Novitas Oncology LCD: The Carnival Continues

 In mid-2022, Novitas MAC proposed a new LCD for oncology tests.   In June 2023, it issued the final version, which was much longer with many topics not covered in the proposal.  After stakeholder protests that this was "bait and switch," Novitas withdrew the final LCD.

And, days later, Novitas issued the "final LCD" of the 2022 proposal, as a new, "proposal" for 2023. Entry point here - from July 27, 2023.  

This triggered a new round of public comments.  I used AI to summarize the 21 presentations at a public hearing.  Here.  

Now, the clock has run out on the one-year time period to finalize the July 2023 draft LCD (which, recall, was the June 2023 final LCD of the 2022 proposal).

What's New?  Still Thinking!

Novitas posts that CMS has granted it an extension (of unstated duration) to continue considering the public comments.  Find it here:

https://www.novitas-solutions.com/webcenter/portal/MedicareJL/pagebyid?contentId=00006150

July 26, 2024

Novitas is considering all the feedback received from interested parties regarding the Genetic Testing for Oncology LCD. An extension has been granted by CMS in order for all comments to be considered thoroughly. Future updates will be published to this website and the Medicare Coverage Database. Please watch our website and consider subscribing to our mailing list for the most timely updates.

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AI Corner

I asked Chat GPT to read this blog, and then, provide an illustration of its own choosing.

Chat GPT 4

CMS CLFS Experts (July 25-26): Links to Transcript, Video, and a Chat GPT Analysis

On July 25, 2024, CMS held its "expert panel" providing advice on the pricing of over 100 new lab codes.

Original blog here.

Agenda for meeting here.

Flash-blog on the "process" discussion held during the panel - here.

CMS will post the voting results during August.

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In this blog, I first provide links to the auto transcript and video links to YouTube.

Then, in the second half, I present discussion of the meeting by Chat GPT 4.

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Auto Transcript (segmented to match the 4 videos)

https://docs.google.com/document/d/1NiSAfNe4ilIzYzbcPBIiQeW4Gyo4icjO/edit?usp=sharing&ouid=110053226805181888143&rtpof=true&sd=true

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Here is a video archive and autotranscripts segmented for the 4 videos.

20240725 CLFS FACA VIDEO ONE (About 1-58)

https://youtu.be/TjA51_WikNM  

20240725 CLFS FACA VIDEO TWO (About 62-70)

https://youtu.be/Favgw6rdwpw

20240725 CLFS FACA VIDEO THREE (About 70-103)

https://youtu.be/356m3mmeYX0

20240725 CLFS FACA VIDEO FOUR (About 103-132 & Holdovers)

https://youtu.be/xvDjMtOwf9g

20240726 CLFS FACA VIDEO FIVE (0726, MISC)

https://youtu.be/nw64rEx1kDU

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AI CORNER

I gave the entire transcript to Chat GPT and asked it to open.  I have preserved my prompts as I wrote them.   Note that at first, it gave a shallow summary, then a better one.  Then, I asked it what evidence it saw in the transcript, for how panelists made pragmatic decisions between "crosswalk" and "gapfill".

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PROMPT #1

Please provide a summary of this transcript.  A ten-person advisory expert panel advises CMS (Medicare) on how to price about 100 new tests.   Primarily by the "crosswalk" method to a smilar test, if none available, then by "gapfill."   Do not try to summarize the individual decisions, as there are >100 of them.

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• The transcript from the CMS CLFS FACA Advisory Panel meeting outlines the process and discussions involved in pricing new lab tests for Medicare. The ten-person expert panel advises CMS on pricing approximately 100 new tests using primarily the "crosswalk" method, which involves comparing a new test to an existing similar test to set a price. If a comparable test is not available, the "gap fill" method is used, where the price is determined based on the cost of resources and technology used for the test.
• The panel's recommendations are based on subcommittees' reviews, public comments, and supporting information. Each new test is reviewed for its methodology, resources, and indications, with the panel voting on whether to use a crosswalk or gap fill approach. The process includes public input, and final decisions are made after considering preliminary recommendations and additional comments.
• For a detailed summary, specific test decisions were not included as the content involves over 100 individual decisions and discussions. Instead, the focus is on the general procedure and methodology applied by the panel in making their pricing recommendations.

PROMPT #2

Could you write a description of the meeting that is about twice as long, going into additional highlights and factors.

The CMS CLFS FACA Advisory Panel meeting held on July 25-26, 2024, focused on establishing payment amounts for new or substantially revised Healthcare Common Procedure Coding System (HCPCS) codes for the upcoming calendar year. The ten-person expert panel, consisting of members with extensive backgrounds in various medical and scientific fields, provided recommendations to the CMS on how to price approximately 100 new laboratory tests. These recommendations were primarily based on the "crosswalk" method and, when necessary, the "gap fill" method.

Key Highlights:

1. Meeting Structure and Process:

   • The meeting began with introductions and housekeeping items, led by Rashida Arthur, the designated federal officer. The process was virtual, allowing broader participation.
   • Two subcommittees were established: the Molecular Pathology Genomic Sequencing (MOG) Subcommittee and the Chemistry, Hematology, Immunology, and Microbiology (CHIMP) Subcommittee. These groups aimed to streamline discussions and leverage panel members' expertise efficiently.

2. Crosswalk Method:

   • The crosswalk method involves comparing the new test to an existing test with similar methodology, resources, and clinical utility. If a suitable comparable test was found, the panel recommended using its established price for the new test.
   • For example, the test code 0445U, related to Alzheimer’s disease, was crosswalked to 0358U due to similar descriptors and methodologies, ensuring consistent pricing based on established precedents.

3. Gap Fill Method:

   • When no comparable test was available, the gap fill method was employed. This method involves determining the payment amount based on the resources and technology required for the new test. This method takes longer as it involves gathering cost data from multiple sources.
   • The code 86041 for acetylcholine receptor binding antibody, lacking a precise comparable test, was recommended for gap fill pricing.

4. Public and Panel Input:

   • The meeting allowed for real-time public comments and responses to questions from the panel, ensuring a transparent and inclusive process.
   • Discussions often included detailed questions about the specifics of the tests, such as the methodologies used, the type of specimens analyzed, and the clinical relevance of the tests.

5. Technical Clarifications:

   • The panel frequently sought technical clarifications to ensure accurate recommendations. For instance, there were detailed discussions on whether certain tests measured qualitative versus quantitative results and how these differences impacted resource use and pricing.
   • For example, discussions around code X0103U for therapeutic drug monitoring involved clarifications about whether the test provided qualitative or quantitative data, impacting the decision to recommend gap fill or crosswalk to an existing code.

6. Complexity of Test Categories:

   • The panel reviewed tests across various categories, such as molecular pathology, immunology, and microbiology. Each category had unique considerations, reflecting the diversity and complexity of modern diagnostic testing.
   • The use of advanced technologies like liquid chromatography-tandem mass spectrometry (LC-MS/MS) and multiplex assays highlighted the evolving nature of laboratory diagnostics.

7. Voting and Decision Making:

   • Each test was individually discussed, followed by panel voting on the recommended pricing method. Votes were cast electronically, and results were immediately shared.
   • Some tests required additional follow-up or were moved to the end of the agenda for further discussion, ensuring thorough consideration of all options.

Additional Factors Considered:

• Methodological Consistency: Ensuring that similar tests were priced consistently to avoid discrepancies and ensure fairness in pricing across the board.
• Resource Utilization: Evaluating the resources required for each test, including equipment, reagents, and labor, to accurately reflect the cost in the pricing recommendation.
• Clinical Utility: Considering the clinical importance and utility of the tests in patient care, influencing the prioritization and pricing decisions.
• Technological Advances: Acknowledging the rapid advancements in diagnostic technologies and how they impact the complexity and cost of new tests.

Conclusion:

The CMS CLFS FACA Advisory Panel meeting was a meticulous and inclusive process aimed at ensuring fair and accurate pricing for new and revised laboratory tests. By leveraging the expertise of the panel members, incorporating public input, and thoroughly evaluating each test's methodology and clinical relevance, the panel provided CMS with well-founded recommendations for the upcoming year.

PROMPT #3

That was excellent! Thanks for the additional insight and color. One of the persistent topics is how to decide if a crosswalk is "close enough" to use, or whether to turf the decision to the gapfill process instead. This was discussed in the panel discussion segment about process, noting there were no objective rules for a "comparable" test. Could you review the whole document and draw any insights into how the panel approached the practical or pragmatic decision of whether a crosswalk was "close enough to use" or whether no such close crosswalk existed, forcing a referral to gapfill instead. How did panelists pragmatically handle this dilemma, as suggested by their transcribed thinking and remarks.

The CMS CLFS FACA Advisory Panel meeting highlighted several discussions around the challenge of determining whether a crosswalk is "close enough" to use or if the decision should be deferred to the gap fill process. This decision-making process lacks objective rules, and the panel often relies on practical and pragmatic considerations, as evidenced by their transcribed remarks and thought processes.

Key Insights from the Panel's Approach:

1. Criteria for Comparability:

   • The panel frequently debated what makes a test "comparable" enough to justify a crosswalk. Factors such as intended use, methodology, number of targets, and resources required were considered. For instance, panelists discussed whether tests with similar methodologies but different targets could still be crosswalked effectively.

2. Information and Documentation:

   • A recurring theme was the necessity of detailed information from sponsors. Panelists emphasized the need for comprehensive descriptions of assays, methodologies, resources, and outcome reports to make informed decisions. When such information was lacking, it often led to recommending the gap fill method due to insufficient data to establish a direct crosswalk .

3. Examples of Decision-Making:

   • For complex assays, such as next-generation sequencing for colorectal cancer, the lack of a direct comparable test led to a recommendation for gap fill​.
   • In cases where a test had a similar methodology and specimen type but differed in complexity or number of analytes, the panel might opt for a crosswalk with a multiplier to account for these differences.
   •  For example, a neurofilament light chain test was crosswalked with a 0.5 multiplier due to its methodological similarity to an existing test with more analytes .

4. Consistency and Precedent:

   • The panel aimed to maintain consistency in their recommendations year over year. This was particularly important for tests that had undergone similar reviews in previous years. Consistent application of crosswalks helps in maintaining fairness and predictability in pricing decisions.

5. Panel Discussions and Votes:

   • The panel’s discussions often involved multiple options for crosswalks, with detailed justifications for each. When no clear crosswalk was identified, and no substantial input was received from labs or stakeholders, the gap fill method was recommended. This approach ensures that the pricing process remains rigorous and justified even in the absence of direct comparability .

Practical Handling of the Dilemma:

The panel's pragmatic handling of the crosswalk versus gap fill dilemma is illustrated by their reliance on detailed comparisons and thorough discussions. They consider:

• The specific methodologies and technologies used in the tests.
• The intended clinical use and outcome measures.
• The completeness and quality of the information provided by test developers.
• Historical decisions and established precedents to ensure consistency.

In conclusion, the panel's approach to deciding whether a crosswalk is "close enough" involves a detailed examination of each test's characteristics, a reliance on thorough documentation, and an emphasis on maintaining consistency. When faced with insufficient information or clear differences in methodology, the panel pragmatically opts for the gap fill method to ensure fair and accurate pricing decisions

Flash Blog: CMS Asks Expert Panel to Discuss the New Test Pricing Process

On July 25, 2024, CMS held its annual expert advisory panel for pricing new lab codes.   In addition to handling over 100 agenda items, CMS gave the panel a half hour in the afternoon to discuss the CMS pricing process as a whole. 

I'll provide my own notes, and then I'll include a "news article" written by ChatGPT from an auto transcript.

This blog is limited to the process-discussion-half-hour - for the whole day, here.

Panelist Remarks Included...  

Here are some viewpoints of the panelists that I captured:

1. The public comment presentations in June are very helpful – it’s frustrating that “half” of codes lack a presentation in that forum.
2. Companies present elaborate and useful info packets to AMA, but they dead-end there and are not part of the crosswalk process. Could the companies/AMA/CMS facilitate sharing, at least as an option?
3. The panelists would like to have patient result reports for each test.
4. Inclusion of an FDA instructions for use would help.
5. One frustrating scenario is when a test in one year (000XU) is sent to gapfill, and the next summer a very similar code is created (00XXU). The new code can’t be crosswalked to 000XU, but it’s a similar code and for consistency the price should be the same. Under today’s rules, 00XXU will get sent to gapfill in the next year, a waste of gapfill resources and potentially a source of price inconsistency.
6. It seems unfair to price two tests differently, one with 10 markers, one with 20, when they output the same result with the same accuracy.
7. There was discussion that the PLA codebook has no structure, and with >500 codes, that’s confusing and makes crosswalk searches unreliable.
8. What does “appropriate crosswalk” mean? Intended use? Method? Number of analytes? CMS noted that both creating such rules – and the lack of the rules – is problematic.
9. When public stakeholders align on a pricing proposal, that’s impressive and helpful.

[I wrote the above points, but Chat GPT reordered them - here's why and how.)

BQ Thoughts

Here are five viewpoints of my own - not the CMS panel.

a. In September, explanations of proposed prices by CMS are very short, making it hard to craft a public response that meets CMS concerns and CMS thinking.  

b. It’s hard to know where the line is for “appropriateness” of fit as crosswalk, but on one side of the invisible line, you crosswalk, on the other side, you gapfill.

c. CMS is highly dependent on the code text, which is inconsistent among codes, as the panel noted.  I had a client pulled into CMS meetings to explain that two terms (in similar PLA codes) were well known synonyms, and it was a long difficult communication.

d. Pricing outliers can occur (errors high or low) which may or may not be propagated by irregular future crosswalks.    For example, a PLA company might go out of business and provide no info, so its code is wildly underpriced, but endorsed by the fee scheduel

e. PLA codes are canceled at a rate of 3-5 per quarter, what happens to a code crosswalked to a canceled code?  Does it carry on at the ghost price, or become unpriced?

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AI CORNER

Using an autotranscript, I asked Chat GPT to take the role of a health policy journalist and describe the meeting.

CMS Public Meeting on
Pricing New Lab Test Codes: 
Insights from the Panel Discussion

Written by ChatGPT 4 via auto transcript at otter.ai

In a lively and informative session, the Centers for Medicare & Medicaid Services (CMS) facilitated a panel discussion to delve into the complexities of the rate-setting process for new lab test codes. The session aimed to gather expert feedback and improve the transparency and efficiency of the pricing process.

The discussion, led by Sarah Harding and Sarah Shirey-Lasso, addressed several key questions that have emerged from public comments over the years. These questions focused on the challenges and potential improvements in setting payment rates for lab tests. The conversation was intended to be informal, allowing panelists to freely share their experiences and suggestions.

Challenges in Crosswalking and Gap Filling

The panelists highlighted several difficulties in the current process. A recurring theme was the lack of detailed information from test sponsors. A seasoned panelist noted, "The number one challenge is when sponsors don't provide any information, and we're left to figure out comparability in terms of method, intended use, or number of targets."

This sentiment was echoed by other panelists, one of whom expressed frustration with the incomplete information provided by some sponsors. "Half of them don't show up for the public meeting in June, which makes it difficult to make informed decisions," she said.

The Need for Detailed Reports and Consistent Guidelines

The panelists agreed that detailed reports and consistent guidelines are crucial for effective crosswalking and rate setting. A panelist suggested that requiring submission of detailed assay reports and methodologies should be considered. "It's very difficult to do this work well without those kinds of details," she emphasized.

The panel also discussed the importance of having clear guidelines on what constitutes comparability. "Some guidelines around what crosswalking actually means would be helpful,"a panelist pointed out. She highlighted the inconsistencies in how different specialties develop and describe codes, making it challenging to find comparable tests.

Coordination with AMA and Improved Communication

Another panelist shared her recent experience from both sides of the process—submitting codes to the American Medical Association (AMA) and serving on the CMS panel. She stressed the need for better coordination between AMA and CMS. "If there was a way for those responsible for submitting codes to get a message from CMS outlining the next steps and the importance of providing detailed information, it would make a significant difference," she said.

The panelists suggested that CMS should facilitate the sharing of supplemental materials, such as instruction for use (IFU) documents and other relevant reports, to aid in the evaluation process.

The Role of Analytical and Clinical Information

A significant point of discussion was the distinction between analytical and clinically reported information. A speaker raised the issue of what should be considered for crosswalking—what's reported out clinically versus what's done analytically. "Payers tend to want to pay for the clinically important information," she noted. This distinction is crucial in determining the value and comparability of new tests.

Looking Ahead: Potential Policy Changes

The panelists concluded by discussing the potential for developing specific criteria for determining comparability. This would involve defining what makes tests comparable in terms of intended use, method, and reporting. While acknowledging the challenges, they expressed optimism about improving the process through better guidelines and more detailed information from sponsors.

In closing, CMS officials thanked the panelists for their valuable insights and emphasized the agency's commitment to refining the rate-setting process. The discussion provided a clear roadmap for future improvements, aiming to balance the needs of innovation with fair and sustainable pricing.

Conclusion

The CMS public meeting on pricing new lab test codes highlighted the complexities and challenges of the current process. The panelists' insights underscored the need for detailed information, clear guidelines, and better coordination with the AMA. As CMS continues to refine its methodologies, the feedback from this discussion will play a crucial role in shaping the future of lab test pricing policies.

Brief Blog: The Experience and Dilemmas of Triple-Negative Breast Cancer

Thanks to Joe Lennerz MD for highlighting, at Linked In, an absorbing new article on the experience and dilemmas of managing triple-negative breast cancer.  The article is Kok et al. (2024) PMID 39038259.

In the study, pembrolizumab was given both as neoadjuvant and as adjuvant add-on therapy, and in the end, we don't know if either phase or both phases made the important contribution.  In addition, while the index patient discussed here at favorable biomarker(s), their scale of impact is uncertain.

Lennerz here:

https://www.linkedin.com/posts/joe-lennerz-90029219_fda-biomarker-regulatory-activity-7221478324882083840-RMei/?utm_source=share&utm_medium=member_desktop

The article is here ("partial open access"):

https://ascopubs.org/doi/full/10.1200/JCO.24.00372

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The July 23/30 JAMA has a pair of letters on tumor infiltrating lymphocytes in TNBC. (332:337). Comment on Leon-Farre 331:1135.

The July 23/30 JAMA has a personal essay by a physician with breast cancer ("Even Better," 332:283)

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AI Corner

Here's an AI summary of Kok et al.

Summary for Cancer Experts: 

Personalizing Treatment for Stage II/III Triple-Negative Breast Cancer

Article: "Academic Uphill Battle to Personalize Treatment for Patients With Stage II/III Triple-Negative Breast Cancer" by Marleen Kok et al. (JCO, 2024)

Key Findings:

1. KEYNOTE-522 Phase III Trial:

   • Investigated the combination of pembrolizumab with neoadjuvant chemotherapy (carboplatin/paclitaxel followed by doxorubicin/cyclophosphamide) for patients with stage II/III triple-negative breast cancer (TNBC).
   • Showed an approximate 7% improvement in pathological complete response (pCR) rates and a 9% improvement in event-free survival (EFS) compared to chemotherapy alone.
   • Despite benefits, only a subset of patients benefit from this combined therapy, and the value of the adjuvant pembrolizumab phase remains unclear.

2. Case Study and Patient Perspective:

   • Highlights the experience of a 48-year-old physician with stage II, node-negative TNBC who questioned the necessity of continued intensive treatment after a favorable early response.
   • [The physician provides an essay about her experience; see Page 10.]
   • Emphasizes the importance of personalized treatment plans based on biomarkers like tumor-infiltrating lymphocytes (TILs) and PD-L1 expression, which were significant in her case but underappreciated by her clinicians.

3. Challenges in Personalized Treatment:

   • The trial design did not incorporate a second randomization post-surgery to evaluate the necessity of continued pembrolizumab, leading to uncertainties about the contributions of neoadjuvant versus adjuvant therapy.
   • Current treatment guidelines recommend continuation of pembrolizumab in the adjuvant setting based on trial protocols, not individualized patient response.

4. Lack of Reliable Biomarkers:

   • There is a significant need for biomarkers to predict which patients will benefit from immunotherapy and to tailor treatments accordingly.
   • Potential biomarkers like TILs and MHCII have not been prospectively validated, making it difficult to personalize treatments effectively.

5. Future Directions and Ongoing Trials:

   • Several ongoing trials aim to refine immunotherapy strategies for TNBC by exploring shorter treatment durations, alternative chemotherapy backbones, and predictive biomarkers.
   • Regulatory and academic collaboration is crucial to ensure trials are designed to minimize overtreatment and toxicity while maximizing patient-specific benefits.

Conclusion: Personalizing treatment for TNBC is a complex challenge that requires a delicate balance between adhering to trial protocols and adapting to individual patient needs. Advancements in biomarker research and trial design are essential to optimize treatment efficacy and reduce unnecessary toxicity. The article underscores the importance of ongoing efforts to integrate personalized approaches into clinical practice for better patient outcomes.

For a deeper dive, refer to the original article: DOI 10.1200/JCO.24.00372

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PATIENT'S ESSAY

Summary of the Appendix: Patient Experience

Appendix - Patient Perspective:

Patient Background:

• The appendix features the personal account of a physician who survived stage II triple-negative breast cancer (TNBC) and underwent the KEYNOTE-522 regimen.
• Initially diagnosed with marked tumor-infiltrating lymphocytes (TILs), the patient had to seek out experts to understand the significance of these findings, as local clinicians were unprepared to discuss them.

Treatment Journey:

• The patient began the prescribed KEYNOTE-522 therapy, consisting of neoadjuvant chemotherapy and pembrolizumab, amidst significant scare tactics emphasizing the importance of following the study protocol.
• Despite discovering high PD-L1 expression and 85% TILs in the tumor, which indicated a potentially excellent prognosis, the patient’s oncologists insisted on adhering strictly to the treatment regimen.

Adverse Effects:

• The patient experienced severe side effects, including loss of thyroid function, fatigue, dehydration, nausea, diarrhea, thrush, sleep disruption, hair loss, bone and joint pain, and significant cognitive and mobility issues.
• These effects resulted in loss of salary, independence, confidence, and overall quality of life.

Advocacy for Personalized Treatment:

• The patient requested reimaging and reassessment to potentially reduce treatment intensity after significant early response, but these requests were denied in favor of completing the full regimen.
• Continued through 12 weeks of paclitaxel, carboplatin, and pembrolizumab, followed by 12 weeks of doxorubicin and cyclophosphamide, despite believing this constituted overtreatment.

Outcome and Reflection:

• Achieved a complete pathological response with no residual tumor detected in the final MRI and surgery.
• Opted against adjuvant pembrolizumab based on personal research, contrary to oncologists' advice.
• Concerns about the potential long-term effects of the extensive treatment and the overall approach to TNBC treatment protocols that do not sufficiently account for individual patient biomarkers.

Call for Change:

• The patient emphasizes the need for more personalized treatment plans, better understanding, and utilization of biomarkers.
• Critiques the influence of pharmaceutical companies on research and treatment protocols, advocating for a more patient-centered approach in clinical trials and medical practice.

Conclusion:

• Highlights the disparity between standardized treatment protocols and the need for personalized, biomarker-driven approaches to improve patient outcomes and reduce unnecessary treatment burdens.

FLASH: Jeff Shuren Leaves FDA

Dr Jeff Shuren, who sheparded LDT regulatory reform through the Hill and through FDA rulemaking, will be leaving the FDA.

See the full story at STAT PLUS (Subscription):

https://www.statnews.com/2024/07/23/jeff-shuren-medical-devices-head-at-fda-to-leave-the-agency/

Shuren, an MD JD, has been with the FDA since 1998, according to STAT.  

See a follow-up article from RAPS here.  MedTechDive here. MassDevice here.

Shuren's FDA bio, accessed 7/23

https://www.fda.gov/about-fda/fda-organization/jeff-shuren

Cloud copy here.
His spouse, Allison Shuren JD, is also an attorney, with Arnold & Porter.

A New White Paper: Medicare Policy and Minimal Residual Disease Testing

Today we're releasing a new white paper that surveys the landscape of Medicare policy for Minimal Residual Disease testing (MRD testing).  

This important new class of oncology diagnostics is having major impacts on the management of cancer patients.   Medicare policy for coverage is based primarily on a master foundational LCD used in the MolDx states - about 29 states.   (The other states, under the NGS MAC and Novitas/First Coast systems, have no policies yet for MRD testing).

But local coverage for MRD, which usually matched to up-to-date cancer guidelines, sometimes collides with a 2018 national coverage decision (NCD) on all cancer testing involving next-generation sequencing.  That 2018 document was based on the then-new coverage for the Foundation Medicine tumor panel test, and targeted coverage to advanced cancers, with one test per patient.   Those principles are now obviously outdated, since MRD testing can be a valuable test for completeness of resection, even in stage 2 cancers, and may be used as serial tests for therapy management or for relapse detection.

We lay out the history, policies, and potential policy improvements in a new white paper.   

• Find the PDF here.

AI Corner

While the 25-page white paper is "manually" written - and this is about the tenth draft! - I don't think I can do a better job of summarizing it than Chat GPT 4 can.  Here's an AI summary of the white paper:

Summary of the White Paper: 

Minimal Residual Disease Testing: A Case Study for Policy Reforms

Introduction and Key Findings The white paper delves into Minimal Residual Disease (MRD) testing, emphasizing its critical role in detecting cancer recurrence, monitoring therapy response, and assessing the completeness of cancer resection. It highlights the transformative potential of MRD tests, particularly those based on circulating tumor DNA (ctDNA), over traditional imaging methods like CT and MRI. The paper reviews current MRD technologies, their applications, and the need for policy reforms to support their broader adoption.

Technologies for MRD MRD tests have evolved significantly, with key players like Adaptive Biotechnologies' ClonoSEQ, Natera's Signatera, and Guardant Health's Reveal leading the field. These tests use various technologies, from bespoke sequencing approaches to standardized tests for specific cancers. The paper discusses the diverse applications of MRD, including:

• Detecting cancer recurrence earlier than imaging.
• Monitoring therapy response.
• Assessing the completeness of cancer resection.

Insurance Coverage and Policy Issues Insurance coverage for MRD testing varies widely. The paper outlines the discrepancies in Medicare coverage across different regions, highlighting the advanced policies of the MolDx program and the lack of systematic policies in other Medicare regions. Key policy issues include:

• The restrictive national coverage decision (NCD) for NGS-based testing, which limits serial testing and coverage for early-stage cancers.
• The 14-day rule for inpatient services, causing delays in test availability post-surgery.
• The complex and fragmented coding system, with a proliferation of PLA codes that are not widely accepted.
• Slow and non-transparent pricing processes for new tests.

Stakeholder Analysis The white paper examines the perspectives of various stakeholders:

• Payers: MRD can reduce costs and improve patient outcomes by enabling more precise treatment decisions.
• Diagnostic labs: Leading labs like Natera emphasize the importance of reimbursement dynamics and intellectual property positioning.
• Biopharma: MRD tests offer new surrogate markers for clinical trials, particularly in adjuvant and neoadjuvant therapy.
• FDA: The regulatory landscape is evolving, with new guidelines and approvals for MRD tests expected to impact the market.

Regulatory and Legislative Uncertainties Two significant areas of uncertainty are highlighted:

• The impact of new FDA regulations bringing lab-developed tests under FDA control by 2027.
• The influence of state biomarker coverage laws, which mandate coverage for biomarker tests by commercial insurers in some states.

Future Directions and Recommendations The white paper concludes with several recommendations to improve MRD testing policies:

• Reopen NCD 90.2 to enhance coverage for early-stage cancers and serial testing.
• Revise the 14-day rule to allow immediate testing post-discharge.
• Develop general CPT codes for major types of MRD testing.
• Increase transparency in coverage decisions, particularly within the MolDx program.

The paper underscores the importance of adapting policies to keep pace with technological advancements in MRD testing, ensuring broader access and better patient outcomes in clinical genomics.

CMS Publishes Agenda for July 25-26 Lab Expert Advisors Meeting (Pricing 2025)

On June 25, 2024, CMS held a public meeting for comments on pricing nearly 100 new lab codes for 2025. (My blog here.)

CMS has published a video link to that June meeting; I've added it on top as an update to the prior link.

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Next, CMS will hold an expert advisors meeting on June 25-26 (the second day depends on needing more time).   

Here's the page, and note that they've posted a 17 page agenda for the June 25-26 meeting.

https://www.cms.gov/medicare/payment/fee-schedules/clinical-laboratory-fee-schedule-clfs/clfs-advisory-panel

Agenda

https://www.cms.gov/files/document/agenda-cdlt-panel-meeting-july-25-26-2024.pdf

Note that while the June 25 meeting had an open zoom link, this one appears to require registration (see Appendix 1.)

The agenda starts at 10 ET, 7 PT (good for us Californians).   

The agenda includes a half hour after lunch to discuss the CLFS pricing process and (I suppose) possible improvements.

Brief Blog: CMS to Cover Mental Health Apps; What's Up?

Medicare has a hard time developing coding, coverage, and payment for software - for AI, for FDA-approved apps, etc.   Witness the extensive discussion of this topic in a recent MEDPAC report to Congress (here).

In early July, as part of annual PFS or "physician fee schedule" policymaking, CMS announced new codes and plans to cover certain mental-health apps, here.   See discussion at AXIOS here.  See FIERCE HEALTHCARE here.

In the currently available "inspection copy" or "typescript" of the PFS rule, the topic has coding on page 227 and discussion on pages 377-384.  

Digital Pathology Connections?

I've included an AI summary below.  I haven't attempted to connect the dots here, but there are probably some potential analogies to Medicare thinking and Medicare payments for other kinds of software, such as FDA approved digital pathology applications.

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AI CORNER

[Start Chat GPT 4]

The Centers for Medicare & Medicaid Services (CMS) have proposed significant updates to the coverage and payment policies for digital mental health treatment (DMHT) devices as part of the CY 2025 Payment Policies under the Physician Fee Schedule (PFS). This proposal is driven by the evolving field of digital therapeutics and the increasing demand for mental health services, particularly given the nationwide behavioral health workforce shortages.

Key Details of the Proposed CMS Policy

Objectives and Justification

CMS aims to:

1. Enhance Access: Increase access to vital behavioral health services using innovative digital therapeutics.
2. Gather Data: Collect information on the effectiveness, adoption, and use of digital behavioral health therapies.
3. Align with FDA and SAMHSA: Follow the regulatory frameworks and definitions set by the FDA and SAMHSA for digital therapeutic devices.

Proposed Policy Specifics

1. New HCPCS Codes:

   • GMBT1: For the supply of a digital mental health treatment device and initial education and onboarding per treatment course. Conditions include:
     • FDA clearance for the device.
     • Costs incurred by the billing practitioner.
     • Use as part of an ongoing treatment plan prescribed by the practitioner.
     • Incident to the practitioner's professional services.
   • GMBT2: For the first 20 minutes of monthly treatment management services related to the DMHT device, including data review and at least one interactive communication.
   • GMBT3: For each additional 20 minutes of monthly treatment management services, with similar requirements to GMBT2.

2. Pricing and Payment:

   • Contractor Pricing: Due to the variability in costs, contractor pricing is proposed for GMBT1.
   • Crosswalk Methodology: GMBT2 and GMBT3 are proposed to be valued based on crosswalks to existing CPT codes for remote therapeutic monitoring (98980 and 98981).

3. Regulatory Compliance:

   • Devices must be FDA cleared under 21 CFR 882.5801, ensuring safety and effectiveness.
   • DMHT devices must generate and deliver mental health treatment interventions with demonstrable positive therapeutic impacts.

Alternatives and Public Comments

CMS has sought public feedback on several aspects:

• Device Clearance: Whether payment should be made for devices cleared by the FDA for uses other than mental health treatment.
• Discontinuation of Use: How payments might be limited if a patient discontinues the use of the device before completing the treatment course.
• Monthly Device Limits: Whether there should be a limit on the number of devices furnished per patient per month.
• National Pricing Methodology: Suggestions on appropriate national pricing methodologies and potential crosswalks.

Public Feedback and Future Considerations

CMS is open to public comments on:

• The proposed elements and requirements for care management services.
• Alignment of the proposed services with other Medicare programs and initiatives.
• Ways to reduce the burden on practitioners while ensuring comprehensive care.

Conclusion

The proposed CMS policy on digital mental health treatment devices aims to leverage digital therapeutics to improve access to behavioral health services while maintaining rigorous standards for safety and effectiveness. The proposal recognizes the rapid evolution of digital health technologies and seeks to adapt Medicare policies accordingly, with significant input from stakeholders to refine and optimize these new coverage and payment policies. Public comments and further research will play crucial roles in shaping the final rules and ensuring they meet the needs of both practitioners and patients effectively.  [/ End Chat GPT 4]  

If you were the author of the MEDPAC report on CMS and software, written several months ago, how would you react to the new publication about mental health apps? Surprises? Or predictable?

[Note that in this answer, GPT 4 referred by hotlink either to the 0601 Medpac chapter or the 0710 PFS rule.]

If I were the author of the MedPAC report on CMS and software, written several months ago, my reaction to the new CMS publication on mental health apps would include several observations and reflections:

Reaction to the New CMS Proposal on Mental Health Apps

Surprises

1. Speed of Adoption: The swift move by CMS to propose specific codes and payments for digital mental health treatment (DMHT) devices might be seen as a surprise. The MedPAC report noted the evolving nature of software technologies and CMS's typically deliberate approach in covering new technologies​​.

2. Focused on Mental Health: The specific focus on mental health apps, particularly digital cognitive behavioral therapy (CBT) and other DMHT devices, indicates a rapid response to the growing need for mental health services, which may not have been anticipated in the broader discussion of software technologies in the MedPAC report​​.

3. Public Feedback Request: CMS's detailed solicitation for public comments on various aspects of the proposal, including FDA clearance, pricing variability, and usage limitations, shows an openness to stakeholder input that might not have been expected to this extent​​.

Predictable Aspects

1. Regulatory Alignment: The alignment with FDA regulations and the clear categorization of DMHT devices as requiring FDA clearance aligns well with MedPAC’s emphasis on regulatory compliance for software as a medical device (SaMD)​​.

2. Complex Pricing and Payment Models: The challenges in setting appropriate pricing and payment models for software-driven technologies were anticipated. The MedPAC report highlighted similar concerns about payment methodologies and the need for a balanced approach between innovation and affordability​​.

3. Incremental Approach: The use of contractor pricing for the new codes and the proposal to potentially adopt new CPT codes in the future mirrors the incremental and cautious approach CMS has historically taken with new technologies​​.

Detailed Observations

1. Three New HCPCS Codes: The proposal to create three new HCPCS codes (GMBT1, GMBT2, GMBT3) for different aspects of DMHT services is a logical extension of CMS’s strategy to clearly define and separate different types of services for precise reimbursement. This aligns with the approach of categorizing software technologies under specific billing codes as discussed in the MedPAC report​​​​.

2. Contractor Pricing: Given the variability in costs and the evolving nature of digital therapeutics, CMS’s decision to use contractor pricing for GMBT1 is a prudent step to manage initial uncertainties in cost estimation, reflecting the cautious approach recommended in the MedPAC report​​​​.

3. Criteria for Payment: The detailed criteria for payment, including FDA clearance and the condition that the DMHT device must be integral to ongoing treatment, are consistent with the MedPAC report’s emphasis on ensuring that new technologies meet stringent safety, efficacy, and necessity criteria before being covered​​​​.

4. Public Comment on Pricing Methodology: The request for public input on pricing methodologies indicates CMS’s recognition of the complexities involved in pricing digital therapeutics, a concern that was thoroughly discussed in the MedPAC report. This step is crucial for developing a sustainable and fair payment system​​​​.

Conclusion

The new CMS proposal on mental health apps aligns well with the broader themes and concerns discussed in the MedPAC report, particularly in terms of regulatory alignment, incremental adoption, and the complexities of pricing. While there are some surprising elements, such as the rapid focus on mental health apps and the extensive solicitation of public feedback, these moves reflect an adaptive and responsive approach by CMS to the evolving landscape of digital health technologies.  

Brief Blog: Thermo Fisher eBook: Unraveling Rare and Inherited Diseases with Genetic Technologies

 With an entry point at an advertisement in THE SCIENTIST, Thermo Fisher offers a 14 page ebook on "Unravelling Rare and Inherited Diseases with Genetic Technologies."

Find the link here:

https://www.the-scientist.com/unraveling-rare-and-inherited-diseases-with-genetic-technologies-72004

AI CORNER

Below, Chat GPT 4 reads and summarizes the eBook.

Introduction

The eBook "Unraveling Rare and Inherited Diseases with Genetic Technologies" explores the complexities and advancements in diagnosing and studying rare genetic diseases. It emphasizes the significant impact these diseases have globally, despite their individual rarity.

Overview of Rare and Inherited Diseases

Rare diseases, although individually uncommon, affect a large portion of the population collectively. Definitions vary by region, but they generally affect a small percentage of people. Many of these diseases have a confirmed genetic origin, and understanding their genetic basis is crucial for diagnosis and therapy development.

Diagnostic and Research Tools

The book highlights various tools and technologies used to diagnose and study rare genetic diseases:

• Next-Generation Sequencing (NGS): Widely used for identifying mutations.
• Sanger Sequencing, PCR, and Microarrays: Traditional methods that complement NGS for confirming findings.
• Quantitative Real-Time PCR (qPCR) and Digital PCR (dPCR): Employed for precise mutation analysis.

Research on Specific Diseases

Key rare genetic diseases discussed include:

• Lupus: An autoimmune disorder with a genetic predisposition.
• Cystic Fibrosis: Caused by mutations in the CFTR gene.
• Muscular Dystrophies: Highlighting Duchenne Muscular Dystrophy (DMD) caused by mutations in the dystrophin gene.
• Huntington’s Disease: Resulting from mutations in the huntingtin gene.

Case Studies and Interviews

The eBook includes interviews with researchers focusing on:

• Huntington’s Disease: Dr. Alexandra Durr’s research on CAG repeats and their expansion with age.
• Duchenne Muscular Dystrophy: Dr. Michael Lopez’s study on the role of Smad8 in dysregulating microRNAs.

Technology Overview

A comprehensive overview of genetic technologies used in research is provided, detailing their applications and benefits:

• Microarrays: Used for detecting copy number changes and genetic variations.
• Fragment Analysis: Applied in mutation detection, microsatellite instability assays, and copy number variability studies.
• Sanger Sequencing: Trusted for obtaining accurate DNA sequences.
• Digital PCR (dPCR): Useful for quantifying sequences in a sample, particularly in detecting rare alleles.

Applications and Future Directions

The eBook concludes by discussing the potential of these technologies in improving the understanding, diagnosis, and treatment of rare genetic diseases. It emphasizes the importance of continued research and the development of new tools to advance the field.

References

The eBook provides extensive sources for further reading and validation of the information presented.

---

 

Question Arising: FDA and "Parallel Review"

 A question arose today about FDA and Parallel Review (for NCDs, and with Medicare).

FDA has a webpage for multiple payor communications programs:

https://www.fda.gov/about-fda/cdrh-innovation/medical-device-coverage-initiatives-connecting-payors-payor-communication-task-force

https://www.fda.gov/about-fda/cdrh-innovation/medical-device-coverage-initiatives-connecting-payors-payor-communication-task-force#cms

Parallel Review 

Q: How many requests have been received for Parallel Review?
A: As of June 2024, there have been 97 formal requests to participate in Parallel Review.

Q: How many devices have completed Parallel Review?
A: Two devices have completed Parallel Review: Exact Sciences’ Cologuard in 2014External Link Disclaimer, and Foundation Medicine’s FoundationOne CDx in 2017.

Q: How much time did the companies save by using Parallel Review?
A: It is estimated that the NCD process typically takes 6-9 months. Cologuard received its FDA approval and the proposed NCD opened on August 11, 2014. The NCD was finalized on October 9, 2014, just under 2 months after the proposed NCD opened. FoundationOne CDx received its FDA approval and the proposed NCD opened on November 30, 2017. The NCD was finalized on March 18, 2018, about 3.5 months after the proposed NCD opened.

Journal Club: NEJM Weighs in on Chevron vs Health Law, and on Ethics of AI

 This week NEJM weighs in on two hot topics, the impact of the CHEVRON Supreme Court decision on health care policy & law, and an article on the ethics of AI in healthcare.

Sachs RE & Brown ECF (2024)  Supreme Power - The loss of judicial defence to health agencies.  Online first.  https://www.nejm.org/doi/full/10.1056/NEJMp2408197

Sim I & Cassel C (2024)  The Ethics of Relationa AI - expanding and implementing the Belmont principles.  NEJM 391:193-6.  https://www.nejm.org/doi/full/10.1056/NEJMp2314771 

(I'm a subscriber, so I'm not sure if either or both are open access.)

The two articles lack abstracts, so I've included an AI Summary below.

###

AI CORNER

[Start Chat GPT 4]

Supreme Power — The Loss of Judicial Deference to Health Agencies

New England Journal of Medicine, July 17, 2024

The U.S. Supreme Court's recent ruling in Loper Bright Enterprises v. Raimondo marks a significant shift in judicial authority, ending the Chevron doctrine, which had guided courts to defer to agency interpretations of ambiguous statutes for 40 years. This decision reallocates power from Congress and administrative agencies to the judiciary, posing potential challenges for health agencies like CMS and FDA.

Key implications include:

• Increased litigation and regulatory uncertainty for the healthcare industry.
• Diminished expert authority over health regulations, risking patient safety and public health.
• Potential disruptions in Medicare payments and challenges to FDA's regulatory capabilities.

Justice Elena Kagan's dissent highlights the loss of valuable agency expertise in statutory interpretation. The decision's lack of clear guidelines for lower courts could lead to more legal challenges and uncertainty, particularly impacting technical healthcare regulations.

The ruling is part of a broader trend of the Court enhancing judicial power, potentially favoring well-funded industry litigants over government regulations, with significant consequences for public health and safety.

[BQ - Post-Chevron, a court just found that HHS was wrong to find that "sexual discrimination" included the concept of "transgender," doing so, literally, by using 1972 dictionaries. That is, it was a "legal" or "judicial" finding (using the judicial method of dictionaries) not a "policy" finding by HHS. Tennessee v Becerra, July 2024.  Here.]

###

The Ethics of Relational AI — Expanding and Implementing the Belmont Principles

New England Journal of Medicine, July 18, 2024

The rise of relational AI, exemplified by ChatGPT, marks a new era in artificial intelligence, transforming how AI interacts with humans through natural language. This shift brings additional ethical challenges beyond those associated with traditional predictive AI.

Key points include:

• Ethical Principles: The Belmont Report's principles of beneficence, respect for persons, and justice must be expanded to include clinicians as well as patients. These principles are crucial for guiding the ethical implementation of relational AI in healthcare.
• Applications and Risks: Relational AI can draft patient messages, provide treatment information, and even create lifelike avatars of clinicians. However, these advancements come with risks such as AI "hallucinations," biased training data, and potential misuse.
• [BQ: For new work by Scott Gottlieb on AI matching clinicians in a "treatment setting," here.]
• Transparency and Fairness: Ensuring AI transparency about data use and decision-making processes is vital. Fairness must be addressed by using representative data sets and managing biases. The benefits of AI should be equitably distributed, considering both commercial gains and efficiency improvements.
• Call for Action: A national network of health AI ethics centers is proposed to develop guidelines, monitor implementation, and ensure AI adheres to ethical principles. These centers should involve diverse expertise and active community participation.

The integration of relational AI in healthcare necessitates a robust ethical framework to protect patients, clinicians, and society at large.

[END Chat GPT 4]

Brief Blog: AMA CPT Releases New Code Applications for Review (CPT & PLA)

Header:  For lab tests, PLA applications are quarterly, and regular CPT applications are 3 times a year.  In July, they overlap.  AMA has released, with the opportunity for public comment, information on CPT lab applications submitted in June and information on PLA lab applications submitted in June.

CPT CATEGORY 1

Here's the website for the CPT meeting in September in Albuquerque:

https://www.ama-assn.org/member-benefits/events/cpt-editorial-panel-meeting

Here's the agenda for lab codes for that meeting:

https://www.ama-assn.org/system/files/september-2024-lab-mopath-agenda.pdf

There will be an update to PLA code guidelines, regarding upgrading your PLA code from PLA to "Category I."  I have not seen the editorial change, but only some PLA codes are eligible for such "upgrades," there has to be a CPT section (like the "MAAA" section) that the PLA code could be upgraded-into.

There are two other items, an application for "dekeratization procedure" andan applicaton for an add on code for "infrared exam of surgical specimen' (category III).

PLA CODES

Her'es the website for PLA:

https://www.ama-assn.org/practice-management/cpt/cpt-pla-codes

Here's the listing of PLA codes submitted in June and therefore being reviewed in July-August:

https://www.ama-assn.org/system/files/august-2024-pla-public-agenda.pdf

• There ar 20 PLA actions. 
• 5 are code deletions.
• 2 are code revisions.

Guardant SHIELD, for colorectal screening, analysis of multiple biomarkers with a categorical result.

Pillar oncoREVEAL, an FDA PMA cut running on an Illumina platform, has deletion of its "lung and colon cancer" code 0448U, concurrent with application for an all-new, pan-cancer code (reflecting updated FDA labeling).  It is a 22-gene panel.

Quest DELETES 0436U, Abeta 40, 42.  This got an underpriced crosswalk in fall 2023 which is reflected on the current 2024 clin lab fee schedule ($93).  A range of new ALZ codes are in play for 2025, at this summer's pricing meetings, and it is a good that 0436U is deleted as a crosswalk target.

Abbott and Biofire each apply for infectious disease PLA codes.  Abbott for an HSV1,HSV2, Varicella test, and Biofire for an elaborate pneumonia test with 18 bacteria, 8 viruses, and 7 resistance genes.

FDA Holds Webinar on Categorization of In Vitro Diagnostics: Relevant to FDA LDT Regulation

In May, the FDA announced a five-year plan to regulate lab-developed tests, although a court challenge is already underway.

On July 16, 2024, FDA provided a 45-minute webinar on categorization of in vitro diagnostics (IVDs), which is highly relevant for labs that will now need to, or want to, submit 510(k) and PMA applications.

I've provided a captured audio recording, an (imperfect) video screen capture, an "auto-transcript" of the webinar, and an AI summary of key points.   

In the last 15 minutes, FDA answered several pre-submitted questions.  See a summary of the 8 questions below.

See a rapid summary of the webinar by Christine Bump, at Linked In, here.

FDA MATERIALS

The webpage for the new plans for FDA LDT oversight is here:
https://www.fda.gov/medical-devices/in-vitro-diagnostics/laboratory-developed-tests

This includes a link for Webinars.  Today's webinar is here:
https://www.fda.gov/medical-devices/medical-devices-news-and-events/webinar-in-vitro-diagnostic-product-ivd-classification-07162024

Here is the 39-slide deck:

https://www.fda.gov/media/180085/download?attachment

MY MATERIALS:

FDA may later provide a high quality YouTube link and a high quality transcript.  In the meantime, I have rough versions "FYI."

An auto transcript:

https://docs.google.com/document/d/1O6KcI87G-paSCpRZqETyRRWXQFICpfju/edit?usp=sharing&ouid=110053226805181888143&rtpof=true&sd=true

At YouTube, an audio recording I made, which is fine, and a video capture, which is imperfect. 

https://youtu.be/yR1DWfZ8WeA 

AI CORNER

Here is an AI summary of the 45 minute webinar:

Report on FDA Webinar: Categorization of Diagnostic Test Devices (IVD)

Date: July 16, 2024

Overview [Chat GPT 4]

On July 16, 2024, the FDA conducted a webinar focused on the categorization of in vitro diagnostic (IVD) devices. This session is particularly relevant for laboratories preparing for 510(k) and PMA submissions in the upcoming years, following the FDA's recent regulation mandating the review of lab-developed IVD tests. This report summarizes the key points from the webinar and provides a detailed summary of the Q&A session.

Key Points from the Webinar

1. IVD Classification System

• The FDA uses a risk-based classification system to ensure the safety and effectiveness of medical devices, including IVDs.
• Devices are classified into three categories: low risk (Class I), moderate risk (Class II), and high risk (Class III).
• The classification is based on factors such as intended use, technological characteristics, patient population, and the context of use.

2. Regulatory Controls

• General Controls: Apply to all medical devices unless exempted by regulation. These include labeling requirements, medical device reporting, establishment registration, device listing, and quality system requirements.
• Special Controls: Specific to Class II devices, including performance standards, special labeling requirements, post-market surveillance, and premarket data requirements.

3. Premarket Review Pathways

• 510(k) Premarket Notification: Generally for moderate risk (Class II) devices, where manufacturers must demonstrate that their device is as safe and effective as a legally marketed predicate device.
• Premarket Approval (PMA): Required for high-risk (Class III) devices, demonstrating reasonable assurance of safety and effectiveness.
• De Novo Classification: For novel devices that are low to moderate risk and have no predicate device. This pathway provides a means to classify new types of devices as Class I or II.

4. Product Classification Database

• The FDA maintains a product classification database that includes information on all medical devices, their classification, product codes, and regulatory requirements.
• Manufacturers are encouraged to use this database to determine the appropriate classification and regulatory controls for their devices.

5. Pending: Reclassification Process

• The FDA follows a formal process to reclassify devices, which includes issuing a proposed order, convening a classification panel, considering public comments, and issuing a final order.
• Many Class III tests, including companion diagnostics and infectious disease, will be reclassifed as Class II by this process.  This plan was announced by FDA in January 2024 and is ongoing.

Summary of Q&A Session

Q1: Does FDA classify laboratory-developed tests (LDTs) as test systems including instrumentation and sample preparation?

• Answer: FDA classifies IVDs, including LDTs, as test systems comprising components like reagents, instruments, and other articles that function together to produce a test result. Classification is based on the intended use and risk of the test system.

Q2: If an IVD test system’s intended use matches a classification regulation but uses a different sample matrix or technology, can it be classified under the same regulation?

• Answer: Generally, yes. However, if the differences in specimen type or technology raise different safety and effectiveness questions, the classification regulation would not be appropriate.

Q3: How does FDA classify an LDT that includes components labeled for Research Use Only (RUO) by another manufacturer?

• Answer: Laboratories can use RUO components in their LDTs if they qualify these components and appropriately manage them under their quality system. These components will be reviewed in the premarket submission for the LDT.

Q4: Are laboratory information management systems (LIMS) incorporated in the classification of IVD test systems?

• Answer: Generally, LIMS are not included as part of IVD test systems and are regulated under their own classification regulation (21 CFR 862.2100, Product Code JQP).

Q5: How does a laboratory manufacturer determine the type of premarket submission required for a test that is not classified?

• Answer: Laboratories should start by searching the product classification database. If the IVD is not listed, manufacturers should assess the risk of the IVD. High-risk IVDs likely require a PMA, while low to moderate risk IVDs may be eligible for De Novo classification.

Q6: What does FDA mean by "low risk"?

• Answer: Low risk devices pose minimal potential for harm and are generally Class I devices.

Q7: What is an FDA product code?

• Answer: A product code identifies the generic category of a device for FDA classification. Each classification regulation may have multiple product codes associated with it, used to delineate technology and indication subgroups.

Q8: What is the process for reclassification?

• Answer: The FDA follows a formal process that includes issuing a proposed order, convening a classification panel, receiving and considering public comments, and issuing a final order.

Conclusion

The FDA webinar provided comprehensive insights into the classification and regulatory requirements for IVD devices. The detailed guidance on utilizing the FDA's product classification database and understanding the premarket submission pathways will be invaluable for laboratories planning their submissions in light of the new regulations on lab-developed tests.

For more detailed information, laboratories are encouraged to review the webinar slides and visit the FDA's website for additional resources and upcoming webinars.   [End Chat GPT 4]

House Committee Asks FDA to Suspend Efforts to Regulate LDTs

You may have heard that the House has asked FDA to suspend its plans to regulates.

In a word, yes.

Find the  House subcommittee on Agriculture and FDA here.  It released its budget plan, and commentary, for FY2025.  Find the 166 page document here.  

Scroll up to page 84-85.

Laboratory Developed Tests.—The FDA’s final rule on Laboratory Developed Tests (LDTs) puts forth a proposed regulatory framework that is a significant shift in the way LDTs are regulated and changes expectations for patients, doctors, and laboratories for the first time since the Clinical Laboratory Improvement Amendments Act was passed in 1988 at the risk of greatly altering the United States’ laboratory testing infrastructure and reducing patient access to information that informs their healthcare decision making. The Committee directs the FDA to suspend its efforts to implement the rule and continue working with Congress to modernize the regulatory approach for LDTs.

Which means...

The language is "report language," which isn't binding.  (If they wanted it to be binding, they'd pass a law telling FDA to suspend.)   And it's not final - actual budgets go through months of revision and pass Senate, House, and go to the President at the end.

##

Coverage at HealthCareDive here.  

For an article at MedTechDive on how the FDA LDT law may be an early major case for a post-Chevron judicial system - here.