Saturday, June 16, 2018

Very Brief Blog: Justice Department Documents on Elizabeth Holmes & Theranos

It's widespread news on Friday, June 15, 2018, that Department of Justice has indicted former Theranos CEO on criminal fraud charges.    See for example here and here.

Not all articles link to the original DOJ documents.

  • The DOJ press release is here.
  • The DOJ indictment, based on Grand Jury investigations, 15pp, is here.

For my contemporary library of about 150 articles, begun and 2014 and running through the famous WSJ articles in late 2015 and continuing into 2016, see here.

In May 2018, WSJ reporter John Carreyou published his book, BAD BLOOD, about his two year investigation into Theranos.   I wrote about two sections in the book.  In one, he describes a previously unknown story wherein a senior FDA executive flies from Maryland to Florida to meet with Gen. Mattis about problem with Theranos (this was long before Mattis joined the company's board of directors.)  Here.   I also highlight anecdotes in the book where an unnamed FDA official leaks confidential non public government information about pending investigation reports and pending reviews of confidential company data submitted to the agency.   Here.   For perspective on that, I highlight a recent criminal case where a CMS official was convicted of having leaked pre public from another HHS agency.

Wednesday, June 13, 2018

FDA Policy Land Grab? FDA Uses Guidance Announcement as Trojan Horse for Price Paradigm Positions

Generally, both in US and Europe, there is a sharp line between regulatory authorities who approve drugs and payers who set up policy and pricing systems for coding and reimbursement.

This week, FDA used a routine press release to make a major land-grab on new paradigms that CMS might float, in the future, for drug payments.    This goes a great deal further than the usual FDA positioning, which is (for example) to support faster biosimilar and generics approvals because that eventually improves competition.

See Endpoints News here, and the original FDA press release here.

The entry point for the press release is a new guidance document (arising from 21st Century Cures Act) for antimicrobial drugs for limited populations (here; comment period to early August).  This is the "LPAD" pathway and provides several approval and postmarketing benefits for qualified drugs.

The press release, however, was positioned specifically as a "Statement from FDA Commissioner Gottlieb" and about half of it discusses long term economic issues with advanced antibiotics and proposed an entirely novel payment paradigm in some detail, commenting that it FDA is "currently discussing [it] with other agencies such as the Centers for Medicare and Medicaid Services (CMS)."  In brief, the proposal is that certain rare antibiotics would be licensed on a per click annual basis by hospitals rather than conventional payment.   Since only a small fraction of all infectious disease patients are FFS Medicare patients, the plan would have to be nationalized across Medicaid and other payers to be impactful for early investors. 


Antibiotics face major hurdles, leading to efforts such as the BARDA-sponsored public private partnership CARB-X, which awards substantial but early stage funds to antibiotic startups (here).  CARB-X is headed by a very sharp Boston University professor, Kevin Outterson, whom I heard speak at a health innovation conference in Berlin a few weeks ago.   We want pharma to develop new high risk next generation antibiotics, and then ideally, they'll be shelved and not used for years (to avoid resistance mutations) as patents expire.  In short, if you don't do something drastic, the current reimbursement system is highly toxic to antibiotic development.   Someone, if not the Presidential Advisory Commission (PAC-CARB), needs to be sure novel ideas are launched into action.  It's also a good fit to the new HHS interest in high octane public private partnerships for better policy and healthcare (here).

HHS' leader, Alex Azar, previously a high profile corporate attorney and pharma business leader, has a vision for bigger and better collaboration between HHS's star divisions, FDA, CMS, and NIH.   And Scott Gottlieb understands CMS and business economics far better than a typical FDA leader.   The press release intrigued me, though, and left me wondering which of these two scenarios apply:

(A) The press release was planned top-down.  A major announcement of potential new policy was given to the FDA's leader, not the CMS leader or Azar.  This could either show new levels of inter agency idea sharing or giving a reimbursement policy topic directly to FDA for variety, somewhat like giving the cello player a solo he wouldn't ordinarily have. 
(B)  Gottlieb knew the policy was being discussed, and FDA used the passing press release as a good vehicle to own the idea and get it out into the public media.   Even though, FDA wouldn't try to get ahead of CMS in CMS's own reimbursement regulations.

To put the comment in perspective - and it's worth reading the press release twice - imagine the CMS administrator proposing a new way to organize and process drug approval departments and claims at FDA, then noting "he was talking to FDA about his idea too." 

To my eye, nothing in CMS reimbursement, especially for hospitals, forbids this type of contracting.  A patient has sepsis, CMS pays $25,000 for the sepsis DRG, and CMS doesn't really get involved in how, when, or why the hospital acquires the needed drugs or equipment for the healthcare.  And as already noted, Medicare must handle only a small proportion of all US sepsis patients on rare antibiotics, so if the policy involved CMS fee for service patients alone, it wouldn't make a big dent in the overall commercialization and incentive system.

See a 2017 PAC CARB white paper on incentives, here.  Historically, CMS presentations at PAC CARB haven't mentioned out of the box issues like new payment paradigms; see Ling.

The press release was timed to the last day of the ASM MICROBE 2018 conference in Atlanta.

In February 2018, FDA issued a report to Congress on its (internal, regulatory) efforts on antibiotics; here.

This is an extremely rich policy areas, with countless proposals, white papers, and review articles.  For some additional current online resources see here.

CMS to Cancel Bizarre Policy that Disallowed CGM if Used By Individual with Smartphone

I've written several times about bizarre CMS policies about Continuous Glucose Monitors (CGMs), most recent in March 2018 (here).

One of the most bizarre tangents was a DME MAC article that disallowed supply payments (such as, oh, say, insulin supply and tubing supply and sensor patch supply) to a CGM system if the user used a smartphone in conjunction with it in any way.   See original article here, and if it is taken down, see archive here.

The pivotal text is:
  • Coverage of the CGM system supply allowance is limited to those therapeutic CGM systems where the beneficiary ONLY uses a receiver classified as DME to display glucose data.  
  • If a beneficiary uses a non-DME device (smart phone, tablet, etc.) as the display device, either separately or in combination with a receiver classified as DME, the supply allowance is non-covered by Medicare
See a September 2017 article at Medscape here, a July 2017 blog here, another article here.

CMS Will Change Smartphone Ban Soon

According to a June 13, 2018 article at Medscape, CMS has now promised to have the above policy statement withdrawn.  Here.  Another June 2018 trade article here and here.

Medscape states in part,
     Although diabetes advocates had praised CMS for the overall coverage decision, they also decried the agency's lack of recognition for the use of modern-day technology, which also left seniors without access to the "share" function, whereby loved ones could remotely follow blood glucose readings.
     One endocrinologist deemed the lack of coverage for use of the device with the smartphone app "absolutely ridiculous."
     Turns out, CMS was listening. "CMS heard from numerous stakeholders who shared their concerns that Medicare's CGM coverage policy limited their use of CGMs in conjunction with their smartphones...After a thorough review of the law and our regulations, CMS is announcing that Medicare's published coverage policy for CGMs will be modified to support the use of CGMs in conjunction with a smartphone, including the important data sharing function they provide for patients and their families," the agency said in a statement.

The source of the news is the DME Center Website at, here.  Cloud here.

click to enlarge

June 2018 Court Case

For a flat-out CMS loss in June 2018, in which federal court even awarded attorney's fees to the plaintiffs, see here.  Courts can award lawyers' fees in cases where the Fed position is unable to "satisfy a reasonable person" or is not "reasonable in law and fact."  There must be a "reasonable connection between the facts alleged and the theory propounded" by the government.  The government failed these tests, so fees could be awarded. 

Interesting reading.  Regarding the tortuous and generally undefined use of "precautionary" in CGM cases, judge finds that the "circular reasoning is entirely unhelpful."   If CGM is not "medical," says the judge, HHS was unable to explain "what non-medical purpose it believes [CGM] serves." 

The court notes that previous cases had found the HHS position to be "head scratching" and that "a string of losses" in many court cases can be indicative of an untenable position.  The standard rate awarded to attorneys, barring exceptions, is $125/hr.  The judge's award in this case (including special rates) was $70,000.  At $500/hr, that would be about 140 hours.

Tuesday, June 12, 2018

Very Brief Blog: Patient Centered....Lab Utilization Services!

A few years ago, everything was -omic: genomics, proteomics, metabolomics, microbiomics...  More recently, one of the flypaper catchphrases has been "patient centered:"  ...patient centered EHRs, patient-centered outcomes, patient-centered trial design

A new one to me is Patient Centered Laboratory Utilization Guidance Services, or PLUGS.   See a website based at Seattle Children's Hospital, here, and this consortium of 70+ entities is holding a conference in Seattle this week, PLUGS Summit 2018, here.   See full agenda here.

For another entry point into the quickly changing economics and management tactics of labs, see nearly any issue of Dark Report and see a recent textbook from MGH, Dr Kent Lewandroski's Utilization Management in the Clinical Laboratory, 300pp, 2017, Springer.

I've clipped a few speech titles below.  MolDx's Dr Girish Putcha is also a speaker.

Very Brief Blog: New Consensus Paper on Liquid Biopsy in Lung Cancer

There is a steady drumbeat of activity in liquid biopsy, especially lung cancer, where both Foundation Medicine and Guardant have NGS panel tests under FDA review.

With an Accepted date of May 26, 2018, Journal of Thoracic Oncology has published a open access position paper by IASLC on the use of liquid biopsy in lung cancer (Rolfo et al.).   See the paper here.

The paper states in part:
A multidisciplinary panel of experts in the field of thoracic oncology with interest and expertise in liquid biopsy and molecular pathology, was convened by the International Association for the Study of Lung Cancer (IASLC) to evaluate current available evidence with the aim of producing a set of recommendations for the use of liquid biopsy for molecular analysis in in guiding the clinical management of advanced NSCLC patients as well as identifying unmet needs....
Currently, there are two important scenarios in which the liquid biopsy might confer an
advantage to patients with advanced NSCLC: initial molecular diagnosis and progression during targeted therapy. However, a treatment strategy that takes into account the patient’s clinical status, clinical relevance of test results, and local feasibility of the different testing methods has to be considered when planning diagnostic procedures in order to avoid potential delays in identifying therapeutically actionable resistance mechanisms. 

CMS Coverage
My reading of the current CMS NCD on genomics in lung cancer is that new NGS based LBX CDx tests will be covered per FDA indications on a rolling basis under the existing text.   PCR based tests would fall outside the NCD but could be covered by LCDs on a rolling basis.


The same issue has a paper on racial disparities in lung cancer survival Jones et al here and a paper on PDL1 immunohistochemistry concordance here (Tsao et al, Blueprint project). 

Monday, June 11, 2018

Very Brief Blog: CMS Posts Preliminary Gapfill Prices for 2018

On June 11, 2018, CMS posted gapfill preliminary prices for the 2018 year long gapfill process.

See the CMS webpage here and look for "Test Codes and Payment Determinations" and then 2018 CLFS Gapfill Preliminary Determinations (zip file containing XLS).   Direct zip file link should be: here (unless they update it again).

The AGENDA the June 25 new codes has also been posted, with 32 agenda items (speakers); here.  Note that while I am listed the agenda here, the New Codes Meeting agenda is basically unrelated to the gap fill proposals.

Note that the first version had errors; see a version dated June 13 or later.

Gapfill prices for 17 codes range from $24 to $2030, but almost all are below $1000.

CMS accepts public comment for 60 days (circa August 10), provides this comment to its MACs, and then publishes MAC final prices in September.

Longest Journey.  The code with probably the longest journey is 81327 SEPT9, which was in the new code crosswalk process in CY2016, the appeal process in CY2017, and is now in the gapfill process throughout CY2018. 

Most Illogical.  The most illogical pricing is probably Genome or Comparator Genome at $349, which must be substantially below real world costs.   For those who can dodge the various firewalls, see a very favorable current article in Washington Post on genome testing for acutely ill children, here.  CMS prices Exome at $4900.

A couple comments from me:
  • No Rationale.  CMS stated in PAMA rulemaking that it would begin providing MACs' "rationales" for prices.  No sign of that publication yet.
  • Median of MACs?  PAMA regulations state that CMS shall calculate medians of "MACs," but rather than listing the circa ten modern MACs, it lists the historical 57 CLFS pricing zones from the 1970s.   
  • MolDx Bloc.  All the MOLDX MACs price together for all codes (Noridian, WPS, CGS, Palmetto and Palmetto/Former Cahaba), except for one code that might be a typo.  
    • This MolDx "Bloc" of states or MACs is large enough to drive the median.
  • All Prices Match MolDX Price.  All median prices matched the MolDx bloc price.

Nerd View

I checked for cases where there was a proposal from any MAC that is lower than the Median.  This occurs for 81327 (where most bids are around $150 or $190), and for 81471, 81470, 0001U, where at least one MAC offered 20-50% less than others.  See the "min" and "max" columns in the table below.  Gapfill proposals:

click to enlarge

Agenda for New Code June 25 New Codes Meeting (this is entirely different than the gapfill table above):

click to enlarge


Social Security Act 1834A(c)(2-4) requires CMS to post rationale for any gapfill or crosswalk price. See also 81 FR 41086, 6/23/2016.

(2) Gapfilling process described.— The gapfilling process described in this paragraph shall take into account the following sources of information to determine gapfill amounts, if available:

(A) Charges for the test and routine discounts to charges.  (B) Resources required to perform the test.  (C) Payment amounts determined by other payors.   (D) Charges, payment amounts, and resources required for other tests that may be comparable or otherwise relevant.   (E) Other criteria the Secretary determines appropriate.

(3) Additional consideration.— In determining the payment amount under crosswalking or gapfilling processes under this subsection, the Secretary shall consider recommendations from the [advisory] panel established under subsection (f)(1).

(4) Explanation of payment rates.—In the case of a clinical diagnostic laboratory test for which payment is made under this subsection, the Secretary shall make available to the public an explanation of the payment rate for the test, including an explanation of how the criteria described in paragraph (2) and paragraph (3) are applied.

Very Brief Blog: HHS Wants Help Setting Up an Effective Public-Private Partnership Channel

On Thursday, June 7, 2018, HHS published a Request for Information to help it set up a new board to discuss and propose ways to improve Public-Private Partnerships within HHS.

It's called, "Facilitation of Public Private Dialogue to Increase Innovation and Investment in the Healthcare Sector."  Comments are due in 30 days (about July 5).

The goal is "constructive, high level dialogue between HHS leadership and those focused on innovating and investing in the healthcare industry."   However, the policymakers don't presume to know exactly what a workgroup should look like or exactly what its agenda should be.  They want your advice.  Should the workgroup start by assessing recent trends in health innovation and investment?  Should it encourage private investment?  How should its membership and meetings be structured?   How can HHS develop a "durable and consistent approach" to public private partnerships and innovation to improve public health?

Find the document and comment homepage here.

See some trade press here and here.


I wrote about something on-tangent a few days ago.  For example, Federal preventive benefit regulations make it far easier to create a new Medicare screening benefit for colon cancer than for lung cancer, ovarian cancer, liver cancer, etc.   Does that really make sense?  It stimulates investment in one cancer and prejudices against investment in other cancers.  My blog here.

Appearing just a few days after the HHS request for advice, FDA's Scott Gottlieb issued a major policy memorandum about the need for innovative commercialization pathways for antibiotics.   See his speech here, and press coverage here.  He focused on "new reimbursement" for antibiotics, such as hospital based licencing, a topic pretty far afield from his home base at the FDA. 

Very Brief Blog: New Legal Actions re Constitutionality of Affordable Care Act

  • Takeaway:   New legal issues for ACA focus on "pre existing conditions."   However, among the legal documents, other issues like "preventive benefits" are also drawn into the fray.  


Much press since Thursday June 7, when HHS filed a brief that key parts of the Affordable Care Act were now unconstitutional, since Congress repealed a penalty aka "tax" for not having insurance.  The brief was part of a case running for months at the behest of numerous states.

Most of the attention has focused on whether or not the Administration should defend the law against threats, or whether it is OK for the Administration to side with those who argue the law isn't constitutional.   Beyond the individual mandate, it's worth looking at what different sides of the case argue regarding other parts of the ACA such as mandating copay free services that are endorsed by the USPSTF.

I'm a non-attorney so I provide only a simple review of my understanding of key facts.  For an entry point, see U Michigan attorney Nicholas Bagley's blog here

Phase One

There was a Supreme Court challenge that the ACA was unconstitutional since it "mandated individuals to buy insurance."   Argued, there was no constitutional authority for Congress to do that.  (Although Congress may regulate interstate commerce, raise an Army, and so forth.)   The Supreme Court actually tries to affirm that laws are constitutional if it can find a way to do so, and Court found that the penalty for not having insurance was, in essence, a tax, and Congress can tax.   Here.

Phase Two

Congress 2017 repeals the ACA tax on individuals who don't have insurance.

Phase Three

A number of states filed suit that without the tax, the Supreme Court judgement is no longer effective, as it was based on "the tax."   See State case here, 33pp.   States argue that without the individual tax, the individual mandate isn't legally justified and without that, US had already argued that other parts of the law like guaranteed issue despite preexisting conditions, don't make sense.   (It's like the scene in the movie where the good guy drops his pistol and the bad guy picks it up.)

Arguing both with US government prior statements, and with reference to a prior "severability" case (Alaska v Brock 1987), States argue that all of the ACA doesn't make sense without the individual tax, which no longer exists.

Note, as below and on several other pages, States argue that guaranteed issue must now be stripped from the law, AND OTHER regulations on insurance such as essential health benefits and the requirement to cover preventive services.  See:

Phase Four

June 7 sees the "Federal Defendants' Memorandum Response" to the above States' application for preliminary injunction against the ACA.  Here.   (See also a 3-page letter from Jeff Sessions to Paul Ryan, here.)

A) Preliminary Injunction not needed. Feds argue that a preliminary injunction against the ACA is not required, but they agree in part with the States' case and would see it affirmed in the court's decision memo.

B) Feds: Concur with States; kill pre existing condition law.  Feds argue that the guaranteed issue aspect of the ACA (no pre existing conditions) is inseparable from the tax, and guaranteed issue should be struck down now, absent the tax.

C) Feds:  Preserve rest of law.  However, Feds do NOT argue (as did States) that "all" of the ACA is unconstitutional.   One section of the Fed document states "guaranteed issue and community rating requirements are NOT severable" and another section states, "ACA's other provisions ARE severable."   Feds also argue that Congress specifically repealed the individual mandate tax (and a range of other tweaks), but if Congress wanted to do so, it could have repealed more of the ACA itself.[*]   For example, "There is no reason the ACA's expansion of Medicaid should hinge on the individual mandate."  At best, the States offer a chain of "speculative hypotheticals" in a difficult attempt to connect various parts of the ACA to the individual mandate.


We are in a rare epoch where the head of HHS, Alex Azar, is not only an attorney, but a really smart attorney, so the Fed position would carry his endorsement.

If the Court sided with the Federal brief, it would strike down the guaranteed issue (re pre existing conditions) but it would leave other aspects of ACA intact (such as Medicaid expansion and preventive services.)

* Of course, following the HHS's own line of thought here, Congressional elves could at one blow have repealed both the tax and the preexisting condition rule, if that was the Hill's intention, rather than repealing the tax while leaving the dependent pre-existing rule for a contentious multi year court case.

Friday, June 8, 2018

Very Brief Blog: CareDx Breaks Market Cap Ceiling of $500M

One of the most heartening stories in specialized diagnostics companies recently is CareDx.  The company markets the AlloMap test for cardiac transplant rejection (where a blood test can sometimes replace a cardiac biopsy) and more recently the AlloSure test (screening for kidney transplant rejection by finding free circulating donor organ DNA in blood).   Both are covered by the Medicare program, specifically, the Noridian/MolDx program.   See an AlloSure publication, Bloom et al, 2017, here.

A year ago, on June 5, 2017, share price was $1.07.  Today, June 8, 2018, it's $15.11, up fifteen times.   This gives a market cap of $523M today, as opposed to about $16M last summer.

2015 revenue was $28M; by 2017 revenue rose to $48M.   Quarterly revenue was up 17% from 2017Q2 to 2018Q1.

2017 net income was -$55M.

Other companies are also looking at the cfDNA & renal transplant space; see a UCSF/Natera collaboration announced in 2016 here.

Very Brief Blog: Tucson's ACCELERATE DIAGNOSTICS Hits Market Cap of $1B

This morning, I noticed that Accelerate Diagnostics has a lead position on June 13, 2018 at a Harvard conference on antibiotic resistance (here).   They also had a cover article in CAP TODAY for May 2018, describing them as part of a "seismic shift" in microbiology.

According to CAP Today, the platform and molecular kits "handily outstrip traditional identification and antibiotic susceptibility testing" for bloodstream infections.  See Anne Paxton's article here.

Besides CAP Today, there have been a flurry of recent articles about Accelerate Pheno on PubMed (Charnot here, Marschal here, Pantel here, Elliott here, Lutgring here). 

Accelerate Diagnostics (symbol AXDX) is based in Tucson.  According to Yahoo Finance, today's market cap is $1.1 billion.  Share price, $21 today, has been in the $18-26 range for several years.   2017 revenue was $4M with a $64M operating loss.  See a recent quarterly transcript at Seeking Alpha, here.  One financial blogger discusses the company here.  Company website here.

See an FDA press release from February 2017 here, which is a good entry point for understanding the test design and positioning.   For more technical detail, see the FDA De Novo 510(k) decision summary here, reclassification order here, DEN160032.  The FDA reviewed a primary clinical study of 1850 positive blood cultures, using slower traditional methods as a gold standard.


Bay Area molecular diagnostics company Karius is working on rapid detection of 1250 pathogens as an NGS based reference lab test; here.  It raised $50M ten months ago in August 2017, here.   Bay Area startup mFluiDx is working on rapid POCT molecular diagnostics; here.

In a talk at ASM June 2018, quoted in Genomeweb, Biomerieux's Alex Van Belkum noted that current approaches to AST are accepted and cheap, and that sequencing based AST has "a long way to go."  Here.

Very Brief Blog; Harvard Genomics Conferences (June, November, November)

The Petrie Flom Center for Health Law Policy, Biotechnology, and Bioethics is part of Harvard Law School and runs an interesting website, publications, and conferences - here.  See their book on big data and health law, here; at Amazon here.

This week they flagged several other conferences at Harvard:

June 2018
On June 26, 2018, the Harvard Medical School Department of Biomedical Informatics hosts a conference in "Precision Medicine 2018: Assembling the Puzzle."   See website here.

November 2018
On November 1-2, 2018, the Program in Quantitative Genomics hosts a conference on Biobanks. * See website here.

November 2018
In November, we'll also be up to the 14th Annual "Personalized Medicine Conference" hosted by the Personalized Medicine Coalition (PMC) and held at HMS.  November 13-15, 2018; Website here.


Harvard also hosts a conference on Antibiotic Resistance, June 13, 2018, here.

*Regarding big biobanking, the All of Us program to sequence 1M genomes established its biobank at Mayo; e.g. NIH website here,  5 year funding is $130M; 35M biospecimens will be handled; articles here and here and here.

Very Brief Blog: Rogers (2018) On Hidden Costs of Shipping Hospital Tests Out

People have been talking about drivers of lab testing costs, including hospital lab tests, for decades (see 1984 here and 1993 here and 2001 here.)    Lately, there's been much attention to "higher costs of hospital based testing," for example, arguments that PAMA pricing would be higher if hospital labs reported their payer prices (here).  Dark Report has recently been reporting that labs buy small hospitals just to access their higher price payer contracts (!), and that large reference labs are again working to tighten their relationships with specific payers, and thus, with select populations of patients within a hospital's system.

Into this whirlpool lands an article by Rogers et al. at Children's Healthcare of Atlanta.  (The context above is by me, not the authors).   See Archives of Pathology and Laboratory Medicine, here.  In the abstract, they write that: 
Disruption of outpatient laboratory services by routing the samples to commercial reference laboratories may seem like a cost-saving measure by the payers, but results in hidden costs in quality and resources to support this paradigm...Outpatient testing was sent to 3 different laboratories, specified by the payer.
My internist is affiliated with a famous health system, and I've had lab reports in different years come back with circa $150 test charges (from the health system outreach lab) or circa $50 charges (from a reference lab), so I can see the payers' point of view. 

Here's the new contribution.   Rogers et al. document that turn around times (TAT) to result rise from 1.3 hrs at the hospital lab to 39 hours at the reference lab, and that thousands of delays per annum occurred (such as miswritten date of birth).   They assert there are many hidden costs to forced routing of outpatient lab tests away from the health system lab.

Article was covered by Genomeweb's 360DX website, here.

The article contains some interesting information on salary costs for different levels of staff, including computer staff (epub p 2), and interest distribution-of-costs of different phases of lab testing (e.g. their p5 color bar chart, epub p 5).

Thursday, June 7, 2018

Very Brief Blog: Survey of Physician Salaries by Specialty for 40-year-olds

Medscape publishes a survey of salaries of physicians who have finished training but are under 40, as below.   Link here.    Pathologists, family medicine, and pediatrics are clustered among the bottom five or six.   The two highest categories are plastic surgery and orthopedics, followed by a cluster that includes gastroenterology, anesthesiology, and otolaryngology.  Psychiatry, which to my memory used to be in the lower 1/4, is in the middle in this survey.

click to enlarge

Tuesday, June 5, 2018

Very Brief Blog: FDA Finalizes Exemption for 510(k) for Some Genetic Tests

FDA has two different processes for downclassifying its regulatory system for diagnostics.  One is to downclassify a product from Class III (PMA) to Class II (510(k).   The next is to downclassify a Class II test so that it is "510k exempt."

Last November, FDA announced it planned to make some genetic tests self-certifying, that is, 510(k) exempt.   The proposed rule appeared November 7, 2017 (here).  The final rule appeared June 5, 2018 (here). 

An Exemption "After" First Review
The exemption applies somewhat confusingly to future 510(k)s after a specific test device has received a one time review by FDA.  Yes, a naive reader might think it's more of a "510k revision exemption" than a "510k exemption."

Mystery Commenter Opposed FDA's Rule
The FDA discussed in the new June 2018 rulemaking that it received "one comment" on its proposal - an objection - although the corresponding webpage lists "0 public comments" (here).     The comment, dealt with in Q&A format as is usual, was from "a professional organization opposing [the] exemption."   It would be interesting to know which organization this was or why it's comment isn't available at

Exemption from 510(k) Followed Downclassification from Class III to Class II
The June 2018 finalization was largely a "coda" to events last November, such as the downclassification from Class III to Class II of the 23andMe personal genome service test (aka Genetic Health Risk Assessment System, per new FDA category 866.5950). 

The Class III to Class II de novo 23 page review is here and an FDA press release here.  Note that these are for DTC tests.

Lengthy Analytical Validity Requirements in Regulation
FDA argues that full analytical validation is established by following stated regulations (see 21 CFR 866.5950(b)(3)(iii)).   FDA allows the self-certification with four limitations.  The health-risk tests cannot be any of these:  (1) indicated for prenatal testing, (2) predisposition to cancer where the may lead to confirmatory treatments or procedures, (3) genetic variants that impact drug metabolism, (4) assessment of autosomal dominant variants.

The device regulation category 866.5950 is 4700 words long; most FDA classification categories are only several words long.

Neither Cleared nor Approved?
Some CMS rules refer to "cleared or approved" tests, such as the spring 2018 NCD on genomic tests in cancer.   Tests that are self-certified under novel types of FDA regulations or potentially under novel lawmaking might not be pigeon-holed as either "cleared or approved" but rather in a different gray space as "authorized."

Trade Press Links

For more information see:

  • June 2018: RAPS, MobiHealth, Becker's
  • March 2018:  WSJ.    
  • November 2017:  STAT, Duke.
    • The DUKE article gives a detailed listing of the initially authorized genes and a bullet point description of the extensive controls.

Friday, June 1, 2018

Brief Blog: VA Endorses Wider Use of Pharmacogenomics

This spring, I had the chance to write a white paper for Thermo Fisher Scientific on adoption of pharmacogenomics in health system (online here).

On June 1, 2018, VA authors issue a report in Genetics in Medicine strongly advocating wider use of pharmacogenetics in their health system.  A nice online article in Genomeweb here.   See the original article by Vassy et al. here.   4 gene drug pairs were strongly recommended and and additional 12 were recommended, totaling 16.   

I believe if you are able to click on the article link from the Genomeweb news article, it will take you to a website that gives you access to read the whole original article online (but not download it.)

On June 27, 2018, I'm chairing a session on genomics and health disparities at the National Academy of Sciences, and we will have Larry Meyer, National Director, Genomic Medicine, V.A., on the panel