PMC Publishes Research Article on Pharmacogenetics Inventories; Notes on Medicare Coverage

What's Up?

There has been a boom in pharmacogenetics interest in the last several years.   The Personalized Medicine Coalition (PMC) has just published a deep dive into how two catalogs of useful pharmacogenetics genes, and gene-drug pairs, compare and differ.  

Concurrently, a UK report recommends wider use of PGx in the NHS health system (here).

________

Background

Shortly after the creation of gene-specific CPT codes in 2014, there was a huge boom in CYP gene testing in Medicare payments - the new codes generally had no controls or edits - followed by a huge fall in CYP payments as stringent LCDs appeared.  (The CMS data for CYP spending around 2013-2016 looks almost like a COVID wave and plummet).

In 2020, MolDx adopted a PGx LCD which covered gene-drug pairs endorsed by either of two authorities external to Medicare, being FDA or CPIC.  

My MolDx PGx blogs here, here.  In late 2021, the Novitas-FCSO MACs followed with a closely similar LCD, blog here.

PMC Publishes Paper, March 2022

PMC has published a deep-dive paper comparing the two inventories references as gold standards by the LCDs, the FDA webpage for PGx genes and the CPIC website for consensus-driven PGx gene reviews. 

The paper is called, Comparison of FDA Table of Pharmacogenetic Associations and Clinical Pharmacogenetics Implementation Consortium guidelines, and appears in Amer J Health System Pharm this week.   

Find the new paper, open-access here.

PMC writes:

Study Finds Incongruities Between Drug-Gene Associations Listed in FDA’s Table of Pharmacogenetic Associations and Guidelines Published by Clinical Pharmacogenetics Implementation Consortium (CPIC)

Bridging Inconsistencies May Encourage More Widespread Utilization of Hallmark Personalized Medicine Tests

WASHINGTON (March 30, 2022) — A comparative analysis conducted by the Personalized Medicine Coalition and published today in the American Journal of Health-System Pharmacy reveals incongruities between the drug-gene interactions that appear in the U.S. Food and Drug Administration’s Table of Pharmacogenetic Associations and those that are referenced in widely consulted clinical guidelines published by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The findings underline differing perspectives regarding the classification of certain gene-drug interactions that may deter clinicians from ordering pharmacogenetic (PGx) tests whose results would be difficult to interpret.

In comparing the drug-gene associations listed in FDA’s table with the guidelines published by CPIC, a team of authors including PMC Senior Vice President for Science Policy Daryl Pritchard, Ph.D., Atrium Health Cancer Pharmacology and Pharmacogenomics Chair Jai N. Patel, Pharm.D., PMC Program Manager Lindsay E. Stephens, and Intermountain Healthcare Executive Clinical Director of Precision Health Howard L. McLeod, Pharm.D., found that the same drug-gene associations and dosing implications were reported for only five of the 126 drugs that were listed by one or both sources. An additional 34 drugs were listed by both sources but with differing gene associations and dosing implications. The remaining 87 drugs were listed by only one of the two sources.

“This study reveals conflicting information regarding potential drug-gene interactions that undoubtedly cause confusion among health care providers, thereby slowing the integration of pharmacogenomics, one of the pillars of personalized medicine, into clinical care,” said PMC President Edward Abrahams.

British Recommendation: More PGx

See an open access article at Genomeweb about a British report 951pp) recommending more PGx in the UK.

https://www.genomeweb.com/policy-legislation/uk-report-urges-widespread-nhs-uptake-pharmacogenomics

Report online - 

https://www.bps.ac.uk/getmedia/b43a3dca-1bbf-4bff-9379-20bef9349a8c/Personalised-prescribing-full-report.pdf.aspx

United Healthcare's 40-Page Guide to Medicare Molecular Policies; MolDx Definition of Algorithm

Worth knowing about.  For its Medicare Advantage plans, United Healthcare needs to follow Medicare policies, and for genomics, that's mostly local or LCD policies.

United Healthcare publishes a 49 page guide, updated regularly, of which pages 5-49 are an index to the numerous local LCDs and billing articles.   Handy to know about.

https://www.uhcprovider.com/content/dam/provider/docs/public/policies/medadv-guidelines/m/molecular-pathology-diagnostics-genetic-testing.pdf

MolDx Defines an Algorithm

One thing I've heard about but not sure I've seen directly, the MolDx definition of an "algorithm" in a lab test.  Find it for example at Article A58677.  From March 2021.

An algorithm being defined as....

_______

An algorithm may be considered a meaningful and independent component of a laboratory process when ALL the following conditions are met:

• It is an unambiguous problem-solving operation that includes deploying a set of rules or calculations requiring computer processing;
• The test result (or a component of the result) is the calculated output of this process, and not an intermediary process;
• The same or similar test result could not be obtained without the use of this process;
• The input for the computation is derived from biological samples using analytical processes, and must include data from the sample submitted for the test;
• The process must:
• Either be required for the analytical result, OR
• If adjunct to the analytical result as a post-analytical process, the calculation itself must be independently found to be reasonable and necessary apart from the other components of the test.

Examples:

• A gene expression profile test wherein sequencing data must be compared in a calculation to an existing and validated set of profiles to bin it in one of several possible risk stratification groups would require the use of an algorithm as defined above.
• A next generation sequencing (NGS) test that uses computation to identify variants in a sample is not considered as using an algorithm in this context. The calculation in this scenario is seen as an intermediary process.

Calculations using only clinical information not derived from analytical services on biological samples are not considered algorithms in this context. 

Examples would include using the clinical information from the patient in a calculation to assess their risk stratification or using a similar process to identify relevant clinical annotations derived from literature as associations with sequencing variants.

A test that inputs resultant analytical processes that are reasonable and necessary (such as gene variants or protein markers) that are post processed by computation, but wherein that subsequent computation is not independently established as reasonable and necessary above and beyond the other lab components, shall not be considered an algorithm as a valid component of a laboratory test.

Brief Blog: OIG Issues Advisory Opinions on Clinical Trial Copays, Digital App Payments

The HHS Office of the Inspector General regularly responds to request for Advisory Opinions (most frequently on endless scenarios for anti kickback regulations).   Sometimes, companies submit for an opinion on behavior of their competitor, hoping to get a negative opinion.   Some opinions are deadly dull; others treat odd topics in a surprising way.

HHS has a homepage for Advisory Opinions, or AO's, here.  There were 20 in 2021, and already 4 in 2022.  (There were only 9 in the 2020 election year and even less, 6, in 2019.)

AO-22-05 Cost Sharing in Trials

AO-22-05 is about a manufacturer subsidizing cost-sharing obligations in a clinical trial.  The context is Category B Investigational Device trials, which are paid by CMS (see webpage here.)   

Note that when Medicare itself does Coverage with Evidence Development, a little widget of statute allows CMS to vary the cost-sharing rules to ensure masking (treatment vs control, don't get different payments).  See my comment about SSA 1833(w) in an earlier blog here.  Text at footnote.

This AO, in contrast, is about the manufacturer and copays, not CMS itself and copays.  

In the case, the OIG found the scenario allowable, for example, because the trial enrollment was fixed, not open-ended (there would be exactly 260 patients with or without the copays), and the trial was a one-time surgical device (so there was no ongoing inducement to a patient.)

AO-22-04 Digital Apps, Payments to Patients

AO-22-04 handles "contingency management" rewards software used as part of addiction treatment software.   The patient using the software completes modules and may get a reward (e.g. Starbucks card).  Is this a kickback or inducement?  

The OIG ruled no, for several reasons, one of which was that the app provider did not itself directly bill the federal government.  

See also a recently introduced bill for FDA-approved digital medicine software, S 3791, HR 7051, here.

___

Text of 1833(w) re: patient copays in CMS-supported trials.

(w) Methods of payment.—The Secretary may develop alternative methods of payment for items and services provided under clinical trials and comparative effectiveness studies sponsored or supported by an agency of the Department of Health and Human Services, as determined by the Secretary, to those that would otherwise apply under this section, to the extent such alternative methods are necessary to preserve the scientific validity of such trials or studies, such as in the case where masking the identity of interventions from patients and investigators is necessary to comply with the particular trial or study design.

CMS Announcement for March 31 Webinar on Transitional Coverage for Emerging Devices

 CMS held a webinar on the theme, "Transitional Coverage for Emerging Devices," on February 17.   CMS will hold a second webinar on the same theme on Thursday,  March 31, at 3 pm ET (12 noon PT).

A February 17 transcript is here.

Note that CMS is consistently using "Transitional Coverage for Emerging Devices" or TCET as a brand name, or programmatic name, but it doesn't have any specific rules or content yet.   

For the next, March 31 webinar, here's the email invitation as I received it:

____________

CMS is hosting the second in a series of public meetings to obtain feedback to help inform CMS’ development of an alternative coverage pathway to provide transitional coverage for emerging technologies.   These meetings are part of several steps CMS is taking to help better achieve the goals of timely and predictable Medicare coverage of devices while ensuring that Medicare covers items and services on the basis of scientifically sound clinical evidence and with appropriate safeguards.   We appreciate all of the helpful stakeholder feedback we received during the first listening session on February 17. The transcript and recording for the February 17 meeting can be found here. The framework for the second listening session on March 31 at 3:00 PM ET  builds upon information gathered in the first session.   During the March 31 listening session, we would appreciate receiving feedback on the following questions:  Do stakeholders find CMS guidance on acceptable outcomes and durations of follow-up useful within specific therapeutic areas? Engagement with CMS should occur after the results of pivotal clinical trials are available, but early enough to expedite coverage after FDA market authorization.  As we streamline the coverage review process, what is the appropriate timing of stakeholder engagement with CMS? As we work to provide a more collaborative evidence development process, what are stakeholders thoughts on:

Should CMS provide early feedback on strengths and weaknesses of the available evidence based upon a preliminary systematic literature review? Should manufacturers propose a fit-for-purpose evidence development plan to resolve any evidence gaps identified during the preliminary systematic literature review as part of the national coverage determination process?

How should CMS approach evidence development requirements for similar devices that are FDA market authorized after a Coverage with Evidence Development decision is finalized?  You can register for the March 31 listening session by following the link below. If you previously registered for the February 17 session, you do not need to register again to attend the second session on March 31.  What: CMS Listening Sessions on Transitional Coverage for Emerging Technologies When: March 31, 2022 3:00 - 4:30 PM ET. Who should attend: This listening session series is designed for all Medicare and Healthcare Partners. RSVP: https://cms.zoomgov.com/webinar/register/WN_gfZYH-txQu2kP4MZVbMSJw

MedCityNews: IBM Dumps IBM WATSON, Gets "Salvage Value"

I wrote two blogs on AI in radiology and pathology so far in 2022, focused on very specific achievements (here, here).

Here's a story that didn't get the headlines it might have.  MedCity reports that "IBM is dumping" IBM WATSON, its much-touted, formerly much-hyped program, and "for salvage value," here.   See also a story at Quartz, "What Went Wrong?" here.   Similarly, NYT last summer here.  On the sale, some additional quotes and links here.

AI has to be approached carefully; see a current JAMA article discussing problems with the historical roll-out in the past decade of computer assisted detection in mammography - here.   

On the Other Hand

On the other hand - in focused domains, there are really interesting things going on.  

See an article on an AI-based improvement in measuring PDL1 and tumor infiltrating lymphocytes, here.  And see a MedCity article on digital pathology companies collaborating with major health centers toward focused goals, here.

___

Memory Lane

In 2010, GE bought Clarient, a specialty pathology lab, here.   One area of major investments by GE was "MultiOmyx" multi antigen slide staining (restaining) technology (here).  I don't think it ever went very far commercially, but, NeoGenomics does have a webpage about MultiOmyx here, and reported a number of 2021 abstracts.  WSJ labeled Clarient a $587M acquisition in 2010 (here).  The 2015 sale to NeoGenomics was reported at $275M.   However, it was also reported at the time that GE was retaining 32% of Clarient, suggesting the sale represented 68% of the market value.    As I was writing this, Neogenomics abruptly sank 30% on March 29, 2022 (here).

Cancer Cells in Culture: The Next Frontier in Clinical Diagnostics?

The idea of using cancer cells in culture to predict chemoresponse has been around for decades, literally back to the 1970s.   However, it's never thrived, and both Medicare and commercial insurers tend to have non coverage policies (see CMS NCD here, see ASCO here).  For Medicare nerds, there's even some colorful legal history online.

But this may change soon.   There's a groundswell of activity in functional cancer cell assays - of the patient's own cancer cells - to predict chemoresponse.  Publications are appearing rapidly and funding of new companies is active.

Here are some entry points:

• For a thorough 2022 review and entry point, see Letai et al., "Functional precision oncology: Testing tumors with drugs to identify vulnerabilities and novel combinations."
• At Cancer Cell here, and open access.
• See two articles in the February 2022 issue of the AACR journal, Cancer Discovery:
• Kornauth, "Functional precision medicine provides clinical benefit in advanced aggressive hematologic cancers and identifies exceptional responders."  Here.
• Malani, "Implementing a functional precision medicine tumor board for AML."  Here.
• See an Op Ed by Letai on the two articles here.
• See a March 2022 article in Nature Medicine by Ganan-Gomez et al:
• Galan-Gomez, "Stem cell architecture drives myelodysplastic syndrome progression and predicts response to venetoclax-based therapy."  Here.
• This is paired with a news article here.
• See also coverage of this report, in Precision Oncology News here.

There's also an active "Society for Functional Precision Medicine" now, here.  It's meeting in New Orleans in April.

Context: Conventional Genomic Medicine is Important, But Results Don't Always Help

Both the Cancer Cell review by Letai, and the Kornauth article (with detailed tables) discuss that broad studies of the population impact of conventional genomic panels often show fairly small results in the whole population, although big results for certain patients (e.g. for the 2% who are ALK fusion positive).  

This same point was made by Adashek et al. last year in Nature Cancer, "Missing the target in cancer therapy," 2:369, 2021.   These comprehensive tests are critically important to run, to find the positives, yet, 10% of patients may have Gene A, 5% have Gene B, 2% have Gene C, and it tails off from there.   

In the same vein, see a December 2021 article in Precision Oncology News, with San Antonio breast conference data, that in a clinical report, the lower-ranked genes or unranked genes (in a 300- or 400-gene panel) do not often contribute to improved survival.    

Potentially, functional assays can step in and fill the gap in finding the best therapy choices for the 50-70% of patients who don't have a clear cut gene-targeted drug, or in whom, their ideal gene-targeted drug just didn't work.  

____

Tidbit.  For those who missed it, see Turna Ray's 2021 year-in-review for precision oncology - January 2022, here.

Duke Margolis Center, Stanford Biodesign Co-Host Workshop on Medicare Coverage for Innovation

In 2020/2021, CMS proposed and finalized "Medicare Coverage for Innovative Technologies," MCIT, then canceled it.  Now in 2022, CMS is hosting "listening sessions" about programs for innovation under the title "Transitional Coverage for Innovative Technology," TCET.   

MCIT would have been based on FDA breakthrough device status.  "TCET" is just a title without specific rules or content yet.  

On March 28, 2022, Duke and Stanford will co-host a two-hour program, "The Need for Transitional Coverage for Emerging Technologies" from 9-11 pacific, 12-2 eastern.  This program brings together the Duke Margolis Health Policy Center and the Stanford Byers Center for Design.

Find the website here.   Find the agenda here.  Find the Zoom registration here.  Find the 9-page white paper "Discussion Guide" here.  In a nice collaborative touch, I noticed the agenda PDF is hosted at Duke.edu, while the Zoom link is hosted at Stanford.

More about MCIT/TCET:

• CMS hosted a "listening session" on the yet-undefined idea of TCET in mid-February; I summarize it in a short video here.   
• More recently, I tried to dollarize the value of MCIT, as it was proposed in 2021, and found that with simple assumptions it was highly value-creating, whereas with similar assumptions, Coverage with Evidence Development (CED) was value-destroying - blog and data here.
• I just turned in galleys for an article covering my views on ways Medicare promotes or blocks innovation, which will appear in the journal Inside Precision Medicine (formerly Clinical Omics) in early April.

CMS March 31

The Duke webinar on March 28 precedes a second CMS-based listening session on TCET on March 31.

Very Brief Blog: Is VALID Back with Momentum?

Update: March 25, 360DX runs an article on how laboratory and genetic experts are viewing the chance for a revived VALID bill: here.

March 20 Blog:

Usually I go further than just pointing to subscription articles, but here, there's one that is worth just pointing to.

On March 16, 2022,  360DX ran a detailed subscription article, by Adam Bonislawski, with the headline:

• FDA Control of LDTs Looms as Momentum Builds for VALID ACT
• https://www.360dx.com/policy-legislation/fda-control-ldts-looms-momentum-builds-valid-act

Recall that the VALID act has been kicking around for a number of years, and has been introduced in multiple versions - the "Verifying Accurate Leading-edge IVCT Development" Act.  For the most current legalese, see the House HR4128 version for 2021-2022 here.   The bill heavily edits existing FDA law, inserting or deleting clauses, which makes it particularly hard to read as a stand-alone document.

The new attention is that DC insiders seem to see momentum for attaching VALID Act to MDUFA, the five-year FDA funding authorization bill which must be past in 2022.    Proponents are happy; opponents like AACC say this is a very bad idea; and ACLA is quoted as saying it is taking this very seriously and looking at it very closely, and if it passes, hopes to input some key edits and improvements.   Most parties seem to agree that part of the political momentum is a January 2022 NYT lead article on NIPT testing, which is an LDT field, including parties that felt that article was an awful article.

____

See a 2021 paper on the cost of VALID Act for cancer labs (here; I'm a middle coauthor) and an article asking whether FDA lessons from the EUA rapid review experience might not benefit efforts like the VALID Act (here).  

As noted in the "update" top section, see also a March 25, 2022, article in 360DX on how ACMG and other genomics experts are viewing a revived VALID.

Bizarre Article: Medicare MACS Seek Repayment for "Stem Cell" Injections

This is one of the oddest stories I've seen in a year.  Since it likely involves a lot of litigation, I'll focus on what MedPageToday has reported.

In a March 16, 2022, open access article (registration might be required) MedPageToday writes, 

• Medicare Claws Back Money for Dubious Birth-Tissue Stem Cell Shots
• Government seeks to recoup more than 2 years of payments for unproven treatments
• https://www.medpagetoday.com/special-reports/exclusives/97707

The article links to a WPS MAC recoupment articles, which announce retroactive claim denials and recoupments for certain HCPCS codes for injections of "manipulated and/or placental tissue biologics for injections."   Find the WPS MAC article here.

The MAC doesn't seem to list the HCPCS codes that are involved, which surprised me a little.  The MAC does cite a Medicare manual passage stating, "The A/B MAC (A), (B), or (HHH), or DME MAC will deny coverage for drugs and biologicals, which have not received final marketing approval by the FDA unless it receives instructions from CMS to the contrary."

The FDA periodically has published alerts to the public about "regenerative medicine products" such as "stem cells."  Here from 2020.

While the MAC doesn't cite HCPCS codes, the in depth MedPage article refers to at least one code, Q4206.  The approval of the HCPCS code is summarized at the CMS HCPCS meeting of May 13, 2019, which is in an online CMS PDF at page 11 (here).   Historically, Q codes were issued for specific Medicare program needs (such as to implement an NCD rapidly) and Q codes were issued quarterly at a time when other HCPCS codes were normally only issued annually.   

Coverage?

Possibly, the coverage could be related to the 21st Century Cures Act, which made it harder for MACs to create and revise LCDs.   Possibly, CMS told MACs to pay claims with legal codes unless (1) they had bandwidth to stop the claim for manual review by clinical staff, or (2) they had an LCD on it.  Lacking either, the codes may have autopaid at the time of submission.  Autopay is common, for example, codes for office visits, or appendectomies, generally autopay.  It sounds like these were "buy and bill" products, so the first line of recoupment is the doctor or clinic that billed Medicare, not the manufacturer.

I found an article A54117 describing coverage of Q4206 at Novitas MAC here.

Payments for the one code mentioned by MedPageToday, Q4206, were $19M in CY2020.  (Here.)  Around Summer 2022, CMS will release 2020 files of which doctors were paid for the code (and all other HCPCS and CPT codes).

Pricing?

I'm not sure how codes for stem cells etc would have been priced.  

CMS has a lot of Q codes in DME pricing files (e.g. here) and a lot of Q codes in ASP drug pricing files (e.g. here).   In the time available, using those 2 sources, I didn't find a published reference price schedule at CMS which would allow autopay of (for example) Q4206.

___

And the lesson is...

For startups that are working they tuckus off to get Breakthrough Approvals and other validations, and finding it dead-hard to get a single dollar from a MAC, they'll be mystified at how tens of millions of dollars allegedly flowed out this way, again, taking the MedPageToday article as the source.

 

____

Cloud copy of WPS article here. 

A54117 here.  A54117 linked to Novitas LCD L35041.

Nerd Note: March 9, 2022: CMS Updates ADUHELM Pricing

There has been extensive news pro and con the Alzheimer drug ADUHELM.  I noted an unexpected reference to ADUHELM pricing when I was looking up ASP pricing on other products.   I'll quote CMS in full; I don't claim to fully understand the inner details of ASP pricing rules.  This points up the complexity of the longstanding ASP pricing rules for injectable Part B drugs.

"WAMP" is "Widely Available Market Prices," see an OIG report here from 2012.

See a February 2022 notification from OIG to CMS, here.

Relatively complicated WAMP rules are online here, with a key section at (d)(3):

(3) Widely available market price and average manufacturer price. If the Inspector General finds that the average sales price exceeds the widely available market price or the average manufacturer price by the applicable threshold percentage specified in paragraph (d)(3)(iii) or (iv) of this section, the Inspector General is responsible for informing the Secretary (at such times as specified by the Secretary) and the payment amount for the drug or biological will be substituted subject to the following adjustments...[continues]

https://www.cms.gov/medicare/medicare-part-b-drug-average-sales-price/2022-asp-drug-pricing-files

2022 ASP Drug Pricing Files

Notice of Pricing Changes for the April 2022 Medicare Part B Quarterly Average Sales Price Pricing File

This announcement serves as notification of the process that we used to substitute the WAMP for the ASP for Aduhelm in the April 2022 ASP pricing files, consistent with our regulations at 42 CFR 414.904(d), based on the findings of the OIG that the ASP used to set the Medicare Part B payment amount for Aduhelm exceeds the WAMP.

 Based on the findings of the OIG that identify the WAMP for a drug, we will substitute the WAMP for the ASP for the HCPCS code that identifies the drug for the following quarter, and we will announce the substitution through the ASP pricing files, which will reflect the substituted payment allowance and include a notation of the substitution.

Consistent with this process, based on findings of the OIG transmitted to CMS in February 2022, we have substituted the WAMP for the ASP for HCPCS code J0172 (Inj, aducanumab-avwa, 2 mg) for the quarter beginning April 1, 2022.

Consistent with the Calendar Year 2011 Physician Fee Schedule final rule (75 FR 73470), we are providing an opportunity to comment on the process and the WAMP substitution for Aduhelm. Comments should be directed to sec303aspdata@cms.hhs.gov by March 30, 2022.

Jeopardy question - Answer, WAMP.   Question, "Alex, what is Medicare Widely Available Market Price?"

Very Brief Blog: MOLDX Posted Infectious Disease Policy, Now Posts Public Comment Document

Earlier in March 2022, MOLDX posted an elaborate LCD for molecular infectious disease panels.  The elaborate LCD included an elaborate "billing and coding" article.  Entry point here. L38988.  See also the TA document here.

Now, on March 17, they've also posted one of the longest public comment responses, I've ever seen.  Medicare article A59005.  25,000 words.  From the CMS website, the article prints out at 72 PDF pages for me.

(For original comments in their original letter form, I found one online at AMP, the June 2021 AMP / AGA / CAP comment here.)

Find the MolDx response to comments online here:

https://www.cms.gov/medicare-coverage-database/view/article.aspx?articleId=59005&ver=8

Given the length of the Q&A, what's in it?  In the left column, they quote comment letters in full.  In many cases, in the right column, they state briefly "Comment has been answered, see above." or "Thanks for comment."

Most head-spinning moments for me were when stakeholders comment, and I read and re-read this stuff, "This looks like an inpatient policy" and MolDx responds, "This is not an inpatient policy, as we state, "This is not an inpatient policy" quote unquote.  And yet the policy and Q&A comments exchanges repeatedly state for many situations patients must be  admitted as critical care facility inpatients or ER patients." In which circumstances, the tests are bundled to the ER APC visit or the facility DRG visit.

___

See an article sponsored by Biofire on its use in identification in blood culture analysis.  Note, that patients getting blood culture will usually be inpatients (or ER patients) where tests are bundled (except if they are human DNA-RNA).

Very Brief Blog: Two New Pieces about Dr Meena Seshamani, Center for Medicare

CMS has two big arms - the Center for Medicaid and the Center for Medicare.  Under the Biden administration the head of "CM," Center for Medicare, is Dr. Meena Seshamani.

See a new op ed by her on the direction of Medicare at Washington Times - here.

See a new interview with her at JAMA - here (podcast), here (text).

CMS org chart here.

For the annual, multi hundred page MEDPAC report to Congress, March 2022, entry point here.

Very Brief Blog: ARPA-H: Gets First Billion Dollars in Budget Act

Missed this news a few days ago.  $1B for ARPA-H.

In early 2021, we began hearing discussions about creating ARPA-H, a special research agency for translational health research.   ARA = Advanced Research Projects Agency.  It would build off government funding successes and design-of-agency ideas from DARPA, BARDA, Operation Warp Speed and others.  See some links from January 2021 and a research February 2022 Hill hearing - here, here.  I collected some links about Operation Warp Speed in January 2022, here.

The recent March 2022 budget legislation gives ARPA-H its first $1B, starting now and for 2.5 fiscal years.   The legislation also gives HHS 30 days to decide if ARPA-H will be "inside" NIH or administratively an entirely new agency (like NIH, NSF, etc).   

See an article in SCIENCE, 15 March, by Jocelyn Kaiser, here.

Very Brief Blog: Jury Awards CareDx $45M in Advertising-Based Lawsuit

In an unusual case, a jury awarded CareDx $44.9M in a false advertising lawsuit against Natera.

But according to an article on Genomeweb, "the jury also found CareDx liable for two instances of false advertising."

See the full article at Genomeweb:

https://www.genomeweb.com/sequencing/jury-awards-caredx-449m-natera-lawsuit-finds-both-companies-engaged-false-advertising

See also coverage at Reuters:

https://www.reuters.com/legal/litigation/caredx-wins-45-mln-verdict-against-natera-false-advertising-2022-03-15/

CareDx and Natera have also haggled over patents (November 2021):

https://www.jdsupra.com/legalnews/caredx-v-natera-extrinsic-evidence-5443760/

Very Brief Blog: JAMA Addresses Alzheimer Testing in View of Patient EHR Access Laws

One of the outcomes of 21st Century Cures (2016) and other legislation has been increased direct access to patient health records, like lab tests, along with interoperability.

In JAMA Neurology this month, see an op ed speculating how these rules should, or could, play out in Alzheimer's disease, as more accurate tests roll into the market.  "Bringing Alzheimer Disease Testing and Results Disclosure into the 21st Century Cures Act," by Largent & Bradbury, here.

The article has a number of interesting citations, including these:

Schindler & Bateman (2021) Combining blood based biomarkers to predict risk for Alzheimer's disease dementia.  Nature Aging here.

Filippi et al. (2022) Amyloid-related brain imaging, systematic review.  JAMA Neurol here.

Jansen et al. (2022) Prevalence of amyloid abnormalities and the Alzheimer disease spectrum [19,000 patients], JAMA Neurol, here.

Very Brief Blog: AMA Launches "CPT Developer Programmer" for Innovators

AMA.   AMA launches a program to help innovators foresee and develop coding for innovative products.  See article on the "CPT Developer Program" at AMA here.  AMA notes it will hold a "developer symposium" in November (I assume November 2022).

See my blog last week on legislation to create a new digital medicine benefit category at Medicare, and notes on recent coding updates in digital medicine at both AMA and CMS HCPCS - here.

Quotes from the AMA CPT announcement - 

The CPT Developer Program facilitates access to the AMA’s expertise, content and resources in medical terminology and coding to those with pioneering ideas at the crucial early stages of product development.

The program is designed to help developers get their innovations in front of the physicians who can use them to help patients. Program participants will have access to a monthly newsletter, quarterly journal and educational webinars on how the CPT code set gets used and why it’s important to innovation.

Here are some other elements of the program.

CPT development licenses. These yearlong licenses allow the developer community royalty-free access to CPT content to build and test innovations in their development stage prior to production.

AMA Intelligent Platform. This central interface allows users to license, access and manage the latest CPT content with modern delivery options including application programming interfaces, web apps and data files.

Developer engagement. Educational and informational opportunities designed to foster collaboration and co-creation with application developers will be offered, including the AMA’s first developer symposium in November.

MolDx MACs Post Final LCD for Infectious Disease Testing

The MolDx MACs have posted a final LCD for infectious disease testing.   The draft LCD was in comment period around May 2021 and finalized at all four MACs on March 3, 2022.  This triggers a 45 day "notice" period (effective date April 17, 2022).   The LCD numbers are L38988 (Palmetto), L39044 (WPS), L39038 (CGS), and L39001/39003 (Noridian).

See the draft LCD here.

See the final LCD here.

See the billing/coding article here.  It's pretty complex at 52 pages.

A "response to comments" was posted a week later, entry point here.

See the "Technical Assessment" guidance document (in Excel) here.  Appeared April 1, 2022.

I have posted a PDF "redline" version of the draft versus final.  There are quite a few changes in the final in this LCD.  (In contrast, a number of LCDs are finalized with minimal if any changes).

Find the PDF redline version here.

I've also put the documents in a single ZIP file here.

Notes

The policy notes it is "not a coverage policy for metagenomic next generation sequencing," or for mass spec or FISH testing.   The policy distinguishes FDA and non FDA tests.  Most of the LCD focuses on when limited panel testing is required (that is, when more than 1 pathogen is tested.)   The LCD also strongly carves out special rules for "expanded" panel testing where "expanded" panel is described as more than 5 pathogens (that is, 6 or more pathogens).

For example, in the >5 pathogens section, bloodstream infection panels are covered "when there is clinical concern for bacteremia" AND ALSO "microbes were seen on a gram stain of blood" AND ALSO the patient is managed in a critical care facility (includes emergency room) AND personnel will rapidly tailor therapy to the result.   Note that from a Medicare Part A, Part B, policy perspective, this seems to limit testing to the hospital and ER setting, where microbial tests are bundled to the DRG or the E.R. facility service anyway (there is no separate payment for MolDx to decide to pay or not pay).  Om tje Q&A document, they insist "This is not a Part A coverage policy" concurrently stating, "Patients must be in a critical care facility." (?!).

For UTI panels, the patient must be at high risk for UTI complications (e.g. elderly) AND (OR) seen in a specialty urologic care setting.

There are also quite strict, and fairly elaborate, rules for the use of panels in GI or pulmonary disease.  Again, for respiratory panels, "the patient must be treated in an appropriate critical care facility," suggesting the patient is already in a hospital or ER, where the microbiology testing would be a bundled service for Medicare patients.

CPT Watchers Note

The policy uses the newest infectious disease panel code, a 2022 AMA CPT code for blood pathogen detection, 6 or more targets, 87154.  This was  crosswalked last fall to $218.

MolDx Watchers Note

I think this is the first time the four MolDx MACs have released a draft or final policy all on the same day across the several MACs.

MAC Watchers Note

I've commented previously that the Novitas MAC issued an extremely vague draft and final LCD for infectious panels (they're covered if timely and expected to affect care).  That might seem like a license to cover anything, but I've warned, the vague wording could also be applied too narrowly by auditors and recoupment entities, creating big headaches for labs.  In contrast, the MolDx LCDs here are quite rule-oriented and granular.  

Digital Medicine & Medicare Law: Bill Introduced for FDA-cleared "Prescription Digital Therapeutics"

In a March 10, 2022, press release, four legislators announced the introduction in House and Senate of a bill that would create a benefit category and payment authority for FDA-cleared Prescription Digital Therapeutics.  The bills are numbered as S. 3791 and H.R. 7051.

See a press release here:

• https://www.capito.senate.gov/news/press-releases/sens-capito-shaheen-reps-mckinley-thompson-introduce-bipartisan-access-to-prescription_digital-therapeutics-act

See a PDF of the proposed legislation:

• https://www.capito.senate.gov/imo/media/doc/03-10-2022%20Digital%20Therapeutics%20Bill.pdf
• 
  

The bill defines a PDT as a software device cleared, approved, or "de-novo'd" by the FDA for prevention, management, or treatment of a medical condition, primarily using software to achieve its effect.  The definition is added to Section 1861(s) of the Social Security Act, where it would become benefit "GG" if enacted.

The bill includes coding and payment rules, modeled in part on the median-market-price surveys implemented for lab tests under PAMA in 2014 (see SSA 1834A).

Like other proposed bills, the proposal will be assigned to House and Senate subcommittees and could be attached to future Medicare updates.

AMCP supports the act, https://www.amcp.org/About/Media/Press-Releases/amcp-statement-prescription-digital-therapeutics-act

Coding Updates

AMA.  In September 2021, AMA created a code for cognitive behavior app management as monthly physician's supervisory service (to be active in CY2023).   (For a discussion of codes up to the newest one, see a November 2021 article by Foley Lardner here.)

AMA.   AMA launches a program to help innovators foresee and develop coding for innovative products.  See article on the "CPT Developer Program" at AMA here.

CMS HCPCS.  In early 2022, the CMS HCPCS group approved a HCPCS code A9291, active beginning April 2022, for "Prescription digital behavioral therapy, FDA cleared, per course of treatment."  Announcement here, page 46.

SEP-1 Quality Measure Under "Appeal" At National Quality Forum; CANCELED APRIL 29

Update - NQF "Dismisses SEP-1 Appeal," see Sepsis Alliance announcement, April 29, 2022, here.

Prior Text:

Update - See an April 2022 article in NEJM, that "quality measures" are a "flawed system" for "fixing a flawed system."  Here.  

Update - when I wrote this, I understood SEP-1 comments were open to March 16, which is what the website still shows, and would be discussed on video at a April 29 meeting.  Now, I don't see an April 29 web meeting (for SEP-1 to be appended to) and my best reading is that they will be discussed at a video meeting on June 3.

https://www.qualityforum.org/ProjectEventsList.aspx?projectID=86057

_____

As I've described from year to year on this blog, the SEP-1 CMS quality measure has an unusual and colorful policy history (for example here.)

That colorfulness continues.  See a story about an appeal filed against the latest SEP-1 decision by Joyce Frieden at MedPage today, March 8 - here.

Despite a turbulent volume of conflicting literature and opinions, and some strong guidelines or position papers from several medical associations such as IDSA, the quality measure got through its five-year review at NQF this summer with relatively limited discussion.   After public comment cycles it was endorsed as renewed around December 1, 2021.

The NQF website can be devilishly hard to navigate, but it shows that an Appeal of the SEP-1 process has been lodged by a number of major associations, such as IDSA, ACEP, SHEA, and others.

This is the master page for the Patient Safety forum, and it shows COMMENT on the APPEAL is open to March 16, 2022:

https://www.qualityforum.org/ProjectMeasures.aspx?projectID=86057&cycleNo=1&cycleYear=2021

This is the project materials website for the Patient Safety forum, and if you track back to March 3, you'll see the APPEAL document is posted (the two page PDF letter).

https://www.qualityforum.org/ProjectMaterials.aspx?projectID=86057

You can read incoming comments to date on this website:

https://www.qualityforum.org/commenting/publiccommentform.aspx?project=86057&form=206

I've put a cloud copy of the appeal letter here:

https://drive.google.com/file/d/1FZaykTutc0bu24UKN1JQW33GHBcrL768/view?usp=sharing

It sounds like a public or video discussion of the Appeal may occur at the upcoming April 29, 2022 committee meeting.

click to enlarge

AMA CPT Posts May 2022 Chicago Meeting, Posts Lab Tests in Advance

Three times a year, AMA opens a webpage that holds calendars and agendas for its upcoming CPT meeting.  The webpage for the May 12-24, 2022, CPT meeting in Chicago is open.

As usually, the first item to go up is a posting of the Lab CPT submissions for comment and review.   These are posted March 4, and commenters may request to review a packet til March 11, and must turn in comments by March 30 )[per handout].  This allows to be reviewed by internal working groups (MPAG for molecular tests and PCC for lab & pathology stakeholders as a whole).  

All the other non-pathology codes will be posted for comment in a few weeks.

Main web page for Chicago meeting here:

https://www.ama-assn.org/practice-management/cpt/cpt-may-2022-editorial-panel-meeting

[Note, March 8, morning, as I write this, AMA has opened the registration process, but it's not showing up at this hour yet on the webpage.]   The registration pathway is open and it's set up for either "virtual" or "in person" registration for May 12-14, 2022.    (The meetings are always scheduled Thurs-Saturday but rarely require Saturday.)

Lab tests with new or revised coding proposals include:

• Actin
• AQP4 antibodies
• Gadolinium
• Cytogenomics/optical genome mapping
• Hep B quant assay
• MOG-IG1 (multi code set)
• MAAA tumor methylation classifier (CNS)
• Respiratory Patho\ogens (editorial revisions)
• Tick-borne organisms (code set)
• MAAA-cfDNA for HPV'

Reliving Medicare's Dumbest Reimbursement Decision Ever (2009)

Last week, at TRICON in San Diego, I gave a talk on CMS policy and incentives and disincentives to innovation (there are some of both).  It's being written up as a small publication.

I was reminded of an impossible, and quickly rescinded, CMS reimbursement decision in 2009.

Doctors were willingly using Product A, which was 10% the cost of Product B, and someone at CMS made a coding change that made Product A impossible to use.   It's also a case study for what happens when you are making strategic decisions but you lack the ability to think 1 or 2 steps ahead.

And there's a broader lesson for how CMS should incent innovation.   In the ACO world, CMS incents costs savings by "shared savings."  If the ACO's expected Medicare budget is $100M, and it comes in at $90M, it gets to share 50% or $5M of the savings.   But in the RVU system, for example, when a product comes in faster or cheaper, CMS immediately seizes 100% of the savings by immediately cutting the price of the innovation to the least possible level.   It would be smarter if CMS would actually incent providers to use the less expensive thing.

The Story

AVASTIN AND LUCENTIS - 2006-2012

Before 2006, there were very limited treatments for wet age-related macular degeneration, which has an incidence of about 200,000, and a prevalence of about 3M, mostly age 55 and older.   The year 2006 saw the approval of LUCENTIS (ranibizumab), which is similar to AVASTIN (bevacizumab) but has a smaller molecular weight.

Even before Lucentis was FDA-approved, its success was known from Phase III trials, and there were some off-label clinical attempts to use ocular injections of Avastin.  You can still see online debates dating to 2006 (here) and 2009 (here and here) while an NIH-supported comparison trial found the clinical efficacy of the two agents was similar (here) in 2012.  In 2012, CMS held a MEDCAC (public policy meeting) on VEGF treatments in diabetic macular disease as well as macular degeneration, (here).

CODING TODAY

Leaving aside biosimilars codes (Q5108, Q5107), the Avastin code is J9035, 10 mg $67 and the Lucentis code is J2778, 0.1 mg $307.   Dosing of Lucentis is 0.5 mg per eye, or $1500 per eye per month.

CODING FIASCO 2009

As I understand the story, and as retold by the Washington Post in 2013 (here), Lucentis at that time cost about $2000 per injection and Avastin about $50 per injection (J9035 10 mg).  

So far so good.  But not for long.  

Someone at CMS decided to focus not on the apparent $1950 price saving for CMS ($2000-$50), but on the fact that Avastin was given in a much smaller dose (like 1 mg) but was being coded and paid for the smallest available code, "10 mg $50" or so. 

In a still-available document, dated August 28, 2009 (T1803, CR6626) CMS created new code Q2024, bevacizumab, 0.25 mg.   Thus, instead of the ophthalmologist being reimbursement in the $50, or $67, range, he would be reimbursed in the range of $1 per 0.25 unit, or $4 per mg meaning $4 per dose.

https://www.cms.gov/Regulations-and-Guidance/Guidance/Transmittals/downloads/R1803CP.pdf

• This coding for Avastin's tiny dose with Q2024 now put the ophthalmologist far below cost, including incorporated burdens like compounding fees.  
• The brouhaha was immediate and loud.  

The August 28 CMS decision led to an October 2  article in Wall Street Journal, ridiculing CMS.  Here (archive here).  

See an October 6 article on the same topic at Healio here.

An OIG report on the topic attributes the recission of the code to letters from Congress to CMS or HHS in October 2009, and the decision to delete the code at the latest by November 2009.  See OIG here.   According to PolicyMed, the Congressional letter came from Senator Kohl (D-WI), here.  Kohl is said to have written, " a variety of medical authorities and advocates are complaining that the new coding system CMS implemented this month will reduce reimbursements to physicians for Avastin to a small fraction of the previous rate.”

Kohl praised CMS's decision to rescind the goofy coding change on October 28, 2009 (here).

Click to enlarge. From OIG report 2012.

______

I haven't identified the exact transmittal that deleted Q2024, but it was deleted by December 31, 2009, according to current HCPCS records. 

Regarding Q2024, see also T1805, CR6594, also dated August 28, 2009 here.

Picture https://pixabay.com/illustrations/april-fools-day-april-1st-joke-day-4756937/ 

At least one MAC would code Avastin today by J7999, a generic compounded-drug code with local pricing (here).

At the time, in 2009, CMS didn't have an administrator, Mark McClellan having left in 2006 and Donald Berwick having arrived in 2010 (a job he held only 18 months).  Here.

There's CMS rulemaking around hospital outpatient drug pricing for Q2024/C9257 (citing Q2024 as deleted), November 20, 2009 74 FR 60491.

Kohl issued a press release October 28, 2009, praising CMS recission of the code, ad the press release contains a link to a PDF letter to CMS, but that link is now a dead link.  See press on the press release at MedPageToday from AAO here.

A note in Fierce Pharma October 14 basically quotes the WSJ October 2 article.

Telehealth Extension Introduced, But Would Block Telehealth Orders for Genomics

The US healthcare system, certainly for Medicare, is looking at a "telehealth cliff" when the emergency rules around telemedicine end.

On February 7, 2022, Sens. Masto (D NV) and Young (R IN) introduced the Telemedicine Extension and Evaluation Act.   JDSupra here.  S.3593 website here.

The bill apparently attempts to implement a MEDPAC suggestion in Spring 2021, recommending that CMS block telemedicine orders for genetic tests due to perceived fraud in this space (e.g. a telemed doc in Tennessee orders 1000 expensive genetic tests one morning for nursing home residents in Florida).

Draft Bill Impacts Genomics in Telemedicine

S.3593 contains language blocking orders for DME and "costly laboratory tests," the latter defined as tests in the top quartile of payments.   (A quick sort of the Medicare fee schedule places the top 1/4 of prices at $140 and up, but that's not volume-weighted).

The bill does allow telemedicine based orders when the patient is also an in-person patient of the provider.

See a  mid-December 2021 OIG report on genetics teste growth, and genetics test fraud (including telemedicine), entry point here.