Brief Blog: CMS Extends Expiration Date for Antibiotic Stewardship Rule

In June 2016, CMS proposed that all hospitals have Antibiotic Stewardship Committees meeting certain regulatory standards, as a Condition of Participation.   Like all CMS proposed rules, the rule would expire in 3 years (June 2019) if not finalized.   See contemporary 2016 coverage here.   See proposed rule here.

Some stakeholders in the antibiotics and public health committee have become increasingly concerned that the rule would expire without being finalized, the equivalent of a "pocket veto."  See press here and here.   The Presidential Advisory Council on antibiotics resistance held a special, rapid, off-cycle meeting on April 8, 2019, and all the experts voted unanimously to urge HHS to finalize the rule.  For my meeting report, links, and a transcript here.

CMS EXTENDS ITS DEADLINE BY A YEAR

Inside Health Policy reports today that CMS will extend the deadline for consideration of this rulemaking by one year, until June 2020, because of its "complexity."   (Subscription; see headline here.)    CMS also noted that at least some stakeholders had originally (in 2016) asked CMS to delay implementation of the new policy.

Rulemaking was published in Federal Register, 84 FR 27069-70, on June 11, 2019.  Web page here, PDF rule here.

The announcement that the antibiotic stewardship rulemaking is deferred, not dumped, comes as the United Nations and others are working to raise awareness of the global antibiotics crisis.  Last week, as I was traveling through airports, I noticed that the cover story of Newsweek is the antibiotics crisis.

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For a comparison of proposed 2016 CMS and Joint Committee standards, see:

https://www.contagionlive.com/publications/contagion/2016/december2016/antimicrobial-stewardship-standards-a-comparison-of-centers-for-medicare--medicaid-services-and-joint-commission-requirements

GRAIL Hires Amgen SVP Josh Ofman MD as Head of Strategy

On June 6, 2019, GRAIL announced it has hired Amgen SVP for Global Value, Access, Policy, Josh Ofman MD, as GRAIL's Chief of Corporate Strategy and External Affairs.  See the press release here.

Ofman spent 16 years at Amgen.  An internist, he holds an MD from UCI, his residency training at UCLA, and a master's from the School of Public Health at UCLA.  See his Linked In here.   See an 2018 interview with Ofman on the healthcare value of drugs here.

GRAIL also announced its current CEO has had to step down for family reasons and the new CEO will be board member Hans Bishop.  Bishop was CEO of Juno Therapeutics, which Celgene acquired for $9B in 2018.   See Stat here,  Fierce Biotech here.

A Fierce Biotech article re GRAIL data from ASCO 2019 is here. A StatPlus article on GRAIL from ASCO is here.

MolDx to Hold National Workshop on Pharmacogenomics for Medicare; June 26, 1-4 ET

Under new 2019 rules, MACs are encouraged to hold Contractor Advisory Committee or CAC panels on topics of upcoming policy interest, and featuring guest expert speakers.   The meetings are available for webinar viewing by the public, and will be archived along with transcripts. 

(If anyone thinks these sound more like CMS MEDCAC meetings, you're right.)

The MolDX MACs will hold a national CAC webinar meeting on Wednesday, June 26, 2019, from 1-4 pm ET, on the topic of pharmacogenomics.   Potentially, if I understand the rules, non-MolDx MACs would have the opportunity to co-sponsor the meeting if they want to.

A more complete agenda will be posted by June 12, and registration must be completed by June 19.

It's unclear from the announcement if the focus will be on psychiatric PGx gene panels or PGx clinical utility in general.

Find the webpage here:
https://www.palmettogba.com/event/pgbaevent.nsf/EventDetails.xsp?EventID=BCVM4D0663

I've also cut and pasted the Palmetto below the break but you need to see the live link above for the most current information and updates.

UPDATE JUNE 12

See another web page with more info here:
https://www.palmettogba.com/palmetto/providers.nsf/DocsCat/Providers~JM%20Part%20A~Medical%20Policies~Contractor%20Advisory%20Committee%20(CAC)%20Meetings~BCVLAV7318?open

See a draft question list for panelists, here:
https://www.palmettogba.com/Palmetto/Providers.Nsf/files/Tentative_Questions_for_the_Multijurisdictional_CAC_Meeting_Regarding_Pharmacogenomics.pdf/$File/Tentative_Questions_for_the_Multijurisdictional_CAC_Meeting_Regarding_Pharmacogenomics.pdf

Very Brief Blog: Entry Points to Patent Law Reform and Genomics

In the wake of several Supreme Court cases on diagnostic test patents five years ago or longer, there is now a flurry of Hill interest in patent law reform. 

This appears to be a highly polarizing topic, with (A) proponents saying some patents are necessary to support investment and commercialization (without instant copycats), while (B) others say gene patenting is fundamentally wrong and also inhibits innovation. 

See a 2019 blog on investments and patents in diagnostics here and the underlying original article here (which is 94pp; Taylor; Cardozo law review journal).

The Hill is considering draft legislation and will hold hearings in early June.  The legal changes wouldn't be specific to genetics, but would have a significant impact on genomics patent law.  The draft bill just adds a few sentences to existing patent law, but they impact on a large number of stacked and intersecting court cases and case law.

I'll provide some entry points to this complex area.  Senate hearings are June 4, June 5, June 11 in the intellectual property subcommittee of the judiciary committee.

• Genomeweb overview on June 4; I believe open access, here.
• At Patent Docs, the frequently quoted patent attorney Kevin Noonan is pro-change, he has two recent open blogs with many hyperlinks,
• Overview, May 23, here.
• Positioning vis-a-vis ACLU, June 3, here.
• Washington Post, June 3, (suspicious of reform; probably firewall), here.
• Science, June 4, here.
• ACLU, June 3, here.

Very Brief Blog: CMS Updates Test Agenda for June 24 Pricing Meeting - Newest PLA Codes

Every summer, CMS holds public meetings that result in setting prices for new lab codes. 

Regular CPT codes are usually priced the summer before the January when they become effective.  In contrast, PLA codes are released quarterly, so they come into use before they hit the CMS pricing process.

On May 28, CMS updated the agenda of codes to be reviewed in its June 24, 2019 meeting.   See the main webpage here.   See the CMS website zip file of codes on the agenda, here.   I've also made my own cloud copy of the Excel, here. 

CMS includes codes on the June agenda that were just submitted to the AMA CPT in early April and voted in early May.   Congrats to both AMA CPT staff and CMS staff on keeping up this speedy schedule. 

95 Tests To Be Priced

The prior agenda had 48 items, through 0104U.  The newest agenda has 95 items, through 0148U.

Webcast and Attendance

The CMS CLFS meeting will be webcast, but if last year is example, the webcast may not be archived.  (Several years prior to 2018 had been both webcast and archived).  As of May 29, 85 seats were available (here).

Very Brief Blog: HHS to Reverse Obama-Era Definition of "Sex" within ACA Regs That Included "Transgender" Issues

As reported by Politico on May 24, 2019, the administration has released rulemaking that will role back what is framed as an error of legal interpretation in prior HHS regulations.

• See Politico article here.  The Hill here.  NYT here.  WSJ here. WaPo here.  Breitbart here.
• See the Notice of Proposed Rulemaking online at HHS here.
• 204 pages.
• The proposed rule has not yet appeared in Federal Register.
• CMS fact sheet released with the rule, here.
• The previous (currently effective) final rule appeared May 18, 2016, 81FR31375, here.
• The 2016 regulations defined "sex" as appears in ACA Section 1557 to include transgender issues.
• The text of ACA Section 1557 is concise (codified as 42 USC 18116, here.)
• As of May 24, HHS website still referred to the May 2016 final rule, here, including a 64-question FAQ on the 2016 rule.  Cloud copy here.  
• The HHS 1557 webpage notes that the May 2016 rule was under an injunction since December 2016 regarding those parts that pertained to gender (Franciscan Alliance).
• CMS published a proposed rule that also touched on transgender issues specifically within Medicare/Medicaid programs, June 16, 2016, 81FR39447, online here.  This was a proposed rule, not a finalized or effective one.

Regarding transgender issues, the new proposed rule states that in the old May 2016 final rule: " the Department defined discrimination “on the basis of sex” to cover, among other things, discrimination on the basis of sex stereotyping [and] gender identity..."    The May 2016 rule covered additional areas such as multi-lingual services (where most of the regulatory costs lie).   

The rule covers litigation history (including Franciscan Alliance).  The rule notes that on April 5, 2019, DOJ filed a brief stating that "Since the 1557 rules was issued, the United States has returned to its longstanding position that the term 'sex' in Title VII does not refer to gender identity, and there is no reason why Section 1557, which incorporates [analogous prohibition] should be treated differently."  HHS notes that the proposed rule being released now in May 2019 would bring HHS regulations into line with the position taken in court by DOJ in April 2019.  In contrast, the 2016 final rule "created confusion regarding Title IX's definition of discrimination on the basis of sex."

Total savings due to decreased regulatory burden are estimated at $3.5B over 5 years (page 124).

The new rule posits $3.5B in 5-year savings whereas the original rule projected only $1B in 5-year costs.  The new rule cites a range of resources for which HHS says it had previously severely underestimated costs (p. 122-123).

HHS adds, "Covered entities would enjoy increased freedom to adapt their Section 1557 compliance programs to most efficiently address their particular needs, benefiting both covered entities and individuals....Covered entities would be free under the proposed rule to implement policies and procedures that comply with Federal civil rights laws in creative, effective, and efficient ways that are tailored to the covered entities and to the communities they serve. (p. 125)."

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Numerous court filings both pro and con Franciscan Alliance online here.

The rulemaking refers to the Attorney General's role in supervising implementation of Title IX. which is applied here (see Executive Order 12250, Jimmy Carter, 1980).  The rulemaking also refers to Executive Order 13771 (see Reducing Regulation and Controlling Costs, Donald Trump, 2017).

For an October 2018 NYT article on Title IX, here.

For a concurrent discussion of CDC and LGBT issues, here.

Brief Curiousity: DOJ Issues Opinion on FDA and Lethal Injections

Over the past several years, states that impose the death penalty by lethal injection have frequently had difficulty obtaining drugs through commercial pathways. 

FDA has also imposed regulatory restrictions. 

This month, in a ruling that former FDA head Scott Gottlieb opposed (video interview here), DOJ has issued a 26 page opinion that FDA authority doesn't extend to drugs used for lethal injection. 

Article at Politico here.

The article has a quite interesting entry point.  It opens by noting that the FDA has authority regulate "drugs and devices...other than food...intended to affect the structure or any function of the body."   However, FDA has not regulated electric chairs and firearms for firing squads - which are devices tht do "affect the structure or function of the body."   However, of course, it does regulate drugs, and it is drugs which come into the question of lethal injection executions.

Although the new legal brief distinguishes its approach, there was a related FDA Supreme Court case brought by opponents of the death penalty in 1985, Heckler v Cheney, pdf of that case here.  In addition, following decisions Beaty and Cook, there is an injunction based on FDA law prohibiting importation of sodium thiopental into the US (it is not manufactured in the US), for any purpose.  (Refs. inside new DOJ brief, p. 7).

In one of many examples, DOJ points out that pesticides impact the human body as defined under FDA law, but are clearly meant to be regulated only under another body of law (federal insecticide act, FIFRA).

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In an interview at CNBC health conference "Healthy Returns," May 22, 2019, Scott Gottlieb discussed this DOJ document.  But he also noted that FDA was under a current active injunction requiring it to forbid importation of execution drugs.   Therefore, DOJ would have to take this new memo, go back to the injunction court, get the injunction lifted (so that FDA could "stop" forbidding importation of execution drugs), which itself would get appealed by various parties up to the Supreme Court over four years.

Very Brief Blog: Agenda and Hot Topics from Advamed's SF Digital Health Conference

Just completed: AdvaMed's annual Digital Health Conference in San Francisco, May 22-23, 2019.

See trade press here.   See agenda still online here for priorities and hot topics.

For archival purposes, I've also clipped the agenda below the break.

The AdvaMed digital conference held in SF exactly overlapped on the same days with a Big Data healthcare conference at Stanford (here).  Their keynote speaker was Jeff Dean, SVP for AI at Google.

Scott Gottlieb Gives Major Speech on Reimbursement Issues (May 10, 2019)

A Scott Gottlieb speech at the National Press Club on May 10, 2019.   New to me, today. 

Gottlieb speaks at length about reimbursement issues and dysfunctional payment policies and how they are maladapted to innovation.   Discussion that investors are forced to use arcane reimbursement rules to guide investments and what products can be brought to market - not medical science and best clinical advances and outcomes.

Find it here:

http://www.aei.org/publication/remarks-before-the-national-press-club-headliners-luncheon/


He builds to this conclusion:

Our biggest obstacles may be policy.   Our biggest challenges may be our inability to devise coverage schemes that can enable the efficient, and when appropriate the rapid adoption of these innovations; allow for a return on capital that maintains investment in these high-risk endeavors; and most important, enables equal access to a cure regardless of a person’s wealth.

We must address these challenges directly. We must be willing to start over with new payment schemes when it comes to these paradigm leaps like cell and gene therapy.

There’s no need to try and fit a cure into the existing payment schemes, when we already know those structures have struggled to keep pace with this innovation.

If of interest, I've included a lightly annotated/highlighted version below the break.

See also an OpEd article by Gottlieb on CNBC, May 20, here.

In a March 2019 speech to the Federation of American Hospitals, the notable senior White House health policy expert Joe Grogan similarly decried a health financing system too dependent on gaming and coding.  Summary here.

Gottlieb 8 minute interview with CNBC, May 21, here.
Gottlieb 24 minute interview during CNBC health conference, May 22, here.

In Unusual Move, CMS Delays Final NCD For CAR-T Therapies

In a very uncommon move, CMS announced on May 17 that it was delaying release of a final version of its National Coverage Determination on CAR-T therapies.

CMS made the announcement in a press release that was only a few words long, here.  They simply state, "A decision is [still] forthcoming."

See coverage at Fierce Healthcare, here.  At Modern Healthcare here.  For a May 10 speech on CMS CAR-T policy by prior FDA commissioner Dr. Scott Gottleib, here.

Background

CMS released a proposed CAR-T decision on February 15, with a final decision normally appearing in 90 days or less, but usually on the 90th day.  See the proposed decision here.

NCDs can include a puzzling mix of obvious and subtle criteria.  For example, the CMS NCD for next generation sequencing requires testing to be provided via a CLIA-certified lab, but other parts of national law also require that.   The NCD proposal for CAR-T requires provision "when prescribed by the treating oncologist" and must have "one physician experienced in cellular therapy" and "a designated care area that protections the patient from transmission of infectious agents."

More to the point, even when the therapy is FDA-on-label, the inpatient or outpatient beneficiary must be enrolled in a registry with follow-up at 3, 6, 12, and 24 months.  Patient-related outcomes must be measured, as well as metrics like disease free survival and overall survival.  If patients are under an indication with NCCN (but not FDA) endorsement, the patient must be in "a CMS approved trial."

Policy Issues

Commenters have raised issues as to whether CMS can/should require clinical trials for patients getting an on-label FDA-approved therapy.   Commenters have also raised issues as to whether the clinical studies required would limit access.   For an open access article on CMS CAR-T policies, here.

CMS determined to pay for inpatient CAR-T via the "New Technology Add-on Payment" process, which pays 50% of the additional costs of a new, costly technology.   Numerous articles have pointed out this may leave hospitals in the red for over $150,000 per patient.  In April 2019, CMS proposed to raise the payment from 50% to 65% beginning with the October 2019 fiscal year (CY2020).  Article at BioPharmaDive here.  Scott Gottlieb discussed CAR-T including CMS policy at some length in a May 10 speech, here.

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The tracking sheet for the NCD is here.  The NCD was requested by United Healthcare here.

To read a summary of a May 2019 speech by CMS administrator Seema Verma on Medicare's approach to new technologies and innovation, here.

Very Brief Blog: Tuesday, May 21, Webinar on CMS NGS NCD and also NGS in Europe

On Tuesday, May 21, 2019, Boston Healthcare Associates hosts a national and international webinar on policies and utilization for next generation sequencing.   It's at 11 eastern, 8 pacific, 4 pm UK, 5 pm Europe.

The first part of the webinar is led by myself - talking about the CMS NCD for next-generation sequencing.   Boston Healthcare Associates presents new data on US/European NGS utilization and coming trends.

Register here before Tuesday.   See the Boston Healthcare Associates homepage here.

Webinar description:

Even though next-generation sequencing (NGS) cancer testing has moved from a rarity to a common feature of clinical practice in recent years, reimbursement policies for NGS testing still vary widely among private and public insurers across different countries 

.
In the United States, both large commercial labs and large health systems offer NGS tumor testing, and it is anticipated that this landscape will change the availability of a US Food and Drug Administration (FDA)-approved NGS tumor panel. Meanwhile, healthcare systems in Europe are taking what is, in many ways, a very different approach to reimbursement of clinical sequencing with NGS. In France, for example, a network of regional laboratories will be reimbursed to provide molecular testing services. Similarly, genomic laboratory hubs will provide access to whole genome sequencing in the UK beginning in 2019. 

In this free webinar, the featured speakers will shed light on the clinical and commercial reality of NGS in oncology, with predictions for what lies ahead in the United States and Europe.

Speakers will be Bruce Quinn, and Joseph Ferraro, President and CEO of Boston Healthcare Associates.

Very Brief Blog: World Biomarker Conference, Boston (June 17-20, 2019)

Today's mail brought a snailmail brochure for the 15th Annual World Biomarker Congress in Boston, held in conjunction with World Pharma Week. 

The agenda looked quite interesting.   Read more online here.

• June 17 highlights "Internet of Diagnostics Things" (IoDT)
• June 18-20 include a several-day track offering an A-to-Z view of immuno-oncology biomarkers, a complex and rapidly moving area.
• Separately, see a DeciBio article on digital pathology and immuno-oncology, here.
• June 20 shifts to "Digital Biomarkers" - sensors, wearables, m-health.

Go straight to the full PDF brochure download here (email registration required).

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Footnote.  I won't be there; I'll be making my third annual trip to a two-day health innovation congress in Berlin sponsored by the Charite' health center; here. Twitter here.

Rapid Advances in Germline and Tumor Genomic Information, Services, Companies

In an excellent posting at Dark Daily on May 15, 2019, Andrea Downing Peck reviews expansion of the Cancer Gene Consensus, part of the UK-based COSMIC program (Catalogue of Somatic Mutations in Cancer).

• See Dark Daily article here.
• See COSMIC main website here.
• See website for Cancer Gene Consensus (CGC) here.
• See an October 2018 article on CGC by Sondka et al. at Nature Reviews Cancer, here.
• Together, COSMIC and CGC provide a wealth of tabular, searchable, and graphically presented information on oncogenes both germline and somatic.  If you haven't heard of these resources, worth looking at their content and approach.

Larger Context

Public Databases

• Association for Molecular Pathology manages a website of Validation Resources and Interpretation Guidelines, online here and here.
• See also Oza et al. at PubMed and, in the right-hand panel, publications PubMed sees as similar.  Find Oza et al. here, go straight into listing of its related articles here.
• Increasingly, the FDA will be able to use public databases as part of genomic test clearance/approvals: see April 2018 FDA guidance here.

CancerMine: Public Literature Database

A searchable database based on public oncology literatur is CancerMine.  See a new publication by Lever et al. in Nature Methods, May 2019, here.   See the open access database here,  See references early in the Lever et al. paper to CGC  and COSMIC, but also to Network of Cancer Genes, IntOGen, TCGA, ONGene, TSGene, and CIViC.


Increased Use of Functional Data in Clinical Diagnostics

Increasingly, genomic interpretation involves big databases, clinical curation, but also goes back and forth between the interpretation suite and an actual wetlab for molecular studies (such as rapid in vitro CRISPR studies, Moses et al. open access here, and transcriptome sequencing as in Cummings et al., 2017 here, and Kremer et al. 2017 here, Gonorazky et al., 2019, here).

In parallel, look for more attention to intronic mutations or intronic epigenomic changes like methylation, coupled with transcriptomic studies to resolve novel driver or risk mutations - see Dvinge 2015 here, Pique 2019 here.

Pipeline Analysis Coming Into Its Own

In addition to setting up clinical variant databases per se, how we get from the patient sample to the variant report follows a long and complex genomic pipeline.

Few papers have compared approaches along the whole A-to-Z clinical pipeline.   This spring, AstraZeneca in collaboration with genomic software company SolveBio published a first-of-its-kind review of the complete clinical variant pipeline, from raw BAM file to final report, for four different clinical ctDNA tests.

• The website for SolveBio here.
• See article by Stetson here, 
• Coverage in Genomeweb here.

Note than an EVP at AstraZeneca recently joined the board of directors of Guardant, here.

Machine Learning for Whole Genome Analysis in the NICU

In April 2019, Clark et al. from Rady Children's Hospital and collaborators published a landmark paper usig machine learning to automate phenotyping and interpretation.  See the Science Translational Medicine article here.

This project was picked up for a laudatory blog by NIH director Francis Collins, here.  (See also Genomeweb here, and a trade journal highlighting the incorporation of natural language processing, here.) 

See a 25 minute May 2019 conference presentation online, by program director Dr. Stephen Kingsmore, here.

The network of collaborators on the Rady paper includes Fabric Genomics, Diploid, Alexion, Codified Genomics, Tessella, and Clinithink.  Sequencing via Illumina NovaSeq.

Mix of Public, Institutional, and Commercial Sources

The field of genomics advances by a mix of platform advances, clinical databases, novel chemistry studies (e.g. transcriptomics for variant calls to reduce VUS), and commercial companies.   I've called the field "Digital Genomics" as a nascent industry, in a December 2017 article in Journal of Precision Medicine (here, here).  In that 2017 article, I laid out a possible conceptual map of digital genomic industry players as here:

click to enlarge; demonstration chart from 2017

PierianDx Webinar Online: A Company Applies Digital Genomics to Clinical Sign-outs

A few weeks ago, PierianDx (with whom Illumina established a formal collaboration last winter, here), held a webinar on its 2019 suite of services to support clinical sign-outs.

• The video, as well as the deck and the transcript, are online at Pierian here.   
• Worth checking out.

PierianDx integrates a suite of databases, sources, and services into a licensed service.   The webinar is designed to show genomic clinicians how PierianDx can support them, but it's also worth reviewing as a model and case study of how the genomics industry structure is rapidly evolving through a mix of public database, wetlab, platform, and SaaS resources.

The TruSight 500 Illumina panel is under FDA review as a breakthrough device (here).


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Footnotes.

PubMed Expertise.  When you look up an article on PubMed, the website shows you "related articles" on the right-hand margin.  ubMed lists several related articles, below which, it gives you little text hyperlinks to "see reviews" (that are related) or "see all" (related articles in their own screen).

It's not a direct fit with the other digital genomics topics in this blog, such as SolveBio and Pierian, but see a very nice article from the consultancy DeciBio on digital pathology and spatial digital analysis in pathology for immuno-oncology - May 2019, here.  They also flag about ten relevant abstracts from the upcoming ASCO2019 meeting.

Very Brief Blog: HHS Finalizes Rule to Require Drug Prices in TV Ads

Last fall, HHS announced a number of possible initiatives regarding drug prices, including requiring prices in TV ads and linking US CMS prices to European prices (via a CMMI demonstration).

On May 8, 2019, CMS finalized the rule requiring TV ads for drugs (costing >$35) to include WAC prices for either "30 days" or "a typical course of treatment."

• Endpoints blog here.
• Federal Register webpage here.
• Early copy of rule here. (CMS-4187-F, modifying 42 CFR 403.1200ff.)
• Original proposal here.
• Discussion at Foley Hoag, here.

The regulation does not include any direct penalties, but Endpoints notes that CMS proposes that other companies might sue a non-compliant scofflaw company under the Lanham Act.   ("We anticipate that the primary enforcement mechanism will be the threat of private actions under the Lanham Act...")

The regulation contains a clause over-riding state or city laws that attempted to be either more stringent or more lenient than this regulation:

No State or political subdivision of any State may establish or continue in effect any requirement concerning the disclosure in a television advertisement of the pricing of a prescription drug or biological product which is different from, or in addition to, any requirement imposed by this subpart. 403.1204(b).

They mention that CMS doesn't have explicit authority to regulate drug price TV advertising.  ("Many commenters stated that the proposal is beyond the authority of CMS to promulgate these regulations under a reasonable interpretation of sections 1102 and 1871 of the Social Security Act...")   For that matter, CMS staff also don't have explicit authority to regulate what States do (states rights!) regarding drug price advertising.

CMS notes in discussion they considered making a special carve-out counseling code payable when the physician discusses drug pricing with patients.  They deferred action for now.  Someone commented that were such a code to be created, it should be available to pharmacists also.

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Footnote.
For a May 2019 article in Health Affairs on Euro reference pricing for Medicare - Yang et al., here.  And for Pharma pushback to international reference pricing, Stat-Plus here.

Brief Blog: UBIOME - What Did They Actually Do?

With the flurry of press this month about FBI and legal actions against UBIOME, I recalled I got a UBIOME test out of curiousity last November. 

I hadn't looked closely at the email chains and paperwork until now.

This blog discusses (1) Email chains and (2) Lab methods report.  Link to Zip file at bottom.

(1) Email Chains

I opened a "uBiome Account" on October 15, 2018, and they confirmed to my email that I had.  Also on October 15, I completed a uBiome Request online (it includes questions like your history of milk intolerance, gas, diarrhea, cramps, etc).   uBiome then sent me a collection kit by mail.  (Hint: You tap their swab to your TP.)

I hadn't noticed before, on October 15 they emailed that "your SmartGut Test has been prescribed."   Apparently this is a teledoc or doc-by-wire situation; I didn't even recall knowing that it happened.  The ordering doc, it turns out, was a [name], National City, CA, NPI 1750358768.  National City is on the south side of San Diego.  This provider billed Medicare for a handful of anesthesia sessions and short office visits in CY2016.

Note that this type of order disqualifies for Medicare, since Medicare requires a payable test to be ordered by the patient's treating physician (42 CFR 410.32).  

At least as of CY2016 public CMS data, uBiome (which has an NPI) had no payments from Medicare.  If the ordering physician had been valid, my case and probably a lot of others wouldn't have met Medicare's public rules for medical necessity; in a cloud zip file here.

My uBiome kit was "on its way" to my house on October 16.  It was received back by uBiome on November 5 (hey, I travel alot for work.)  uBiome refers to the collection date as October 27.  This includes a link (I don't recall ever opening this email) to their Billing FAQ for billing insurers.  The 2019 version of that webpage is here (see also Zip at bottom).  An email says:

On November 8, I got an email asking for my feedback:

• Do you think uBiome is a TRUSTWORTHY company?   
•    (A) Not really, (B) kind of, or (C) Yes.

I don't recall a paper explanation of benefits from my insurer, but if they had paid $1000 or $2000 to uBiome and I found out about it I would have complained loudly (or blogged or tweeted.)

In fact, by checking online, there were some denied claims from uBiome to my insurer, Blue Shield CA.  It doesn't provide CPT codes but does say that "information was requested from the provider" which apparently never appeared.   BS-CA also classes some of the claims as "duplicates" (a common term in insurance for same provider, same date of service.)  Sterilized (redacted) cloud EOB here.  There are various bills for $135, $1080, $1755, $2835, $2970.  Score: BCBS 1, Lab 0.

My uBiome lab report is dated November 20, which is after the insurance billing events memorialized by BCBS.  They appeared to use my collection date or postmark date of October 27 as the "date of service" although it didn't reach the lab til November 5 nor be signed out til November 20, and in between, November 12 is memorialized by BCBS as the claims submission date for services in October.

(2) REPORT

The report is in a cloud copy in the zip file at the bottom of this blog.  In addition, I've been told a sample John Doe report is online at uBiome.

Methods and Limitations are on Page 15-16.

In the SmartGut test, microbial DNA is extracted and marker genes are amplified by polymerase chain reaction (PCR) and then sequenced using the Illumina® NextSeq 500 sequencer. The sequence data is processed using a proprietary phylogenetic analysis algorithm. On average, the sensitivity, specificity, precision, and negative predictive value for the microorganisms on our target list are 97.7%, 99.9%, 98.0%, 100.0% for the species, and 97.2%, 99.9%, 99.1%, 99.9% for the genera,  respectively.
This test detects the presence of the following microorganisms: Alistipes, Alloprevotella, Bacteroides, Barnesiella, Bifidobacterium,
Blautia, Butyricimonas, Campylobacter, Catenibacterium, Clostridium, Collinsella, Coprococcus, Dialister, Escherichia/Shigella,
Faecalibacterium, Flavonifractor, Fusobacterium, Gelria, Holdemania, Lactobacillus, Odoribacter, Oscillibacter, Oscillospira,
Parabacteroides, Paraprevotella, Phascolarctobacterium, Prevotella, Roseburia, Ruminococcus, Streptococcus, Tyzzerella, Veillonella,
Akkermansia muciniphila, Anaerotruncus colihominis, Bacillus coagulans, Bacteroides fragilis, Bifidobacterium animalis,
Bifidobacterium bifidum, Butyrivibrio crossotus, Clostridium butyricum, Clostridium difficile, Collinsella aerofaciens, Desulfovibrio
piger, Dialister invisus, Enterococcus italicus, Lactobacillus brevis, Lactobacillus coryniformis, Lactobacillus delbrueckii, Lactobacillus
fermentum, Lactobacillus helveticus, Lactobacillus kefiranofaciens, Lactobacillus kunkeei, Lactobacillus rhamnosus, Lactobacillus
salivarius, Lactococcus lactis, Leuconostoc kimchii, Methanobrevibacter smithii, Oxalobacter formigenes, Pediococcus pentosaceus,
Propionibacterium freudenreichii, Ruminococcus albus, Ruminococcus flavefaciens, Salmonella enterica, Vibrio cholerae, and Weissella
koreensis. 

Some of these microorganisms may not be considered pathogenic but are included as they reflect the state of the patient's microbiome. The microbiome and its clinical relevance is an area of active investigation. This sample has passed all laboratory and sample quality metrics.

For more information about the methods underlying uBiome's SmartGut test, please see Almonacid et al., 2017 (http://ubiome.com/gutpaper).  [also in zip file below]

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0176555&type=printable

Detection of a microorganism by this test does not imply a diagnosis. Similarly, a lack of detection does not exclude the presence of a disease-causing microorganism or a diagnosis of disease. Please consult your healthcare provider to interpret the results provided in this report. 

The SmartGut test was developed, and its performance characteristics were determined, by uBiome, Inc. For more information about the methods underlying uBiome's SmartGut test, please see Almonacid et al., 2017 (http://ubiome.com/gutpaper).

This test has not been cleared or approved by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary.

This test may be used for clinical purposes and should not be regarded as investigational or for research only. uBiome's clinical reference laboratory is accredited by the internationally recognized College of American Pathologists (CAP) and is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) as qualified to perform high complexity clinical laboratory testing.

This test is a next-generation sequencing-based assay that can identify 33 species and 32 genera of gastrointestinal microbiomerelated microorganisms from a stool swab sample, including 5 pathogenic organisms. The detection (or lack thereof) of
microorganisms is reported to the medical professional in this report. The report should be considered in context with other clinical criteria (e.g. patient history, physical exam), as well as other studies (such as laboratory, pathology, and imaging) by a qualified
medical professional prior to initiating or changing a patient diagnostic work-up or treatment plan.

Patient management decisions must be based on the independent medical judgment of the treating medical professional. The test and accompanying report are not intended to be used as the sole means for clinical diagnosis or patient management decisions.
The report may include information on the relevance of reported microorganisms. This information is derived from peer-reviewed studies and other publicly available databases and may include associations between the microorganism and a health condition.
Careful consideration must be made by the medical professional when using this information, as it may or may not be relevant to this patient. Organisms not included in this test may also have an effect on the mentioned health conditions. The organisms on this test may affect additional health conditions not mentioned on this report.

SmartGut is a clinical test, successfully validated using samples collected from individuals of mainly adult age, with a subset of minors. When ordered for minors, the results may still provide valuable information about the minor's health; however, the
accuracy of the results will differ from what was validated for the adult age range.
The reference range for each organism was established using 865 samples from self-reported healthy individuals.

ZIP FILE

Zip file of cited materials here.