AMP Files Lawsuit Against FDA Over LDT Regulation

On August 19, 2024, Association for Molecular Pathology (AMP) filed an 83-page legal case against the FDA and its regulation to govern lab-developed tests.    

Law suit here.

Press release here.   360Dx here.  STAT here.

This follows a similar lawsuit by ACLA on May 29.

While the FDA's case in May was 450 pages and this is 83, the original FDA filing was only 59 pages of legal complaint, followed by various testimonials and attachmeents.  In that sense, the AMP legal case is actually longer.  It's filed in the Southern District of Texas; I think the ACLA was filed in the Eastern District.  

##

See my blog on why a loss in a Texas court by the FTC is relevant to the ACLA and AMP.

##

AI Corner

Chat GPT 4o reads the case.  

I'm not a lawyer, neither is Chat GPT, so comments below are "FYI" only.

FDA's Overreach and the Impact on Laboratory Developed Tests: A Critical Analysis

The recent legal case, Association for Molecular Pathology (AMP) et al. v. United States Food and Drug Administration (FDA), presents a pivotal moment for the laboratory industry, particularly in the regulation of Laboratory Developed Tests (LDTs). The plaintiffs, including AMP and Dr. Michael Laposata, challenge what they describe as an unprecedented regulatory overreach by the FDA. This case, now under the jurisdiction of the United States District Court for the Southern District of Texas, could reshape the landscape of diagnostic testing in the United States, with significant implications for laboratories, healthcare providers, and patients.

Background: The Regulatory Landscape

Historically, the regulation of LDTs has been distinct from that of medical devices. LDTs, which are developed and performed within a single laboratory, have been subject to the Clinical Laboratory Improvement Amendments (CLIA) of 1988, overseen by the Centers for Medicare & Medicaid Services (CMS). This framework was designed to ensure the accuracy and reliability of laboratory tests while allowing laboratories the flexibility to develop innovative diagnostic procedures tailored to patient needs.

In contrast, medical devices, which include commercially distributed diagnostic tools, have been regulated by the FDA under the Federal Food, Drug, and Cosmetic Act (FDCA) since 1938, with significant amendments in 1976. These regulations impose strict premarket review and postmarket control requirements, designed primarily for mass-produced devices used widely across the healthcare industry.

The FDA's Final Rule: A Shift in Authority

The FDA’s recent Final Rule marks a significant departure from the established regulatory framework. For the first time, the FDA asserts its authority to regulate LDTs as medical devices, subjecting them to the same stringent premarket review, postmarket controls, and compliance requirements that apply to mass-produced diagnostic devices. This shift is seen by the plaintiffs as a direct challenge to the legislative intent of both the FDCA and CLIA.

According to the complaint, the FDA’s move not only disregards the distinct regulatory structure Congress established but also threatens to impose significant financial and operational burdens on laboratories. The FDA itself estimates that compliance with its new mandates could cost the laboratory industry billions of dollars annually, a figure that many in the industry believe to be a conservative estimate.

Impact on Laboratories and Healthcare

The plaintiffs argue that the FDA's regulation of LDTs will have far-reaching consequences for laboratories, particularly those serving specialized or underserved populations. Smaller laboratories, which often operate with limited resources, may struggle to meet the new regulatory demands, leading to closures, consolidations, or the abandonment of innovative testing procedures. This, in turn, could reduce competition and stifle innovation, ultimately harming patients who rely on timely and accurate diagnostic tests.

Moreover, the FDA's Final Rule is expected to exacerbate the existing shortage of pathologists in the United States by increasing the regulatory burden on laboratories and driving professionals out of the field. This shortage could further reduce access to critical diagnostic services, particularly in rural and underserved areas.

Legal Arguments and the Path Forward

The legal arguments presented by the plaintiffs hinge on the interpretation of the FDCA and CLIA, as well as the Administrative Procedure Act (APA). They contend that the FDA has overstepped its authority by unilaterally expanding its regulatory reach without clear congressional authorization. They also argue that the FDA's Final Rule is arbitrary and capricious, relying on unverified and anecdotal evidence to justify its new regulatory scheme.

The outcome of this case will have significant implications for the laboratory industry. If the court sides with the plaintiffs, it could lead to the invalidation of the FDA's Final Rule, preserving the existing regulatory framework under CLIA. However, if the court upholds the FDA's authority, laboratories across the country will need to navigate a complex and costly regulatory environment, with potentially profound effects on the availability and quality of diagnostic testing.

Conclusion

The AMP et al. v. FDA case is more than a legal battle; it represents a critical juncture for the future of diagnostic testing in the United States. As the laboratory industry waits for the court's decision, the stakes are clear: the outcome will either reinforce the regulatory status quo or usher in a new era of FDA oversight that could reshape the industry for years to come.

This case serves as a reminder of the delicate balance between innovation and regulation in the healthcare sector. As laboratories continue to push the boundaries of diagnostic science, the need for a regulatory framework that supports both innovation and patient safety has never been more apparent.

Compare the ACLA case and the newer AMP case.  Thanks!

The May lawsuit filed by the American Clinical Laboratory Association (ACLA) and the August lawsuit from the Association for Molecular Pathology (AMP) share similarities in their fundamental opposition to the FDA's regulatory approach toward Laboratory Developed Tests (LDTs). However, they differ in their legal strategies, the scope of their arguments, and the specific relief they seek. Here's a comparative analysis:

Similarities Between the ACLA and AMP Lawsuits

1. Challenging FDA's Authority: Both lawsuits fundamentally challenge the FDA's authority to regulate LDTs as medical devices under the Federal Food, Drug, and Cosmetic Act (FDCA). They argue that LDTs are services, not products, and therefore fall outside the scope of the FDA’s regulatory jurisdiction.

2. Reliance on CLIA: Both cases emphasize that LDTs are already regulated under the Clinical Laboratory Improvement Amendments (CLIA) of 1988, which they argue is the appropriate regulatory framework for these tests. They assert that CLIA, overseen by the Centers for Medicare & Medicaid Services (CMS), provides sufficient oversight to ensure the safety and efficacy of LDTs.

3. Legal Grounds: Both lawsuits cite violations of the Administrative Procedure Act (APA), arguing that the FDA’s Final Rule exceeds the agency’s statutory authority and is arbitrary, capricious, and contrary to law.

4. Concerns About Innovation and Access: Both the ACLA and AMP highlight the potential negative impact of the FDA’s rule on innovation and patient access to critical diagnostic tests. They argue that subjecting LDTs to the FDA’s medical device regulations would impose significant financial and operational burdens on laboratories, stifling innovation and reducing the availability of important tests, particularly for rare diseases or specialized patient populations.

Key Differences Between the ACLA and AMP Lawsuits

1. Scope of Plaintiffs:

   • ACLA: The ACLA lawsuit represents the broader laboratory industry, including large national clinical laboratories and organizations like HealthTrackRX, which is involved in infectious disease diagnostics. The lawsuit emphasizes the role of these laboratories in providing a wide range of diagnostic tests to clinicians and patients across the country.
   • AMP: The AMP lawsuit, while also representing the interests of clinical laboratories, is more focused on the specific concerns of molecular pathologists and the impact of the FDA’s rule on molecular diagnostic testing. AMP’s legal arguments are closely tied to the specialized nature of molecular pathology and the unique challenges that the FDA’s rule poses to this subset of the laboratory industry.

2. Legal and Regulatory Arguments:

   • ACLA: The ACLA lawsuit places significant emphasis on the long-standing regulatory framework under CLIA and argues that the FDA's Final Rule overreaches by attempting to regulate professional laboratory services as medical devices. It also highlights Congress's repeated refusal to grant the FDA the authority to regulate LDTs as devices, as evidenced by the failure of the VALID Act to pass.
   • AMP: The AMP lawsuit builds on these arguments but also delves deeper into the specifics of molecular diagnostics. It argues that the FDA's attempt to regulate LDTs ignores the complex and specialized nature of these tests, which are often tailored to individual patients and require a high degree of professional judgment and expertise. AMP also emphasizes that the FDA’s rule could disrupt the practice of precision medicine, which relies heavily on molecular diagnostics.

3. Requests for Relief:

   • ACLA: The ACLA lawsuit seeks declaratory and injunctive relief to vacate the FDA’s Final Rule and prevent its enforcement. It argues that the rule is unlawful and would cause irreparable harm to the laboratory industry.
   • AMP: While the AMP lawsuit also seeks to overturn the FDA’s rule, it goes further in requesting that the court recognize the unique nature of molecular diagnostics and explicitly limit the FDA’s regulatory authority in this area. AMP’s lawsuit includes detailed arguments about the potential impact on molecular pathology practice, making a case for why these tests should be exempt from the FDA’s regulatory reach.

4. Focus on Specific Types of Tests:

   • ACLA: The ACLA lawsuit broadly addresses all LDTs, covering a wide range of diagnostic services provided by laboratories across the country.
   • AMP: The AMP lawsuit specifically focuses on molecular diagnostics and the specialized nature of these tests. It argues that the FDA’s rule would disproportionately harm this area of laboratory medicine, which is critical for personalized medicine and the treatment of complex diseases like cancer.

What's in the AMP Lawsuit but Not in the ACLA Lawsuit?

1. Emphasis on Molecular Pathology: The AMP lawsuit goes into greater detail about the implications of the FDA’s rule for molecular pathologists and the practice of precision medicine. It highlights the unique challenges that molecular diagnostics face under the FDA’s regulatory framework, which is designed for mass-produced medical devices rather than highly specialized laboratory services.

2. Impact on Precision Medicine: The AMP lawsuit specifically addresses the potential disruption to precision medicine, arguing that the FDA’s rule could undermine efforts to provide personalized care to patients with complex conditions. This argument is less pronounced in the ACLA lawsuit, which focuses more broadly on the impact of the rule on the laboratory industry as a whole.

3. Detailed Critique of FDA’s Interpretation: The AMP lawsuit provides a more detailed critique of the FDA’s interpretation of the FDCA as it applies to LDTs, arguing that the agency has failed to consider the distinct nature of molecular diagnostics and the professional services provided by laboratory pathologists.

In summary, while both lawsuits share common ground in opposing the FDA’s regulatory approach to LDTs, the AMP lawsuit offers a more focused and detailed argument related to molecular diagnostics and the practice of precision medicine. The ACLA lawsuit, on the other hand, provides a broader industry perspective and emphasizes the role of CLIA in regulating laboratory services. Both lawsuits are crucial in shaping the future of LDT regulation, but they approach the issue from different angles and with varying emphases.

CMMI's Terrible, Awful, Really Bad Day on the Hill

The policy website, Policy and Medicine, covers a range of interesting topics.  Here, in its August 4 issue, it covers a recent House hearing about CMMI, the CMS Center for Innovation.

Policy & Medicine here:

https://www.policymed.com/2024/08/cmmi-under-fire.html?utm_source=feedblitz&utm_medium=FeedBlitzRss&utm_campaign=policymed

The June 13 House web page, here:

https://energycommerce.house.gov/events/health-hearing-checking-in-on-cmmi-assessing-the-transition-to-value-based-care

The webpage includes links to prepared statements and embeds a full 2 hour YouTube video of the hearing, but doesn't provide a transcript.   One of the stimuli for this summer's hearing was a September 2023 CBO report that CMMI hadn't saved any money - here.   (And one of the saving graces for CMMI it that it's historically score as "savings" making it hard to delete, legislatively).

In addition to the readings linked - Policy & Medicine August 4, and CBO, September 2023 - I used free software called 4KDownloader to pull down an audio file of the YouTube video, then uploaded the audio file to Otter.AI for an autotranscript.  I then fed the autotranscript into Chat GPT 4, asking it to play the role of a healthcare journalist attending the House hearing.   The result is below.

AI Corner

Chat GPT 4o reads audio file of June 13 House hearing.

The recent House committee hearing on the CMS Center for Innovation (CMMI) was a stormy session, with Director Liz Fowler facing sharp criticism from several legislators. The session highlighted the Center's struggles to deliver on its original mandate to reduce costs while improving the quality of care. 

The hearing was a significant moment for CMMI as it grappled with intense scrutiny over its performance, particularly in light of a recent Congressional Budget Office (CBO) report that criticized the agency for increasing federal spending by $5.4 billion rather than achieving the promised savings.

Criticism and Adversity:

During the hearing, several legislators were openly critical of CMMI’s performance. They pointed out that despite being established with the dual goals of lowering costs and improving care, the agency had fallen short. The CBO report served as a focal point for much of this criticism, with members expressing frustration that CMMI, instead of saving money, had actually cost the government billions.

For instance, one legislator expressed disappointment, saying, "I have a hard time believing any objective observer could look at the results thus far and describe CMMI as a success." This sentiment was echoed by others who questioned why CMMI models have not led to the anticipated savings and have instead created more financial burden.

Another key criticism centered around specific CMMI models. Legislators were particularly concerned about the Accelerated Clinical Evidence (ACE) model, which proposed slashing payments to Part B providers for therapies [drugs] approved by the FDA through the accelerated approval pathway. This move was seen as undermining the FDA’s authority and potentially stifling innovation. Legislators argued that this could harm patients who rely on these therapies, particularly those with rare diseases where treatment options are limited.

Moreover, the Cell and Gene Therapy Access Model, another initiative by CMMI, was criticized for potentially inhibiting states' ability to negotiate drug prices and utilize value-based agreements effectively. Legislators voiced concerns that this could weaken states’ bargaining power and limit access to cutting-edge treatments for patients in need.

Fowler’s Defense and Strategic Overview:

In response, Dr. Liz Fowler acknowledged the challenges faced by CMMI but defended the agency's work. She pointed out that innovation is inherently unpredictable, and while not all models have succeeded in generating savings, they have provided valuable lessons. Fowler emphasized that CMMI’s role is not just about cutting costs but also about improving the quality of care, particularly in underserved areas.

Fowler highlighted successes like the Accountable Care Organizations (ACO) model, which has demonstrated cost savings and improved care coordination. She also discussed new initiatives aimed at addressing healthcare disparities and improving outcomes in areas like dementia care, maternal health, and behavioral health.

Fowler also admitted that voluntary models had led to risk selection, where providers enter and exit based on favorable conditions, which has undermined the ability to generate consistent savings. She assured the committee that CMMI is learning from these experiences and making adjustments where necessary, including shutting down models that do not perform as expected.

A Balanced Overview:

The hearing painted a picture of an agency under pressure but also one that is pivotal to the ongoing transformation of the U.S. healthcare system. While the criticisms were fierce, the discussion also underscored the complexity of the challenges CMMI faces. The agency's efforts to shift the healthcare system towards value-based care are ambitious, and its successes in areas like ACOs should not be overlooked.

However, the CBO’s findings and the concerns raised by legislators about specific models indicate that CMMI must do more to meet its financial targets and prove that it can deliver on the promise of better care at lower costs. The path forward for CMMI will require a delicate balance between innovation and fiscal responsibility, ensuring that new models not only improve care but also achieve the cost savings that are crucial to the sustainability of Medicare and Medicaid programs.

As CMMI moves into its second decade, the stakes are high, and the outcomes of these hearings will likely shape its future direction. For healthcare policy experts, this hearing is a reminder of the complexities of healthcare reform and the ongoing challenges in achieving a more efficient and effective healthcare system.

Imagine a Congressman is introducing legislation to de fund CMMI. Provide his speech giving his justification and seeking suport (concurrence) from listeners.

Speech by Congressman [Name] on the Proposed Legislation to Defund the CMS Center for Innovation (CMMI):

"Mr. Speaker, my fellow colleagues, I rise today to introduce legislation that calls for the defunding of the CMS Center for Innovation, commonly known as CMMI. This is not a decision I take lightly, nor one that I make without thorough consideration of the facts. But the facts, as they stand, make it clear that CMMI has not lived up to its promises, and it is time we act decisively to protect taxpayer dollars and ensure that our healthcare system is both effective and sustainable.

CMMI was established under the Affordable Care Act with noble intentions: to test innovative payment and service delivery models that could improve healthcare quality while reducing costs for Medicare, Medicaid, and CHIP beneficiaries. It was given sweeping authority, a ten-year budget of $10 billion, and the hope that it would lead the charge in transforming our healthcare system.

But after more than a decade of operation, what do we have to show for it? According to a recent report from the Congressional Budget Office (CBO), instead of saving money, CMMI has increased federal spending by $5.4 billion. That's right—$5.4 billion more in costs to the American taxpayer with little to no evidence that the healthcare system is any better for it. The original promise that CMMI would generate $1.3 billion in savings in its first decade has proven to be a gross overestimation. Even more alarming, the CBO now projects that CMMI will continue to cost the government an additional $1.3 billion in the coming years.

These numbers aren't just disappointing; they are a stark indication that CMMI has failed in its mission. We were told that this agency would revolutionize healthcare by shifting the system toward value-based care, but after testing over 50 models, only a handful have produced any meaningful results. The rest have either stagnated or, worse, driven up costs.

Take, for example, the Accelerated Clinical Evidence (ACE) model, which proposed slashing payments to Part B providers for FDA-approved therapies. Not only did this model threaten to undermine the FDA's gold standard for drug approval, but it also risked limiting access to critical treatments for patients with serious conditions. Another model, the Cell and Gene Therapy Access initiative, could have restricted states' ability to negotiate drug prices effectively, ultimately harming patients who rely on these groundbreaking therapies.

We must ask ourselves: Is this the kind of 'innovation' we want to fund with billions of taxpayer dollars? Is it responsible to continue pouring money into an agency that has consistently failed to deliver on its promises? I say no.

By defunding CMMI, we are not turning our backs on healthcare innovation. On the contrary, we are taking a stand to ensure that innovation is driven by effective, results-oriented policies that truly improve care and reduce costs. We can and should encourage innovation within our healthcare system, but it must be done with accountability and transparency—qualities that CMMI has sorely lacked.

Mr. Speaker, my colleagues, the time has come to take a hard look at the value—or lack thereof—that CMMI has brought to our healthcare system. We have a duty to our constituents to spend their hard-earned dollars wisely, and continuing to fund a program that has consistently failed to meet its objectives is not a wise use of their money.

I urge you all to support this legislation to defund CMMI. Let us work together to redirect these funds toward initiatives that will genuinely improve healthcare delivery in this country—initiatives that are accountable, transparent, and effective. Thank you."

ARPA-H Launches "POSEIDON" - For a $100 MCED Test

ARPA-H has launced a Poseidon Adventure of its own - an RFP that moves us toward developing a $100 MCED test.  It's in the news this week.

##

See the ARPA-H home page for POSEIDON - Platform Optimizing SynBio for Early Intervention and Detection in Oncology.  (Get it?)  There will be a "Proposers' Day" September 4 in Washington.

https://arpa-h.gov/research-and-funding/programs/poseidon

It's part of the Biden Moonshot.  See the White House briefing document from August 13, 2024, below; it has a paragraph for Poseidon, among several other innovation programs.

https://www.whitehouse.gov/briefing-room/statements-releases/2024/08/13/fact-sheet-biden-harris-administration-announces-150-million-from-arpa-h-to-deliver-progress-on-biden-cancer-moonshot-goals-and-improve-health-outcomes/

This contracts webpage gives you an 8 page PDF about Proposers' Day and links to an online FAQ page.

https://sam.gov/opp/2c5036c43e434d389370c612d7558adc/view

##

Find coverage at Everglade here.  And at Becker Hospital Review here.

ARPA-H also has a "Precision Surgical Invervention" to make more cancers surgically curable.  Read about it at ASCO POST here.

AI Corner

Here is an AI "TLDR" summary of POSEIDON.

The POSEIDON program, spearheaded by the Advanced Research Projects Agency for Health (ARPA-H), is an ambitious initiative designed to transform cancer detection and treatment. It aims to create a next-generation, at-home multi-cancer early detection (MCED) system that uses synthetic biology to detect over 30 types of solid tumors at Stage I. The key innovation lies in its use of synthetic sensors that are both highly sensitive and specific, capable of identifying cancer in its earliest stages through simple breath or urine samples, making it possible to detect cancer when curative treatment is most likely.

POSEIDON’s vision is to develop an over-the-counter, user-friendly device that can be easily administered at home without requiring a visit to a healthcare professional. This device will be connected to a digital platform, integrating with telemedicine services and electronic health records (EHR) to ensure seamless communication with healthcare providers. The program's focus on affordability, accessibility, and integration into clinical practice aims to significantly reduce the incidence of late-stage cancer diagnoses, which are currently a major driver of cancer mortality and healthcare costs.

The program is divided into two main technical areas (TAs). Technical Area 1 (TA1) focuses on the design and development of synthetic biology-based sensors and reporters that can detect cancer-specific molecular signatures. These synthetic circuits will use advanced techniques such as multi-layer logic gates and signal amplification to accurately distinguish between different types of cancer. Technical Area 2 (TA2) involves the creation of the MCED kit, a hardware-software combination that will include a low-cost detection device, a user-friendly interface for at-home testing, and digital tools for reporting results and integrating with healthcare systems.

POSEIDON is structured into three phases over five years. The first phase, lasting 36 months, will involve the initial design, development, and testing of both the sensors and the detection device. Phase two, spanning 15 months, will conduct IND-enabling nonclinical studies to evaluate the safety and pharmacokinetics of the sensors. The final phase, lasting 9 months, will focus on first-in-human clinical trials to assess the safety and efficacy of the MCED kits.

The program encourages collaboration between academic institutions and commercial entities, particularly those with experience in regulatory processes and commercialization, to accelerate the development and deployment of these innovative cancer detection tools. By the end of the program, POSEIDON aims to have a commercially viable product ready for widespread use, drastically improving early cancer detection and potentially saving millions of lives.

This initiative also emphasizes the importance of human-centered design, ensuring that the end product is not only scientifically advanced but also user-friendly and accessible to a broad population. The program's success could revolutionize cancer care, making early detection as simple as a quick test at home and drastically improving survival rates.

CMS Press Release: MolDx Transplant LCD In Turnaround

Update:  I didn't know, until September, there was a press release from CareDx discussing this on August 16.    It makes my point - MolDx insisted (in writing) that the draft version 2 LCD was an editorial update only, and made no change in coverage.   Yet CareDx insists, also in writing, that the draft version 2 LCD would have changed and limited coverage.   My only conclusion: The LCD text cannot be clear [discussion below].

https://investors.caredx.com/news/news-details/2024/CareDx-Announces-Transplant-Community-Secures-Win-Reaffirming-Longstanding-Medicare-Coverage-for-AlloSure-and-AlloMap-Testing/default.aspx

##### Original Article:

Where I live, in Hollywood, we talk about scripts being "in turnaround."  According to a new CMS press release today, MolDx's LCD for transplant genomic tests is "in turnaround," too.

Find the CMS press release here:

https://www.cms.gov/newsroom/press-releases/moldx-local-coverage-determination-statement

The press release is brief - there is no change in coverage; the old LCD remains in effect; the new LCD (which they had asserted in writing made zero change in coverage) is canceled and not finalized.

CareDx share price popped from $28 to $32 - an increase in market cap of $250M.  

See coverage at 360Dx.  According to 360Dx, CareDx CEO John Hannah "cheered the decision."

See coverage in a (not entirely accurate) WSJ Op Ed here.

History

Back in Spring 2023, there was a tsunami of news (and stock price impacts) regarding nuances of policy and billing practices around transplant genomics.  Principally, these are tests from CareDx and Natera that detect when sick transplant organs have dying cells that are releasing their non-native DNA.   

In Summer 2023, MolDx released a slightly edited version of the LCD "for clarification only" but I found the rules confusing at best.  

Could the LCD be Way More Clear?  Yes.

The LCD could be far more clear, as I pointed out in a July 7 blog.  MolDx now uses multiplex Z codes for specific covered clinical scenarios, like "test for cause" versus "test for surveillance."  Why not simply rewrite the LCD on the same lines?    As I wrote in July, it would be something like this:

We cover these donor DNA tests under two situations, "for cause" and "replacing surveillance."   For "For cause" coverage, the patient and situation will meet these four rules.  (1,2,3,4)    For "For surveillance" coverage, the patient and situation will meet these other five rules (5,6,7,8,9).  

As I remarked then, the structure of the LCD would become clear, if it just mapped and matched to the structure of the Z codes that MolDx already has.

###
###

Wall Street Journal

I quote from my July blog:

Over the past year, there have been debates in the WSJ about MolDx's coverage regarding donor DNA testing (the saga started in March 2023 and reached WSJ September 10, September 22,  September 26, February 22,  April 18) and along the way, see also at least one CMS press release (February 29).  See also brand new WSJ Op Ed on August 21, 2024 (here).

The Draft That's NOT Being Finaled

I quote again from my July blog, here giving links to redlines of the old and proposed LCD.  For even more detail, see an August 10, 2023, blog by me.

MolDx issued a revision of the LCD (DL38568) on August 10, 2023, currently pending finalization. I posted a cloud-copy redline of the draft compared to the prior active version - here.   The effective coverage rules are intertwined and reach circa 900 words long in the proposal.  MolDx noted in August 2023 that the  various revisions (here) were "clarity" only and that "no change in coverage" was implied by the new text and definitions and rules (stated as "synopsis of changes" in DL38568).

DL38568 (click to enlarge). Changes for clarity only (per MolDx own synopsis).

Heads Up: Illumina's Strategy Call (Aug 13); Decibio's Future of Sequencing Webinar (Aug 20)

A reminder, a very interesting webinar from Decibio on August 20, 2024, looking at the future of NGS as a centralized or a distributed resource.  Here.

See also Illumina's public investor website for their August 13, 2024, two-hour Strategy Call.  The website has both a 50-slide deck and a two-hour video archive.   (The posting online may be time-limited).

(Side note - article on Baylor developing clinical, multiomic assays here).

AI Corner

Here's an auto-article based on the transcript and deck. Chat GPT 4o.

Illumina’s Strategic Pivot: 

A Deep Dive into the August 2024 Investor Strategy Call

In a two-hour Strategy Call on August 13, 2024, Illumina, the global leader in next-generation sequencing (NGS), presented a robust strategic vision to investors, outlining a path forward aimed at stabilizing its base, accelerating growth, and unlocking the power of the genome on a scale previously unseen. 

The call, led by CEO Jacob Thaysen, Chief Technology Officer Steve Barnard, and Chief Financial Officer Ankur Dhingra, detailed Illumina’s multi-faceted approach to maintaining its leadership in genomics while navigating a challenging economic and competitive landscape.

The New Strategic Vision: From Cost to Value

One of the most significant shifts articulated during the strategy call was Illumina’s transition from focusing on the cost per gigabase—a metric that has long been the industry standard for measuring sequencing efficiency—to a broader emphasis on delivering the highest quality insights at the lowest end-to-end cost. This pivot reflects Illumina’s recognition that its future lies not just in sequencing more data at a lower cost but in providing comprehensive, actionable insights that drive value across the entire healthcare ecosystem.

Jacob Thaysen, CEO, emphasized that Illumina is moving towards becoming a "biology platform company," which underscores the company’s commitment to expanding beyond traditional NGS into multiomics—an integrated approach that includes genomics, transcriptomics, proteomics, and more. This multiomics strategy is designed to catalyze deeper biological insights and scientific breakthroughs, positioning Illumina at the forefront of personalized healthcare.

Stabilizing the Base: Progress in 2024

The strategy update highlighted the substantial progress Illumina has made in 2024, particularly with its flagship NovaSeq X platform. Since its launch, the NovaSeq X has seen rapid adoption, with 469 installations by mid-2024 and contributing to 45% of Illumina's total high-throughput gigabase output. This platform has not only advanced Illumina’s market position but also driven innovation, enabling customers to succeed with more sophisticated workflows.

Illumina’s operational efficiency has also improved markedly, with non-GAAP gross margins improving by approximately 360 basis points [3.6%] from FY’23 to Q2’24. These gains reflect the company’s ongoing efforts to streamline R&D processes, reduce operating expenses, and maximize revenue growth, even amid a challenging economic environment.

Accelerating Growth: A Vision for 2027

Looking ahead, Illumina is targeting high single-digit revenue growth by 2027, driven by three key factors: core sequencing, scalable entry into multiomics, and expanded services, data, and software offerings. The NovaSeq X platform, in particular, is expected to play a critical role in this growth, with projected increases in sequencing intensity and a broad shift to more complex, multiomic applications.

Illumina’s multiomics product portfolio, which is already generating revenue, is poised to add another layer of growth by 2027. This portfolio includes solutions that enable high-intensity sequencing across various applications, from whole-genome sequencing (WGS) to single-cell analysis and spatial transcriptomics. By offering a universal readout across these applications, Illumina aims to capture a larger share of the rapidly growing market for integrated biological insights.

Financial Outlook: Navigating Challenges, Leveraging Opportunities

Despite the optimistic growth targets, Illumina’s financial outlook reflects a cautious approach, given the macroeconomic headwinds and competitive pressures. The company reported a modest revenue of approximately $4.3 billion for FY’24, with a non-GAAP free cash flow of $900-$950 million. However, the leadership expressed confidence in achieving a 500+ basis [5%] points improvement in operating margins from FY’25 to FY’27, supported by ongoing cost savings initiatives and strategic realignments.

Illumina is also focusing on realigning investments to support its growth ambitions. The company plans to increase investments in core sequencing technologies, build out its multiomics capabilities, and accelerate the development of software and AI tools for more actionable data interpretation. Additionally, Illumina is exploring new business models to better serve customers, particularly those who require easier access to sequencing technologies.  [Business models, eg. balance between capital equipment, chemistry, and services].

Conclusion: A Strategic Transformation in Progress

Illumina’s August 2024 strategy call underscored the company’s commitment to transforming its business model in response to the evolving needs of the genomics market. By shifting its focus from cost efficiency to delivering comprehensive biological insights, Illumina is positioning itself to lead the next wave of innovation in personalized healthcare. The strategic initiatives outlined during the call—ranging from the expansion of the NovaSeq X platform to the development of multiomics solutions—reflect a bold vision for the future, one that could redefine the landscape of genomic medicine over the next decade.

For investors and industry stakeholders, the message was clear: Illumina is not just a sequencing company; it is a platform for unlocking the full potential of the genome, with the promise of improving human health on a global scale.

###  SIDEBAR: 15 POINTS

15 Key Takeaways from Illumina's August 2024 Strategy Call

1. Strategic Shift: Illumina is transitioning from a focus on cost per gigabase to delivering the highest quality insights at the lowest end-to-end cost.

2. Multiomics Expansion: The company is expanding its platform to integrate genomics, transcriptomics, proteomics, and more, aiming to lead in multiomics.

3. NovaSeq X Success: Rapid adoption of the NovaSeq X platform with 469 installations, contributing to 45% of total high-throughput gigabase output.

4. Operational Efficiency: Significant improvement in non-GAAP gross margins, up 360 basis points from FY’23 to Q2’24.

5. Revenue Growth Target: Illumina aims for high single-digit revenue growth by 2027, driven by core sequencing, multiomics, and expanded services.

6. New Customer Segments: The company plans to serve distinct customer segments in clinical, research, and pharma markets, each reinforcing the others.

7. Innovation Pipeline: Continued development in AI-powered analysis and integrated workflows to unlock deeper biological insights.

8. Product Portfolio Expansion: Launch of new multiomics products expected to drive additional growth by 2027, including single-cell and spatial analysis.

9. Financial Prudence: FY’24 revenue is projected at $4.3 billion, with non-GAAP free cash flow of $900-$950 million, amid macroeconomic challenges.

10. Margin Improvement Plan: Illumina targets a 500+ basis point improvement in operating margins by FY’27, supported by cost savings and realigned investments.

11. Software and AI: Accelerated investment in software and AI for actionable data interpretation, scaling up to meet the needs of pharma and large genomic programs.

12. Customer-Centric Models: Introduction of new business models to make sequencing technology more accessible to a broader customer base.

13. Sustainability and Scalability: Focus on sustainable growth with innovations like the NovaSeq X series, designed for scale and quality.

14. R&D Realignment: Increased investments in core sequencing technologies and the development of multiomics capabilities to maintain leadership.

15. Long-Term Vision: Illumina’s vision is to become a biology platform company deeply embedded in healthcare, transforming the understanding of biology and improving human health.

####

###

Sidebar to the Sidebar!

How did you put the 15 points in that order?  Were they merely chronological to the transcript we gave you?

[Chat GPT 4o]

I chose the order of the 15 key takeaways based on a mix of thematic importance and logical flow, rather than simply following the chronology of the transcript. 

This is how I approached it:

1. Strategic Overview First: 
1. I started with points that highlight Illumina’s strategic shift and vision, setting the stage for understanding the broader context of their initiatives (points 1-3). These foundational changes shape the rest of the discussion.
2. Operational and Financial Health: 
1. After establishing the strategic vision, I shifted the focus to concrete achievements and financial performance (points 4-6). This provides readers with a sense of how well the strategy is being executed and the impact on the company’s finances.
3. Innovation and Product Development: 
1. In the middle section, I covered innovations in technology and product portfolio expansion (points 7-10). These points are crucial as they represent the engine driving Illumina’s growth and competitiveness.
4. Customer and Market Focus: 
1. Next, I turned the focus to how Illumina plans to address its customer base and market segments (points 11-12). This felt like a natural progression from discussing products to their application and customer engagement.
5. Sustainability and R&D: 
1. Following the customer focus, I shifted attention to sustainability, scalability, and R&D realignment (points 13-14). These points emphasize how Illumina is preparing for long-term success and leadership in the industry.
6. Concluding with the Vision: 
1. Finally, I reiterated Illumina’s overarching vision (point 15), bringing the focus back to the big picture, tying all the elements together.

This structure ensures that readers first understand the strategy and vision, then see the evidence of progress, and finally grasp how Illumina plans to sustain and expand its leadership in the genomics field. I balanced thematic grouping and logical sequencing to create a cohesive narrative.

##

Thaysen (Abridged from 2023 press release)

Illumina, Inc. (NASDAQ: ILMN), a global leader in DNA sequencing and array-based technologies, announced the appointment of Jacob Thaysen, Ph.D., as Chief Executive Officer, effective September 25, 2023. Dr. Thaysen joins from Agilent Technologies, where he served as Senior Vice President and President of the Life Sciences and Applied Markets Group.

Dr. Thaysen brings extensive experience in genomics, life sciences, and technology, closely aligning with Illumina's mission. At Agilent, he drove significant revenue growth and improved operating profits, leading a division with over $4 billion in revenue and 50,000 customers. He also spearheaded the transformation of analytical labs with innovative digital ecosystems and smart instruments.

Before this role, Dr. Thaysen led Agilent's Diagnostics and Genomics Group, nearly doubling its operating profit. He holds an M.Sc. and Ph.D. in physics from the Technical University of Denmark and has a strong background in clinical diagnostics, particularly in oncology.

Dr. Thaysen, 48, will also join Illumina's Board of Directors and relocate to San Diego from Northern California.

Ai Corner: AI Reviews the FDA Book, "Reputation and Power," 2010

 In 2010, Harvard professor Daniel Carpenter published a landmark and widely-cited book, REPUTATION AND POWER, about the FDA and its control of its public perception.

For fun, here is an AI-generated lookback at the book and an update to 2024.

###

AI CORNER (Chat GPT 4o)

What is known about the book, REPUTATION AND POWER, by Carpenter, about the FDA and how it works?

Reputation and Power: Organizational Image and Pharmaceutical Regulation at the FDA by Daniel P. Carpenter is a comprehensive examination of the U.S. Food and Drug Administration (FDA) and its influence on the pharmaceutical industry. Published in 2010, the book is widely regarded as a seminal work in understanding the FDA's role in regulating drugs and protecting public health.

Here are some key points about the book:

1. Historical and Analytical Approach: Carpenter uses a combination of historical analysis, political science, and organizational theory to explore how the FDA has built and maintained its reputation as a powerful and credible regulatory agency. He examines the agency's evolution from its early days in the 20th century to its status in the modern era.

2. Reputation as Power: A central theme of the book is that the FDA's power and influence are largely derived from its reputation for scientific rigor, impartiality, and public accountability. Carpenter argues that this reputation has allowed the FDA to resist pressures from the pharmaceutical industry, politicians, and other stakeholders, enabling it to effectively regulate drug safety and efficacy.

3. Case Studies and Examples: The book is rich in case studies that illustrate how the FDA has navigated various challenges and controversies. These include the regulation of thalidomide, the introduction of new drug application processes, and the agency's response to the AIDS crisis in the 1980s. Carpenter also delves into the FDA's role in the approval of blockbuster drugs and the balancing act between drug innovation and safety.

4. Interdisciplinary Perspective: Carpenter's analysis draws on multiple disciplines, including history, sociology, political science, and law, providing a nuanced view of how the FDA operates within the broader context of U.S. government and society.

5. Impact on Policy and Research: The book has been influential in both academic and policy circles, shaping discussions on how regulatory agencies function and the role of reputation in governance. It is frequently cited in studies related to public administration, health policy, and pharmaceutical regulation.

6. Critical Reception: Reputation and Power has been praised for its thorough research and depth of analysis. Critics have noted that it provides valuable insights into the complexities of drug regulation and the importance of institutional reputation in maintaining regulatory effectiveness.

Overall, Reputation and Power is a detailed exploration of the FDA's organizational behavior and the critical role that reputation plays in its ability to regulate the pharmaceutical industry. It's an essential read for anyone interested in health policy, regulatory science, or the history and functioning of the FDA.

Hypothetically, from what you know about Carpenter and his book, how might it be updated if he updated it today in 2024

If Daniel P. Carpenter were to update Reputation and Power in 2024, several areas could potentially be expanded or revised to reflect changes and developments in the FDA's regulatory landscape over the past decade. Here’s how an updated edition might differ from the original:

1. Impact of COVID-19 on the FDA’s Reputation and Power

• Emergency Use Authorizations (EUAs): The COVID-19 pandemic introduced widespread use of EUAs, allowing for the rapid approval of vaccines, treatments, and diagnostics. Carpenter might analyze how the FDA’s handling of these authorizations impacted its reputation, both positively (e.g., rapid vaccine deployment) and negatively (e.g., controversies over treatments like hydroxychloroquine).
• Public Trust and Vaccine Hesitancy: The FDA’s role in the approval and distribution of COVID-19 vaccines could be examined in terms of public trust. The agency faced significant scrutiny, and Carpenter might explore how this affected its power and reputation, especially in the context of vaccine hesitancy and misinformation.

2. Advances in Biotechnology and Precision Medicine

• Regulation of Gene Therapy and CRISPR: The emergence of gene-editing technologies, such as CRISPR, has raised complex regulatory challenges. An updated book might delve into how the FDA has adapted its frameworks to address these innovations and how its reputation for scientific rigor has been tested in overseeing cutting-edge treatments.
• Personalized Medicine: With the rise of personalized and precision medicine, the FDA’s role in regulating genetic testing, biomarkers, and individualized treatments would be a key area of focus. Carpenter might explore how the FDA’s reputation has evolved as it grapples with these new medical paradigms.

3. Increased Political Polarization and its Impact on the FDA

• Political Pressures: In recent years, the FDA has faced increasing political pressures, particularly during the Trump administration, which sought to accelerate drug approvals and criticized the agency’s cautious approach. Carpenter might examine how these political dynamics have affected the FDA’s independence and its reputation for impartiality.
• Legislative Changes: Updates to legislation, such as the 21st Century Cures Act, which aimed to streamline drug approval processes, could be analyzed in terms of their impact on the FDA’s power and effectiveness.

4. Digital Health and AI in Drug Development

• Regulation of AI and Machine Learning: The growing use of AI in drug development and digital health technologies would be a significant new area of focus. Carpenter might explore how the FDA is navigating the regulatory challenges posed by AI-driven diagnostics, treatment planning, and digital therapeutics.
• Real-World Evidence: The integration of real-world evidence (RWE) in regulatory decision-making could be another area for exploration, looking at how the FDA’s approach to data and evidence has evolved and how this impacts its reputation and decision-making power.

5. Globalization and International Collaboration

• Global Regulatory Harmonization: With the increasing globalization of pharmaceutical development, Carpenter might examine how the FDA’s role has evolved in the context of international regulatory collaboration and competition. This could include the agency’s interactions with counterparts like the European Medicines Agency (EMA) and its influence on global drug standards.
• Supply Chain and Drug Shortages: The FDA’s response to global supply chain disruptions, particularly during the COVID-19 pandemic, and its role in addressing drug shortages could be explored in terms of how these challenges have affected its reputation and regulatory authority.

6. Public Engagement and Transparency

• Increased Demand for Transparency: The FDA has faced growing demands for greater transparency in its decision-making processes. An updated edition might explore how the agency has responded to these demands and the impact on its reputation, particularly in an era of social media and instant information dissemination.
• Patient Advocacy and Involvement: Carpenter might analyze the increasing role of patient advocacy groups in shaping FDA policy and how this has influenced the agency’s power dynamics and decision-making processes.

7. Emerging Controversies and Scandals

• Recent Controversies: Any significant controversies or scandals involving the FDA in recent years, such as the approval of Alzheimer’s drug Aduhelm (aducanumab), could be analyzed in terms of how they have impacted the agency’s reputation and authority.
• Drug Pricing and Access: The FDA’s role in the broader debates over drug pricing, access to medications, and its interactions with pharmaceutical companies could also be a focus, particularly as these issues have become increasingly contentious.

In summary, an updated Reputation and Power in 2024 might delve into the FDA’s responses to contemporary challenges, technological advances, and political pressures, examining how these have shaped the agency's reputation and influence in new ways.

Hypothetically, the head of the FDA is being interviewed (has given consent to be interviewed) on a live TV program like Nightline about Carpenter's second edition book (as above, 2024). How would she/he respond to the 7 new points?

In a live TV interview on a program like Nightline discussing Daniel Carpenter’s hypothetical second edition of Reputation and Power (2024), the head of the FDA might respond to the seven new points with a mixture of pride in the agency’s adaptability and transparency, acknowledgment of challenges, and a defense of the FDA's ongoing mission to protect public health. Here’s how the responses might unfold:

1. Impact of COVID-19 on the FDA’s Reputation and Power

Interviewer: "Dr. [Name], Carpenter's updated book discusses how the FDA's role during the COVID-19 pandemic, particularly with Emergency Use Authorizations, has impacted its reputation. How do you respond to this?" FDA Head: "The pandemic was an unprecedented global crisis, and the FDA had to balance speed with safety in ways we've never done before. While EUAs allowed us to bring critical vaccines and treatments to the public quickly, we also maintained our commitment to rigorous scientific evaluation. Yes, there were challenges, and we faced criticism, but overall, I believe our work during the pandemic has strengthened our reputation as a science-based agency capable of responding to emergencies effectively."

2. Advances in Biotechnology and Precision Medicine

Interviewer: "Carpenter also highlights how the FDA is navigating new technologies like CRISPR and personalized medicine. Can you speak to how the agency is handling these advances?" FDA Head: "The FDA is at the forefront of regulating cutting-edge technologies. With gene therapy and personalized medicine, we've developed new regulatory frameworks that prioritize safety while allowing innovation to flourish. We're working closely with industry and academia to ensure that these groundbreaking treatments reach patients without compromising the rigorous standards that have built our reputation."

3. Increased Political Polarization and its Impact on the FDA

Interviewer: "The book mentions that political pressures, especially in recent years, have tested the FDA’s independence. How do you see the agency's position in today's polarized environment?" FDA Head: "Political pressures are nothing new, but our commitment to science and public health remains unwavering. We operate with transparency and base our decisions on the best available evidence, regardless of external pressures. It's true that the political environment can be challenging, but our mission is to protect the health of Americans, and we do that by staying true to our scientific principles."

4. Digital Health and AI in Drug Development

Interviewer: "What about the FDA’s role in regulating AI and digital health technologies? Carpenter suggests this is a growing challenge for the agency." FDA Head: "AI and digital health are revolutionizing medicine, and the FDA is adapting accordingly. We've established clear guidelines for AI in healthcare, focusing on ensuring these technologies are safe, effective, and equitable. Our approach is to foster innovation while maintaining our gold standard of patient safety. We're committed to evolving with these technologies, and I believe we're on the right track."

5. Globalization and International Collaboration

Interviewer: "In the context of globalization, how has the FDA adapted its role, especially in collaboration with international regulatory bodies?" FDA Head: "Globalization has made collaboration more critical than ever. The FDA works closely with international partners to harmonize standards and ensure that our regulatory practices are aligned globally. This collaboration helps us respond to global health challenges, such as supply chain disruptions, and reinforces our leadership in setting high standards for drug safety and efficacy worldwide."

6. Public Engagement and Transparency

Interviewer: "Carpenter suggests that there is an increasing demand for transparency from the FDA. How is the agency addressing this?" FDA Head: "Transparency is a cornerstone of public trust, and we’ve made significant strides in this area. We’re more transparent than ever in our decision-making processes, providing the public with access to data and information about how and why we make our decisions. We’ve also increased our engagement with patient advocacy groups and the general public to ensure that our policies reflect the needs and concerns of those we serve."

7. Emerging Controversies and Scandals

Interviewer: "Finally, the book discusses recent controversies, such as the approval of certain drugs that have sparked debate. How does the FDA navigate these challenges?" FDA Head: "Controversies are part of the nature of regulating complex and life-changing products. The FDA's role is to make the best possible decisions based on the evidence at hand, even when those decisions are difficult or unpopular. We stand by our processes, which are designed to be rigorous and impartial. When controversies arise, we address them with transparency, open communication, and a willingness to learn and improve. Our goal is always to protect and promote public health."

In summary, the FDA head would likely emphasize the agency's adaptability, commitment to scientific integrity, and ongoing efforts to maintain transparency and public trust while addressing the challenges highlighted by Carpenter. The responses would aim to reassure the public and stakeholders that the FDA remains a vigilant, science-driven, and resilient institution.

Decibio's Cool Free Stuff: Here, Quarterly Update on Digital Health, AI

Decibio provides industry-leading reports on sectors like genomics or digital health.  In addition, they provide significant open-access resourecs like their new blogs on Linked In.  

See their Q2 update for digital health on Linked In.

https://www.linkedin.com/pulse/digital-health-informatics-q2-2024-update-decibio-ydagc/

Hofmarcher's Paper on Value of Precision Medicine: Lung Cancer (2023)

Steven Haken is great for drawing attention to important recent papers.  This week, he also flagged Hofmarcher et al. (2023), a excellent paper on the value created by precision medicine, case in point, non small cell lung cancer (NSCLC).

Find it open access here:

https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1119506/full

##

• Pair Hofmarcher 2023, with Bogdan et al. 2024, Clinical Utility of NGS Panel...advanced solid tumors; open access here, and covered in July at Precision Medicine Online by Alison Kanski, here.

##

AI Corner

Chat GPT 

Here are five key takeaway pointson the value of precision medicine (PM) in non-small cell lung cancer (NSCLC), based on the Hofmarcher 2023 paper:

1. Survival Benefits of Precision Medicine: The study highlights the significant improvement in survival rates with the use of multigene testing in advanced non-small cell lung cancer (aNSCLC). Compared to no testing, the five-year survival rate increased dramatically from 2% to 13-19% with multigene testing, demonstrating the life-extending potential of precision medicine when applied to genomic testing of each patient's cancer​.

2. Reduction in Treatment-Related Adverse Events: The paper underscores that multigene testing not only improves survival but also reduces the incidence of treatment-related adverse events (AEs). With multigene testing, the occurrence of AEs dropped by up to 72% in the first year, which enhances the overall quality of life for patients undergoing cancer treatment​.

3. Cost-Effectiveness of Multigene Testing: Although multigene testing initially increases healthcare costs due to the higher prices of newer targeted therapies and the cost of the tests themselves, these are partially offset by reductions in other medical expenses, such as the treatment of adverse events and end-of-life care. This suggests that while the upfront costs are higher, the long-term benefits of more accurate and effective treatment provide substantial value​.

4. Global Variability in Outcomes: The study shows that the benefits of precision medicine are not uniform across all regions. For example, East Asian countries, where there is a higher prevalence of targetable mutations like EGFR, saw the most significant improvements in survival rates. This indicates the importance of tailoring precision medicine strategies to the genetic profiles of different populations​.

5. Broader Societal Impact: Beyond direct healthcare costs, the study also considers the societal benefits of precision medicine, such as reduced non-healthcare costs (e.g., sick leave and disability pensions) due to prolonged survival and better quality of life. These factors are crucial in evaluating the full impact of precision medicine, making a compelling case for its broader adoption​.

These points emphasize the clinical and economic value of precision medicine in NSCLC, reinforcing its importance in modern oncology practice.

Denis Horgan's Paper on the European LDT Mess Caused by New Regulations

 Last week, I cited the Horgan 2024 paper on the gap between medical guidelines and payor policy (here).

This week, at Linked In, Steven Haken flagged a 2022 paper -also by Horgan et al - that's equally timely (here).

The paper is, "The gaps between the new EU legislation on in vitro diagnostics, and the on-the-ground reality." (Clin Chem Lab Med, 2022, 61;224.)   You'd be excused for having leafed past it in 2022, but now in 2024 with the FDA LDT tsunami, it's acutely timeline reading.

Open access:

https://repository.ubn.ru.nl//bitstream/handle/2066/290872/290872.pdf

  

AI Corner

Summary by Chat GPT.

Here are five key takeaway points about the 2022 Euro paper on the EU In Vitro Diagnostic Regulation (IVDR), which is now highly relevant given the new 2024 FDA regulations on lab-developed tests (LDTs) in the USA:

1. Regulatory Challenges and Delays: The paper highlights significant regulatory challenges with the implementation of the IVDR, including delays in processing approvals for in vitro diagnostics (IVDs). These delays, caused by insufficient infrastructure and the limited number of notified bodies (NBs), have led to a backlog in approvals and pose a risk to the continuous supply of essential diagnostic tests. The 2024 FDA regulations on LDTs in the USA may face similar hurdles if the regulatory framework is not adequately prepared​.

2. Impact on Laboratory-Developed Tests (LDTs): One of the critical concerns raised in the paper is the impact of the IVDR on LDTs, which play a vital role in personalized medicine and rare disease diagnostics. The new stringent requirements under IVDR may lead to the discontinuation of essential LDTs, as they become commercially unviable under the new regulatory framework. This scenario is directly relevant to the USA's experience with the FDA's new LDT regulations​.

3. Innovation at Risk: The paper discusses the potential stifling of innovation due to the IVDR's rigid regulatory requirements. The uncertainty and complexity of the new rules could discourage the development of novel diagnostics, particularly in niche areas like molecular oncology and genetic testing. This concern is equally applicable to the USA, where the new FDA regulations might hinder the progress of cutting-edge diagnostic technologies​.

4. Inconsistent National Implementation: The IVDR has been inconsistently implemented across EU member states, leading to disparities in regulatory enforcement and patient access to diagnostics. The lack of uniformity in regulatory practices across the EU has created confusion and uncertainty. As the FDA rolls out its new LDT regulations, the USA could face similar issues if there is a lack of coordination and standardization across states​.

5. Recommendations for Improvement: The paper emphasizes the need for greater collaboration between regulators, manufacturers, and the diagnostic community to address the gaps in the IVDR. It calls for increased capacity for NBs, streamlined certification processes, and more transparent guidance to ensure the continued availability and innovation of diagnostics. These recommendations are also relevant to the FDA's approach to regulating LDTs in the USA, highlighting the importance of stakeholder engagement and regulatory clarity​.

These points provide a comprehensive overview of the critical insights from the 2022 paper, which now serves as a valuable reference for understanding the potential challenges and opportunities posed by the new FDA regulations on LDTs in the USA

##

Steven Haken also flagged an important review by Hofmarcher et al, 2023, on the value of precision medicine in NSCLC - here, here.

A New Article on Healthcare Policy in a Post-Chevron World (Includes ACLA FDA LDT Lawsuit)

There was no shortage of reactions in the healthcare policy world, to the over-ruling of the "Chevron" principal in June.  (This blog here, Tennessee v Becerrra here, JAMA here, NEJM here, policy associations here, here.)

A new essay on August 8 at the center-right think tank, American Action Forum.  Find it here:

https://www.americanactionforum.org/insight/post-chevron-impacts-on-health-three-case-studies/

The article discusses post-Chevron jurisprudence as it may apply to three cases:

• How FDA defines "same drug."  (See skirmishes over Lymryz and Xywav for narcolepsy).
• What is a medical device?  Yes, a discussion of ACLA vs FDA over LDTs.
• Medicare, Medicaid, and places where statute is "silent."  One discussion area here is CMS, AMA, and RVU's.

The article was an easy read and a worthwhile one.  Here's the closing paragraph.

The Supreme Court’s decision to overturn Chevron deference in Loper Bright v. Raimondo marks a major shift in regulatory oversight within the health care sector. By requiring courts to independently interpret ambiguous statutes, this ruling affects key areas such as drug and device definitions and reimbursement determinations. As a result, Congress now faces the imperative to provide clear legislative guidance and potentially even expand agency authority in technically complex domains to foster effective health care regulation. The outcomes of ongoing legal battles will further shape the future landscape of health care policy and regulation after Chevron.

 

Hansson et al 2022: A Remarkable "Case Study" for Anyone Accelerating Progress in Precision Medicine

Header:  We often complain about the path to clinical adoption in precisoin medicine.   Alzheimer's biomarkers are booming with large scale, powerful, accurate studies.  Perhaps in no small part to a crystal-clear project for the future, laid out in 2022 by Hansson et al.

###

One of the most  active and fast-moving areas of diagnostics is Alzheimer's disease.  There is a boom in large, well-designed studies on the new generations of proteomic tests that are reaching the Holy Grail of accurate-plasma based diagnoses.  Such tests promise to supercede costly and uncommon PET and CSF tests.

See a current "most read" Palmqvist paper in JAMA on the accuracy of phos-Tau-217.  See a detailed press release from the international Alzheimer's meeting last month.  The documents refer back to a 2022  appropriate use criteria (AUC) for plasma biomarkers in dementia - Hansson et al.  These 2022 AUC are perhaps a little dated now, only in that so much highly positive confirmatory research has appeared in 2023 and 2024  -- making their 2022 reservations less necessary.  

Here's my point.  It's well known that new technologies often hear a wall, or at least high barriers, to implementation.  Horgan et al. 2024 are the best recent paper on "bridging the gap" to the clinic (my blog here).

Hansson et al. 2022 is more than one report - it's a case study

Reading it carefully, I realized that Hansson et al., the AUC on blood biomarkers, is more than just one good report.   It's a rare example of a "master class" in assessing the present and laying out a roadmap for the near future.  

Both a Project and a Paradigm Approach

The Hansson et al. paper is in the first place, a significant contribution to the field of blood-based biomarkers (BBMs) in Alzheimer's disease (AD). However, its value extends far beyond being just another set of specific Appropriate Use Criteria (AUC) for one scenario. From A to Z, it serves as a paradigm of forward-thinking in medical diagnostics, offering not only a thorough and up-to-date review of the current state of BBMs but also projecting into the future with well-justified and creative recommendations for clinical use and research directions.

The authors have provided a comprehensive roadmap that identifies the gaps in current knowledge - that's hard enough.  They then have thought-through and prospoed detailed future steps to fill these gaps, making it an essential case study for anyone involved in the implementation of new medical technologies. The authors emphasize the need for continued research in areas such as the robustness of BBMs across diverse populations, the development of new assays, and the integration of BBMs into clinical trials. They also highlight the importance of using BBMs not just for diagnosis but as tools to accelerate the development and validation of new treatments.  Much of this is happening in 2023, 2024, perhaps aided by the clarity of planning in 2022.

Health Policy to Commercialization

For those in the fields of diagnostics, commercialization, and health policy—areas often criticized for their slow pace—this paper offers a blueprint for how to approach the rapid implementation of new technologies. By systematically addressing current limitations and providing a clear path forward, Hansson et al. exemplify how to bridge the gap between innovation and clinical application. This is a model not just for Alzheimer’s disease but for the broader medical community looking to integrate novel diagnostics into routine care.

I was so favorably struck by this as a "case study" independent of its particular topic, because I have worked in strategy consulting for 20 years.  Every work phase - assessing the present, enumerating the gap analysis, and then projecting multiple lines of work into the future - is hard.  Strategists and policymakers should study Hansson et al. as a template for advancing the adoption of emerging technologies across various fields of medicine.   And getting over the cliche' that it takes 10 or 15 years to bring innovation to the clinic.

 Update 0812.  While new articles appear constantly, Schindler et al. is a new one, finding P217Tau is the best of 6 markers.  It's covered in 360Dx and published at MedRxiv pending publication in Alzheimer & Dementia (journal).  Compare also Palmqvist et al. July 28 in JAMA.
__

Illustration and some text assistance, Chat GPT 4o.