Sunday, February 16, 2025

State Laws: Prior Authorization as well as Biomarkers

Many in the precision medicine community track the progress of state biomarker access laws which regulate insurance - here, here.

States are also passing laws in the policy area of "prior authorization."  Catch up here:

AMA Chart

https://www.ama-assn.org/system/files/prior-authorization-state-law-chart.pdf

AIMED Alliance Chart

https://aimedalliance.org/prior-authorization-enacted-laws/

Kaiser update; Focus on Montana, 2/2025

https://kffhealthnews.org/news/article/montana-legislation-bills-prior-authorization-denials-delays-2025/

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Medicare regularly updates Prior Auth rules for Medicare Advantage; look for the next final rule around April 2025.



Friday, February 14, 2025

Changes at HHS; RFK Jr Sworn In; CMS Deadlines; CMS Use of "Equity"

#1

RFK Jr - Secretary of HHS

On Wednesday, February 12, RFK Jr was approved by the Senate as Secretary of HHS (vote, 52-48), and on Thursday he was sworn-in in the Oval Office in a 15-minute ceremoney.

See a full transcript in Google Doc, here.  AI news summary at bottom (below).


#2

CMS Proposals on Upcoming Deadlines

Transmittals

CMS normally sends a constant stream of Transmittals to contractors and providers - these appear to have stopped a month ago, on January 17 (2025 Transmittals).

Medicare Advantage Final Rule

Several documents are timely this spring, either in pending final form, or pending proposed form.   CMS issued its proposed Medicare Advantage / Part D rule in November, with comment through January.   That final rule would be expected in April 2025

Inpatient Proposed Rule

CMS issues its annual inpatient proposed rulemaking in April (e.g. on April 10, 2023), with finalization in August, effective for the fiscal year October 1.  


#3

Use of the Word "Equity" in CMS Rulemaking

Numerous news reports have discussed current scanning of government websites and grants for the use of words like "equity."   I checked for usage in the Fall 2024 PFS final rule, OPPS final rule, and Medicare Advantage proposed rule.  Word counts were 329, 306, and 50.  Bar chart below.  

I then looked back to the last CMS rules under the first DJT administration.  In the November 2020 PFS final rule, uses of "equity" were 11.  In the November 2020 OPPS final rule, uses of "equity" were 1 (in a citation to an executive order.)



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AI Corner

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I asked Chat GPT 4o for a summary of the swearing-in Google doc.  Quotes may be paraphrases.

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Robert F. Kennedy Jr. Sworn In as Secretary of Health and Human Services

February 13, 2025 — Washington, D.C.

Robert F. Kennedy Jr. was officially sworn in as the Secretary of Health and Human Services (HHS) in an Oval Office ceremony on Tuesday. The event, attended by President Donald Trump, Supreme Court Justice Neil Gorsuch, and members of Kennedy’s family, marks a significant moment in the administration’s approach to healthcare policy.

President Trump, in his remarks before the swearing-in, praised Kennedy’s commitment to public service and his willingness to cross party lines in pursuit of shared national goals. Trump highlighted Kennedy’s background as an advocate for environmental and health issues, as well as his ability to build a broad coalition of supporters during his 2024 presidential campaign. The president framed Kennedy’s appointment as part of a broader initiative to address what he called a "chronic disease crisis" in America.

“There’s no better person to lead our campaign of historic reforms and restore faith in American healthcare,” Trump stated. He cited concerns over increasing rates of chronic illnesses, including cancer and autism, and announced the creation of a new presidential commission, chaired by Kennedy, to investigate these issues and recommend policy solutions. “We’re going to figure it out, and Bobby is going to lead the way,” he said.

Justice Gorsuch administered the oath of office, after which Kennedy addressed those in attendance. He thanked President Trump for the opportunity and expressed gratitude for the support of his family. Kennedy reflected on his family’s legacy in public service, recalling a childhood visit to the Oval Office to meet with his uncle, President John F. Kennedy, and discussions about physical fitness and environmental conservation.

Kennedy reiterated his longstanding focus on public health, emphasizing his desire to investigate and combat the rise of chronic diseases among Americans. He acknowledged skepticism about his views on vaccines but argued that his position has been misrepresented. “When people actually hear what I think about vaccines, which is common sense—that vaccines should be tested, they should be safe, and everybody should have informed consent—people support it,” Kennedy said.

The new HHS secretary also laid out his early priorities, emphasizing “radical transparency” and reforms at key public health agencies, including the National Institutes of Health (NIH), the Food and Drug Administration (FDA), and the Centers for Disease Control and Prevention (CDC). He pledged to root out conflicts of interest and restore what he described as “gold standard science” in federal health policy.

Kennedy’s appointment has been met with mixed reactions. Supporters see his leadership as a needed shake-up in federal health policy, while critics remain concerned about his history of controversial statements.

“I’m going to do everything I can to work with you, whether you’re a Democrat or Republican, to restore children’s health in this country,” Kennedy said.

The event concluded with Trump reaffirming his confidence in Kennedy’s leadership. “He’s going to be running it. He’s going to do a great job,” the president said. When asked about Kennedy’s first steps as secretary, Trump indicated that uncovering “secrets” within the health system and addressing systemic health challenges would be top priorities.  [DJT also discussed an executive order for a MAHA commission, chaired by RFK Jr, to understand drivers of ill-health in the U.S.]

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One of the DJT executive orders bans agencies from using "genderin the context of sex; in the proposed M.A. rule, which CMS will soon review and finalize, besides 50 uses of "equity," "gender" occurs 5 times, including in regulation 422.112 (a)(8)(i)(E).  (In the 2024 Medicare finalized PFS rule,"gender" appeared 11 times, in the OPPS rule, 9 times.)

Thursday, February 13, 2025

RFK Jr Confirmed as Secretary of HHS: AI Predicted 65% Chance Using Hearing Transcripts

On February 13, 2025, RFK Jr was confirmed by the Senate as Secretary of Health.   

Chat GPT predicted a 65% chance of his confirmation, on January 30, based on "reading" the two-day confirmation hearings transcript.  The Chat GPT analysis was quite detailed:

https://www.discoveriesinhealthpolicy.com/2025/01/ai-corner-chat-gpt-assesses-rfk-jr.html


See coverage at Politico.

HHS has 80,000 employees, including CMS, NIH, FDA, CDC.   The vote was 52-48, the only exception to the 53 Republican senators being Mitch McConnell.


Where Coverage Policy Comes From: Notes on Medicare Advantage; and on Preventive Services

Coverage under Medicare and under the Affordable Care Act comes from multiple sources, and there's a storm blowing in terms of potential changes.  Just a couple highlighted here.

Braidwell Case - Update on Prevention

Kaiser Foundation provides a  detailed but readable analysis of the Braidwell case, which would up-end the Affordable Care Act's policies about preventive services coverage (predicated on USPSTF decisions).   See the Kaiser report here.    The cases has been ping-ponging up and down between  federal district court and federal appeals court but is likely to eventually reach the Supreme Court.   

CMS and AHRQ/USPSTF and Coverage

Meanwhile, Medicare coverage for new preventive benefits can be created, through an NCD, for services newly endorsed by USPSTF.   

However, there said to be efforts to "cancel" funding for AHRQ, the division that USPSTF sits inside of.   

(And note also - Besides preventive services, CMS NCD "coverage with evidence development" is predicated on a statutory interaction with AHRQ, which couldn't occur if AHRQ were disbanded.)

Should Medicare Advantage Govern Drug Policy? A 180 Degree Flip?

Current policy for Medicare Advantage plans is predicated on having M.A. coverage at least match fee for service coverage, such as LCDs.   At least for drugs, a Manhattan Institute proposal would invert that 180 degrees, and set fee for service coverage to what half the M.A. plans cover, and ditto for drug pricing in Part B.    

See a detailed white paper at Manhattan Institute here.

EU HTA

See a report from Evidera on getting past health technology assessment (HTA) in the E.U. - here.

Sidebar: WSJ

Meanwhile, WSJ runs a long article on insurance denials (here) and how to fight them (here).


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AI CORNER
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Here's an AI summary of the Manhattan Institute drug proposal.
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Market-Based Reform for Medicare Part B Drug Pricing

The Manhattan Institute proposes a market-driven approach to lower Medicare Part B drug prices for expensive, limited-competition drugs, arguing that current price controls (IRA) and Trump’s MFN pricing do not effectively address these costs.

Key Issues Identified:

  • Medicare Overpays for Part B drugs due to the ASP + 6% reimbursement model, which works well for competitive drugs but fails for high-cost, single-source drugs (e.g., oncology, ophthalmology, rheumatology).
  • IRA price controls only begin affecting Part B in 2028 and exclude biologics for 13 years, meaning most costly new drugs remain unaffected.
  • Most Favored Nation (MFN) pricing may not work since the U.S. gets novel drugs first, and manufacturers could withhold drugs in foreign markets to avoid price suppression.

Proposed Reform:

  • Medicare Advantage (MA) plans negotiate drug prices. If 50% of MA plans reach an agreement, the drug is covered at the highest negotiated price, which then becomes the reimbursement rate for both MA and traditional Medicare.
  • Manufacturers must accept the “clearing price” (highest MA-negotiated price minus 1%) to participate in Medicare.
  • If not enough MA plans reach a deal, the drug won’t be covered for the next year.

Expected Benefits:

  • Reduces Medicare’s role as a “price taker” by forcing negotiation rather than passively accepting high prices.
  • Avoids government price controls (IRA), allowing market participants to determine drug value.
  • Encourages competition while keeping provider reimbursement intact.

The report argues that market-based pricing is superior to government price controls since it accounts for patient demand, provider input, and insurer cost-balancing while adapting to changing market conditions.

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According to some sources like Washington Post, NSF and other grant-giving agencies are searching grants for keywords like "equity."   According to Chat GPT, in last fall's final CMS PFS rulemaking (November 2024), the word "equity" occurred 329 times, in the CMS OPPS final rule, "equity" occurred 306 times, and in the December proposed Medicare Advantage (Part C & D) rule, the word "equity" appeared 50 times.
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I checked these results against the final PFS and OPPS rules of December 2020 (the last work products of the first DJT administration.)   The OPPS rule for CY2021 appears to have "equity" only once (and by quoting a WH executive order) and the PFS rule, 11 times.  
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The easiest way to count is to upload to Chat GPT and ask it; or, to save as TXT file and upload to Word and search "equity" for matches. (The two methods matched to about 2%).



Wednesday, February 12, 2025

Digital Pathology Applications: Progress, Headwinds

 A flurry of brief items in digital pathology.


Tailwinds?

The Israeli company IBEX gets FDA approval for Prostate Detect, an AI system based on H&E whole slide imaging (WSI) to detect missed prostate cancers.  Discussion at PMO Precision Medicine Online - here.   Also noted at Katie Maloney's Decibio article on Linked In here.

Tracking a couple other items from Katie Maloney.  She writes about TEMPUS collaborating with IMAGENE bring together molecular profiling with "H&E based biomarkers."  Here.    Separately, see also TEMPUS again, this time with ARTERA here.  

Maloney also discusses companion diagnostics from digital pathology, with nods to Roche, AstraZeneca, Leica, and Indica. Here.

Headwinds?

Over at AMA CPT, potential changes to PLA coding rules were on the publicly posted agenda for the February meeting last week.   Results of changes, if any, won't be published by AMA until September, meaning, the 2026 code book.

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AI CORNER

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Some of the news items, AI summaries, Chat GPT 4o.   See full details at the links above.  See also more Dig Path articles by Katie Maloney.

AI and Digital Pathology: The Next Frontier in Precision Medicine

AI-driven digital pathology continues to gain momentum. Ibex Medical Analytics secured FDA 510(k) clearance for Prostate Detect, an AI tool assisting pathologists in detecting missed prostate cancers. This marks a major step in computational pathology, making Ibex the second company, after Paige, to receive FDA clearance, though reimbursement remains a challenge. 

Meanwhile, Tempus AI and Imagene are combining H&E-based biomarker prediction with NGS, streamlining AI-powered oncology diagnostics. In companion diagnostics (CDx), major partnerships like Roche-AstraZeneca and Leica-Indica Labs are accelerating progress toward DP-based CDx applications. These developments highlight the increasing convergence of AI, pathology, and molecular diagnostics, with data validation remaining the key hurdle. 

As AI-powered tools become more sophisticated, the industry moves closer to integrating digital pathology into routine clinical practice, paving the way for enhanced diagnostic accuracy and personalized medicine. The question now is: Are we at the tipping point for digital pathology CDx?

Sunday, February 9, 2025

Brief Blog: NIH Announces Steep Cuts to R&D Grant Payments

On February 7, 2025, NIH announced steep cuts to the total awards going to R&D grants, by capping the indirect rate at 15%.   Some universities have indirect rates as high as 60%.  

Indirects have gotten into the news periodically; see a Wikipedia page about a Stanford "scandal" in the 1990s.   Trump 2017-2021 administration talked about indirect rate cuts.

Some of this weekend's news reports described only the information released as an NIH tweet on "X".   I'd point out, you need to see the full policy justification at the NIH website, which most articles do not link to.

https://grants.nih.gov/grants/guide/notice-files/NOT-OD-25-068.html

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AI Corner

This is a Chat GPT "neutral summary" of the NIH announcement and rationale.

The National Institutes of Health (NIH) has announced a standardized 15% indirect cost rate for all NIH grants, replacing the previously negotiated indirect cost rates for both new grants and existing grants to institutions of higher education (IHEs), effective immediately.

Rationale for the Change:

  • NIH aims to maximize the portion of grant funding that directly supports scientific research by reducing the share allocated to indirect costs (which cover expenses like facilities and administrative overhead).
  • Historically, NIH has reimbursed indirect costs at an average rate of 27–28%, with some institutions receiving over 50–60% in indirect cost recovery.
  • NIH notes that private research funders, such as the Bill & Melinda Gates Foundation, often impose lower indirect cost rates (e.g., 10–15%), and universities regularly accept grants with these lower rates.
  • The decision is framed as aligning NIH's policies with private sector benchmarks and ensuring that taxpayer-funded research investments are used as efficiently as possible.

Implementation:

  • The 15% cap applies to all future NIH grant awards and to existing grants at IHEs for expenses incurred after February 10, 2025.
  • NIH states that this rate is higher than the 10% minimum indirect rate set by federal regulations, aiming to balance institutional needs with NIH’s funding priorities.

NIH presents this policy as a strategic decision to optimize federal research funding, ensuring that more money directly supports scientific discovery and innovation while maintaining a uniform and predictable indirect cost structure across all grant recipients.

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Friday, February 7, 2025

Brief Blog - Medicare Document Websites - Crickets

Medicare issues  hundreds of miscellaneous policy updates ("Change Releases" or CR's) each year, plus innumerable LCD updates.

As of February 7, 2025, the last Change Release seems to be January 17; the last LCD proposal notice, months ago (empty page); the last LCD update (new final effective) January 9.

  • Side note: See a report by AgencyIQ in LinkedIn that effective immediately, all agencies must delete 10 regulations for each new one they produce.  Here.

https://www.cms.gov/medicare/regulations-guidance/transmittals/2025-transmittals?page=0

https://www.cms.gov/medicare-coverage-database/reports/local-coverage-proposed-lcds-state-report.aspx?stateRegion=all&contractorNumber=all&proposedStatus=C&sortBy=commentStart

https://www.cms.gov/medicare-coverage-database/reports/local-coverage-proposed-lcds-state-report.aspx?stateRegion=all&contractorNumber=all&proposedStatus=F&sortBy=noticeStart






Thursday, February 6, 2025

Friends of Cancer Research: Diagnostics Meeting Review

On February 4, 2025, Friends of Cancer Research held a half-day meeting in DC about diagnostics and regulatory innovation.

Find their summary here:

https://api.neonemails.com/emails/content/B60mE3Jx82Jht6EkTFcSukdCdM6R-8jeHaTXRcapjwo=

Find the YouTube stream here:

https://www.youtube.com/live/wFHolEBYx48

The FOCR summary notes,

  • Discussions at Friends public meeting titled “Advancing the Future of Diagnostics and Regulatory Innovations,” reflect a pivotal moment at the intersection of artificial intelligence (AI) and regulatory frameworks for diagnostics, precision medicine, and healthcare. The three sessions emphasized the dual objectives of ensuring patient safety while fostering an environment conducive to innovation—a balance that is becoming increasingly critical in an era marked by rapid technological advancements.
  • Key takeaways and meeting resources, including Session 1 presentation slides by Mark Stewart, Friends of Cancer Research and Session 2 presentation slides by Megan Doyle, Eli Lilly & Company are available below.


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AI CORNER
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I have not seen the full video - this is an unedited AI report (Chat GPT 4o).
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FOCR Meeting Highlights AI’s Role in Diagnostics and the Need for Standardization

Washington, D.C. | February 4, 2025 – The Friends of Cancer Research (FOCR) convened its first public meeting of the year, focusing on the future of diagnostic testing and the evolving role of artificial intelligence (AI) in pathology. The event brought together experts from academia, industry, and regulatory agencies to examine the challenges and opportunities of AI-driven diagnostics, particularly in the assessment of biomarkers like HER2 in breast cancer.

Ensuring Diagnostic Consistency in the AI Era

A major discussion centered around variability in diagnostic testing, particularly in biomarker assessment. The meeting featured data from the Digital Pathology Harmonization Project, a collaborative effort analyzing the performance of AI-based pathology tools. The project assessed HER2 scoring by comparing seven AI models with three human pathologists. The data showed strong agreement in identifying HER2-positive (3+) cases but notable variability in distinguishing HER2-low (1+ and 2+) cases.

As HER2-low has become an actionable biomarker with new targeted therapies, accurate classification is increasingly important. The variability in scoring raised concerns about how AI models are trained, validated, and ultimately integrated into clinical practice.

Reference Data Sets: A Critical Need for AI Validation

Speakers emphasized the importance of common reference data sets in evaluating AI models, noting that consistency across different tools remains a challenge. The data set used in the FOCR study, curated from a single institution in Belgium, allowed for a controlled comparison of AI models and pathologists. However, participants discussed whether a more diverse dataset—including multiple scanners, staining techniques, and patient demographics—would provide a more robust validation framework.

The study also highlighted that AI models showed similar levels of variability as human pathologists. This finding raised a key question: Should AI aim to replicate human interpretation, or should it establish a new standard of accuracy based on objective quantitative measures?

Regulatory and Implementation Challenges

The discussion also touched on regulatory hurdles in deploying AI-driven diagnostics in clinical settings. Current FDA review processes require clear definitions of ground truth when assessing AI models. However, variability among expert pathologists complicates this effort. The traditional method of using a panel of three pathologists for adjudication remains standard, but panelists debated whether new methods are needed to establish a more consistent framework for validation.

Another barrier is infrastructure readiness. Today, only a small percentage of pathology labs have the necessary digital pathology infrastructure, including high-resolution scanners and cloud-based computational tools, to support AI-driven workflows. The transition to digital pathology and AI-assisted diagnostics will require significant investment in technology and training.

Operational Considerations in AI Deployment

Panelists also addressed operational concerns related to model development and reproducibility. AI models must be trained on diverse datasets to ensure generalizability across different lab conditions, tissue processing methods, and scanner types. The study’s post-hoc analysis of discordant cases suggested that staining artifacts, heterogeneous expression patterns, and sample type (biopsy vs. resection) contributed to variability in HER2 scoring.

The potential for AI to augment, rather than replace, human pathologists was another key point. While AI can process large datasets rapidly and provide quantitative assessments, panelists discussed the importance of AI-pathologist collaboration rather than full automation.

Next Steps: Expanding AI’s Role in Cancer Diagnostics

Building on the insights from this study, FOCR announced plans for a new initiative, AI-RECIST, which will apply AI validation strategies to imaging-based tumor response assessments. This effort aims to improve consistency in radiological evaluations, another area where human interpretation varies widely.

As FOCR President Jeff Allen emphasized, continued collaboration between researchers, industry, and regulators is necessary to ensure that AI-driven diagnostics enhance patient care without introducing new sources of error. The meeting reinforced the need for standardized validation frameworks, robust reference datasets, and regulatory clarity as AI takes a greater role in precision medicine.

The event marked a significant step forward in aligning technological innovation with clinical and regulatory realities, ensuring that AI-driven diagnostics contribute to improved patient outcomes.


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Conference Documents.  Each session (Digital Biomarkers, and Rare Biomarkers) had an online PPT document and an online WP.  I gave the 4 documents to Chat GPT in a separate session, to summarize.

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Summary and Analysis of Four Conference Documents - for Experts Who Could Not Attend

Document 01: Digital and Computational Pathology Tool Harmonization (PATH) Project

This presentation focused on the role of AI-driven digital pathology in improving HER2 biomarker scoring for breast cancer. Key points included:

  • Clinical Relevance of HER2: HER2 scoring guides treatment, particularly with new therapies targeting low and ultra-low HER2 expression.
  • Challenges in HER2 Assessment: Variability in manual scoring has led to inconsistencies in treatment selection, making AI-based solutions attractive.
  • AI’s Potential Contributions:
    • Reproducibility: AI models reduce observer variability.
    • Efficiency: High-throughput capability enables large-scale analysis.
    • Granularity: AI can detect subtle biomarker variations beyond human visual capabilities.
  • Study Design:
    • A common dataset of 1000+ whole-slide images (WSIs) was created and shared among AI developers.
    • AI models applied HER2 scoring, and results were compared against pathologists’ assessments.
  • Findings:
    • Greatest agreement in HER2 3+ cases.
    • Significant variability in 1+ and 2+ cases, making AI refinement crucial.
    • Sample attributes (Ki-67, PR, ER status) may influence AI-pathologist discordance.
    • Post-review, AI models improved accuracy, but challenges remain for complex cases like Paget’s disease and sparse tumor cells.
  • Next Steps:
    • Developing best practices for AI validation.
    • Expanding reference datasets for AI training.

Implications for Experts: This research supports AI-assisted standardization in pathology, highlighting the need for collaborative validation efforts between AI developers, regulatory bodies, and clinicians.


Document 02: Considerations for Developing Reference Data Sets for Digital Pathology Biomarkers

This discussion document from Friends of Cancer Research outlines the need for publicly available, standardized datasets for AI-driven computational pathology. Key takeaways:

  • The Problem:
    • Computational pathology lacks universal validation datasets, leading to inconsistent results across AI models.
    • PD-L1 assay variability serves as a precedent—different antibodies and scoring methodologies led to regulatory challenges.
  • The Role of Reference Data Sets:
    • Support comparability across AI models.
    • Enhance regulatory evaluation.
    • Enable more efficient FDA review.
  • Considerations for Building Reference Data Sets:
    • Intended Use: Should datasets validate AI’s accuracy, precision, or clinical validity?
    • Data Diversity: Ensure demographic, clinical, and specimen representativeness.
    • Interchangeability: AI outputs should align with pathologist consensus.
    • Infrastructure & Governance:
      • Datasets must be securely stored, version-controlled, and validated.
      • Federated learning models may allow AI testing without sharing raw WSIs.
  • Defining a Reference Standard:
    • Traditional pathologist-scored benchmarks have limitations.
    • Alternative reference methods include molecular assays (mRNA, in situ hybridization) or clinical treatment outcomes.
  • Metadata Considerations:
    • Clinical and patient data should be de-identified but well-documented.

Implications for Experts: AI models will need standardized validation benchmarks, particularly as digital pathology becomes integral to precision oncology.


Document 03: Innovative Processes for Validating Diagnostic Tests for Rare Biomarkers

This Eli Lilly-led presentation tackled the challenges of validating diagnostics for rare biomarkers, given limited clinical samples. Key themes:

  • Defining Rare Biomarkers:
    • Prevalence ≤1% in a given cancer type.
    • Limited availability of well-characterized clinical samples.
  • Regulatory Challenges:
    • Traditional validation relies on clinical trial samples, but rare biomarkers lack sufficient specimens.
    • Compressed drug development timelines exacerbate validation difficulties.
  • Alternative Validation Strategies:
    • Clinical trial samples: Prioritize for clinical validation.
    • Representative clinical approaches: Use data from similar genomic contexts.
    • Real-world evidence (RWE): Consider post-market validation.
    • Procured human specimens: Use archival tissue or commercially available samples.
    • Cell lines & contrived samples: Useful for analytical validation (accuracy, stability, reproducibility).
    • In silico datasets: Validate bioinformatics pipelines.
  • Regulatory Engagement:
    • Developers should engage with FDA early.
    • Consider a pre-submission “snapshot” to outline sample justifications.

Implications for Experts: Given rare biomarker challenges, a flexible regulatory approach is needed, balancing rigor and practicality in CDx validation.


Document 04: Innovative Validation and Regulatory Processes for Companion Diagnostic Tests for Rare Biomarkers

This Friends of Cancer Research white paper expands on regulatory flexibilities for rare biomarker companion diagnostics (CDx). Key points:

  • The Core Challenge:
    • Precision therapies rely on companion diagnostics to identify patients.
    • Rare biomarkers lack ample clinical samples for traditional validation.
  • Regulatory Flexibility Considerations:
    • Prevalence Threshold: Biomarkers ≤1% prevalence may qualify.
    • Sample Accessibility: Factors like tumor location, biopsy feasibility, and sample degradation impact validation feasibility.
    • Unmet Need & FDA Prioritization: Expedited pathways (e.g., Breakthrough Therapy) may warrant validation flexibility.
  • Proposed Validation Approaches:
    • Prioritize clinical trial samples for validation.
    • Use alternative samples where necessary, ensuring biological and technical justification.
    • Consider RWE to supplement clinical validity assessments.
  • Framework for Regulatory Discussions:
    • Structured justification for sample selection.
    • FDA pre-submission meetings for alignment on validation strategies.
  • Recommendations for Future Efforts:
    • Proactively bank clinical trial samples for future diagnostics.
    • Establish aligned reference datasets for standardization.
    • Consider shared regulatory frameworks for efficient biomarker validation.

Implications for Experts: CDx validation must evolve to accommodate rare biomarkers, requiring strategic regulatory engagement and innovative validation methodologies.


Conclusion

This forum provided a comprehensive examination of AI-driven pathology and rare biomarker validation challenges. Key takeaways:

  1. AI in Digital Pathology: AI models show promise for HER2 biomarker scoring, but require further refinement—especially for HER2-low cases.
  2. Standardized Reference Data Sets: Lack of publicly available validation datasets hinders AI model standardization, requiring collaborative efforts.
  3. Rare Biomarker Validation: Limited clinical samples necessitate regulatory flexibility. Alternative sample sources and real-world data can help bridge the gap.
  4. Regulatory Engagement: Developers should proactively engage with the FDA to align on alternative validation strategies.

For experts in oncology, computational pathology, and regulatory science, these discussions underscore the importance of data harmonization, AI validation, and regulatory adaptability in the evolving landscape of digital pathology and rare biomarker diagnostics.


Legislation: Let AI Do Prescriptions ?? Implications.

 It seems like yesterday that Eric Topol had a new Op Ed in NYT about the  revolution in primary care offered by AI (here).  

David Schweikert (R-AZ) has introduced a bill  that would allow AI to qualify as a practitioner and issue legal prescriptions, under certain constraints.

See excellent coverage at Policy & Medicine by Thomas Sullivan - here.   (Also MedpageToday). The bill, HR 238, is only a few sentences long.  According to Sullivan, it was also introduced in the prior session of Congress.

  • H. R. 238  To amend the [FDA Act]  to clarify that artificial intelligence and machine learning technologies can qualify as a practitioner eligible to prescribe drugs if authorized by the State involved and approved, cleared, or authorized by the FDA, and for other purposes.

Like physicians or nurse practitioners, the AI entities would need to be licensed at the state level.



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While prescriptions could be written under FDA law, CMS law intervenes as well, Medicare generally requires diagnostic orders to be made by the treating physician (with a few exceptions for radiologists and pathologists) and drug orders (Part B) to be incident to a physician.   In Part D, drug ordering persons must have an NPI and (since a change in 2019) do not have to be enrolled in Medicare.  For Part D see 42 CFR § 423.120(c)(6).

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AI Corner

Chat GPT found 42 CFR 423.120(c)(6) in a half second for me.
Sidebar on the 2019 change re: Part D Rx requirements - here.


Wednesday, February 5, 2025

Exclusive at WSJ: DOGE Searching Medicare Records for Fraud



Medicare fraud can be large-scale, and even obvious fraudulent claims can be paid out by Medicare contractors for a long time.  

We expected this: the WSJ headlines that DOGE has been let loose to search Medicare records for suspicious claims and payments.  Anna Wilde Mathews & Liz Essley Whyte report.  So far, DOGE has access to some CMS systems and not others.

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Also Washington Post, Bloomberg.

##Going back several years, Medicare had colossal abusive payments under gene sequencing code 81408 (billed in pairs on the elderly for $4000, plus related codes 81406,  81407).  It took a long time for CMS to catch on, it should have taken a quarter or two.  Damage?  A billion dollars.  See OIG report (which only skims the real story, July 2023) - here.  I wrote about the same story several years before the OIG - back in September 2000 - here.

More recently, JAMA raised concerns for abuse of molecular microbiology codes (here), and CMS has official, but complicated, and perhaps poorly enforced, rules about gene code stacking versus use of code 81479 (Medicare policy manual).   Any or all of these could be quirkly found by DOGE.

We discussed possible future DOGE use of MolDx rules in a January 1 blog.



Tuesday, February 4, 2025

AI in Action: Chat GPT Explains WHY a Clinical Utility Paper is a Clinical Utility Paper

This week, we have a press release from neurology diagnostics firm CN2, about a new clinical utility study of their test, PRECIVITY AD2.   The paper is Monane et al, 2025.

Here's a highlight posting at Linked In.

Here's the open access article at the journal Diagnostics.

I think of a Clinical Utility study for diagostics like this - you run a test, have a result, give to the clinician.  At that point something changes - diagnoses, drug prescriptions, or outcomes.

I found it a bit hard to extract exactly what was going on from the abstract.   Chat GPT read the paper and gave the summary below.   (And at bottom, I clip the authors' original abstract).

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AI CORNER

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This paper qualifies as a clinical utility study because it demonstrates how the PrecivityAD2 blood biomarker test influences real-world clinical decision-making for patients with cognitive impairment, following the model you described:

  1. Test Performed: The PrecivityAD2 blood test measures plasma Aβ42/Aβ40 and p-tau217/np-tau217 ratios to generate an Amyloid Probability Score (APS2), indicating the likelihood of Alzheimer’s disease (AD) pathology.

  2. Results Provided to Clinicians: Memory specialists received APS2 scores for 203 cognitively impaired patients.

  3. Impact on Patient Care:

    • Diagnoses Changed: The probability of an AD diagnosis shifted significantly based on the test results. Clinicians’ diagnostic certainty either increased (for positive APS2) or decreased (for negative APS2), with changes noted in 75% of cases.
    • Treatment Altered: Anti-AD medication prescriptions decreased for patients with negative APS2 results (from 74% to 19%) and increased for those with positive results (from 71% to 96%).
    • Further Testing Adjusted: Additional brain amyloid imaging decreased, particularly for APS2-negative patients, reflecting reduced reliance on more invasive or expensive confirmatory tests.

In essence, the study shows that actionable changes in diagnosis, treatment plans, and resource utilization occurred as a direct result of the blood test outcomes, fulfilling the criteria for demonstrating clinical utility.  (I would treat the AI text as a smooth first draft, but only that).

##

This morning, I haven't double checked the AI findings which I would do, if it were part of my regular workstream.

###
Here's the original abstract.


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Separately, CN2 won a $1.5M grant from MJ Fox Fndtn to study Alzheimer-Parkinson's links.

Sunday, February 2, 2025

AI Corner: Chat GPT at Work: Simplifying Dense Science Text

An important paper came out recently, Kerle et al., comparing whole-genome and 500-gene somatic testing in 20 advanced cancer patients.



The authors are from Dresden, and in several places, the English text uses long and dense sentences ("germanic.')

I asked Chat GPT4 to redline and edit.  I've added " _ " to highlight the use of periods.  You can judge for yourself if it is an advantage or not.

###

ORIG   Since the pathognomonic rearrangements in, for example, fusion-driven sarcomas, are generally of diagnostic rather than therapeutic value, and non-rearrangement-driven bone and soft-tissue sarcomas repeatedly demonstrate genomic alterations in various clinically actionable signaling pathways as well as complex biomarkers such as multiple genomic imbalances and deficiencies in homologous DNA repair genes, a broad molecular analysis, such as whole-exome (WES) or whole-genome (WGS) and transcriptome sequencing (TS), is warranted but is thus far mostly limited to clinical sequencing programs or scientific projects.   -  The Molecularly Aided Stratification for Tumor Eradication Program (DKFZ/NCT/DKTK MASTER) of the German Cancer Research Center (DKFZ), the National Center for Tumor Diseases (NCT), and the German Cancer Consortium (DKTK) is a prospective multicenter clinical sequencing program using WES, WGS, and TS for the identification of therapeutically relevant alterations in patients with rare tumor entities or those under the age of 51 years with advanced tumors and limited or no further treatment option

CHAT REWRITE

Pathognomonic rearrangements, such as those found in fusion-driven sarcomas, are typically of diagnostic value rather than therapeutic significance.  _    In contrast, non-rearrangement-driven bone and soft-tissue sarcomas frequently show genomic alterations in clinically actionable signaling pathways, along with complex biomarkers like multiple gene imbalances and deficiencies in homologous DNA repair. _    Broad molecular analyses—such as whole-exome sequencing (WES), whole-genome sequencing (WGS), and transcriptome sequencing (TS)—are warranted, but remain largely limited to clinical sequencing programs and scientific research projects.

The MoleculArly Aided Stratification for Tumor Eradication Research (MASTER) program is a prospective, multicenter clinical sequencing initiative.  _    It is led by the German Cancer Research Center (DKFZ), the National Center for Tumor Diseases (NCT), and the German Cancer Consortium (DKTK). _     MASTER uses WES, WGS, and TS to identify therapeutically relevant alterations in patients with rare tumors or in individuals under 51 years old with advanced cancers and few or no remaining treatment options.


###

ORIG The advantages of panel sequencing, such as simpler logistics due to the possibility of using archived, formalin-fixed instead of fresh tumor tissue, a generally shorter turnaround time from the start of DNA/RNA extraction to molecular results compared to WGS/TS, as well as generally lower costs, are of a more practical nature but are nevertheless important for everyday clinical practice.      ...

In conclusion, WGS, with its additional layers of complex biomarkers such as aneuploidy, viral integration, the possibility of discovering potential novel chromosomal rearrangements, the addition of RNA sequencing, the integration of DNA methylation profiling for entity prediction, (phospho-)proteomics, pharmacogenomics, and preclinical drug testing in patient-derived organoids, spheroids, and cell cultures into the MTB discussion, enables a multidimensional tumor characterization beyond the capacities of a predefined panel.  _  This approach offers the possibility to investigate new genes of interest, genomic patterns of tumorigenesis, and drug resistance and may, therefore, significantly improve the development of effective targeted therapies in the future.


CHAT REWRITE

The advantages of panel sequencing are largely practical. _ These include simpler logistics, as it allows the use of archived, formalin-fixed tissue instead of fresh samples, and faster turnaround times from DNA/RNA extraction to results compared to WGS or TS. _  Additionally, panel sequencing is generally more cost-effective. _ While these benefits are practical rather than scientific, they are still highly relevant for routine clinical practice. ...

Conclusions. Whole-genome sequencing (WGS) offers several advantages due to its ability to detect complex biomarkers. _ These advantages include aneuploidy, viral integration, and novel chromosomal rearrangements. _ Adding RNA sequencing and DNA methylation profiling improves the identification of specific tumor entities. _ Furthermore, incorporating proteomics, pharmacogenomics, and preclinical drug testing using patient-derived organoids, spheroids, and cell cultures enhances tumor characterization beyond what predefined panels can achieve.

This multidimensional approach allows for the discovery of new genes related to tumor development, progression, and drug resistance.  _ Ultimately, it may significantly advance the development of more effective targeted therapies.


REDLINE:

redline after AI - click to enlarge



AI Bonus.

We translate the concluding paragraph of the paper, back into German.

Schlussfolgerung:
WGS ermöglicht mit seinen zusätzlichen Ebenen komplexer Biomarker wie Aneuploidie, viraler Integration, der Entdeckung potenziell neuer chromosomaler Umlagerungen, RNA-Sequenzierung, der Integration von DNA-Methylierungsprofilen zur Entitätsvorhersage, (Phospho-)Proteomik, Pharmakogenomik sowie präklinischen Medikamententests in patientenabgeleiteten Organoiden, Sphäroiden und Zellkulturen im Rahmen der MTB-Diskussion eine multidimensionale Tumorcharakterisierung, die über die Kapazitäten eines vordefinierten Panels hinausgeht und somit die Untersuchung neuer Gene von Interesse, genomischer Muster der Tumorentstehung und Arzneimittelresistenz ermöglicht, was wiederum die Entwicklung effektiver, zielgerichteter Therapien in der Zukunft maßgeblich verbessern könnte. 

Saturday, February 1, 2025

The State of Women in Academic Medicine (AAMC Deck)

 Recently, Joe Lennerz posted an article about the JanuaryPathology Innovation Consortium meeting.   Article,  and meeting agenda.

The agenda included a 64-page deck from the American Association of Medical Colleges - AAMC, on the "State of Women in Academic Medicine 2023-2024."

Find it here.

Many good takeaways, such as, the percentage of woman as full-time faculty rose from 38% in 2013 to 45% ten years later in 2023 (p. 15).

##

Although much less important than content, the design was strong.


#



Consortium Completes 5-Article Series on AI in Lab Med and Pathology

The five-part AI in pathology series has now been published.   

It's a joint effort of College of American Pathologists (CAP), Digital Pathology Association (DPA) and Association of Pathology Informatics (API), appearing in Arch Path Lab Med.

Find the home page here:

https://www.pathologyinformatics.org/api-cap-dpa-joint-publication-series-on-ai

Find a summary article by Joe Lennerz MD PhD here:

https://www.linkedin.com/posts/joe-lennerz-90029219_ai-generative-wsi-activity-7291510249729982465-AXDS/

###

AI Corner

It's shooting fish in a barrel, but let's see an AI summary of all five articles.

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Here's a detailed overview of the five-part series on Generative Artificial Intelligence (GenAI) in pathology, jointly published by the College of American Pathologists (CAP), the Digital Pathology Association (DPA), and the Association for Pathology Informatics (API). This landmark series, featured in the Archives of Pathology & Laboratory Medicine (APLM), represents a significant step forward in thought leadership on AI’s role in pathology, spanning both laboratory medicine and anatomic pathology.

Friday, January 31, 2025

Genomics Listicle: Worthwhile Items Today from Linked In

 A flurry of interesting articles at Linked In today.

### EU AND INNOVATION

The prolific Denis Horgan writes about EU at a "crucial turning point in healthcare innovation."  (And not hard to draw some dotted lines between EU issues and US issues).   

Here.   (He cites to a new EU document.)


### LDT REGULATORY ARTICLE

Frequent Linked-In contributor Shannon Bennett links us to a new (firewall) article on "Regulatory Requirements for Laboratory Developed Tests in the United States," in J Imm Meth, 27 January 2025.  Find it here.  Bennett et al.


### ALL ABOUT THE FDA LDT CASE

Xander van Wijk updates at Linked-In on the FDA LDT case, with numerous links to months of major court filings.  Note the most recent, a court filing that has led to an oral arguments hearing on February 19.   His article here.   (He closes by saying, expect an update on the new adminstration, soon.)


### SURVIVING A MOLDX REVIEW

Becky Winslow of IngeniousRx gives a case study of a genomics lab that failed its MolDx tech assessment and was ready to throw in the towel.  She helped them understand how they could turn-around and succeed with MolDx.   Find the story here.


### CGP WITH WGS VS LARGE PANELS

Svetlana Nikic carefully assesses a new paper comparing WES-WGS (plus transcriptome) in tumors, compared to large panels (e.g. several hundred genes).   Read her assessment here.

See the original papaeer, Kerle et al., in Nature/ Precision Oncology, published January 10.  Looks like open access here. Most authors from Dresden.


## WHY UNDERSTANDING THE NEWS MATTERS

Not from Linked In, but from Bloomberg.  A few weeks ago I noted news about the declining numbers of Wall Street analysts who assess buy/sell news.  (Blog).  

Update - More of the same idea at Bloomberg on January 31 (see Justina Lee.)  Is the market becoming irrational due to the mass investments in (rational) index funds? 

My takeaway is - Given the extra high volatility of Genomics stocks (quick example here), the decline of analysts in general should create even more value in those analysts who DO understand and track (bet on) genomics by using a deep and hard-won understanding of the policy and technology complexities.

###

AI CORNER

Chat GPT 4 reads & summarizes Kerle et al. on WGS in tumors.

TL;DR: Whole Genome vs. Panel Sequencing in Precision Oncology

This study compares whole-exome/whole-genome sequencing (WES/WGS) + transcriptome sequencing (TS) versus broad panel sequencing (Illumina TSO500/TST170) for precision oncology.

  • Key Findings:

    • Therapy Recommendations (TRs): WGS/TS provided slightly more therapy recommendations per patient than panel sequencing.
    • Overlap: ~50% of TRs were identical between WGS/TS and panel sequencing.
    • Advantages of WGS/TS:
      • Captures RNA expression, mutational signatures (e.g., SBS3, HRD scores), and structural alterations not covered by panels.
      • Some actionable fusion genes and copy number variations (CNVs) were missed by the panel.
    • Panel Sequencing Advantages:
      • Faster turnaround, lower cost, and easier logistics (can use FFPE samples).
      • Panel sequencing successfully detected 4/5 pathogenic germline variants, recommending genetic counseling in three cases.
    • Clinical Impact:
      • 10 molecularly informed therapies were implemented, 8 of which were supported by the panel.
      • 2 therapies were based on biomarkers only detected by WGS/TS, supporting the added clinical value of comprehensive sequencing.
  • Conclusion: While WGS/TS provides a broader molecular profile, panel sequencing remains a more practical choice for routine clinical use. Further randomized trials are needed to assess the true cost-benefit of WGS/TS in oncology.

Thursday, January 30, 2025

AI Corner: Chat GPT Seeks "Most Humorous Moments" in 6 Hours of RFK Jr

RFK Jr was interviewed on the Hill for more than six hours (two days).  I fed both transcripts to Chat GPT and asked it to pick out "five humorous moments."

I'd say the pickins' were slim, and so are the results.  However, Chat GPT could understand the gist of the request for "humorous moments," and at least shows "some idea" of what was requested.   And Chat GPT had to read about 60,000 words of auto-transcripts in a couple of seconds. Result below.

See also, sidebar, Chat GPT assessing the two days in the voice of Lewis Black.  

##

AI CORNER

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Here are the five most humorous moments from Day 1 and Day 2 of Robert F. Kennedy Jr.'s Senate confirmation hearing for Secretary of Health and Human Services:


1. Senator Cassidy’s "Florida Gator" Roast (Day 2)

📍 What happened?
At the start of Day 2, Senator Bill Cassidy (R-LA) welcomed Kennedy and his family, then jokingly singled out his nephew:

“I like your family—except for the nephew who's a Florida Gator. We’ll let that go.”

📍 Why it’s funny?
Cassidy, a LSU guy, took a good-natured jab at Kennedy’s relative supporting the University of Florida, a rival SEC school. It added some casual SEC football rivalry into an otherwise tense hearing.


2. Kennedy's "I'm Not Anti-Fish" Defense (Day 1)

📍 What happened?
Kennedy tried to reframe his reputation by comparing his vaccine advocacy to his environmental work:

“I worked for years to raise awareness about mercury in fish, and nobody called me anti-fish!”

📍 Why it’s funny?
The idea of someone being labeled ‘anti-fish’ is so absurd that it momentarily lightened the mood. But the comparison fell flat, because vaccines and fish regulations aren't exactly the same thing.


3. Rand Paul’s "Submit to the Government" Rant (Day 2)

📍 What happened?
Senator Rand Paul (R-KY) launched into a passionate tirade against government-mandated vaccines:

“You people up here are so separated from real people at home! There’s such a belief in submission—submit to the government! Do what you’re told! No discussion allowed!”

📍 Why it’s funny?
Paul sounded like a rebellious teenager arguing with his parents about curfew, except he’s a U.S. senator. The exaggerated “submit to the government” line could have come straight from a dystopian sci-fi movie.


4. Kennedy’s “I Will Apologize... Eventually” Dodge (Day 2)

📍 What happened?
Both Senator Cassidy and Senator Sanders demanded a clear yes or no:

Cassidy: “Can you unequivocally state that measles and hepatitis B vaccines do NOT cause autism?”
Kennedy: “If you show me data, I will apologize for any statements that misled people.”

📍 Why it’s funny?
Kennedy dodging the question like Neo in The Matrix frustrated senators. The phrasing was also unintentionally amusing—it was like a politician's version of ‘I’ll apologize... if I have to’.


5. The “Lyme Disease Bioweapon” Backpedal (Day 2)

📍 What happened?
Kennedy was cornered on his past suggestion that Lyme disease was created as a military bioweapon:

Cassidy: “Do you still believe Lyme disease was a military bioweapon?”
Kennedy: “I’ve never believed that... but we should always follow the evidence.”

📍 Why it’s funny?
Kennedy pivoted so hard he almost fell over. He didn’t deny saying it before, but also tried to distance himself from it while keeping the door slightly open. A classic conspiracy walk-back!


Final Takeaway: Laughter in the Chaos

Despite the high-stakes nature of the hearing, these moments added levity—whether through Senator roasts, exaggerated speeches, or Kennedy’s verbal gymnastics

AI Corner: Chat GPT Assesses RFK Jr Hearing on Day 2; Also Sums Up Both Days

Previously, I posted a Chat GPT analysis of RFK Jr Hearing, Day 1.

https://www.discoveriesinhealthpolicy.com/2025/01/ai-corner-chat-gpt-assesses-rfk-jr-hhs.html

Here is a similar analysis of Day 2, following by a conjoint analysis.  The conjoint analysis resulted in a 60-65% prediction of success for RFK Jr.

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HealthcareDive was unimpressed by RFK Jr's Medicare/Medicaid answers, day 1 or day 2.

IDSA summed up both days here.  

Endpoints summed up here, noting that RFK can lose 3 Republican senators (and he's expected to) but still squeak by with the Veep tie-splitter.  But if he loses one more, like Sen. Cassidy, a physician, he's toast.

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CHAT GPT

Here is a detailed summary and insightful analysis of Day Two of Robert F. Kennedy Jr.’s Senate confirmation hearing for Secretary of Health and Human Services.


Summary of Key Moments

Opening Statements

  • The hearing opened with Senator Bill Cassidy (Chairman) acknowledging Kennedy’s family legacy and stating his concerns about Kennedy’s past vaccine positions. He praised Kennedy’s stance on reducing ultra-processed food but pushed him on whether he would publicly affirm vaccine safety and work to restore public confidence.
  • Senator Bernie Sanders (Ranking Member) focused on healthcare system failures, high costs, and lack of universal coverage. He challenged Kennedy’s ability to stand up to corporate interests and address economic inequality in healthcare.
  • Robert F. Kennedy Jr. introduced himself, emphasizing his background in environmental law and arguing that chronic disease is the primary driver of America’s health crisis. He expressed support for President Trump’s “Make America Healthy Again” movement, framed himself as a reformer, and said he would base decisions on science rather than personal opinions.

Vaccine Controversy & Kennedy’s Stance

  • Cassidy and Sanders grilled Kennedy on his history of casting doubt on vaccine safety. They asked whether he would unequivocally state that measles and hepatitis B vaccines do not cause autism, citing extensive scientific evidence.
  • Kennedy refused to give a direct answer, saying he would need to review the studies but would apologize if proven wrong.
  • Sanders was visibly frustrated, saying Kennedy should have already been familiar with this evidence before applying for the position.

COVID-19 Vaccine Debate

  • Sanders confronted Kennedy on his past opposition to COVID-19 vaccines, citing studies showing they saved millions of lives.
  • Kennedy refused to acknowledge the vaccines' impact, saying "we don’t have a good surveillance system" and that the data was unclear.
  • Sanders accused him of spreading dangerous misinformation, calling his refusal to accept scientific consensus "really problematic."

Other Controversial Moments

  1. Lyme Disease Bioweapon Theory

    • Kennedy denied believing that Lyme disease was created as a military bioweapon, but acknowledged that he had read books making that claim.
  2. Conspiracy Theories & 9/11

    • Senator Tim Kaine pressed Kennedy on a 2024 social media post where he questioned what was "conspiracy theory and what isn’t" about 9/11.
    • Kennedy refused to take a stance, saying, “I haven’t investigated it.”
    • Kaine called this "deeply disturbing" and suggested it showed Kennedy had difficulty distinguishing fact from conspiracy theory.
  3. HPV Vaccine & Sexual Harassment Allegation

    • Senator Patty Murray criticized Kennedy for calling the HPV vaccine "dangerous and defective" and falsely claiming it increases cervical cancer risk.
    • She also raised a past sexual harassment accusation against Kennedy, pressing him on why he apologized to the accuser.
    • Kennedy denied the allegations, saying his apology was for something else.
  4. Abortion & Birth Control

    • Senator Tim Scott (R-SC) asked whether Kennedy’s deputies would be pro-life.
    • Kennedy said he would implement Trump’s policies, which include restrictions on late-term abortion.
  5. Medicaid & Healthcare Cuts

    • Sanders pressed Kennedy on whether he would oppose Republican-led Medicaid cuts.
    • Kennedy refused to commit, instead arguing that the entire healthcare system is broken.

Analysis: Strengths & Weaknesses of Kennedy’s Performance

Strengths

Chronic Disease Focus – Kennedy effectively shifted the conversation to chronic disease, arguing that the healthcare system focuses on treatment instead of prevention. His emphasis on ultra-processed food and environmental toxins resonated with some lawmakers.

Populist Messaging – His anti-corporate stance, particularly against Big Pharma and the food industry, was popular among Republicans and some Democrats.

Pledged to Follow the Science – He repeatedly stated that he would change his position if presented with data, though his refusal to engage with existing evidence raised doubts.


Weaknesses

Vaccine Doublespeak – Kennedy refused to make a clear statement affirming vaccine safety, even when presented with overwhelming evidence. His "Show me the data" response seemed deliberately evasive.

COVID-19 Vaccine Misinformation – His refusal to acknowledge that COVID-19 vaccines saved lives put him at odds with Trump himself, who has praised Operation Warp Speed.

Conspiracy Theory Ambiguity – His refusal to “take sides” on 9/11 conspiracy theories played into concerns that he engages in misinformation.

Ethics & Financial Conflicts – His financial ties to lawsuits against vaccines raised concerns about bias in how he would regulate pharmaceutical policies.

Clashes with Democrats – His responses to Sanders, Murray, and Kaine reinforced Democratic fears that he would be an untrustworthy steward of public health.


Final Takeaway: Can Kennedy Be Confirmed?

Kennedy clearly has support from Republicans, particularly those who favor individual choice in healthcare and distrust public health agencies. However, his evasiveness on vaccines, history of promoting misinformation, and refusal to engage with established science may make it difficult for him to secure bipartisan support.

LIKELY SUPPORTERS:

  • Republicans who want a populist disruptor at HHS.
  • Anti-regulation conservatives who favor his criticism of public health bureaucracy.
  • Vaccine skeptics and anti-corporate advocates.

LIKELY OPPONENTS:

  • Democrats who see him as a dangerous choice for public health.
  • Public health experts who view him as a misinformation spreader.
  • Some Trump allies who fear his vaccine stance conflicts with Trump's legacy.

Bottom Line

Kennedy framed himself as a reformer, but his vaccine stance, conspiracy rhetoric, and financial conflicts raise serious credibility issues. His confirmation remains uncertain as senators weigh whether his populist appeal outweighs his public health liabilities.


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Discuss the odds of success.  (Spoiler alert - 65%).

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Assessment of Robert F. Kennedy Jr.’s Confirmation Prospects for Secretary of Health and Human Services

Based on the transcripts from both Day 1 and Day 2 of Robert F. Kennedy Jr.’s Senate confirmation hearing, his chances of being confirmed for Secretary of Health and Human Services (HHS) depend on several key factors: Republican party unity, his stance on controversial issues, and the pressure on swing votes.


1. Summary of Key Findings from the Hearings

Day 1: Introduction, Policy Proposals & Early Resistance

  • Republican Support: Chairman Senator Bill Cassidy (R-LA) and others praised Kennedy’s focus on chronic disease, processed foods, and transparency in public health.
  • Democratic Opposition: Senator Ron Wyden (D-OR) delivered a scathing attack, accusing Kennedy of promoting conspiracy theories, spreading anti-vaccine rhetoric, and undermining public trust in health agencies.
  • Vaccine Safety Debate: Kennedy claimed he was not anti-vaccine, but Democrats confronted him with past statements, including a petition to block COVID-19 vaccines for children.
  • Abortion & Medicaid Issues: Kennedy refused to commit to protecting Medicaid from Republican cuts and was evasive on abortion policies, raising concerns among Democrats.
  • Samoa Measles Outbreak: Democrats accused Kennedy of fueling vaccine hesitancy that contributed to deaths in Samoa—an accusation he vigorously denied.

Day 2: Pressure on Vaccines, Medicaid, and Partisan Dynamics

  • Republican Reservations on Vaccines: Senator Cassidy and Senator Rand Paul (R-KY) pressed Kennedy on his willingness to change positions based on data. Cassidy asked him point-blank if he would tell the public that measles and hepatitis B vaccines do not cause autism. Kennedy refused to directly say yes, instead asking for more data, which frustrated even Republican allies.
  • Democratic Attacks Escalated: Senator Bernie Sanders (D-VT) hammered Kennedy on COVID-19 vaccines, quoting studies that estimate millions of lives were saved. Kennedy refused to acknowledge this, saying there was no good surveillance system to prove it—a response Sanders called "deeply troubling."
  • Medicaid & Healthcare Reform: Democrats, including Sanders, pushed Kennedy on whether he would fight Trump’s rumored Medicaid cuts. Kennedy deflected, saying Trump has not discussed cutting Medicaid with him. This failed to satisfy Democrats.
  • Partisan Pressure on Republicans:
    • Most Republicans seem reluctant to break ranks, even if some (Cassidy, possibly Romney or Collins) have concerns about Kennedy's vaccine rhetoric.
    • Even doubtful Republicans may not want to risk becoming a target by voting against him, given Trump’s strong backing.
  • Trump Factor: Kennedy frequently invoked Trump’s name, emphasizing that he was aligned with Trump’s “Make America Healthy Again” movement and that Trump personally trusted him.

2. Key Factors Affecting His Confirmation Prospects

✅ Reasons Why RFK Jr. Could Be Confirmed

Republican Majority (Even if Slim): With only a narrow Republican majority in the Senate, Kennedy doesn’t need bipartisan support, just near-total GOP unity. Given Trump’s backing, many Republicans may feel compelled to vote yes

Trump’s Direct Endorsement: Trump hand-picked Kennedy, framing him as a health reformer. Republicans who vote against him risk angering Trump’s base

Strong GOP Support on Non-Vaccine Issues: Kennedy’s focus on nutrition, ultra-processed foods, and chronic disease prevention aligns well with many Republican health policies

Pressure on Swing Republicans to Stay in Line: Senators like Mitt Romney (R-UT), Lisa Murkowski (R-AK), and Susan Collins (R-ME) may have doubts, but voting against Kennedy would expose them to fierce backlash from Trump-aligned forces. 

Anti-Bureaucracy Stance Appeals to Conservatives: His criticism of the FDA, CDC, and NIH resonates with Republicans who distrust public health institutions.

❌ Reasons Why RFK Jr. Could Be Rejected

Deep Republican Concerns About Vaccines: Some Republicans (like Cassidy and Paul) have serious reservations about Kennedy’s anti-vaccine reputation. Cassidy’s pointed questioning about whether Kennedy would definitively say vaccines do not cause autism showed lingering doubt

Unified Democratic Opposition: Every single Democrat is likely to vote against him. Even moderate Democrats see Kennedy as a public health risk

Baggage on Conspiracy Theories: His past remarks on vaccines, Lyme disease, and 9/11 make him a politically toxic pick for some senators

Potential GOP Defections on the Vaccine Issue: If two or three Republicans defect, Kennedy could be blocked—especially if Vice President Vance's tie-breaking vote isn't enough to override resistance

Concerns About Medicaid Cuts: Even some moderate Republicans may worry that Kennedy would not fight against potential cuts to Medicaid, harming seniors and low-income Americans.


3. Final Prediction: Does Kennedy Have the Votes?

Kennedy’s confirmation is uncertain but still slightly favored due to Republican pressure to stay in line.

LIKELY PATH TO CONFIRMATION:

  • Kennedy is likely to secure most Republican votes despite some concerns.
  • Trump’s influence on the party is a major factor—Republicans who oppose Kennedy risk blowback.
  • If only one or two Republicans defect, Kennedy would still be confirmed with VP Vance’s tie-breaking vote.

WHAT COULD DERAIL HIM?

  • If three or more Republican senators (e.g., Cassidy, Romney, Murkowski, Collins) vote no, his nomination would fail.
  • Last-minute GOP pressure over his vaccine stance could tip the scales if Republicans fear long-term backlash from public health advocates.

Final Probability Estimate

🔵 Kennedy Confirmed: ~60-65% Likely 🔴 Kennedy Blocked: ~35-40% Likely


4. Strategic Takeaways

  • If Kennedy wants to secure confirmation, he must assure Republican swing votes (Cassidy, Romney, Collins) that he will not undermine vaccine policies.
  • Democrats will use this hearing as a campaign point against Republicans in 2026, portraying Kennedy as a public health risk.
  • If Kennedy fails to win confirmation, Trump may nominate a more traditional Republican to avoid a prolonged fight.

Conclusion

RFK Jr.’s confirmation is not guaranteed, but he remains slightly favored to be confirmed due to the Republican majority and Trump’s backing. However, his vaccine views remain a significant liability, and if just a few key Republicans break ranks, he could be blocked.