Five Interesting Law Firm Essays about FDA LDT Proposals

In the last couple weeks, I ran across a number of interesting articles from law firms about the FDA proposal to regulate lab developed tests  - LDTs.

ESSAY #1

FDA LDT & LAW [Amin/Morrison & Foerster]

The first one, I did highlight in a blog back on November 10.  This is an essay by stacy Amin, a former FDA attorney, now at Morrison & Foerster.  Her essay focuses on potential legal weaknesses of the FDA's proposal to regulate LDTs, and how the FDA has attempted to preempt them with various parts of its justification.

https://assets.contentstack.io/v3/assets/blt5775cc69c999c255/bltff2f4e0cf88d3aac/654d7a74b4ccc3040a594e45/231108-fda-lab-developed-test-rule.pdf

ESSAY #2

FDA SWOOPS INTO MCED [Mullen, Gibbs/Hyman Phelps Mcnamara]

This fits the "FDA LDT" topic because Mullen and Gibbs give a no-holds-barred account of the surprisingly sudden appearance of an FDA workshop on the MCED topic.  They suspect tie-ins to the FDA's LDT agenda as a whole.  They note several oddities about the workshop.  Good essay. "FDA Stealthily Convenes Multi-Cancer Testing Panel Meeting."

• Here.

ESSAYS #3,4,5

The Mullen/MCED essay includes three track-backs to prior essays about aspects the LDT rule.  

• The first simply introduces the FDA's land grab, by Cato, Mullen, Javitt on September 29.  
• Here.
• The second is a livelier style and opens with the headline, "Raises Many Questions, Provides Few Answers."  By Mullen, Javitt, Won on October 6.
• Here.
• The third tracks to the same topic as Stacy Amin's essay, the legal weaknesses of the FDA's position.  "Would a Final Rule Withstand Judicial Scrutiny?"  By Mullen, Javitt, et al, on November 2.
• Comparing Amin's essay and Mullen's may be of interest to legal eagles.  See "AI Corner" on the comparison. 
• Here.
• You can find the home page for HPM's law blog here.

My Two Cents

I liked Mullen's tie-in of the rushed MCED workshop with the FDA LDT proposal.  

In the same spirit, I'd add, the LDT proposal in September also has precedents in the FDA's June proposal to provide guidelines under which LDT cancer biomarkers could be considered equivalent to biomarkers used in clinical trials for a cancer drug.  I think is because FDA foresaw declaring LDT's illegal, yet knowing that sometimes drugs are approved prior to a companion diagnostic, a gap that has hitherto been peacefully bridged by LDTs for the biomarker. 

I think the FDA LDT proposal also ties to FDA's flip-floppy and messy actions against PGx software in the past couple months (see Genomeweb here.)  FDA's new LDT proposal has no space for an FDA approved lab test coming from multiple locations (chemistry here, software there) as exists under some current CAP-CLIA models.

##

AI Corner.

Chat GPT 4 provides us with its comparison of the Amin and the Mullen legal authority articles.

Chat GPT 4:

The articles by Amin and Mullen offer differing perspectives on the FDA's proposed rule to regulate Laboratory Developed Tests (LDTs). Here is a comparison and contrast of their key points:

Similarities

Background of FDA’s Claim to Regulate LDTs: Both Amin and Mullen acknowledge the FDA’s historical claim that it has the legal authority to regulate LDTs as medical devices under the Federal Food Drug and Cosmetic Act (FD&C Act)​​​​.

Proposed Rule Details: Each article outlines the FDA's proposed rule that aims to regulate LDTs like other medical devices, noting the shift from the agency's historical enforcement discretion policy​​.

Differences

Legal Basis and Challenges:

Mullen: Mullen focuses on the questionable legal basis for the FDA’s authority to regulate LDTs, highlighting the challenges and counterarguments against the FDA’s jurisdiction. This includes the historical failure of FDA-supported legislative efforts to amend the FD&C Act and the potential major questions doctrine challenge​​.

Amin: Amin emphasizes the FDA's effort to establish its jurisdiction over LDTs through historical evidence, suggesting that the agency has always asserted its authority in this area. Amin also discusses the potential major questions doctrine but in the context of supporting the FDA's position​​.

Scope and Impact of FDA Regulation:

Mullen: Highlights the economic and political significance of the proposed rule, hinting at potential overreach by the FDA and the major costs involved, as well as the possibility of broad legal challenges​​.

Amin: Discusses the evolving nature of LDTs and the FDA's justification for the rule based on public health concerns, including issues with false positives/negatives and inadequate validation studies​​.

Administrative and Legal Precedents:

Mullen: Raises concerns about the FDA’s potential overestimation of its authority and underestimation of challenges, referencing specific legal cases and doctrines that might be used to challenge the rule​​.

Amin: Focuses on the legal and administrative procedures the FDA has undertaken to strengthen its rulemaking, discussing the role of the major-questions doctrine and the agency's attempt to preempt arguments against its authority​​.

Public and Industry Reaction:

Mullen: Suggests a likely strong reaction from stakeholders against the FDA’s rule, including potential lawsuits and challenges based on the rule's economic impact and legal basis​​.

Amin: Notes the historical resistance to FDA regulation of LDTs and the intricate efforts the FDA has made to counter these arguments, acknowledging the potential for significant legal battles but focusing more on the FDA's preparedness and justification for the rule​​.

Implications and Predictions:

Mullen: Predicts that the proposed rule will lead to significant legal battles and scrutinizes the FDA’s legal standing and the potential impact of recent Supreme Court decisions on the agency's regulatory authority​​.

Amin: Also anticipates significant litigation but frames it in the context of a historic moment for the FDA, underscoring the importance of the rulemaking and the potential for precedent-setting outcomes​​.

Conclusion

While both articles recognize the significance of the FDA's proposed rule on LDTs and its potential to invoke major legal challenges, Mullen's article is more critical of the FDA’s legal standing and potential overreach, whereas Amin's article places greater emphasis on the FDA's historical assertions of authority and the public health implications of the rule.

NEJM Op Ed Tackles CMS Efforts to Modernize Coverage Policy

 

A policy opinion piece in the November 30, 2023 NEJM, by Kadakia et al., provides a fairly detailed overview of coverage problems at CMS, and the historically unsuccessful attempts to navigate them with either Parallel Review or with CED (Coverage with Evidence Development).  

The authors describe the Trump administration MCIT proposal, its collision (and sinking) with Biden policymakers, and the still-in-progress CMS proposal to create "TCET," temporary coverage for emerging technologies.  A table compares MCIT and TCET. (Below, click to enlarge).  

click to enlarge

While having a somewhat guarded view of TCET - it relies on CED and strongly mirrors the Parallel Review flop in terms of the proposed process - the authors seem to conclude that at least CMS is moving forward with something (TCET).   

While the citation list in their short paper is brief, I'd add they might have cited the Dartmouth/Zeitler paper last year on CED (here).

NEJM includes a 9 minute podcast interview with coauthor Robert Yeh.  Yeh is director of the Center for Outcomes at Beth Israel.

___

AI Corner

See AI summary of Kadakia, here.

New Alzheimer Codes Dominate Lab Agenda for AMA CPT Feb 2024

Registration is open for the February 1-3, 2024, AMA CPT Editorial Meeting in San Diego.  Registration may be both in person or virtual.  Here.

Lab codes were posted in mid-November for an early comment cycle (request Nov 20[*], comment Dec 4).  All other codes will be posted for comment December 1.

Here's the lab agenda link:

https://www.ama-assn.org/system/files/feb-2024-path-lab-mo-path-agenda.pdf

There's a bonanza of codes for Alzheimer's disease.  Note that the codes have "placeholder" codes at this time, which I'm also using here.

• Amyloid Protein in plasma or CSF (82XX0, 82XX1)
• 40 and 42
• Possibly, one code for plasma and one for CSF
• Usually measured as a pair for calculating the ratio, not the absolute amount
• Neurofilament light chain, blood (83XX0)
• Immunoassay Alzheimer Pathology (835XX)
• This is puzzling, possibly tau isoforms??
• Tau protein, Total (8X3XX)
• Tau protein, Phosphorylated (8X3X0)

Some of these tests are represented by PLA codes; the 80,000 series  codes will apply to any user.  The 80,000 series codes do not differentiated FDA and LDT versions.  Different brands or different isoforms may have different clinical accuracy.

There are several other lab codes: 815XX, brain tumor methylation; 8156X, kidney transplant gene expression; 81XX0, fetal recessive conditions (mentions XX28U, a PLA code).

###

[*] As the agenda PDF indicates, someone wanting to review and comment on the code packetts for lab tests is directed to an AMA software portal [select the tab for Interested Party, not the tab for Applicant].  However, AMA locks out requests after 11/20/23, the lab request deadline.  This early request deadline ensures that any lab comments are available to internal subcommittees like MPAG and PCC.  

FDA Posts Agenda and Questions for MCED Panel November 29, 2023

On November 29, 2023, FDA is holding   ^held  an all-day panel on how the FDA should plan for trials and evaluations of MCED, multi cancer early detection.   

See original blog about the FDA workshop, by me, here.

• Update November 30 - I've put several different AI summaries of the 6-hour meeting in a Google doc, here.  
• This includes a 10-page bullet point summary by Otter.AI, my transcription program.
• Also short summaries by Claude.AI and Chat GPT4.  (And then, having got the 2 summaries, I asked them to compare the two summaries, too.) 
• See an excellent pre meeting article by Hyman Phelps here.

# # #

FDA has posted the agenda 9-5, the key questions, and an executive summary of 10 pages.

Find them all at the FDA, here, as "Event Materials," as well as the FDA's link to the streaming video for November 29.

AI CORNER

I've posted a Claude.ai summary of the ten-page executive summary written by FDA.

##

The FDA is convening an advisory panel to get input on regulatory considerations for multi-cancer early detection (MCED) tests. These blood-based tests aim to screen for multiple cancers simultaneously in asymptomatic individuals. Currently no MCED tests have FDA authorization.

The panel will provide recommendations on study design to demonstrate clinical validity of MCED tests. This includes determining appropriate methods to confirm cancer status, diagnostic workup following positive results, and follow-up for negatives. The panel will also discuss use of tissue-of-origin assays to help localize tumors after initial MCED positive, as well as benefit-risk considerations.

Key questions for the panel include [for original FDA text see FDA link above]:

• Should MCED tests be evaluated by cancer type or in aggregate? What minimum sensitivity per cancer?
• How to evaluate MCED versus existing single cancer screening tests? Risk of patients foregoing current methods?
• Definition of "early detection"? Supportive data needed?
• Acceptable false positive rates? Should specificity be fixed to support low false positives?
• Harms of false negatives/positives? Diagnostic odyssey? Overdiagnosis/overtreatment?
• Use of stage shift as surrogate endpoint to show benefit?
• Role of real-world evidence for expanding cancer claims, validating rare cancers, demonstrating stage shift?

The panel's discussion and recommendations will inform the FDA's thinking on evaluation of safety and effectiveness for future MCED test marketing submissions.

NEJM AI: With Complex Cases, GPT-4 Usually Beats Humans (Eriksen et al.)

Last April, NEJM announced it would launch ai.NEJM, a new AI-focused journal (see coverage at MedPageToday).  At the time, it publishes Lee et al., a Microsoft-based article on "benefits, limits, risks of GPT-4" in medicine (here).

In today's news, NEJM publishes Erikesen et al, on the success rate of GPT-4 to "diagnose complex clinical cases."  Based on online data, the authors found GPT-4 (which was right 57% of the time) outperformed 99% of human readers.

See the article here:

https://onepub-media.nejmgroup-production.org/ai/media/000de933-9406-4f17-87b5-8e28c5cf5da7.pdf?

See open-access coverage at MobiHealthNews by Jessica Hagen here:

https://www.mobihealthnews.com/news/gpt-4-outperformed-9998-simulated-human-readers-diagnosing-complex-clinical-cases

Glitch: The article refers to supplemental information, including methods, but at least on the day of release, I couldn't find any at NEJM/

##

Here's a summary from Claude.ai:

Eriksen et al. Use of GPT-4 to Diagnose Complex Clinical Cases. AI.NEJM.ORG.

In this perspective article published on ai.nejm.org, Eriksen and colleagues assessed the performance of the AI system GPT-4 in diagnosing complex real-world medical cases. They compared GPT-4's diagnostic accuracy to that of medical journal readers answering the same questions online.

The authors utilized 38 open-access clinical case challenges with comprehensive patient information and a multiple choice question on the diagnosis. They provided the cases to GPT-4 along with instructions to solve the case and select the most likely diagnosis. They ran GPT-4 on the cases multiple times to assess reproducibility.

GPT-4 correctly diagnosed 21.8 out of the 38 cases on average (57%), with very high reproducibility across runs. In comparison, simulated medical journal readers answering the same cases [based on 248,000 online answers) only diagnosed 13.7 cases correctly on average (36%). 

Based on distributions of reader answers, GPT-4 performed better than 99.98% of a simulated population of readers.

The authors conclude that GPT-4 performed surprisingly well on these complex real-world cases, even outperforming most medical journal readers. However, GPT-4 still missed almost half of diagnoses. More research is needed before considering clinical implementation of such AI systems. Specialized medical AI models, additional data sources beyond text, transparency of commercial models like GPT-4, and further evaluation of safety and validity are still required first. But these early findings indicate AI could become a powerful supportive tool for clinical diagnosis in the future.

MolDxOlogy - Payments for 2022 Category 1 Genomic Codes, by MAC

Header:  Of Category I genomic CPT codes, about 65% MolDx payments, 20% NGS MAC, 15% Novitas.  But, most NGS MAC payments represented Cologuard, an NCD-driven code.  Otherwise, NGS MAC had 4% of payments.

____

In October, I posted some data on national CY2022 spending by CPT code (here).  

This week, in prior blogs, I broke out spending by MAC, first by 81479 miscellaneous code (here) and then by PLA code (here).

In this third and final blog for today, I show Category I CPT code spending by MAC (or MolDx).  I pulled cloud data for all 2022 payments on codes starting with (811, 812, 813, 814, 815).  

I then used an Excel pivot table to sum spending by "carrier" (usually "state") and rolled the results up by MAC and MAC system. The MAC policy systems are MolDx, Novitas/FCSO, and NGS MAC.

Results

Of $1.5B in genomic spending in this code set, 63% was via MolDx, 22% via NGS MAC, and 15% from Novitas/FCSO MACs.

However, I would rush to point out, nearly all the NGS MAC spending in this code set was driven by a single national decision (not local MAC LCDs).  It's the NCD for Exact Sciences Cologuard (state Wisconsin, payments $268M under NCD, code 81528).  Minus that, NGS MAC in all other states and codes altogether paid $64M for Category I codes (811xx etc) in 2022, or 4% of payments of $1.5B.

Click to enlarge.

Summary of 3 Posts

For the following data, I simplified each data set (e.g. dropping lines <$100K), so the numbers vary a tiny bit from exact nationwide numbers.

For Category I codes (811nn-815nn), payments were $1.4B, of which 63% MolDx, 22% NGS MAC, 15% Novitas MAC.   Excluding the NCD for Cologuard, which is close to $300M, NGS MAC payments fell to 4%.

For PLA codes, payments were about $330M of which 81% MolDx, and about 10% each to Novitas/FCSO and NGS MACs.  However, most of the 10% to NGS MACs can be accounted for by FMI payments driven by NCD 90.2 for FDA PMA NGS tests.

For 81479 miscellanous codes, payments were about $470M, of which 98% was paid by MolDx MACs.  90% of that, was via Noridian MAC.  81479 was the national highest-paid genomic CPT code.

Bonus

This fall, I used the Medicare coverage database to tally MAC Articles about genomic codes (811nn to 815nn).   There were 82 MolDx articles, 8 Novitas articles, and 4 NGS MAC articles.

 

MolDxOlogy - Payments for 2022 PLA Codes, by MAC

Header: 80% of PLA codes were paid via MolDx.  About 10% each for Novitas and NGS MAC, but the NGS MAC PLA payments were mostly NCD-driven payments for Foundation Medicine.

___

In the previous blog, I looked at payments for Genomic Miscellaneous Code, 81479, by MAC - here.  I used the CMS cloud data archive for 2022 Part B payments - here.

In this blog, I pulled the CPT codes ending in "U" - the PLA codes - and sorted them in Excel for "Carrier" (usually a state), and sorted those into  the three  MACs for policies - the MolDx MACs, the NGS MACs, and the Novitas/FCSO MACs.

To save manual work, I deleted rows less than $100,000, leaving $330M of PLA payments (97% of the total).   Of this $330M, about $18M were paid out to diverse MACs (such as for a Cepheid IVD, 0241U), which I didn't try to parse by MAC.  

Of the $312M paid to specific MACs for PLA codes, I tallied $252M or 81% to MolDx MACs, and roughly $30M each to Novitas MACs and NGS MACs (about 9-10% each.)

Note, however, that much of the NGS MAC payments come from  PLA codes 0037U and 0239U, Foundation Medicine FDA CDx codes (FFPE and LBX, respectively) - these are controlled by an NCD, NCD 90.2, and are not discretionary payments under the judgment of the NGS MAC.   If you tallied NGS MAC payments NOT controlled by NCD 90.2, it would be very low.

Click to enlarge.

click to enlarge

I previously posted, in October, that national payments for PLA codes were highly concentrated, with the highest-paid codes mostly being FDA approved.  Just 3 of 500 PLA codes, had half the PLA payments.

MolDxOlogy: In 2022, MolDx Captured 98% of 81479 Payments

Header.  Genomic test spending under miscellaneous code 81479 was a third of 2022 Part B spending for Tier 1 lab codes at $470M.   98% was via MOLDX MACs.

___

Back in October 2023, CMS released data for CY2022 Part B payments by CPT code.   (Payments by doctor or lab will be released in summer 2024).  See October blog here.  Molecular spending was about $1.5B for Tier 1 codes, another $340M for PLA codes.   In either code set, the top few codes garnered most of the spending.

I noted that about a third of Category I spending was Unlisted Code 81479.  For a client project, I've gone back to that data and analyzed 81479 spending in CY2022 by MAC.

I analyzed all the states with 81479 over $100K (I had 99.96% of 81479 payments.)  98.3% was in MolDx states, or about $462M of $470M.  More was spent on 81479 than all PLA codes together.  

Also for 81479, $7.5M was in Novitas (PA), and just $500K in NGS MAC states (specifically, Illinois).

70% of 81479 spending was in California (61% northern, 9% southern) and 13% was in Arizona.  

About 90% of 81479 spending was via the Noridian MAC.  

The table below can be clicked to view.

click to view

__

81479 spending at MOLDX was paired with "Z codes," allowing granularity in claims processing. 

However, large amounts of molecular spending fall outside of PAMA and fall outside of public code data that can be used for academic and public health purposes.   For example, one cannot tally up how many Medicare patients had BRCA testing in 2022, if it is recoded as "81479."  (In contrast, you CAN tally up how many FFS patients had prostatectomies, colonoscopies, and so on).  

AMP Hosts FDA LDT Webinar: Monday November 27

 On Monday, November 27, 2 pm ET  11am PT, AMP will host a webinar on FDA LDT, the goal being "to stop this overreaching rule."  Hosts will be Dr Eric Konnick, chair of AMP professional relations, and Annie Scrimenti, Assoc. Director of Public Policy & Advocacy at AMP.

Here's AMP's 6 page PDF briefing on the rule:

https://amp.org/AMP/assets/File/advocacy/Summary%20FDA%20Proposed%20Rule.pdf?pass=75

Here's November 27 ZOOM registration:

https://us06web.zoom.us/webinar/register/WN_P-QgnfjISauUajGoGXP6Bg#/registration

AMP adds,

You can stop this overreaching rule from being finalized by submitting comments on how the proposed rulemaking will affect your ability to practice laboratory medicine and provide critical lifesaving tests to patients. Unique, individual and institutional comments telling the FDA why this rule is bad for patients, bad for medicine, and bad for innovation are critical.

AI Corner: Trying Out Anthropic "CLAUDE"

Since February, I've been a subscription user of Chat GPT.  With their recent management turmoil, I tried a similar competitor service, ANTHROPIC CLAUDE, in its free version.[*]   

I found CLAUDE did a good job of summarizing my recent detailed white paper on FDA proposal for LDTs (October white paper here.)  

In both ChatGPT and CLAUDE, you can now just click a "paperclip" button and upload a PDF.

###

Here's the CLAUDE link (once you're registered): https://claude.ai/chats

Here's home for Anthropic, where I email-registered for CLAUDE: https://www.anthropic.com/product

Free Claude gives you 5-10 questions per 8 hours, I think.  $20/mo Claude gives you much higher bandwidth.

Here's the test:

 Please summarize in detail this complicated white paper about a new policy proposed by FDA for regulating laboratory tests [upload it]. I am the author of the white paper, and I would like to see how you summarize it. I expect a detailed summary to be in the area of 500 words long. Thank you.

ANTHROPIC CLAUDE:

Here is a 475-word detailed summary of the white paper about the FDA's proposed policy for regulating laboratory tests:

The white paper analyzes a new proposal released on September 29th, 2023 by the FDA to regulate laboratory-developed tests (LDTs). The proposal would phase out the FDA's enforcement discretion and subject LDTs, including those solely used within a single lab, to FDA oversight as medical devices. This would require LDTs to comply with requirements like registration, quality systems, premarket review pathways, and labeling rules.

The proposal lays out a 5-year timeline for phasing in compliance. However, the white paper author, Dr. Bruce Quinn, argues that the dramatic costs of compliance, estimated by FDA to be around $50 billion over the first 5 years, make the timeline wholly unrealistic and the proposal “simply impossible to execute.” The FDA also projects over $300 billion in benefits over 20 years, but the white paper contends these are based on speculative assumptions about LDT accuracy improvements.

The paper critiques how the high costs were obscured in the publicly released documents and summary. It analyzes the underlying FDA assumptions and calculations, including estimating over 200,000 regulatory expert-years and thousands of FDA reviewers would be needed in Years 3 and 4 alone to handle the influx of LDT applications. It compares this to the total yearly profits of less than $4 billion for LabCorp and Quest combined.

The white paper further examines the FDA's claimed legal authority to regulate LDTs as devices, noting this remains a disputed view. It contrasts the FDA arguments with analyses suggesting labs conducting testing may fall outside device definitions and commerce clause restrictions on federal power over intrastate activities.

In conclusion, the paper argues the proposed rule is essentially unworkable as written. It expects court challenges if finalized unchanged, as well as continued debate over the appropriateness and legality of FDA reaching into lab operations. But it suggests there may be alternative approaches, short of the complex VALID Act legislation, that could address FDA’s concerns on LDT claims and LDT accuracy without imposing such dramatic bureaucratic and financial burdens.

[*] Both ChatGPT and Anthropic Claude have good free versions, while a $20 subscription to either one gets you more bandwidth and priority when servers are overworked.

FDA Holds Panel on Multi Cancer Early Detection: November 29, 2023

On Wednesday, November 29, 2023, FDA will hold a molecular advisory panel on the topic of Multi Cancer Early Detection.  Here's a clipping:

• On November 29, 2023, 9-5 ET, the Molecular and Clinical Genetics Panel will discuss and make recommendations on the design of multi-cancer detection (MCD) in vitro diagnostic devices (tests) as well as potential study designs and study outcomes of interest that could inform the assessment of the probable benefits and risks of MCD screening tests. The committee’s discussion and recommendations from this meeting will help inform future Agency regulatory efforts for these novel tests.
• FDA intends to make background material available to the public no later than 2 business days before the meeting.  NOTE: POSTED BY NOV 28; KEY QUESTIONS; 10 P BACKGROUND.
• The meeting presentations will be heard, viewed, captioned, and recorded through an online teleconferencing platform.

The web page is here:

https://www.fda.gov/advisory-committees/advisory-committee-calendar/november-29-2023-molecular-and-clinical-genetics-panel-medical-devices-advisory-committee-meeting

The page includes a Webcast Link.

See FED REG and comments submission portal:

https://www.federalregister.gov/documents/2023/11/13/2023-24896/molecular-and-clinical-genetics-panel-of-the-medical-devices-advisory-committee-notice-of-meeting

It's published as 88 Fed Reg 77588-90, November 13, 2023.

Check yourself for updates but the YouTube link appears to be:

https://youtu.be/xyOrADJQj4U

ARUP Hosts Webinar on FDA-LDT: Wednesday November 29

Heads up:

Live Webinar, November 29: What the FDA’s Proposed Rule to Regulate Lab-Developed Tests Means for Hospitals and Health Systems

An ARUP expert will answer questions about a proposed FDA rule to regulate laboratory-developed tests (LDTs) as medical devices, which will potentially limit patient access to essential medical care.

https://www.aruplab.com/webinar-fda-proposed-rule-further-regulate-lab-developed-tests-hospitals-health-systems

Webinar Description (10 PT, 11 MT, 12 CT, 1 ET)

Join ARUP’s Jonathan Genzen, MD, PhD, chief medical officer and senior director of governmental affairs, on Wednesday, November 29, at 11 a.m. MST for a conversation about the FDA’s proposed rule to regulate LDTs as medical devices. He’ll address patient safety, test availability, and the impact on innovation. ARUP’s compliance officer, 

Jonathan Carr, JD, will moderate a Q&A during the webinar.

CMS Posts Final Prices for New Lab Codes CY2024

CMS has posted final prices on new lab codes for CY2024.  .

What Happened?

By my informal tally, there are 84 agenda items.  13 changes.   

10 changed from a crosswalk recommendation to a Gapfill, and 3 changed from gapfill to crosswalk or from one crosswalk to a different one.  WIth the 10 new Gapfills and a couple gapfill "losses," I tally 30 codes for the 1H2024 gapfill process, out of 84.

6 New CGP Codes Get Gapfilled, Not $600

In likely the most-watched codes, CMS had proposed that 6 new AMA CPT comprehensive genomic profiling codes (CGP) be priced at about $600 (CW 81445).  All 6 of those $600 crosswalks met with strong complaints, and CMS has split the difference by turfing them to the 2024 gapfill process. 

3 Slide-AI Codes All $600

There were 3 codes for AI-enhanced slide-based imaging, 0376U (Artera AI Prostate), 0414U (former X084U, LungOI Imagene), 0418U (former X088U, PreciseDX Breast Bx).  Requested prices were as high as the $2500 range (Artera request).   

The expert panel, the CMS proposed  price, and the CMS final price were all crosswalk to 0220U (PreciseDx Breast) at about $700.    (I've noted earlier that if you views "slides + AI" as a category, prices have reached as high as $5435 for ADLT pricing of the Prelude DCISioniRT test 0295U).  Labs in this group can appeal, meaning the price would be revisited next summer.

Crosswalk = Crosswalk to 1 Code

Of about 56 codes crosswalked, all but 4 were crosswalked to a single target code.  One was crosswalked to a 0.5 fraction, and three were crosswalked to addition of 2 or 3 codes.

Read For Yourself

Find the new final spreadsheet at this link.  Scroll down for Agenda and Announcements, and find a Zip file link for CY2024 final prices.

https://www.cms.gov/medicare/payment/fee-schedules/clinical-laboratory-fee-schedule-clfs/annual-public-meetings

Stanford Biodesign Posts Webinar on FDA LDT Proposal

 Last week, Stanford Biodesign hosted a webinar on the FDA proposal to regulate LDTs.

They've now posted the one-hour video online at their YouTube channel.  Find it here:

https://www.youtube.com/watch?v=9zVlwbWp2Lo

In a conversation moderated by Stanford Biodesign Policy Program director Kavita Patel, ACLA president Susan Van Meter, physician executive Bruce Quinn, and Stanford Biodesign's director of policy research Sandra Waugh Ruggles discuss the Food and Drug Administration's proposed language on laboratory developed tests (LDTs), and the potential impact on clinicians, patients, and innovators.

My white paper on the FDA proposal is here:

https://www.discoveriesinhealthpolicy.com/2023/10/online-ahead-of-print-white-paper-on.html

Not mentioned in the webinar, a former FDA attorney's guide to the FDA's legal weaknesses:

https://www.discoveriesinhealthpolicy.com/2023/11/a-lawyers-view-potential-weakness-of.html

###

AI CORNER

I've included an AI summary below from ChatGPT [some manual edits].

This webinar from the Stanford Biodesign Center focused on the FDA's regulation of Laboratory Developed Tests (LDTs). The discussion centered on the FDA's proposed rule which appeared following Congress's failure to pass the VALID Act.  (VALID hadsought to establish a new framework for the regulation of LDTs.)

The panelists expressed disappointment with the proposed rule, seeing it as a blunt instrument that could stifle innovation and patient access to essential tests. They highlighted the need for a regulatory framework that acknowledges the unique characteristics of LDTs, as opposed to applying the legacy  1976 medical device regulatory framework.

The proposed rule's timeline was criticized for being too short to accommodate the industry and FDA's needs adequately. There were concerns about the ability to maintain access to high-risk LDTs due to the short timeline for submission requirements. The panelists also expressed legal concerns, doubting the FDA's authority under current law to regulate LDTs as medical devices.  The FDA's somewhat irregular approach to laying out a cost-benefit argument was critiqued.

Significant points of contention included the lack of a grandfathering policy for existing LDTs, the absence of provisions for rare disease testing, and the potential negative impacts on innovation, particularly for small-scale tests and those from academic medical centers. The discussion highlighted the potential chilling effect on new diagnostics development, increased capital requirements, and the need for more strategic planning to navigate the regulatory landscape.

The panelists suggested that the FDA should seek a more nuanced, goal-oriented approach, with a focus on ensuring test safety and controlling claims without imposing excessive costs. They stressed the importance of legislative involvement to create a diagnostic-specific regulatory framework and advised stakeholders to submit comments during the open period to influence the final rule. There was a consensus that the FDA's rule, as it stands, may not be implementable and that any effective regulation must balance patient safety, access, and the facilitation of innovation.

GRAIL Announces Investigational Device Study (IDE) of GALLERI Test

GRAIL announces its IDE (investigational device exemption) for the GALLERI test in Medicare-age patients.   See a detailed press release accompanied by a two-minute YouTube video. 

Find the press release here:

https://grail.com/press-releases/grail-to-initiate-reach-study-to-evaluate-clinical-impact-of-galleri-multi-cancer-early-detection-mced-test-among-the-medicare-population/

Find the video here:

https://www.youtube.com/watch?v=nksTA6B2w-o

Find a news report at Clinical Trials Arena here.  (By the way, CTA is an interesting news source).

The press release is pretty long, at 1100 words.

Find a short summary of the GRAIL information here:

On November 20, 2023, GRAIL announced the initiation of the REACH/Galleri-Medicare study, which aims to evaluate the clinical impact of its multi-cancer early detection (MCED) test, Galleri®, among Medicare beneficiaries. 

This pivotal study, greenlit by both the FDA and CMS, will assess the potential of Galleri® to improve cancer outcomes and reduce healthcare costs by detecting multiple cancer types early. The study will compare the health outcomes of 50,000 Medicare beneficiaries using Galleri® alongside standard cancer screenings against a control group receiving usual care. With a focus on inclusivity, the study will emphasize recruitment from historically under-represented groups, ensuring broad access to this innovative technology. 

The study’s findings will contribute to a growing body of evidence supporting the use of MCED tests in diverse populations, aiming to advance early cancer detection and address health disparities.

In General: What's a CMS IDE Study vs Para Review Coverage vs TCET?

CMS manages an intake portal for applicants with FDA-approved IDE studies and a roster of current studies, here.  The FDA-CMS-IDE program should be kept separate from the Parallel Review program (here) and the proposed but not yet enacted  TCET program (here).  

• The CMS FDA IDE program is for products or services fully engaged in the FDA clinical trials for FDA labeling, which studies are called "IDE" studies.  Hundreds of such studies have had CMS coverage of the device under investigation, on the basis that the device is providing a service for each Medicare patient receiving it.   
• FDA FAQ here.
• The Parallel Review program engages CMS in the writing of an NCD during the last phase of  FDA approval, and has been used only a very few times in a decade. 
• Article on Para Review here.  
• Finally, the TCET program is only a proposal for a future program, a main part of which would be sheparding the new device into an NCD with CED quickly and efficiently.    
• Law firm's update on TCET here (Holland Knight).  Academic article on CED here. 

____

 The 1995 rule establishing the IDE coverage  was an agreement  between FDA and CMS and was very well written, still very lucid and readable today (1995, 60 FR 48417) (here).  Compared to the clarity of the logic, writing, and justification,in the 1995 FDA rule, the FDA's more recent "FDA LDT" rule proposal was just a train-wreck.