The Rise and Fall of Paxlovid - HIV and ID Observations HIV and ID Observations

APRIL 8TH, 2024

The Rise and Fall of Paxlovid

It’s been quite the ride for our “preferred” outpatient therapy for COVID-19, nirmatrelvir with ritonavir — much better known as Paxlovid, so allow me the license to use the licensed name.

Let’s recap the astonishing success and now failure of this intervention (some dates approximate):

1. December 2021, the FDA issued an Emergency Use Authorization for Paxlovid:  Action is based on the efficacy shown in the EPIC-HR study of high-risk outpatients with COVID-19. Compared to those receiving placebo, Paxlovid-treated participants had an 89% reduction in risk of hospitalization or death. Exciting times.
2. Early 2022, that annoying rebound thing. No, it’s never been quite clear whether Paxlovid caused rebounds, or just didn’t prevent them, or whether it just happened in those people for whom COVID-19 illness lasted longer than the treatment’s 5 days (a large group!), but regardless — it was a major disincentive to clinicians and providers alike.
3. December 2022, the protocol for the EPIC-SR in “standard risk” outpatients was amended to increase the sample size. Though an interim analysis suggested such patients would benefit from treatment, the change in sample size signaled that such a benefit observed in this analysis might be small — or nonexistent.
4. August 2023, the negative results of EPIC-SR were posted on clinicaltrials.gov. Yes, these results have been in the public domain since last summer.
5. Last week, the disappointing EPIC-SR results appeared in the New England Journal of Medicine. This is the primary endpoint (from the Research Summary):

It wasn’t all bad news for treatment: Risks of severe outcomes (hospitalizations, ICU admissions, or deaths) were very low overall — hooray! — and numerically lower in the Paxlovid group; medical visits were significantly lower as well. However, as anyone who has taken Paxlovid can attest, the taste alone could have made study participants aware that they were already on treatment, hence discouraging them from seeking further evaluations.

What about rebounds? From these limited data, it appeared there was no difference:

By day 14, viral load rebound had occurred in 4.3% of the participants in the nirmatrelvir–ritonavir group and 4.1% of those in the placebo group; symptom rebound occurred in 11.4% and 16.1%, respectively, and symptom and viral load rebound together occurred in 1.2% and 0.5%, respectively.

So where does that leave us right now? There’s no doubt that the EPIC-SR data further confirm that this treatment has many limitations. Here’s a teaching slide I recently made:

But before we completely abandon Paxlovid for outpatient use, let’s remember that our options for outpatient treatment of COVID-19 remain highly limited. Furthermore, people at high risk for adverse outcomes still require hospitalization and still die from this infection — as they do from other viral respiratory illnesses. As a result, based on EPIC-HR, these EPIC-SR data, and the observational studies, I’d still recommend treatment for this very high-risk group.

The Rise and Fall of Paxlovid - HIV and ID Observations HIV and ID Observations

A summary of Digital Health Space, my other Blog

Title: Revolutionizing Healthcare: Exploring the Digital Health Space

Introduction:

In recent years, the healthcare industry has witnessed a dramatic transformation with the advent of digital health technologies. From wearable devices and telemedicine to health tracking apps and artificial intelligence, the digital health space is revolutionizing the way we approach healthcare. In this blog, we will delve into the exciting developments and key trends shaping the digital health landscape.

Wearable Devices and Remote Monitoring:

Wearable devices, such as fitness trackers, smartwatches, and biosensors, have become increasingly popular in the digital health space. These devices enable individuals to monitor their health and fitness levels in real-time, providing valuable insights into their well-being. Remote monitoring has also gained traction, allowing healthcare professionals to remotely track patients' vital signs, detect abnormalities, and intervene when necessary. We will explore the impact of wearable devices and remote monitoring on preventive care and personalized medicine.

Telemedicine and Virtual Care:

Telemedicine has emerged as a game-changer, especially in the wake of the COVID-19 pandemic. Virtual consultations and remote healthcare services have become the new norm, providing convenient and accessible care to patients. We will discuss the benefits and challenges of telemedicine, including improved access to healthcare, reduced costs, and potential limitations, such as the digital divide and privacy concerns.

Health Tracking Apps and Personalized Medicine:

Mobile applications dedicated to health tracking and wellness have gained immense popularity. These apps allow users to monitor their diet, exercise, sleep patterns, mental health, and more. Furthermore, they facilitate the collection of real-world data, which can be leveraged for research and development of personalized medicine. We will explore the potential of health tracking apps in promoting preventive care, disease management, and individualized treatment plans.

Artificial Intelligence and Machine Learning:

Artificial intelligence (AI) and machine learning (ML) are driving significant advancements in the digital health space. AI algorithms can analyze vast amounts of medical data, identify patterns, and assist in diagnosis, prognosis, and treatment decisions. ML models can predict disease outcomes, identify high-risk patients, and optimize healthcare workflows. We will delve into the transformative potential of AI and ML in enhancing patient care, drug discovery, and population health management.

Data Security and Privacy:

With the proliferation of digital health technologies comes the need to address data security and privacy concerns. The collection and storage of sensitive health information raise ethical and legal implications. We will discuss the importance of robust data protection measures, compliance with regulations such as HIPAA, and the role of blockchain technology in ensuring secure sharing and access to health data.

Future Trends and Challenges:

Finally, we will explore emerging trends and challenges in the digital health space. This includes the integration of genomics and precision medicine, the rise of health-focused wearables, the role of big data analytics, the impact of Internet of Medical Things (IoMT), and the need for regulatory frameworks to keep pace with technological advancements.

Conclusion:

The digital health space is transforming healthcare delivery, empowering individuals, and improving patient outcomes. From wearable devices to AI-driven solutions, the possibilities are endless. In this blog, we have provided an overview of the key aspects of the digital health space, highlighting its potential to revolutionize the healthcare industry. As technology continues to evolve, it is crucial to navigate the ethical, legal, and practical challenges to harness the full potential of digital health for the benefit of individuals and society as a whole.

health train express

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Health Train Express is a popular healthcare blog that provides insightful articles, news, and analysis on various topics related to healthcare. The blog covers a wide range of subjects, including healthcare policy, medical technology, patient care, healthcare economics, and industry trends. It aims to keep healthcare professionals, policymakers, and the general public informed about the latest developments and issues in the healthcare field.

The blog's content is written by experienced healthcare professionals, researchers, and experts in the industry. They offer their expertise and perspectives on current healthcare issues, providing valuable insights and thought-provoking discussions.

Some common topics covered on Health Train Express may include:

Healthcare Policy and Reform: The blog explores the impact of healthcare policies and reforms on the industry and discusses the challenges and opportunities they present.

Medical Technology and Innovations: Health Train Express highlights the latest advancements in medical technology, such as telemedicine, robotics, artificial intelligence, and wearable devices, and examines their potential to improve patient care and outcomes.

Patient Care and Safety: The blog emphasizes the importance of patient-centered care, sharing best practices, and discussing strategies to enhance patient safety and quality of care.

Healthcare Economics and Finance: Health Train Express delves into the economic aspects of healthcare, including healthcare financing, reimbursement models, cost containment, and the impact of healthcare expenditures on the overall economy.

Healthcare Delivery and Organization: The blog explores different healthcare delivery models, such as accountable care organizations (ACOs) and patient-centered medical homes (PCMHs), and analyzes their effectiveness in improving care coordination and population health.

Healthcare Technology Adoption: Health Train Express examines the challenges and benefits of adopting new technologies in healthcare settings, addressing issues such as interoperability, data privacy, and the integration of electronic health records (EHRs).

Public Health and Health Promotion: The blog covers public health initiatives, preventive medicine, disease surveillance, and community health programs aimed at improving population health and reducing healthcare disparities.

Health Train Express strives to provide evidence-based information and foster constructive discussions on important healthcare topics. It serves as a valuable resource for healthcare professionals, policymakers, students, and anyone interested in staying informed about the latest developments in the healthcare industry.

Health Justice Monitor – Medicare Advantage: How Private Insurers Exploit Medicare

Medicare Advantage: How Private Insurers Exploit Medicare

An excellent interview with the former head of CMS, which oversees Medicare, lays out how Medicare Advantage insurers manipulate costs and quality, grabbing massive profits from public funds with no clinical benefits for patients. He wants its growth stopped and its problems fixed.

March 2, 2024

Obama CMS Chief: Medicare Advantage Plans Game the System
MedPage Today
March 1, 2024
by Cheryl Clark

(HJM bolding)

Donald Berwick, MD, MPP was the administrator of the Centers for Medicare & Medicaid Services (CMS) during the Obama administration and is president emeritus and senior fellow at the Institute for Healthcare Improvement.

MedPage Today interviewed him about his concerns that too many Medicare beneficiaries are being misled into enrolling into private Medicare Advantage plans, which he said should be slowed or stopped because the plans have gamed the system to receive billions more than what is spent for traditional Medicare beneficiaries’ care.

Cheryl Clark: Medicare Advantage, or MA, plan enrollment has been growing so fast; 52% of beneficiaries are now enrolled, with 60%, 70% projected in a few years. … I hear a traditional Medicare patient can’t find a primary care provider in some parts of the country because all the doctors are locked in MA.

Will every eligible beneficiary have no choice but Medicare Advantage? … And is that a good idea, given your concern about how MA plans have gamed the system to get more money?

Berwick: I think MA growth should be slowed or stopped, at least until we end the extraordinarily high subsidies for MA plans, which are unfair to traditional Medicare and burdensome to the public treasury and many beneficiaries. Many beneficiaries can get better care for themselves and greater choice through traditional Medicare, and that option should remain robust and available. …

Clark: Let’s talk about … how MA plans are overpaid. They’ll receive $88 billion more this year than what is spent for the same patients in traditional Medicare. That is a huge concern. But I don’t think it’s clear to readers how the plans are paid, that it’s not necessarily for better care.

Berwick: It’s a really complicated process and, I must say, possibly intentionally so, because I think it serves the interests of the private plans to have payment rules that are so hard to understand.

What the benchmark begins with is a comparison to the traditional Medicare population: people like me, who are in fee-for-service, traditional Medicare. There’s a calculation of the cost of my expected care… based on demographics and county, because care is more expensive in some counties than others. ..

Most importantly, the amount that an MA plan gets is adjusted for the number of codes for diagnoses that a beneficiary has, like atrial fibrillation or diabetes, and for each code the plan gets more money, supposedly reflecting the additional care the patient needs. And that’s where the gaming nonsense occurs. Many codes have no real implications at all for evidence-based clinical care, but they carry with them extra payment nonetheless. The coding system has created opportunities for these plans to upcode. They comb through patients’ histories and try to stuff in as many diagnoses as they possibly can, even if they have nothing to do with the care of the patient.

Clark: During a January 12 MedPAC meeting, one of the commissioners mentioned that the plans were paying doctors to go through each record and look for anything that could add to capitated payment.

Berwick: That’s right. That’s worth a bit of a dive. There are three ways health plans manipulate the coding processes. What they’re after is what you said, which is, comb through the patient’s record, send a nurse into the patient’s home to find additional diagnoses. Sometimes, in some of the MA systems, they actually pay the doctor to code using a software package the insurance plan gives to the doctor. …

And a third and now much more popular, certainly to insurers, is to simply employ the doctors. Once the doctor is an employee, then you can set up all sorts of ways to accelerate upcoding. You can train the doctors or give them incentives to upcode. And now, the largest employer of doctors is a health plan, an MA plan. In this third tactic, the MA plan gets the benefit of all the upcoding, and that’s part of the game they are playing.

Now rather than lower costs, MA has much higher costs — something to the tune of $80 billion a year. Other estimates are as high as $120 billion. For the most part, that money doesn’t represent the needs of the patient. In fact, we know that beneficiaries in MA are, on the whole, healthier than those in traditional Medicare, and ought to cost less, not more.

It’s just a transfer of money to the private sector. Most of that goes to profit for the plan, or for stock buybacks, high compensation for plan executives, …

And further, because of all the gaming of diagnoses, it gets really, really hard to compare quality of care and outcomes between Medicare Advantage and traditional Medicare patients.

Clark: You’ve said you think MA plans should be slowed or stopped. How do you think that should happen?

Berwick: … We need to stop these abuses as quickly as possible. And we need simultaneously to improve the attractiveness of traditional Medicare, which is what tens of millions of Americans still have. …

Clark: [The MedPAC director] said that for chronic conditions, there is evidence that MA plans deliver better care.

Berwick: … There is some information that suggests that for some conditions, some MA plans do offer better chronic care but that’s a really hard statement to prove, and it certainly doesn’t apply across the board. And remember: MA plans are upcoding patients, so they make the patients look sicker, so when you try to assess outcomes, adjusted for severity, you’ve already fallen into the hole created by this game in which you’re no longer comparing apples to apples….

Clark: You spoke of the quality bonus program, which is a factor in MA capitated payments. How does it work?

Berwick: … the quality bonus system needs a big overhaul. It now has been pretty thoroughly gamed by MA plans. They focus on the scored variables, not overall better care – “teaching to the test,” as it were. Something like 80% of plans now are four-star or five-star on a five-star scale. I call that the “Lake Wobegon” effect, where everybody is above average. It’s a tricky system with unintended consequences. For example, when you’re treating a very distressed population with limited resources and there are barriers to treatment, you don’t want to take money away from the very organizations that need more money because their populations are harder to treat. But it has just become too easy to get a high score. …

The rating system is flawed and amounts to a check off the box analysis.

Other restriction for care require prior authoization for certain expensive tests, or imaging (MRI), and durable medical equipment (DME) for which they have strict limited vendors

On the other hand Advantage plans provide free transportion to senior citizens, many of which have no transportation

Caveat emptor---Let the buyer beware

 Comment by: Jim Kahn

Don Berwick is a hero for many of us, for his decades of foundational work in quality of medical care and his forthright criticism of Medicare Advantage, the private insurance arm of Medicare.

In this interview, he reviews how insurers thoroughly game the MA systems for payment and quality rating, yielding tens of billions in excess payments with no evidence of clinical benefit. Indeed, there is evidence of impaired access to care for the sickest and poorest, and financial harm to providers who treat the most needy.

You should read the entire interview, it’s wide-ranging and informative, and only a little technical. We’ll be writing more on Medicare Advantage issues in coming days.

As Dr. Berwick points out, traditional Medicare – in which the government pays providers directly – works more efficiently to assure access to care. But it needs some coverage gaps closed. That is, we need an improved traditional Medicare. Then we could extend that to everyone. That’s an “improved Medicare for All”. Aka: single payer.

About the Commentator, Jim Kahn

Jim (James G.) Kahn, MD, MPH (editor) is an Emeritus Professor of Health Policy, Epidemiology, and Global Health at the University of California, San Francisco. His work focuses on the cost and effectiveness of prevention and treatment interventions in low and middle income countries, and on single payer economics in the U.S. He has studied, advocated, and educated on single payer since the 1994 campaign for Prop 186 in California, including two years as chair of Physicians for a National Health Program California.

Health Justice Monitor – Medicare Advantage: How Private Insurers Exploit Medicare

Senators’ Latest Attempt to Enrich Big Pharma Must Not Prevail - The American Prospect

The Revolving Door Project, a Prospect partner, scrutinizes the executive branch and presidential power.

Sadly, the American patent system has drifted far from that ideal, especially in the realm of pharmaceuticals. Americans pay on average more than twice as much for prescription drugs than people in other high-income economies, while U.S.-based pharmaceutical companies are twice as profitable as companies in other sectors. The impact of high drug prices is keenly felt in Americans’ daily lives: 80 percent of adults describe drug costs as unreasonably high.

Sadly, the American patent system has drifted far from that ideal, especially in the realm of pharmaceuticals. Americans pay on average more than twice as much for prescription drugs than people in other high-income economies, while U.S.-based pharmaceutical companies are twice as profitable as companies in other sectors. The impact of high drug prices is keenly felt in Americans’ daily lives: 80 percent of adults describe drug costs as unreasonably high.

The first of these bills, PERA, would enable companies to patent things that have been off-limits for centuries because humans did not and could not invent them—namely, products of nature, natural laws, and abstract ideas. If PERA becomes law, it would allow companies to patent isolated human genes, correlations between specific genes and health conditions, and methods of using those correlations to give patients information about their health that could be critical to improving or saving their lives.

Patenting isolated genes poses a grave threat to the health and safety of the American population. Before the Supreme Court confirmed in 2013 that existing law prohibits such patents, one company, Myriad Genetics, had patents on isolated gene sequences, which are highly correlated with breast, ovarian, and prostate cancers. Myriad used its patents to prevent other laboratories from developing or offering their own tests, even those that were more comprehensive and accurate. The day the Supreme Court issued its decision in Association for Molecular Pathology v. Myriad Genetics, Inc., everything changed. Five different laboratories announced they would provide tests for those mutations for far less than Myriad had charged. Prices quickly dropped from $4,000 to between $1,000 and $2,300 per test. By bringing patents like Myriad’s back to life, PERA would also bring back exorbitant prices for diagnostic genetic tests, including those that have been critical to the fight against COVID-19.

The second bill, PREVAIL, which is co-sponsored by Senate Judiciary Committee Chair Sen. Dick Durbin (D-IL), would enable companies to keep patents that cover things that were already known or obvious to scientists in the relevant field. Currently, patents are typically required to be original, non-obvious findings—in line with the Constitution’s language about “Progress.” Coons is also engaged with the House Judiciary Subcommittee on Intellectual Property on a separate version, which aims to impose additional restrictions on procedures for challenging these problematic patents.

The currently proposed bill would protect these wrongly granted patents by restricting access to the only mechanism the public has for challenging them outside of federal court: the Patent Trial and Appeal Board (PTAB). Congress deliberately created the PTAB to make it easier, cheaper, and more efficient to invalidate wrongly granted patents. And it has been a success: 46 percent of patents challenged at the PTAB have been found invalid in whole or part.

Patents are meant to encourage actual innovation, not monster corporate profits.

That’s why the Biden administration is pushing on multiple fronts to lower drug prices. However, the administration has run into some roadblocks in the form of the pharmaceutical industry’s loyal defenders in Congress. In the Senate, two industry stalwarts, Chris Coons (D-DE) and Thom Tillis (R-NC)—both of whom were among the biggest recipients of pharma checks in Congress during their last election cycle—are lead signatories to the Biotechnology Innovation Organization–endorsed letter opposing the National Institute of Standards and Technology’s new draft guidance framework, which outlines potential uses of march-in rights to reduce prescription drug prices.

Worse, Coons and Tillis have introduced legislation that would fuel Big Pharma’s abuse of the patent system and exacerbate the drug-pricing crisis in this country. Recently, they’ve informed their colleagues that their latest attempt to push forward the misleadingly named Patent Eligibility Restoration Act (PERA) and Promoting and Respecting Economically Vital American Innovation Leadership (PREVAIL) Act has enough steam to make it out of committee. Enacting these bills, alone or together, would richly reward pharmaceutical companies for their donations, and encourage them to give more to support Coons and Tillis’s re-election bids in 2026.

The first of these bills, PERA, would enable companies to patent things that have been off-limits for centuries because humans did not and could not invent them—namely, products of nature, natural laws, and abstract ideas. If PERA becomes law, it would allow companies to patent isolated human genes, correlations between specific genes and health conditions, and methods of using those correlations to give patients information about their health that could be critical to improving or saving their lives.

Patenting isolated genes poses a grave threat to the health and safety of the American population. Before the Supreme Court confirmed in 2013 that existing law prohibits such patents, one company, Myriad Genetics, had patents on isolated gene sequences, which are highly correlated with breast, ovarian, and prostate cancers. Myriad used its patents to prevent other laboratories from developing or offering their own tests, even those that were more comprehensive and accurate. The day the Supreme Court issued its decision in Association for Molecular Pathology v. Myriad Genetics, Inc., everything changed. Five different laboratories announced they would provide tests for those mutations for far less than Myriad had charged. Prices quickly dropped from $4,000 to between $1,000 and $2,300 per test. By bringing patents like Myriad’s back to life, PERA would also bring back exorbitant prices for diagnostic genetic tests, including those that have been critical to the fight against COVID-19.

The second bill, PREVAIL, which is co-sponsored by Senate Judiciary Committee Chair Sen. Dick Durbin (D-IL), would enable companies to keep patents that cover things that were already known or obvious to scientists in the relevant field. Currently, patents are typically required to be original, non-obvious findings—in line with the Constitution’s language about “Progress.” Coons is also engaged with the House Judiciary Subcommittee on Intellectual Property on a separate version, which aims to impose additional restrictions on procedures for challenging these problematic patents.

The currently proposed bill would protect these wrongly granted patents by restricting access to the only mechanism the public has for challenging them outside of federal court: the Patent Trial and Appeal Board (PTAB). Congress deliberately created the PTAB to make it easier, cheaper, and more efficient to invalidate wrongly granted patents. And it has been a success: 46 percent of patents challenged at the PTAB have been found invalid in whole or part.

Naturally, Big Pharma hates this board. Gutting government capacity with the elimination of PTAB would only allow for an explosion of wrongly granted patents, which are crucial to pharma’s ability to block competition and lock in exorbitant prices for decades.

Two of the biggest supporters of these bills are former U.S. Patent and Trademark Office (USPTO) directors David Kappos and Andrei Iancu. This is no surprise. Since leaving their roles, Kappos and Iancu have committedly opposed efforts to remodel our clearly anti-competitive patent system. What’s more, the former directors advocate loudly for changing the law while remaining silent about the corporate interests they represent. After leaving the USPTO, David Kappos joined the partnership of Cravath, Swaine & Moore, which represents Amgen, Johnson & Johnson, and Novartis, among other pharma heavyweights. Iancu is now a partner at Sullivan & Cromwell, which lists AbbVie, Bayer, and Merck among its life sciences clients. He also founded the Council for Innovation Promotion as an outfit to more systematically support the entrenchment of the current anti-competitive system.

The former directors’ current roles reveal the other primary beneficiaries of the proposed bills: law firms and lawyers. Patent litigation is big business, with costs ranging from $2 to $4 million per case on average. But recently, patent litigation rates have begun to decline sharply. Given the business they stand to lose, it’s no wonder that law firm partners are pushing for changes that would ensure more patents are granted and litigated in court. Lawyers have every right to advocate for their own interests and those of their clients. But when they do, they should be transparent about it, instead of using the veneer of their former roles in the public sector to paint their positions as anything other than advocacy on behalf of their corporate clients’ interests.

The patent system exists to promote scientific innovation to benefit the public, not to enrich private interests regardless of the merits of their scientific contributions. Yet that is precisely what PERA and PREVAIL would do by granting Big Pharma even more sweeping government monopolies and associated price-gouging power. We hope the senators who have shown their willingness to stand up to Big Pharma will stand up to their colleagues’ efforts to reward their benefactors.

Senators’ Latest Attempt to Enrich Big Pharma Must Not Prevail - The American Prospect