Wednesday, January 31, 2024

Big Day for Proteomics: MolDx Takes Jurisdiction for Proteomic MAAA Tests

Header:  A pretty crazy ride is now over for many proteomic tests in MolDx MACs. File under, MolDxOlogy.


There's been a tempest in some states since 2021 focused on which MAC in a MolDx region will take responsibility for proteomic tests.  

Historically, MolDx made coverage decisions on some high-visibility proteomic tests, such as the Opko 4kscore test or the Biodesix XL2 test or the Crescendo Vectra test.   However, in Spring 2021, MolDx announced it was now only reviewing human DNA and RNA tests (later expanded to include pathogen DNA and RNA tests).   That is, it would stop viewing such LCDs for proteomic tests as within its jurisdiction.

Since proteomic tests were no longer reviewed by MolDx, they remained the responsibility of the local MAC of the lab...  

I had a front row seat at this adventure, and participants in last fall's California Clinical Laboratory Association meeting saw some of the sparks.   Over time, I saw two labs (first hand) being told by the California MAC, Noridian, that it would NOT consider LCD applications for proteomic tests, because they were the jurisdiction of MolDx.   Then, at the CCLA last fall, there was a remarkable moment where MolDx stated point blank it would handle only DNA-RNA tests, and Noridian told the audience the policy jurisdiction of proteomic tests was still actively being deterined by CMS.  A few weeks later, a lab I worked with was told by its MAC that its California proteomic test would be handled by MolDx, pending a future publication of policy.  But MolDx had just said, only DNA RNA tests.   

It's happened.  MolDx has published a new article, MolDx: PROTEOMIC TESTING, A59636, posted 12/31/2023.  Find it here:

The article has a listing of proteomic test CPT codes (it looks like multiomic or multiple proteomic tests) that will in the future be regulated by MolDx policies.  Note, importantly, this article is not a coverage or a non coverage document, it is simply a listing that defines test domain (does the test go to MolDx for edits, or to the local MAC.)   


Nix Autopay? This may not be good news for any tests that were "autopaid" previously, as the tests will now (1) be required to have Z codes issued and have (2) a TA submitted, which could result in quick step to non-coverage (fail the TA).  The policy is effective from January 31, 2024.

"Given the complexity of these tests and the ambiguity of services rendered, all proteomics tests in MolDX jurisdictions must register with the DEX® Diagnostics Exchange Registry and obtain a Z-Code® identifier. To determine if the submitted tests are compliant with relevant policy requirements, these tests will undergo Technical Assessment by Palmetto GBA as part of the MolDX program. This is effective 1/31/2024."

Proteomics on slides.  What about multiplex proteomics on slides - immunohistochemistry plus AI?   I have a quick list of 5 codes that are slides + imaging + algorithms (ML or AI?).  These are 0220U, 0295U, 0376U, 0414U, 0418U.   (See pricing here).   MolDx seems to have included exactly 1 of these 5 codes in the Proteomics Article.  Why 0295U is included as "proteomics" and some of the others not, I haven't determined yet. 

click to enlarge

Nerd Note.

The article steps around delicately around the change in protocols.  The article opens by saying that proteomic tests are found in MANY parts of the CPT for lab tests - Except, not in the section 81105-81408, molecular pathology, which is the "scope of the MolDx program."

However - and closely echoing last fall's FDA push to regulate LDTs - MolDx says that now, there have been advances in lab testing, and "more complex services" defined here as "proteomics" are used.  Due to the complexity and ambiguity of such tests, they must have DEX registration ( Z codes) and Tech Assessments before coverage.  Readers will pick up that this framing is very similar to FDA saying, it used to not monitor LDT tests, but now it wants to, because such tests have "advanced" and become more complex.

Medicare Nerd Tip: A Back Door to Putting Together Labs and their PLA Codes

Header: Michigan Blue Cross publishes a PDF which lists every PLA code, name of test, and name of lab owner.  You can't easily get this from AMA or CMS.


One of the pitfalls of PLA codes is that there are some 500 of them, and they are in random order (from date of approval).   Another problem is that it's very painful to search the AMA CPT manual page by page looking for all the PLA codes a lab (say, Biodesix) might have.  The CMS CLFS fee schedule and even the subscription AMA RVU database, list PLA codes but not owners.

Aha.  Michigan Blue Cross publishes a PDF of all active PLA codes, with the code number, the code name (or brand name like "Cxbladder-TM", and then the owner.  Since this is a PDF file, you can search it for keywords (say, Biodesix).  This shows in a second that Biodesix has 2 PLA codes,  PLA 0080U for BDX-XL2 test, and 0360U for Nodify CDT test.

Find the table here:

AI Corner

This is how GPT4 created the illustration from the blog text alone.



For your blog header, it sounds like you're looking for an illustration that captures the essence of navigating through the complexities of Proprietary Laboratory Analyses (PLA) codes, highlighting the unique resource provided by Michigan Blue Cross. Given the content, an effective illustration could depict a maze of PLA codes leading to a simplified, clear guide, symbolizing the PDF published by Michigan Blue Cross as a key to unlocking this maze.

Imagine a visual metaphor where the maze walls are made up of jumbled PLA codes and names, with frustrated healthcare professionals or researchers navigating through it. In contrast, one figure could be shown confidently walking a straight path, thanks to the guiding light or map provided by the Michigan Blue Cross PDF, symbolized by a glowing document or a magnifying glass highlighting the codes for "Biodesix."

The background could subtly feature the logos of AMA and CMS, perhaps faded or in the shadows, to signify the contrast in accessibility and user-friendliness of their resources compared to the Michigan Blue Cross document. The overall color theme could be a blend of healthcare blues and greens, with a touch of Michigan Blue Cross blue for brand recognition.

This illustration will communicate the blog's key message visually: that while navigating PLA codes can be a daunting task due to their disorganized nature and the lack of comprehensive, user-friendly resources from AMA and CMS, Michigan Blue Cross offers a valuable solution that simplifies this process.

Would you like me to proceed with creating an image based on this description?


Here's the illustration capturing the essence of navigating through the complexities of Proprietary Laboratory Analyses (PLA) codes and the clarity provided by the Michigan Blue Cross PDF. This visual metaphor illustrates the contrast between the maze of PLA codes and the straightforward path made possible by the valuable resource from Michigan Blue Cross. I hope this aligns well with your vision for the blog header!

Nerd Note: Why Some MolDX LCD's Heavily Cite "Expert Opinion"

Header: Why do some MolDx LCD's have paragraphs citing "expert opinion," and others dont?


A frequent question I get is, can we submit "expert opinion comments" along with our LCD request?   Or, should those expert opinions be submitted much later, if and when MolDx decides to open a draft LCD?   

We should be able to get a clue, from how MolDx handles actual LCDs.   

When a final LCD appears, all MACs are required to include an online supplement that reviews all comments submitted during the public comment phase - this is separate from the LCD, but hotlinked to the LCD.   (In contrast, NCDs include an embedded discussion of public comments, both arising in the first comment phase, which usually precedes a draft, and arising in the second comment phase, on the public draft.)

The MolDx LCD for pharmacogenomic testing (L38337) is associated with an online comments supplement (A58238) but it also included an extensive summary of expert opinion back in the first draft of the proposed LCD (DL38337).    I've extracted the expert summary in the body of the LCD, here.

Why This Happens?

The answer lies in the CMS instruction manual for LCDs which is "Program Integrity Manual Chapter 13."  Last revised in 2019.  A "CAC" is a Contractor Advisory Committee with expert speakers and is held as a public webinar.

I paraphrase as follows:   When a MAC seeks CAC consultation for a proposed LCD, the CAC's recommendations must be included in the final LCD, along with clear details of the CAC meeting. Consultation frequency is at the MAC's discretion. During LCD development, MACs should use clinical guidelines, consensus documents, or expert consultation, informing and obtaining consent from experts for public disclosure of their opinions in the LCD. Expert acceptance does not imply general medical community acceptance.

So, when a  MAC holds a CAC (advisory meeting) ahead of the draft LCD production, the MAC is required to clearly detail the results in the body of the draft LCD.   This can include live CAC comments and also, expert opinion solicited by the MAC "for the CAC" but delivered in writing instead.  This is why we see the extended discussion of both live comment, and written KOL opinion, in the draft PGx LCD.   

In October 2023, MolDx held a open public comment session on 3 proposed-LCD topics.  (See links here).  Where does that fall?   Nowhere!  The MAC isn't required in any of the rules to specifically respond to verbal open comments, though it must hold a verbal open comment meeting.   However, assuming the speakers submitted written documents (like PPTs and memos) the MAC must respond to written public comments in its attached public comments article for the final LCD.  

QED: By inference, expert opinion submitted early (with a dossier) may or may not be entertained by the MAC, at the MACs discretion, but such statements don't have to be cited in the LCD as they are neither (1) CAC-solicited comments nor are they (2) written open-comment-period comments.


As a result, some LCDs have extensive embedded citation of "expert comments" and others do not.

click to enlarge

AI Corner

In addition to the illustration, Chat GPT paraphrased a 294 word guidance manual down to 72 words.  I could have done this myself in a couple minutes, but Chat GPT did it with equal quality (for the task at hand) in 2 seconds.

Sunday, January 28, 2024

Two Extra Thoughts About the FDA LDT Regulation

Header: Everyone is aware that in September, FDA issued rulemaking to take over regulation of all lab-developed tests in about 4 years.  Here, I review briefly then add two thoughts.


Last fall, FDA released a regulatory proposal to take control of essentially all lab developed tests (LDTs) in about 4 years, a proposal that it estimated (obscurely) would cost some $40B over a few years, which is 200,000 man-years of regulatory expert time at $200,000 per person per year.   See my white paper.  

By December 4, many thousands of comments were submitted, which, subtracted form letters, over 1000 were individualized by entities like ACLA, CAP, Mayo Clinic, AHA, and many others.  A few days ago, CMS and FDA issued a joint press release confirming their viewpoint that any form of "enhanced CLIA" was off the table.  In a few days, Jeff Shuren MD JD, head of devices at FDA, will be giving a talk on the FDA's current thinking at a Friends of Cancer Research conference in DC (also streamed; Feb 1).

Last week, I had the pleasure of attending the Precision Medicine World Conference in the Bay Area.  On Thursday,  There was an excellent talk on the FDA proposal by Sheila Walkoff, head of Goldbug Strategies.  Afterward, I was  toying with two ideas.

Idea 1 - FDA and "Clinical Utility"

Several sources have said that FDA won't evaluate "clinical utility" in this effort, but only "analytical validity and clinical validity."   I find this unbelievable, and can show why.  What FDA does have to show is that benefits exceed risks, and the value of [benefits - risk] pretty much defines the clinical utility.  There might be this difference between FDA and payors or other health technology assessments.  The latter will try to quantify clinical utility - for example, dollars per QALY, unnecessary surgeries  avoided per 10 tests, and so on.   FDA doesn't need to "quantify" clinical utility, but, it darn well does need to verify that [benefits - risks] is positive.

And it can be a tortuous process.  See the recent FDA approval of the AvertD pharmacogenetics test.  Though accurate, reading the genes, the test failed an FDA ad board because of net clinical benefit and harms concerns (e.g. clinical utility, not analytical validity of sequencing).   And the FDA fussed with the test for a couple years, even moving around the regulatory category from de novo 510k to PMA for the final.   It was all about benefits and harms, and the balance of each, and the net benefit, which I can't distinguish from "clinical utility" for patient care.  My blog here.

Idea 2 - FDA and LDT Risk Category

FDA makes much of sorting each of the thousands of LDTs into "risk category."  But first, this isn't how the 1976 device law is defined; it's defined by things on the market before and after May 1976.   And second, bigger, LDTs don't come with indications for use, as FDA products do.   There aren't any uniform, vetted, "indications for use" in CLIA as in an FDA label.  And "indications for use" and connected limits and warnings that set risk level at FDA and fought over for months by companies, FDA staff, and ace regulatory lawyers.  This idea of defining test risk (by implication, only with intended use or indications for use) for LDTs is far from a simple one or self-implementing.   

Auto-generated illustration (!) based on blog text; GPT4 to Dalle3.

Friday, January 26, 2024

Very Brief Blog: Friends of Cancer Research (FOCR) Dx Policy Meeting (Feb 1)

On February 1, 2024, Friends of Cancer Research (FOCR) will hold a four-hour meeting in DC on "The Future of Diagnostic Tests."  The lead speaker is Dr. Jeff Shuren, head of devices and diagnostics at FDA, on the FDA LDT regulatory proposal.

Scott Gottlieb, former head of FDA, will be the lunchtime keynote speaker.   Registration is available both for the live meeeting and for the streaming audience.

FDA-LDT is not the only topic.  The meeting will also update with panels on digital pathology and HRD harmonization.

UPDATE:  48 hours ahead of the workshop, FOCR releases its 147 page, 2023 Scientific Report, "Regulatory Advancements for Patients." Here.

Thursday, January 25, 2024

MolDx Publishes Transcript of October 2023 LCD Meeting

 On January 9, 2023, MOLDX released transcripts (and YouTube files showing PPT) of its October 2023 open meeting on proposed LCDs.

Here are the topics:

  1. MolDX: Molecular Testing for Risk Stratification of Thyroid Nodules DL39646
  2. MolDX: Molecular Biomarkers for Risk Stratification of Indeterminate Pulmonary Nodules Following Bronchoscopy DL39654  
  3. MolDX: Gene Expression Profile Tests for Decision-Making in Castration Resistant and Metastatic Prostate Cancers DL39636
See video files and transcripts at the link at top of this blog.


AI Corner

For fun, I asked to make a 300 word summary.

The transcript is from an open meeting hosted by Palmetto GBA's MolDX program regarding proposed local coverage determinations (LCDs) for molecular diagnostic tests. 

Five speakers presented on the topics of gene expression profiling tests for prostate cancer, molecular biomarkers for lung and thyroid nodules, and Percepta's genomic classifier test. The speakers generally expressed support for the proposed LCDs, which aim to establish Medicare coverage criteria for these types of molecular tests. 

Specific recommendations included: 

  • removing the requirement for a bronchoscopy procedure to allow coverage of tests prior to biopsy for lung nodule risk stratification; 
  • clarifying that coverage can include patients at low or high risk of cancer, not just intermediate risk; 
  • allowing coverage of testing for additional thyroid nodules in patients with multinodular goiters; 
  • using molecular test results for Bethesda 5 thyroid nodules to guide optimal surgical treatment; and 
  • ensuring coverage of new lesions during disease progression for prostate cancer patients. 

The speakers emphasized the clinical utility of molecular testing to avoid unnecessary procedures, reduce delays in cancer treatment, and optimize patient management. They requested modifications to make the proposed LCDs more general to enable coverage of emerging molecular tests that can meet validity and utility requirements.

CAP Weighs in on FDA LDT Proposal

College of American Pathologists has weighed in on the FDA LDT proposal, for which comments were submitted December 4, 2023.   Here are four of their resources:

  • Comment press release here.
  • Actual comment letter here.  10pp.
  • Opinion piece in CAP TODAY here.
  • Detailed comments from a dozen thought leaders, in CAP TODAY, here.

AI Corner:

I read CAP's letter in full and can confirm that Chat GPT4 provides a good bullet-point summary, as follows...


[begin chat gpt]

The letter from the College of American Pathologists (CAP) to the FDA, regarding the proposed rule "Medical Devices; Laboratory Developed Tests", can be summarized in bullet points as follows:

  1. Introduction: CAP's appreciation for the chance to comment on the FDA's proposed rule regarding Laboratory Developed Tests (LDTs).
  2. CAP's Role: Highlighting CAP as a leading organization in pathology and laboratory medicine, advocating for excellence in these fields.
  3. Historical Perspective: CAP's historical role in advocating for a regulatory framework that balances patient safety, quality testing, and innovation without excessive burdens.
  4. Concerns Over Proposed Rule: CAP's view that the proposed rule could significantly reduce the availability of high-quality LDTs, impacting patient care.
  5. Specific Areas of Comment: CAP's intention to offer detailed comments on various aspects of the proposed rule.
  6. Requirements for Continued Enforcement Discretion: Emphasis on certain test categories that should remain under FDA's enforcement discretion.
  7. Exempt Tests: Suggestion to exempt certain tests offered before the rule's enactment.
  8. Manual and Forensic HLA Tests: Advocacy for continued enforcement discretion for certain manual tests.
  9. LDTs Developed Locally: Recommendation for discretion in small-scale, local LDT development.
  10. Adverse Events Reporting: Support for adverse event reporting with a need for educational programs.
  11. Use of Existing Regulatory Authority: Discussion on leveraging existing frameworks and avoiding redundant regulations.
  12. Quality Systems (QS): Concerns about the duplicative nature of proposed QS controls.
  13. Corrections and Removal: Suggestion to maintain enforcement discretion for documented corrective actions.
  14. Registration and Listing Requirements: Concerns about the regulatory burden and suggestion to exempt low-risk LDTs.
  15. Labeling Requirements: Proposal for continued discretion in labeling if information is provided upon request.
  16. Regulatory Framework and Risk Classification: Discussion on the impact of FDA's regulations on clinical laboratories and LDT development.
  17. Recommendations: Calls for public hearings, extended compliance periods, and a focus on least burdensome approaches.
  18. Conclusion: CAP's overall concerns about the proposed rule stifling medical innovation and increasing regulatory burden.
  19. Final Remarks: Invitation for further discussion and contact details.

The letter comprehensively addresses CAP's concerns, suggestions, and recommendations regarding the FDA's proposed rule on LDTs.

[end chat gpt]


The grand-daddy of all  comment letters on the topic is ACLA's, here.

See American Hospital Association letter here.

PMWC: Roche and PathAI Discuss Trends in Digital Pathology

This week at the Precision Medicine World Conference (PMWC), there was a 30 minute session on the status of digital pathology, by Dr. Eric Walk (Chief Medical Officer of PathAI) and Michael Rivers (VP, Digital Pathology, Roche).  The panel was moderated by Pavan Anne', partner at ZS Associates.


On a whim, I gave an auto transcript to Chat GPT 4 and asked for a journalist-style article and a sidebar of 10 take-home lessons.   Having just attended the live talk, I can vouch the entirely AI-written article is pretty accurate.


Precision Medicine World Conference 2024: 

Trends in Digital Pathology and AI

January 25, 2024, Santa Clara, California — The Precision Medicine World Conference 2024, held in Santa Clara, showcased a pivotal discussion on the integration of artificial intelligence (AI) in healthcare, specifically focusing on digital pathology. Moderated by Pavan Anne’, a partner at ZS Associates, the panel featured distinguished speakers including Dr. Eric Walk, Chief Medical Officer at PathAI, and Michael Rivers, VP of Digital Pathology at Roche Diagnostics.

Transformative Role of AI in Digital Pathology

The panel opened with a discussion on the transformative role of AI in digital pathology. Michael Rivers from Roche Diagnostics discussed the journey of AI in this field, emphasizing the shift from traditional methods to more advanced AI techniques such as Convolutional Neural Networks and weakly supervised methods like multiple instance learning. These approaches have opened doors to novel associations and discoveries in pathology.

Potential and Challenges in AI-Enabled Pathology

A significant part of the discussion revolved around the potential of digital pathology and AI in transforming anatomic pathology workflows. The ability for clinicians to remotely access patient images was highlighted as a game-changer. Additionally, AI's potential in drug development and biomarker discovery was discussed, particularly in creating AI-enabled companion diagnostics for more precise treatment responses.

Despite these advancements, the panel acknowledged the barriers to clinical adoption of AI in precision medicine. These include the need for standardization and validation of AI algorithms and the challenges of integrating these new technologies into existing clinical workflows.

Digital Pathology Adoption and Federated Learning

An interesting insight was the current state of digital pathology adoption, with only about 10% of pathology labs being fully digital. However, a larger number of labs are undergoing digital transformation. The concept of federated learning was also brought up, highlighting its potential to expedite the creation of AI models by capturing data more efficiently.

The Future of Pathology with AI

Looking ahead, the panel envisioned a future where AI enhances the role of pathologists by automating tedious tasks and allowing them to focus on high-value activities like interpreting biomarkers. This shift is seen as crucial given the increasing workload on pathologists and the relatively stagnant growth in their numbers.

Conclusion: Collaboration is Key

The discussion concluded with an emphasis on collaboration between academia, industry, and healthcare providers to successfully integrate AI into digital pathology. This collaborative effort is necessary to bridge the gap between developing AI tools and effectively deploying them in clinical settings.

In summary, the Precision Medicine World Conference 2024 shed light on the exciting developments in digital pathology and AI. While challenges remain, the potential for transformative change in healthcare is immense, with AI poised to revolutionize how pathologists work and contribute to precision medicine.


10 Key Takeaways from the Precision Medicine World Conference 2024 

on Digital Pathology and AI

Transformation through AI: AI is revolutionizing digital pathology, moving from traditional methods to advanced techniques like Convolutional Neural Networks and multiple instance learning.

Remote Access Efficiency: Digital pathology enables clinicians to access patient images remotely, significantly improving efficiency in diagnosis and treatment planning.

AI in Drug Development: AI has immense potential in drug development and biomarker discovery, particularly in creating more precise companion diagnostics.  [AI will be more accurate than historic "+1 or +2" ad hoc systems.]

Barriers to Adoption: Key challenges to AI integration in healthcare include the need for standardization, validation of algorithms, and integration into clinical workflows.

Current State of Digital Adoption: Only about 10% of pathology labs are fully digital, though a larger number are in the process of transitioning.

Federated Learning for Data Capture: Federated learning can play a significant role in capturing data and creating AI models more efficiently.

Enhancing Pathologist Roles: AI can automate routine tasks, allowing pathologists to focus on high-value activities such as interpreting complex biomarkers.

Addressing Workload Issues: AI can help address the growing workload on pathologists, which has not been matched by an increase in their numbers.

Collaboration is Crucial: Successful integration of AI in pathology requires collaboration among academia, industry, and healthcare providers.

Future Vision: The future of pathology with AI involves a balance between technological advancement and enhancement of the pathologist’s role, ensuring better patient outcomes in precision medicine.


Tuesday, January 23, 2024

A Blog and a Podcast: A16Z on AI "Jobs to be done in life sciences;" and A16Z Joe Grogan on Health Policy

 A blog and a podcast.  a16z is a trademark for Andreessen Horowitz.

The article "AI Jobs to be Done in Life Sciences" at Andreessen Horowitz explores the transformative impact of AI in biotech and healthcare. It discusses how AI is reshaping drug discovery and development, offering insights into AI-driven research, partnerships in pharma, and the future of life sciences R&D. Key topics include AI's role in hypothesis generation, therapeutic area selection, preclinical development, and clinical trial enhancement. The blog is a valuable read for those interested in AI's evolving role in life sciences.

In the podcast from A16Z, RAISING HEALTH, hear a 30 minute interview with Republican health policy and government affairs expert Joe Grogan.  He discusses the early experience of COVID policy inside the White House; he discusses the IRA drug price controls bill and what alternatives might have focused on; and he discusses regulation of AI and how it could misfire.

See "Raising Health" from a16z at Apple Podcasts (back library)

AI Corner

Chat GPT 4 offers 8 take-aways from "Jobs to be Done."

  1. AI's Emerging Role in Drug Discovery: The article emphasizes AI's growing significance in reshaping drug discovery and development processes.
  2. AI-Driven Research and Partnerships: Insights into AI's application in research and the formation of AI-driven partnerships in the pharmaceutical industry are discussed.
  3. Life Sciences R&D Future Vision: The article provides a vision of the future of R&D in life sciences, heavily influenced by AI technologies.
  4. Impact on Hypothesis Generation: AI's role in hypothesis generation and prioritization in scientific discovery is highlighted.
  5. Therapeutic Area Selection and Pipeline Prioritization: The authors discuss how AI can aid in selecting therapeutic areas and prioritizing development pipelines.
  6. Advancements in Preclinical Development: AI's disruption in various aspects of preclinical drug development, including target discovery and formulation, is explored.
  7. Clinical Trial Enhancement: The potential of AI to streamline and enhance clinical trials, thereby saving time and costs, is a key point.
  8. Broader Bioeconomy Implications: The blog extends its scope to discuss AI's role in the broader bioeconomy, including biomanufacturing and climate change initiatives.

Monday, January 22, 2024

Understanding the CMS Lab Price Gapfill Process for 2024

Header: Each January I like to remind us that the Gapfill lab test pricing process is underway, because CMS and the MACs do so haphazardly.


Here's my article from a year ago, January 2023.

Each summer for the last several years, CMS has had about 100 new lab codes to price.  It prices about 70 of them by crosswalking to the price of an existing test.   The other 20-30 are "gapfilled" under which three groups of MACs (the MolDx group; the NGS MAC group; and the Novitas-FirstCoast group) submit proposed prices for each code to CMS around March-April 2024.

How do those MACs decide on those proposed prices?  

In past years, sometime circa late January, the Novitas, First Coast, and NGS MAC contractors post a web article about how interested parties can submit info for pricing, usually against a deadline of mid to late February.   

The MolDx MACs generally make no web posting, and say that, when asked, they know how to reach each gapfill lab if needed.   However, sometimes it's not clear how MolDx pulls that off (by emailing ""?)   If you have a code under gapfill and if you haven't heard outreach from MolDx by Feb 1, I usually recommend you email them.

Novitas, FCSO, NGS MACs Usually Publish Web Info

In recent past years, MolDx has used an excel spreadsheet template for inbound information and Novitas/FCSO have used a web portal questionaire.  This is a year old, but it's last year's info page at NGS MAC (here).


By using the 2024 lab fee schedule and using codes finalized by last summer and with a $0 price for 2024, I tally 21 new PLA codes in "gapfill" now.  (Counting 80,000-series codes, I tallied 30 for gapfill in November; the table below is the PLA codes).

How 2024 Plays Out

MACs get their proposed pricing to CMS by April 2024, and CMS publishes those prices for comment.  in the fall, CMS publishes final gapfill prices, having shared those public comments with its MACs over the summer.

CMS sets prices as the median of the MAC proposal, but for quirky reason does this basically by state.  Since MOLDX has 29 states, it controls that median value and only the MolDx value sets the next year's national median.

FDA Regulation of LDT's: Stated April 2024 Date

Someone asked me today about a benchmark that FDA would launch its regulation of LDT's with a final rule in April 2024.  I said the FDA wants to move quickly, during 2024, but whether it's April or October is anybody's guess.

Reading a report from healthcare equities research firm Nephron, they flagged that the official website for the rule launched with an "action data" of April 2024.

So that's a credible source, and a footnote-able one.  Will the LDT rule come out during April?  I have no idea, but would tend to be doubtful; I think that April was just as likely chosen as a six-month-placeholder when the draft proposal was filed.

MEDPAC releases 80 page report on Dual Eligibles in Medicare



MedPac releases 80 page report on Dual Eligibles in Medicare/Medicaid.

AI Corner

The dialog below shows the necessity of engaging with AI through repeated sequential questions.  Often, a "request to summarize" may result in a "lazy" three sentences of generalities.  However, it's capable of granular deep dives if asked.  

Chat GPT offers a summary of the 80 page report, with 5 take-home points.

The "2024 Medpac 0115 Duals" report is a comprehensive analysis focusing on individuals dually eligible for Medicare and Medicaid. It provides detailed insights into the demographics, characteristics, eligibility, managed care enrollment, spending, and service utilization of dual-eligible beneficiaries. The report compares these individuals with non-dual-eligible beneficiaries, highlighting differences in healthcare needs and resource utilization.

Here are five key take-home lessons for experts:

  1. Complex Needs of Dual-Eligible Beneficiaries: The dual-eligible population is diverse, often with multiple chronic conditions, physical disabilities, and cognitive impairments, which necessitates a more integrated and personalized approach to healthcare.
  2. Spending and Utilization Patterns: There are significant differences in Medicare and Medicaid spending and service utilization between dual-eligible beneficiaries and non-dual beneficiaries, underlining the importance of tailored funding and policy measures.
  3. Challenges in Coordination of Care: The existence of separate Medicare and Medicaid programs poses barriers to effective care coordination, potentially increasing costs and leading to suboptimal health outcomes.
  4. Variability in State-Level Implementation: Eligibility, benefits, and managed care enrollment for dual-eligible beneficiaries vary significantly across states, impacting the accessibility and quality of care provided.
  5. Evolving Policy Landscape: Continuous policy evolution, particularly in managing eligibility pathways and integrating service delivery, is critical to address the unique needs of the dual-eligible population effectively.

The report underscores the need for ongoing research and policy adaptation to better serve this vulnerable group within the healthcare system.

Can you amplify point #3 on challenges of care coordination, with a summary of key points and with the 5 most important take-aways or action points on this topic.  

The challenges of care coordination for dual-eligible beneficiaries are significant due to the structural and operational complexities inherent in navigating Medicare and Medicaid systems. Here are five key takeaways and action points:

  1. Integrated Care Models: Implementing integrated care models that combine Medicare and Medicaid services can significantly improve coordination and outcomes.
  2. Policy Alignment: There is a need for greater policy alignment between Medicare and Medicaid to reduce administrative complexities and streamline care for dual-eligible individuals.
  3. Data Sharing and Technology: Enhanced data sharing and technology systems between the two programs can facilitate better care coordination, tracking, and management of patient needs.
  4. Provider Education and Training: Providers should receive specialized training and resources to understand the intricacies of both Medicare and Medicaid, aiding in better care delivery.
  5. Patient-Centered Approaches: Adopting patient-centered approaches that consider the unique needs and circumstances of dual-eligible beneficiaries can lead to more effective care coordination.

These actions are aimed at addressing the underlying issues of fragmented care and differing program rules that often lead to inefficiencies and poorer health outcomes for dual-eligible beneficiaries.

Home in on point #2.  What are actual problems caused by this poor policy alignment and what specific changes might be recommended?  What are barriers to change (for example, statutes).

The report identifies specific problems caused by poor policy alignment between Medicare and Medicaid and suggests potential changes and barriers to implementation:

Problems Caused by Poor Policy Alignment:

  • Complexity in Benefits Administration: The division of benefits between Medicare and Medicaid can lead to administrative complexities, making it difficult for beneficiaries to navigate the system and access the care they need.
  • Overlap and Gaps in Coverage: There may be areas of overlap or gaps in coverage between the two programs, leading to confusion and potential denial of critical services.
  • Inconsistent Eligibility Criteria: Different eligibility criteria for Medicare and Medicaid can result in beneficiaries losing coverage in one program while retaining it in another, disrupting continuity of care.
  • Fragmented Provider Networks: Dual-eligibles often have to navigate two separate provider networks, which can lead to fragmented care and difficulties in accessing appropriate services.
  • Differing Payment Structures and Rates: Disparities in payment structures and rates between Medicare and Medicaid can discourage providers from accepting dual-eligible patients, limiting access to care.

Recommended Changes:

  • Unified Eligibility Criteria: Establish unified eligibility criteria for Medicare and Medicaid to streamline access and reduce administrative burden.
  • Integrated Care Plans: Develop integrated care plans that combine benefits from both programs, ensuring seamless coverage and access to services.
  • Harmonized Provider Networks and Reimbursement Rates: Align provider networks and harmonize reimbursement rates to encourage providers to accept dual-eligible patients.
  • Simplified Enrollment Processes: Implement simplified and coordinated enrollment processes for Medicare and Medicaid.
  • Enhanced Communication and Outreach: Improve communication and outreach to ensure dual-eligible beneficiaries understand their benefits and how to access services.

Barriers to Change:

  • Statutory Limitations: Existing statutes may limit the extent to which Medicare and Medicaid can be integrated or aligned.
  • State-Federal Coordination: Effective change requires coordination between state and federal governments, which can be challenging given differing priorities and resources.
  • Budget Constraints: Financial constraints at both the state and federal levels can impede the implementation of necessary changes.
  • Stakeholder Resistance: Providers, insurers, and other stakeholders may resist changes that affect their reimbursement or operational models.
  • Complexity of Health Systems: The inherent complexity of the U.S. healthcare system makes it challenging to implement widespread policy changes.

Addressing these issues requires a concerted effort from policymakers, healthcare providers, and stakeholders to create a more unified and patient-centric system for dual-eligible beneficiaries.

Milliman Update on Medicare Advantage "Industry 2024"

Milliman has released its annual update on Medicare Advantage 2024.

Find it here:

The website explains they have one report for general MA plans and a separate report for dual-eligible (Medicare Medicaid) MA plans.  Note that MEDPAC has also just released an 80 page report on Dual Eligibles in Medicare - here.

The take-home lesson is that after several years of significant "benefit growth," this has slowed or even reveresed year to year 2023/2024.

AI Corner

Chat GPT offers 5 take-home lessons from the PDF report:


The "2024 Medicare Advantage Annual Report" by Milliman focuses on the valuation and benefit offerings of general enrollment Medicare Advantage plans. Here are five key takeaways:

  1. Stabilization of Value Added: The average value added of general enrollment Medicare Advantage plans stabilized from 2023 to 2024, showing minimal growth compared to previous years.
  2. Reduced Premium Reductions and Benefit Enhancements: There were less significant premium reductions and a smaller increase in Part B buydowns. The Part C benefit value saw fewer reductions or remained level, indicating a trend of reduced benefit enhancements.
  3. Increase in Part D Benefit Value: The value of Part D benefits increased due to programmatic changes mandated by the Centers for Medicare and Medicaid Services, largely influenced by the Inflation Reduction Act.
  4. Supplemental Benefits Trends: Popular supplemental benefits like dental, vision, hearing, and fitness continue to be key attractions in general enrollment plans, with some increases in limits and new innovative offerings in fitness benefits.
  5. Growth in Combined Benefits: There's a notable increase in the prevalence of combined (combo) benefits, which include multiple supplemental benefits in one package, reflecting a trend towards offering more flexible and comprehensive benefit options.

This report provides insights into the trends and changes in the Medicare Advantage market, specifically focusing on general enrollment plans and their value propositions to beneficiaries.

Bad News from Novitas: Nixes Payment on Digital Pathology Codes

Header: AMA has created numerous Category III codes for digital pathology slides (whole slide imaging).  Novitas had a payment-related article in 2023, but has a new NON PAYMENT article in 2024.


AMA has created two large batches of Category III codes for digital pathology.  See CAP:

Initially the codes covered major surgical pathology codes, and for 2024 more codes were created for pretty much any CPT code that creates a slide.   However, I've pointed out in the past some drawbacks.  One, they are add-on codes, so that they must be billed on the same claim same day as the original slide creating code (like 88305).   Second, the codes are bundled, not paid separately, for both Medicare inpatients and outpatients, where  most major specimens originate.

Novitas had an article offering limited payment circumstances.  However, on Jaunary 18, 2024, Novitas issued an update that it had "re-evaluated" these codes and would convert them to non payable status.   (As just mentioned, they were already nonpayable/bundled for hospital outpatients.)

Read the Novitas article below.


Billing for digitization of glass microscope slides, CPT codes 0751T-0763T

Effective for claims received on or after February 19, 2024

Novitas recently re-evaluated the pricing and billing instructions related to the 2024 allowances for CPT codes 0751T-0763T, concluding that these add-on codes were developed for tracking purposes and as such should receive no additional payment. The reporting instructions previously provided for submission of these codes, including requiring information in Box 19, will be retracted as no longer required.

Effective for claims with dates of service on or after February 19, 2024, no additional payment will be made for 0751T-0763T.

Thursday, January 18, 2024

FDA and CMS Repeat a 2015 Message: That FDA Must Regulate LDTs, and CLIA Can't Handle "Validity"

On January 18, 2024, CMS and FDA issued a joint communication to Americans, headlining that FDA must regulate LDTs, and that CLIA cannot handle topics like clinical validity and utility of LDTs.

Find it here:

Or here:

FDA writes that, "The current approach has enabled some tests to enter the market with unfounded claims of innovation."

The phrasing, "The message is attributed to Jeff Shuren" seems quirky to me. 

See a law firm article by Gonzales & Mullens here

Deja Vu

This is exactly the same messaging as was presented to Congress in 2015 and by the same parties - being Jeff Shuren MD, FDA, head of devices, and the Chief Medical Officer of CMS, in this case, being Dora Hughes MD [Acting].  (The new 2024 press release actually does mention the 2015 hearing).

Here's my 2015 blog on the LDT hearing:

Even earlier - the 2015 hearing stuck close to CMS's 2013 fact sheet.

AI Corner

Here's an AI summary of the new 2024 document.

The FDA and CMS emphasize the critical need for accurate and reliable diagnostic tests, addressing the evolving landscape of laboratory developed tests (LDTs). Here are three key takeaways:

  • Critical Role of Laboratory Tests: Laboratory tests are integral to healthcare decisions, with about 70% of such decisions relying on these tests. The accuracy of these tests is vital, especially for critical illnesses like cancer, where an incorrect test result can have life-altering consequences.
  • FDA and CMS Oversight and Proposed Changes: Historically, the FDA had a hands-off approach to LDTs due to their simplicity and local utility. However, with the increasing complexity and risks associated with modern LDTs, the FDA proposes new regulations to ensure their safety and effectiveness, bringing them under similar oversight as other diagnostic tests. CMS, through CLIA, plays a complementary role in ensuring test accuracy but lacks the expertise to assure test functionality, which is the FDA's domain.
  • Importance of Reliable Testing and Regulatory Adaptation: The recent pandemic highlighted the need for reliable testing. The FDA and CMS aim to adapt their regulatory approaches to ensure the clinical accuracy of all tests, including LDTs. This adaptation seeks to protect patients from risks associated with inaccurate tests and encourages responsible, science-based innovation in test development.

Decibio's 8-Page Review of JP Morgan Take-Home Lessons (including ELE)

Over at Linked In, see Decibio's excellent 8-page PDF on the take-home lessons from JP Morgan 2024.

Hint: It's not a good sign when a review of the state of an industry, introduces terminology like "extenction level event."

AI Corner

An AI pitch for the 8-page deck:

The 8-page PDF titled "Themes from JPM" by DeciBio Consulting provides insights into key trends and shifts in the life sciences sector for 2024. 

It covers topics like the reality check post-hype era, rising mergers and acquisitions in life sciences, preparation for extinction level events in the industry, intensifying competition in next-generation sequencing, the leading role of cancer monitoring and minimal residual disease, the expansion of precision medicine beyond oncology, and the support of gene and cell therapy for life sciences research and technology growth. 

These highlights will be particularly useful for professionals and investors in the life sciences and healthcare sectors who are looking to stay informed about the latest industry trends and strategic insights.

Click to enlarge: 

click to enlarge


Wednesday, January 17, 2024

Natera at JP Morgan: Big Lessons on Reimbursement Strength


Header: Among the genomics industry, Natera was one of the lead presentations at JP Morgan last week.   What I caught, from news reports and the transcript, is that reimbursement is a major core competence at Natera.


The chart above, used by Natera at JPM, shows year-on-year growth in Q4 revenue alone - from $67M in 2018, to $300M in 2023.   They highlight average sales price - a reimbursement issues - as a key driver.   Not shown here, Natera's bar chart for test volumes looks similar - from 670K in 2014 to 2,490K in 2023.   

Like many genomics players, they've had high burn rates.  But in Natera's case, there's a strong trend downward, from $162M in 1Q2022 to $38M in 3Q23, 7 quarters later.   This cash burn has decreased as revenue and margins have climbed - and [nearly] all their revenues come from "reimbursement."  Their market cap is $8B and Natera's share price is up from $17 (2019) to about $70 (today).

The transcript makes it clear that "reimbursement" isn't something that's delegated five levels down at Natera - it's something that has a large share-of-mind, including the hands-on details, at the CEO level.

The Reimbursement Ecosystem - Policies, Price Lists, Guidelines, and State Laws

What is Natera doing right?  It's clear from the transcript [fn1] and from coverage at Genomeweb, that Natera views "reimbursement" as an ecosystem, which includes coverage policies (driven by publications and guidelines), price lists (leveraging special rules like Medicare's ADLT pricing rule), guideline positioning (which drives both CMS and Commercial coverage), and State biomarker laws - which Natera's CEO referred to several times, suggesting it's really got share-of-mind for him.

Here's how different parts of Natera's half-hour presentation were brought together to capture reimbursment topics, at Genomeweb:

GW: Improving reimbursement has been a key focus for Natera, and the company has taken strides to boost test payments. It has improved its billing operations to further raise its ASP, Chapman said. "Just in the core business, without new guidelines coming in, without new Medicare coverage, without going and getting new commercial coverage, we're getting paid a higher percent of the time because we're operating better." 

The firm has also made multiple submissions to Medicare's MolDx program to expand Signatera into further cancer indications that will hopefully boost reimbursement, said Solomon Moshkevich, the firm's president of clinical diagnostics. "These are areas where we're already doing a decent amount of testing commercially and just not collecting as much as we will after getting the approval [the additive types of Medicare cancer approval(s) will boost the corresponding types of commercial cancer collections]."

Reimbursement Ecosystem includes State Laws and Medical Guidelines

Chapman also emphasized that state biomarker laws could start having a substantial impact on reimbursement, although he cautioned there were no guarantees and it's a novel policy space.  This would be most impactful on the 60% of Signatera MRD tests that are going to commercials with uncertain payments before those state laws take hold.  The laws will, it's expected, require commercials to more often match Medicare coverage.   

Guidelines are also a priority to watch at Natera.   The company highlighted for investors updates at the American Collge of Medical Genetics on 22Q11 testing in the prenatal space.  But it required that burn rate, in this case, involving a 20,000 patient registry called "SMART."

 CMS Pricing Rules

Natera noted that it understood the ins and outs of CMS pricing regulation. Chapman remarks,

We also have a unique status, which is the Advanced Diagnostic Laboratory Test designation [ADLT], and that's allowed us to get pricing on the clinical lab fee schedule of $3,500 per recurrence monitoring Signatera test. Now, there's one other competitor that has a tumor-informed test that's been priced on the clinical lab fee schedule and their rate is $795. So this ADLT is a very big differentiator and, in fact, the price point for 2025 has already been determined as well and the price will be back at $3,900 in 2025.

Improving Billing Operations Means Operating Better

Finally, in the "core" of reimbursement, the claim hitting the payor and an adjucated payment returning to the lab, let's close with these remarks from the transcript:

I think we did see volume improvements in ASP, strong Signatera growth. I think it's just that core execution of the business is what's driving the revenue beat. 

We've been saying for a long time that we think there's some improvements in the average selling price that we can hit just by turning the crank and improving the billing operations.

I've personally been working on that, along with Mike and others for now over a year, and so we're starting to see just in the core business, without new guidelines coming in, without new Medicare coverage, without going and getting new commercial coverage, we're just getting paid a higher percent of the time because we're operating better. Then, with that, we're seeing improvements in Medicare Advantage and I think all this is leading to increased revenue

A New White Paper on Genomics Due Diligence

For a primer on how all this fits together for genomics valuations, see my January 2024 white paper, 
"Agile Due Dilegence in Genomics."  Here:


[fn1]  Like many publicly held companies, Natera posted an audio file of its JPM presentation on its financials and investors website.  This file, along with its 16-page JPM PPT, are usually posted for a period of days.  For an AI picture of this blog, which I didn't use, here.

Sunday, January 14, 2024

Did Caris Skate to Where the Puck Will Be? (& Tie-in to My PMWC Multiomics Session on Jan 24)

 There's a famous Harvard Business School article about preparing now for "skating to where the puck will be."  I was reminded seeing two headlines (one, two) at Genomeweb last week about Caris:

Capitalizing on Multiomics Biobanks

The Abbvie article refers to "Caris' real-world, multimodal clinical and genomic database" and the Flatiron article notes that, "Caris has whole-exome sequencing DNA coverage and whole-transcriptome sequencing RNA coverage for every patient tested with its technology."  In short, Caris' initially quite forward-thinking approach to IHC and then transcriptomics may be paying off soon.


Meanwhile, AMA has recreated new comprehensive sequencing codes for RNA-specific genome analyses, and some payers like NGS MAC are already adding the codes to their CGP policies (e.g NGS MAC L37810 and A56199).   

A Transcriptomics Tie-in to PMWC - Precision Medicine World Conference 2024

I just was on a prep call for a panel on multiomics and transcriptomes on Wednesday, January 24, 2024, at Precision Medicine World Conference.   Find the conference here.  The track with the transcriptomics panel is Track 3, Oncology Applications, here.  

This panel is chaired by Dr Razelle Kurzrock, and its panel includes Andreas Califano (Columbia Univ), Charles Perou (UNC), Eytan Ruppin (NIH), Bruce Quinn, and David Craig (City of Hope).  The 3-day conference is held at the Santa Clara Convention Center.

Very Brief Blog: AMA Posts 29 PLA Code Applications

 Each quarter, AMA accepts new PLA code applications, and after about 3 months, releases the results (with the AMA's edits.)

On January 2, 2024, AMA released 11 new PLA codes (the October submissions) - here.

On January 12, 2024, AMA released its current new batch of submitted applications for review.  Here

There are 29 new code applications, and 2 revisions, and 2 deletions.   If you want to comment on any of them, you must review the list very quickly and submit a request-to-comment very quickly (within a couple days).


AI Corner

I asked Chat GPT 4 for a press release about the 5p document.


Take the role of an expert health policy journalist who specializes in oncology.   Provide a detailed press release announcing the release of this PDF document, raising readers' interest, and letting readers in health policy know the document is available open access.  If the document has guidance for submitting comments, highlight that also.


Press Release: Comprehensive Oncology Test Codes List Now Available for Open Access


[City, Date] – The American Medical Association (AMA) has released a groundbreaking document titled "2023 PLA Applicant Code List," now available for open access. This pivotal release marks a significant stride in the field of oncology, offering a detailed list of 43 unique laboratory tests, including 15 dedicated to cancer research and diagnostics. [I count 29 not 43]

As an expert health policy journalist specializing in oncology, I'm excited to announce that this document not only provides a comprehensive overview of the latest advancements in cancer testing but also reflects the AMA's commitment to transparency and collaborative development in medical practice.

Key Highlights of the Document:

Diverse Oncology Tests: The document details an array of oncology tests, ranging from gene expression analysis to minimal residual disease detection, providing invaluable resources for researchers, clinicians, and policy makers.

Advanced Diagnostic Techniques: These tests leverage cutting-edge techniques such as PCR, mass spectrometry, NGS, and ELISA, underscoring the rapid evolution of cancer diagnostics.

Open Access for Enhanced Collaboration: By making this document publicly available, the AMA fosters an environment of shared knowledge, crucial for the ongoing battle against cancer.

A Call to Action for Health Policy Experts:

This release is more than just a list; it's a beacon for interdisciplinary collaboration. Health policy experts, researchers, and clinicians are encouraged to delve into this rich resource to aid in developing more effective cancer treatment and management strategies.

Participation and Feedback Welcome:

In line with the AMA's inclusive approach, the document contains guidance for submitting comments and feedback. This is a unique opportunity for professionals in the field to contribute their insights, ensuring that the list remains relevant and comprehensive.

Accessing the Document:

The "2023 PLA Applicant Code List" is readily available for download and review. Visit [AMA's website or the provided link] to access this crucial resource.

About the Author:

As a health policy journalist with a focus on oncology, [John Smith] has dedicated his career to bridging the gap between medical advancements and policy implications. 

Contact Information:

For more information or to schedule an interview, please contact [Your Name] at [Your Contact Information].



Which 3 of the many tests, do you think is most unusual, interesting, and/or important?   please list these 3 tests and explain why each was selected from the nearly-30-test list.

Selecting the most unusual, interesting, and important tests from the document, here are three that stand out:

RightMed Oncology Medication Report (ID 101392): This test uses SNP genotyping by real-time PCR to analyze 24 genes from whole blood or buccal DNA. It's significant because it provides insights into gene-drug interactions and impacted phenotypes, which is crucial for personalized cancer treatment.

EarlyTect® Bladder Cancer Detection (ID 101532): This test is noteworthy for its use of methylated PENK DNA detection in urine, a novel approach for bladder cancer likelihood assessment. Its non-invasive nature and focus on early detection make it a significant advancement in oncology diagnostics.

Afirma Xpression Atlas (ID 101542): This test involves mRNA gene expression analysis of 593 genes from thyroid fine needle aspirates. It's important for its comprehensive approach in identifying various sequence variants and rearrangements, including BRAF, RAS, RET, PAX8, and NTRK, which are critical in thyroid cancer diagnostics and treatment planning.

[note!! It did not see this was a deletion of 0204U.]

These tests were selected for their innovative approaches in cancer diagnostics, potential impact on personalized medicine, and their representation of the advancement in molecular techniques in oncology.


Please provide an illustration highlighting one of the 3 tests.