comments, and use an expert panel (as now exists; the "CAC" panel).
  • Post a record of meeting minutes within 14 days.
  • Provide for written comment as well.
  • Provide a response to all issues raised and finalize the LCD, adding descriptions of any additional qualifying evidence.
  • Effective date "not less than" 30 days.
  • A MAC may not finalize an LCD that applies outside its geographic area, and if importing an LCD, the new MAC must independently "evaluate and consider the qualifying evidence."
  • A specific CMS ombudsman for LCD disputes is to be appointed.
The bill also makes some small modifications to the existing LCD definition and reconsideration process.  For example, during reconsideration, the MAC must consider if it "did not apply or inaccurately applied" the relevant evidence.

After the break, I walk through the bullet points with comments in regard to current policy, and then provide a cut/paste of the legislation.
Note that the changes in S.794 are much larger than a few sentences about LCD process clarity that have already appeared as Section 4010 of the 21st Century Cures Act.   
Those sections are effective as law in June 2017, and required that:  (1) Final LCDs be posted at least 45 days prior to the effective date, (2) Trackback to the proposal LCD date and original proposed text, (3) Provide discussion of all comments received and (4) rationale for LCD decision.  See pp. 408-409 of 21CC in the cloud, here.

Brief Blog: CMS MACs by Jurisdiction and by Contractor

CMS provides a website with detailed information on its Medicare Administrative Contractors (MACs) for traditional fee for service Parts A and B.   The website is here.

I recently needed to consolidate the information for a project, and provide the Excel spreadsheet in the cloud, here.  Dates and figures are current as of April 2017.

A snapshot summary is below - click to enlarge.   There are four numbered MACs (the old system), and eight lettered MACs, so there are twelve contracts.  However, four MACs (Novitas, NGS, Noridian, WPS) hold two contracts, so there are only eight MAC companies.

While I do not understand the full corporate structures, I believe that two pairs of MACs have some type of higher level joint ownership or umbrella corporation (Palmetto, CGS; and Novitas, FCSO).*  This would leave six MACs or sets of MACs that are unrelated.

Together, four multi-jurisdiction MACs, Novitas (24%), NGS (20%), Noridian (15%) and WPS (11%) have about 65% of Medicare beneficiaries.  A CMS MAC Map is here. LCD Legislation Re-Introduced in New Congress

In both 2016 and 2017, legislation supported by AdvaMed has been introduced which would improve the clarity and independence of MAC LCD policymaking.  For the text of 2017's S.794 bill, see here.  For a 2017 press release, here.  For 2016 trade press, here.  For more detail, my blog here.

MolDX States & MACs

MolDX is a multi-MAC policy system for genomic test LCDs and pricing.   There are six MolDX jurisdictions (JE, JF, J5, J8, JM, J15) under four different MACs (Noridian, WPS, Palmetto, CGS.)   Therefore, MolDX spans 24 states and 41% of US claims (16.4M of 37M Medicare beneficiaries).  (Click to enlarge).


*  E.g. Celerian Group "is a consortium of companies" including MAC CGS and MAC Palmetto GBA, here.  Similarly, in a 2012 press release, "Diversified Service Options, a wholly owned subsidiary of Florida BCBS, acquired MAC [Novitas Solutions] from its parent company..." - here.


For economics nerds, the MACs have a Herfindahl or oligopoly index of 0.15.  The Herfindahl  index varies from 0 to 1, with 1 representing monopoly.  It is mostly driven by at least one company having a very large share (e.g. 1 company has 70% or 80%).  (Calculated by summing the squares of each participant's market share.)    Wikipedia.

Wednesday, April 19, 2017

Brief Blog: Gene Test Management for Payers and Others: ECRI-GENE

I recently gave a talk in Berlin and talked about US payer reactions over the last four years to what they perceived, fairly or not, as a "Versicherungsblitzkrieg" (Insurance Blitzkrieg) coming from rapidly growing pharmacogenetic and cardiac testing labs.   (Several such labs fell equally rapidly into bankruptcy amidst commerical payer, DOJ, or CMS actions).

Companies developing to help payers manage genomic test policies include BeaconLBS (covered frequently by Dark Report); the former NextGxDx, now Concert Genetics; and eviCore, which developed for other types of benefit management, like imaging.  To my knowledge, BCBS Evidence Street is another major HTA, but focuses on providing the evidence assessments* rather than outsourceable payer claims handling functions.

Add a specialized service at nonprofit HTA firm, ECRI, called ECRIgene.  Website here.  It's not brand new; see a July 2016 press release, here.

Their homepage states:
Think of ECRIgene as your genetic test control center with experts constantly monitoring activities in this rapidly evolving universe. Our  analysts, nurses, clinicians, and medical librarians research, analyze, and synthesize the key features and evidence on each relevant test using the GRADE-based evidence-rating system. These experts are dedicated to researching your custom requests and answering your specific questions. 
We can imagine sales reps from large and small labs lined up to talk to a clinician; and sales reps from Beacon, Concert, eviCore, and ECRIGene lined up to talk to the patient's health plan. (For a few years, I've used a slide that refers to the growing HTA medical-industrial complex.)

It's been reported that at some point in 2017, BCBS Evidence Street and MolDX will use a common portal, here.

Foundation Publishes 100,000 Patient Study on "Total Mutational Burden" (TMB)

Very early on, before sequencing 200 or more genes in tumors was really commercialized, it occurred to me that from a business strategy perspective you would need to come up with a clinical reason for assessing 200+ genes.   Even today there are a very finite number of effective drugs for targeted mutations (EGFR, ALK, BRAF, etc), not anywhere near 200-500.   Adding referral to clinical trials will have limited impact; although tallies count "hundreds, or even thousands" of oncology clinical trials, they are likely counting things like phase I drug dosing arms.

Two approaches to making use of all 500 genes are being discussed.
  • One use would be to make very complex in silico models of tumor cell biology.  Companies like Cellworks and Darwin Health are exploring this.  I think of this as a growing industry for "digital genomics."  
  • Another use is finding something about those 500 sequenced genes that can be assessed and applied clinically -- but requiring the exponential jump in gene data and unrelated to the small number of approved drug-gene pairings.  
    • An approach here is Total Mutational Burden (TMB), and Foundation Medicine has just published a large new study.
Note that while either or both of these areas may prove to be clinically effective and important, you would come across these kinds of ideas, just by working backwards, Sherlock Holmes-style, from assuming you already have built the 500- or 1000-gene test and want to reverse-engineer applications for it.  As an if-then statement;  if one of these ideas proves important, then the market for 500 gene tests would rise while not depending on the trickle of a few new individual FDA-approved gene-drug pairs.

Total mutational burden is being cited as a potential biomarker for the effectiveness of immuno-oncology checkpoint drugs.   Chalmers et al. report the results from 100,000 patient studies conducted in a wide range of tumors from the FMI archives (Genome Medicine, Open Access, here.) FMI finds that:
  • They confirmed the previous understanding that lung cancer and melanoma are most likely to have rampant mutations, but found that rampant mutations also occurred at lower rates in many cancers.
  • You get most of the information for 0.5MB DNA; an exome confirms the high or low mutation burden you already low, whereas accurate assessment falls off below 0.5MB.
  • PMS2 mutations tend to be associated with rampant mutations, as is aging.
One proposed use of this type of data is predicting immunotherapy outcomes with a biomarker (TMB) orthogonal to markers like PDL1.   Last December, MolDX providing coverage of comprehensive genomic profiling in several additional cancer types (colon, melanoma, ovarian) based in part on the contributory value of TMB to therapy choices.

The authors also used Cancer Genome Atlas (TCGA) data.  Coverage at Genomeweb, here.

For AACR news with a re-analysis of Opdivo data using TMB, BiopharmaDive, here.

Brief Blog: DC Conference on Tumor Heterogeneity, May 11-13, 2017

The classic paper in the US literature on tumor heterogeneity remains Gerlinger et al, in NEJM 2012 (here.)   On May 11-13, there will be a (free) international conference in Washington DC on the topic.  The conference is sponsored by the Menarini Foundation, the University of Hamburg, and MD Anderson.

See the website here and here the PDF brochure here.  It's at the "Congress Center of the Old Post Office Building," which I believe is now Trump International Hotel.

New papers appear regulary across a range of cancers, e.g. new work by Morissy on medulloblastoma heterogeneity in Nature Genetics, April 2017, here.

Monday, April 17, 2017

Brief Blog: CMS Publishes CY2018 Inpatient Rulemaking; Six New Technologies Seek Add On Payments

CMS has released its Inpatient Proposed Rule for FY2018.

The typescript version is online here (1832 pp).
On April 28, the typeset Federal Register version will appear here.
The CMS press release is here.

New Technology in Brief Review

In addition to the annual rejuggling of some DRG codes, an area of recurring interest is the "new" New Technology applications - beginning on page 349 of the current public review version.  CMS received 9 applications, of which 3 were withdrawn before publication.   The remaining six new technologies for add-on payments are:

  1. ZINPLAVA (bezlotoxumab)
  2. Edwards INTUITY ELITE Valve and Liva Nova PERCEVAL Valve
  3. STELARA (ustekinumab)
  4. KTE-C19 / Axicabtagene ciloleucel
  5. VYXEOS (cytarabine/daunorubicin liposomes)
  6. GammaTile
Drugs must be costly enough to substantially exceed the inpatient DRG for the conditions where they will be used, the same standard as for devices.   The products must be "literally new" (meeting carefully defined dates and rules) as well as technologically new, and must have have clinically impactful new benefits, and it must also fail to be "substantially similar" to existing therapies.  

Qualifying new technologies earn hospitals a bonus to each DRG for which the product qualifies, for 2-3 years.

Brief summaries of each product below the break.

Sunday, April 9, 2017

ACLA Generally Supportive of Statutory FDA Reform for CLIA Labs and IVDs

On March 21, Dr. Larry Bucshon (R-IN) and Diana DeGette (D-CO) released a discussion draft of the Diagnostic Accuracy and Innovation Act (DAIA), along with summary documents.  In general, this is built on the Diagnostic Test Working Group (DTWG) approach circulated in the previous session of Congress.  ACLA has come out as generally supportive.  Details follow.

Hill Lab Proposal Released in Late March

An initial press release for the legislation is here, with a 2-page summary here, a 5-page summary here. and the whole 215-page statutory proposal here.

ACLA Generally Supportive in Early April

On April 7, ACLA issued a generally favorable press release in support, here, also releasing ACLA's detailed letter to the Hill, here (should open in window) or here (should open in Google docs) or here.

Get all six documents in one cloud zip file here.

In March, ADVAMED initially released a rapid, generally favorable short press release, here.  Similarly, Labcorp, here.  For an initial summary at RAPS, here, and for early coverage at Genomeweb, here.

Friday, April 7, 2017

Scott Gottlieb Senate Testimony; Unique Transcript HERE

On Wednesday, April 5, Scott Gottlieb testified before the Senate HELP committee for two and a half hours.

For a unique unofficial transcript of the hearing: click HERE

The Senate website is here.   (Click on "Open in New Window" for video).

Gottlieb's 5-page prepared statement is here.

Video also archived at CSPAN, here.

The Senate vote on Gottlieb's confirmation is scheduled for April 26, here.

Open access coverage at:
  • Xconomy, here.
  • Healthcare IT News, here.
  • BioPharma Dive, here.
  • The Hill, here.
  • Endpoints, here.
  • Health Affairs, here.
  • Heritage Foundation "thumbs up," here.
  • Endpoints also excerpted and published later responses from Gottlieb to the committee, here.

Thursday, March 30, 2017

CMS Extends Deadline to Submit PAMA Pricing by Two Months (May 30)

Note that technically, CMS is not "extending the deadline" but rather saying they will "not enforce late penalties" except for submissions that arrive after May 30.

60-Day Enforcement Discretion Period Announced for Laboratory Data Reporting

CMS Announces 60-Day Period of Enforcement Discretion for 
Reporting Applicable Information Under the 
Medicare Clinical Laboratory Fee Schedule

Today, the Centers for Medicare & Medicaid Services’ Center for Medicare (CM) announced that it will exercise enforcement discretion until May 30, 2017, with respect to the data reporting period for reporting applicable information under the Medicare Clinical Laboratory Fee Schedule (CLFS) and the application of the Secretary’s potential assessment of civil monetary penalties (CMPs) for failure to report applicable information. This enforcement discretion applies to entities that are subject to the data reporting requirements adopted in the Medicare Clinical Diagnostic Laboratory Tests Payment System final rule published on June 23, 2016 (81 FR 41036).

Industry feedback suggests that many reporting entities will not be able to submit a complete set of applicable information to CMS by the March 31, 2017 deadline, and that such entities require additional time to review collected data, address any issues identified during such review, and compile the data into CMS’s required reporting format. This 60-day enforcement discretion period is the maximum amount of time CMS can permit to still have sufficient time to calculate the CLFS payment rates scheduled to go into effect on January 1, 2018.

This enforcement discretion period does not prevent reporting entities prepared to report applicable information from doing so before May 30, 2017. CMS is committed to the successful implementation of the new private payor rate-based CLFS and looks forward to working with the laboratory industry to ensure accurate payment rates. CMS will continue to closely monitor this process and provide guidance as necessary.

Wednesday, March 29, 2017

Head of FDA: Scott Gottlieb's Senate Hearing Set for April 5, 2017

Dr. Scott Gottlieb, the administration's nominee to head the FDA, has been scheduled for Senate hearings on April 5.

Media coverage has focused on Gottlieb's extensive industry consultations and ties during the 8 years since he served in the Bush administration.  Current news articles refer to a 41-page federal ethics filing.   For more details see:
In 2006, Gottlieb became a Hodgkin's lymphoma survivor. cites Gottlieb's nomination as "a big win for science" (here),   Global Healthy Living Foundation endorses him (here) as does Patients Rising (here) and DrugWonks (here).  Some other sources praise faintly ("To his credit, Gottlieb is not certifiably crazy...;" MedPageToday, here.)  One of Gottlieb's major position pieces, on changing the FDA's culture, appeared in National Journal in 2012 (open access, here.)

Per the NYT, Gottlieb's financials from January 2016 to February 2017 included $1.8M from investment firm T.R. Winston, and additional compensation from venture capital firm NEA, direct pharma consulting, and positions on boards.  His position as a scholar at American Enterprise Institute is also compensated.   Gottlieb is a graduate of Mt. Sinai Medical School and its internal medicine residency, maintains a Connecticut medical license, and has often worked weekend shifts at a hospital there while maintaining other positions such as a senior policy position at FDA during the Bush 43 administration.   In 2016, Gottlieb donated to support Congressman Ben Sasse, who was one of the most vocal opponents of the Trump candidacy (US News, here.)

Tuesday, March 28, 2017

National Academy Releases: "Evidence Framework for Genetic Testing"

On March 27, 2017, the National Academies (of Science, Engineering, Medicine) released a 149-page ebook on "Evidence Framework for Genetic Testing."  The federal consensus report  was requested by the Department of Defense Office of Health Affairs.  Download the free ebook here.

My 2014 coauthor Felix Frueh and I were surprised and pleased that an evidence framework we published was cited as one relevant example among six or seven approaches to assessing genetic tests.

At the time, Frueh and I were dissatisfied that the conventional framework of "analytical validity, clinical validity, clinical utility" - while "true" - lacked much guidance for resolving disputes.   We suggested that dividing analysis into six questions was a happy medium - one or two questions is not enough ("Does the test have clinical utility?") while a list of twenty to forty questions was not really manageable.   The six questions, developed entirely by Frueh, were:

  1. Who should be tested and under what circumstances (e.g. population, scenario)?
  2. What does the test tell us, that we did not know without it?
  3. Does the outcome change in a way we find value in?  
  4. Can we act on the information provided by the test?  (E.g., ideally)
  5. Will we act on the information provided by the test?  (E.g. decision impact studies)
  6. If the test is employed, is it affordable?
In my experience, at least at the time, a successful test like Oncotype DX allows fairly straightforward answers to all six questions, whereas a generally unsucessful test (with payers) like beta-amyloid PET tracers, was hard to answer for nearly any of the six questions.   Perhaps understanding the test pretty well and then taking five minutes to jot down freehand answers to the six questions would be a good predictor of payer success or failure.   

We noted that tests have many ways in which they can represent improvements (more accurate, faster, providing results that were unknowable before) and that since tests map to such broad health scenarios, the range of relevant health outcomes is also broad (whether survival, pain, shorter hospital stay, etc.)   We believed that if payers and lab developers communicated on the various axes, there would be fewer situations where the payer can do no more than state vaguely "there is not enough evidence" and where the lab complains equally vaguely that "payer standards are too high."   

Frueh-Quinn was published here.

Brief Blog: CMS Rolls Out CGM Coverage; Window into Numbingly Complex Policies

In the summer of 2016, CMS began losing administrator judge cases when it tried to defend its poorly-enunciated policy that continuous glucose monitors were not a medical product  category eligible for Medicare payment.

In January 2017, CMS released a lengthy, legalistic ruling reversing its position.

On March 23, 2017, CMS DME MACs released a provisional policy that describes actual coverage of CGM through claims processing.

Details after the break.

Brief Blog: ACLA asks CMS to Delay PAMA and Expand Hospital Lab Reporting Too

Last week, ACLA held its annual meeting in Washington.  ACLA has formally asked CMS to delay PAMA for a year - and not only delay it, but re-write the rules on the scope of labs which will be obligated to report.   A CMS administrator made comments suggesting that CMS was considering the possibility of a PAMA delay.

  • See open-access coverage at Dark Daily (here). 
  • See also a flurry of several press releases in recent days on the ACLA news website, here.
  • Subscription coverage at Genomeweb (here).

Senior CMS administrator Carol Blackford, head of all outpatient services for Medicare, spoke at the conference.  According to the news reports, Blackford publicly acknowledged some difficulties in computer processes supporting PAMA data submission, such as periods when the systems have been down.  Overall, data submission so far is less than anticipated by CMS.   The current deadline for data submission is Friday March 31, and failure to submit carries substantial penalties.

CMS Has Difficulty Handling 81162 Claims

Blackford's comments included the fact that "files were rejected based on a valid HCPCS code 81162."   81162 is one of several confusingly priced CPT codes related to BRCA testing (here).  

ADLT Instructions: In the Pipeline

Blackford also noted that while no instructions for applying for Advanced Diagnostic Laboratory Test (ADLT) codes have been provided, a submission form has been created by now, and is being reviewed by general counsel at CMS before release.  ADLT codes received privileged coding and pricing processes under PAMA.

OIG Reports from September 2016

Genomeweb's article pointed me to two September 2016 OIG reports that relate to PAMA changes; I had missed these.  OIG home page for the articles, here.   OIG issued one report (16-00040) on 2015 baseline CLFS payments, here, and a second report on "CMS Progress in Implementing PAMA (16-00100), here.   ReedSmith summarized the two OIG reports last October, here.

Brief Blog: New Term, Narcissome (Genomeweb)

On March 28, 2017, Genomeweb's Julia Karow runs an article on discussion of elective exome or whole genome screening, a topic of discussion at American College of American Genetics (ACMG) last week.  New term:  "Narcissome."  Subscription article here.

Separately, in a meeting last week, I heard a reference to the "economicsome," the payment system for advanced lab tests.

NEW YORK (GenomeWeb) – Exome and whole-genome sequencing have been firmly established as diagnostic tools for rare genetic diseases that can pinpoint molecular causes missed by more targeted tests. More recently, though, several labs have started to move genome-scale sequencing into preventive medicine, with the goal to detect increased disease risks and predict atypical drug responses in seemingly healthy individuals.
At the American College of Medical Genetics and Genomics annual meeting in Phoenix, Arizona, last week, representatives from Harvard Medical School, Illumina, Baylor College of Medicine, the HudsonAlpha Institute for Biotechnology, and the National Human Genome Research Institute talked about their experience with genomic tests catering to individuals that neither have cancer nor a rare inherited disorder, variedly referred to as "genome screens," "elective genomes," or >>> "narcissomes." In addition, several commercial labs spoke about recently launched or planned genomic tests for so-called healthy adults at the conference, including WuXi NextCode, Ambry Genetics, and Invitae.

Friday, March 24, 2017

How To Quickly Explain Medicare BRCA Pricing Policy to Your Sixth Grader

My kids are in high school, but you may need to explain Medicare BRCA pricing policy to your sixth grader, when they are learning bar charts.

Medicare currently pays for BRCA genetic testing services at any of four different price levels, depending on coding choices and the state where the lab is [click to enlarge]:

In 25 states, the MolDX program lists 81433 as a nonpayable code, so the $931 cap applies for panel testing in those states.  I use the MolDX pricing in the next two charts.

Here's a bar chart where the price axis is normal, and the work of genes tested is unnaturally expanded or compressed (a couple genes is very tall and a dozen genes is very tiny):

Here's what it looks like if you set the bar charts to show the laboratory work -- more genes makes taller bars than a couple genes -- this will make the Medicare price axis turn UPSIDE DOWN:

Based on 2015 claims data, Medicare paid well over $50M for BRCA testing services.  If the MolDX price policy were applied with consistency, Medicare would have paid only $18M - saving over $30M per year or $300M over ten years.  

Was Implementation of Panel Pricing Policy Frozen by Executive Order?

If CMS was planning to implement its long-standing panel pricing policy for genetic testing 1Q2017, it may have been derailed by the executive order to freeze federal agency rulemaking and policymaking.


In August 2016, CPT Assistant, the AMA's correct coding resource, fielded a question on what to do with multiples of genetic tests that didn't meet a gene panel code.   AMA responded that Tier 1 codes should be stacked, Tier 2 codes used in multiples as necessary, and additional services represented by an unlisted code (81479).

Let's say a lab does a panel of 9 or 10 genes, including BRCA 1 & 2, so the lab is performing a panel that falls short of the AMA CPT panel definition for 81432 ($931).   And let's assume the 7 genes after BRCA 1 & 2 are on fee schedules at $400 each.  

Then you get the following charts, with the hypothetical 9-gene stack coding paying about $4800 - and this is still less work than the 14-gene panel which would pay only $931.   In some places, without special manual edits, CMS or other payers' computers might autopay the price in the left bar.

We can also map this approach onto the format with a reverse-price axis on the left, running the payment from about $5000 (for nine genes at far left) to $2500-2700 for two genes and down to only $931 for 14 genes (at far right):

Thursday, March 23, 2017

CAP, AMP Release New Gene Panel Validation Guidelines

On March 23, 2017, CAP and AMP released a new, 25-page guideline to validation of next generation sequence panels.   The article, Jennings et al, has its journal home page here, PDF link here, and in the cloud, here.

For coverage at Genomeweb, here.  This is the third recent guidance for standards in next generation sequence; see also Ritter et al. for guidelines on new standards for annotating and curating somatic tumor variants (here) and Li et al. on new standards for clinically reporting somatic tumor variants (here).

Abstract of Jennings et al. clipped after the break.

Guidelines for Validation of Next-Generation Sequencing–Based Oncology Panels

A Joint Consensus Recommendation of the Association for Molecular Pathology and College of American Pathologists

Wednesday, March 22, 2017

Rapid Transcript HERE: CMS Diabetes Prevention Program Webinar (3/22/2017)

The home page for the Medicare Diabetes Prevention Program is here:

CMS is in the process of policy and rulemaking to implement the program nationally in January 2018.   CMS held a webinar on the collaborative roles of CDC and CMS on March 22, 2017.   The webpage for this webinar is here:

CMS is expected to post slides and an official transcript in the near future.  
In addition, CMS stated it was preparing an updated and expanded FAQ.   

In the meantime, this blog provides a rapid unofficial transcript of the March 22, 2017 webinar.

The rapid unofficial online transcript is in the cloud: here.

Thursday, March 16, 2017

12, 8, 4, and 2: Revisiting BRCA Policy and Pricing

Today, March 16, the USPSTF task force released for public comment the framework for an updated assessment of BRCA risk assessment, testing, and counseling (here).  It's the 12th anniversary of the USPSTF first guidance statement, in 2005 (here). Meanwhile, BRCA policy mavens will recall that this year is the 8th anniversary of AMA/ACLU filing a court case challenging the validity of some claims of the BRCA patent (here).   And in a couple months we hit the 4th anniversary of the Supreme Court decision that followed (here, here).   Meanwhile, we just crossed the 2nd anniversary of the resolution of several ongoing aspects of the patent litigation (e.g. Cook-Deegan, here), and College of American Pathologists/CAP TODAY just published an article on how the SCOTUS case has impacted diagnostic pathology (here).

I recently reviewed the cumbersome CPT/CMS approach to coding and pricing BRCA testing (here).  The flurry of anniversaries and events led me to look up some of the original SCOTUS documents this evening.

Comment Through April 12 on USPSTF BRCA Research Plan (Risk Assessment, Counseling, Testing)

USPTF has a December 2013 current recommendation on BRCA-related cancers, covering risk assessment, counseling, and genetic testing.  Based on an earlier ruling of HHS, and now pretty clearly incorporated in the 2013 guideline,  HHS and USPSTF view genetic testing as part of the preventive guideline, which makes it copay-free under most insurance plans.

On March 16, USPSTF released a new plan to update its guidance.   The public can comment through April 12.   Arising issues include restriction of preventive screening to high-risk families versus population-wide screening.  As far as the draft plan goes, it continues to focus only on increased-risk families.

Comment here:

In general, under ACA, most health plans are required to provide USPSTF A and B preventive benefits and without copay.  CMS can adopt (import) USPSTF A and B benefits into Medicare via the NCD process. To date, it has done that for quite a few preventive services, but not for BRCA preventive screening.  CMS does cover BRCA testing in women already diagnosed with breast cancer, where results can guide ongoing management decisions.

Wednesday, March 15, 2017

Do CMS Panel Pricing Policies Apply to Gene Panels?

In a previous blog, here, we discussed that CPT and CMS had generated a complex web of coding and pricing options to pay for BRCA testing, one of Medicare's top three genetic tests (by dollar volume).

Beginning in January 2017, CMS has a fee schedule priced gene panel test that includes BRCA-1 and BRCA-2 testing, but has a much lower total price.

Does this conflict with CMS's decades-old policy to never pay more for components of a panel that it would pay for the entire panel?

My answer is "probably so," but CMS has not faced the issue yet.  Research on the topic indicates that CMS's lab panel pricing policies are memorialized in varies program documents, but not fixed in law or regulation.

Because PAMA is a law, and raises some thorny issues for CMS regarding the interaction of PAMA law and CMS internal lab test policies, CMS should probably put its panel policies into formal, enforceable regulations.   When doing so, CMS should assess the fit of its panel policies to gene test panels.  It looks like this could quickly become a multi-hundred-million dollar issue for CMS.  Details after the break.

It's a Chaotic Mess: CMS Pricing of BRCA Testing

When assessed by CY 2015 payments in the fee-for-service Medicare Part B system, BRCA testing is the third-largest expenditure, at about $52M per year.  However, the situation for CY 2017 is going to be much more complex, as there are now three different coding approaches, all recognized by CMS, resulting in drastically different Medicare expenditures for BRCA testing.

Depending on which set of rules and codes are applied,  payments could be anyone from $931 all-in for a BRCA panel including full dup-del analysis, all the way up to $2,780 for individual genetic components of BRCA 1 and BRCA 2 testing.

Assuming similar test utilization in 2017 as in 2015, Medicare's total payments could be as low as $17.9M this year or as high as $51M.   This article discusses how Medicare backed itself into this mess.   A shorter second blog (here) asks whether CMS panel pricing rules can or should apply to BRCA testing.

Tuesday, March 14, 2017

Brief Blog: A Large Scale Private Payer CED Project: Genetically Informed Mammography

On March 14, 2017, Health Affairs runs a detailed blog by Rosenberg-Wohl et al. (here) about a "Coverage with Evidence Development" study supported through the collaboration of diverse stackholders, including multiple University of California campuses, Blue Shield of California, and other collaborators.

The study, WISDOM (see website here), looks to assess the impact of randomized use of a genetic breast cancer risk profile on mammography outcomes.   The idea is simple: if breast cancer is risk based, then one-size-fits-all screening based on projected risk/benefit is like one-size-fits-all clothing or shoes.   The authors describe the study as benefiting from the use of $225 breast cancer genetic risk testing.  There will be 100,000 total participants, with half of them receiving the test.

The authors explain that imposing numbers of hurdles that had to be maneuvered to launch the program.   The 5-year study is new and will be enrolling into 2017.

Brief Blog: Seema Verma Confirmed As Head of CMS

On March 13, the Senate voted to confirm Seema Verma as head of CMS.

Coverage at Medscape here, at Becker's Hospital Review here, at New York Times, here.

Verma built an Indiana-based healthcare consulting helping multiple states redesign their Medicaid programs.   For a full transcript of her Senate interview testimony, here.   For an earlier blog on her background, here.  For her August 2016 blog on Indiana's Medicaid reform, in Health Affairs, here.

Monday, March 13, 2017

CMTP/Green Park Issues White Paper on Genomics, Liquid Biopsy

On February 7, we covered a Real World Evidence information center set up by the Green Park Collaborative and the Center for Medical Technology Policy (CMTP).

On March 13, the GPC and CMTP issued a 19 page white paper summarizing their November 2016 two-day stakeholder workshop on the adoption of genomic technologies.  One focus of the workshop was Liquid Biopsy.   See the web page here, the white paper here.  Table of contents is clipped below the break.

Friday, March 10, 2017

Brief Blog: Could GINA's Genetic Privacy Protections Change?

This week, a flurry of articles on an obscure legislation proposal that could chip away at GINA's protections regarding genetic privacy in the workplace and with health insurance.

See coverage at PLOS.ORG here, at Genomweb here, at STAT here, at Dark Daily, here.

STAT writes,
A little-noticed bill moving through Congress would allow companies to require employees to undergo genetic testing or risk paying a penalty of thousands of dollars, and would let employers see that genetic and other health information.
Giving employers such power is now prohibited by legislation including the 2008 genetic privacy and nondiscrimination law known as GINA. The new bill gets around that landmark law by stating explicitly that GINA and other protections do not apply when genetic tests are part of a “workplace wellness” program.
The PLOS article quotes from a letter from the President of the American Society for Human Genetics to the Hill.
Nancy J. Cox, PhD, ASHG president, in a letter to the U.S. House Committee on Education and the Workforce, provides a frightening overview:

“If enacted, this legislation would undermine fundamentally the privacy provisions of the Genetic Information Nondiscrimination Act (GINA) and the Americans with Disabilities Act (ADA). It would allow employers to ask employees invasive questions about their and their families’ health, as well as genetic tests they and their families have undergone. It would further allow employers to impose stiff financial penalties on employees who choose to keep such information private, thus empowering employers to coerce their employees into providing their health and genetic information.”

Brief Blog: Scott Gottlieb Announced as FDA Nominee

Early on March 10, Bloomberg ran an article citing Scott Gottlieb as the leading candidate for head of FDA.   See the open access article here.   Around noon, WSJ stated that Gottlieb is the expected FDA nominee, here.   And the NYT also, here.  WaPo. here.  At around 5 eastern, Reuters posted that the White House has confirmed that Gottlieb "is" the nominee.  Further analysis at Endpoints, here, and Vox, here.  A later update at Endpoints (on March 29, here) covers some of Gottlieb's pharma connections that have to be unwound.

Wall Street Journal hails the nomination as potentially "one of Trump's most important appointments" (here).  See a detailed analysis of Gottlieb's views on drug pricing is providing by the DrugChannels blog (here), with a callout to Gottlieb's insightful 10/2016 Hill testimony (here).

This blog highlighted Gottlieb's promising candidacy on December 13, January 21, and February 6.

For MedCityNews, "Statistical Guide to Scott Gottlieb," March 15, 2017, here.

A interesting pre-election (9/2016) interview with Gottlieb is online, here.

A colorful article about the new administration, Peter Thiel, and FDA, at Vox, here.  A negative article on Gottlieb at LA Times, here.

Thursday, March 9, 2017

Brief Blog: AMA Releases Results of February 2017 CPT Meeting

The AMA CPT Editorial Panel meets three times per year, most recently in early February in New Orleans.  A number of molecular codes were on the agenda, for single genes, for MAAA tests, and for genomic sequencing procedure panels.   
  • The results of the AMA panel were posted today by the AMA, on this webpage, here.  
  • See the document, 2017 February: CPT® Editorial Summary of Panel Actions.

Wednesday, March 8, 2017

Brief Blog: Comparing the FDA BRCA Approvals for Myriad & Foundation Medicine

Myriad Genetics received FA approval for its BRCA1/BRCA2 companion diagnostic (BRACAnalysis CDx (TM)), on December 19, 2014.

Foundation Medicine received FDA approval its its NGS-based BRCA1/BRCA2 companion diagnostic (FoundationFocus CDx[BRCA] Assay (TM)), on December 19, 2016.

The tests fall under different FDA PMA classifications (Cancer Germline Detection System, for Myriad; and Next Generation Sequencing Oncology Panel, Somatic or Germline Variant Detection System, for Foundation.)

Each has detailed Safety & Effectiveness documentation and Labeling documentation online at FDA (these are 34 and 16 pages, respectively, for Myriad, and 31 and 18 pages, for Foundation).
  • The FDA homepage for FoundationFocus (P160018) is online at FDA here.

  • The FDA homepage for BRACAnalysis (P140020) is online at FDA here.  
    • This approval also has 8 links to minor supplements (such as changes in software or polymerase reagents.)
The FMI approval order is linked directly to clinical use with Rubrca, and the Myriad approval is linked directly to clinical use with Lynparza.

  • A collated ZIP file with the five core FDA documents for each product (and the 8 minor supplements for Myriad) is in the cloud, here.
Update: An April 27, 2017 article in Genomeweb discusses that FMI's test is less-validated for longer insertions and deletions or large rearrangements, and that Clovis Oncology is getting approval for on-label use of the Myriad test with its PARP inhibitor Rubraca (here).

Tuesday, March 7, 2017

Brief Blog: PMC Releases 2017 Policy Report, Holds Hill Briefing

Last month, on February 7, the Personalized Medicine Coalition released a report on barriers and disincentives to personalized medicine (here).  The report was based on multi-stakeholder workgroups and interviews, and appeared as a 5-page summary plus a 12-page academic paper in the journal Personalized Medicine.   The paper by Pritchard et al. is entitled, "Strategies for Integrating Personalized Medicine into Healthcare Practice."

Now, on March 7, PMC released its annual full-length report on the personalized medicine movement in healthcare (64 page PDF, here.)

Also today, PMC will hold a 90 minute Hill briefing on issues in personalized medicine (here).   The Hill briefing, co-hosted by Sen. Markey (D-MA), will include four panelists:

  • Stephen D. Eck MD PhD, Astellas Pharma
  • Emily Kramer-Golinkoff, Co-Founder, Emily's Entourage
  • Miachel Sherman MD, Harvard Pilgrim Health Care
  • Jay Wohlgemuth MD, Quest Diagnostics
[Update, Coverage of the Hill hearing by "Science & Enterprise," here.]

The 64-page annual report discusses opportunities and challenges.  Opportunities include medical benefits and the fast past of science.  Challenges include regulatory policy, coverage/payment policy, clinical adoption rates, and health information technologies.

Coverage at Genomeweb, here.  At STAT, here.

Wednesday, March 1, 2017

Brief Blog: Grail Raises $900M For Advanced Liquid Biopsy Sequencing

As it promised to do at the beginning of the year, GRAIL has raised almost a billion dollars to push the horizons of next-generation sequencing from blood samples.   The press release is clipped after the break.

Grail recently announced it was hiring Elizabeth Mansfield PhD, one of the senior leadership team for precision medicine at the FDA over the past decade (here).

Monday, February 27, 2017

Brief Blog: The Villainization of Obamacare

While this blog doesn't normally touch on the broadest health policy issues, I was struck by a series of video clips of politicians denouncing Obamacare as the worst legislation in the history of the U.S., as the biggest crisis facing America, or as the number one disaster on the American continent.*

This doesn't make much sense.

For one thing, Obamacare is not that big.

One layer of Obamacare is the health exchanges.  While about 12M are enrolled in them in 2016, about 5M switched to exchanges from other individual or small group plans.  Exchange enrollment is about 3.8% of the US population (12M/320M).   For some of these people, exchanges offer a better group rate than individual insurance (e.g. the one thing worse than Exchange insurance is individual plans).  Many others have subsidized commercial insurance via the Exchanges, although the high deductibles create problems both for lower middle class enrollees and for providers.

The subsidized participants in Exchanges are funded by a combination of long term Medicare payer and hospital cuts made in 2010, special pharma and med device taxes, and taxes on incomes over $250K.   So the exchanges were paid for, and directly unwinding them, point for point, would meet the social need of lowering taxes on pharma and on people making over $250K.

To the extent Exchanges are now trending worse (an adverse risk death spiral), they can't produce worse results than the individual insurance market, or people would choose the latter rather than Exchange insurance.  And to the extent ACA Exchanges don't work or stop working, Congressman who never wanted them to exist don't have much to complain about.  Neither the declining exchanges (if that happens) for a few million people nor a new replacement plan would be the worst crisis in America.

Another layer of Obamacare is an expansion of Medicaid to not-quite-destitute poor people, which was voluntary at the state level and involves about 6M people - that is, about 1.6% of the US population.   (Data here.)   While this involves inbound federal taxes dollars being redirected outbound back to state Medicaid programs, let's remember the money comes from the states' taxpayers in the first place.    In poorer states, there is a net inflow of tax dollars, while in richer states, there is a net outflow of tax dollars, flowing to the poorer states.   From voting patterns, it seems that the richer states are generally OK with this, while voters in the poorer states want this process stopped right now.  Well, OK.**

I propose that neither (A) having tiny percentages of people in Exchanges funded by pharma and wealthy person taxes nor (B) voluntary expansion of Medicaid which is in part a wash (tax dollars out, tax dollars back) and in part a transfer from richer to poorer states, are the worst things to happen in the history of America.

There are a lot of things to criticize Obamacare for - excessive federal bureaucracy, failure to address larger cost issues, insurance death spirals, or dysfunctional plan design (e.g. $5000 deductibles for people who have $100 in a good month.)   But presenting it as the worst problem the nation has ever faced is inane.  

Healthcare has to solve three problems outside the employer-based system:

  1. Care and support for the severely or profoundly ill such as the quadriplegics and elders with Alzheimers;  
  2. Care for those was just use a wide range of routine care, let's say from vaccinations to insulin.  These are the 80% who use 5-10% of health costs; and finally,
  3. Those with healthcare needs that crash the employment based insurance system because you are too sick to work.  
Handling those three categories, there are enough problems to address without the crazyland rhetoric.

* From Last Week Tonight, which admittedly is liberal-biased but was showing genuine Obamacare ultra-villainy clips.  Here.
** The same argument applies with provincial versus national funding of Canadian healthcare (here). Let's say Manitoba complains it doesn't get enough funding from Ottawa.  It doesn't want to raise taxes in Manitoba.  But the only place Ottawa can get funding from is to raise taxes on Canadians, e.g., in Manitoba.   For US states, somewhere there is a state that is federal tax and federal benefit neutral for Medicaid - let's say State A sends $5B in US taxes to Washington and gets back $5B in Medicaid support.   In theory, you could cancel the federal taxes, displace them with $5B of state taxes, and you'd have exactly the same Medicaid program in that state and exactly the same tax burden.   In a wealthier state, State B, it sends $8B to the feds, and gets $5B back.  Where does the extra $3B in its Medicaid federal tax share go?  Somewhere there is a poorer state, State C, that sends $2B in Medicaid taxes to the feds, and gets $5B back.