Amyloid and other battles from statistics readers

The first opinion is a statistical platform for large-scale articles of interesting, lighting, and provocative articles on life sciences written by biotechnology insiders, healthcare workers, researchers and more.

To encourage robust and honest discussion of the issues raised in the first opinion essay, STAT publishes selected letters to editors received accordingly. You can send a letter to the editor hereor find the submission form at the end of your first opinion essay.

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“How the Amyloid Mafia took over research into Alzheimer's Disease“Charles Pills

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Dennis Serco has it Already responded In this article. He was too kind. Pillar describes the advantages of Leqembi as “minimum” and “minimum”. My wife has been at Rekanemab since August 2023. She remains an active and happy 59 year old. Lecanemab has given us more years. That's not “minimum” or “minimum” for me. Pillars allow us to have “tragic and rare cases of young people featured in the media.” Two million Americans develop Alzheimer's disease before the age of 65. Perhaps the media should ignore them. Pillar is critical of the pharmaceutical company's economic motivations. However, he uses patent sensationalism to promote his book along with Monica of the “Amyloid Mafia”, “Cabal”, and “The Church of Holy Amyloid”. Hypocrisy is profound.

– Fred has him

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Finally, an incredible essay on “religious” like the enthusiasm surrounding amyloid myth! When I read this article, what surprised me was the use of the word “science” which was mentioned many times by “scientists” who were obsessed with this hypothesis, and the overwhelming rejection of it. Despite the data, I believed it. Of course, this data is the number of amyloid targeting trials that have been unsuccessful (at an enormous cost) conducted over the years! Many of them have no demonstrable clinical benefits for their patients, but they have shown some effect on the accumulation of amyloid. The main outcome should be clinical improvement in patients, both through validated equipment beyond a specific time frame compared to placebo controls and patient-reported results between the trial groups. Although biomarker observation and measurement has a role, this must be secondary to clinical improvement in patients.

– Brian Levy, Flamx Treatment Drugs

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Through thorough effort and an obsession with reproducible facts, Charles Pillar bares the characteristics of Alzheimer's research decades ago. In doing so, Pillar emphasizes a systematic crisis in a much broader sense, abandonment of scientific principles. According to philosophy of science, no journalists or so-called detectives are the ones who question scientific theory. It depends on the scientist himself. Instead, modern Alzheimer's research has cultivated supporters for the cause. The group attitude in ways like letter writing from the highest levels of academia, opinion articles from scientific magazines and mainstream outlets, cheerleaders on social media, are all 180 degrees apart in scientific inquiry mode. However, each of these is embedded in the fabric of modern Alzheimer's disease research.

Thoughtful, science-oriented consumers can only wonder whether the data presented to them is part of a broader strategy driven by secondary benefits. Pillar effectively works as a scientist. He is challenging Orthodox and provides transparency to the public, who are largely underwriting the effort. It reads as Clarion's call to medicine for a return to fundamental challenges, rather than a promotion of one's own observations, which is very important to scientific methods and scientific advancements. If medicine flourished through salesmanship and advocacy, questionable data and confirmation biases would find a way to a highly influential journal. The only question is the scope. In the meantime, Alzheimer's patients and their families continue to be victimized by false hopes, sometimes paying for it along with their own pocketbooks and their lives.

– Rudy Castellani of Northwestern University's Feinberg School of Medicine

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Charles Piller's recent views on STAT raise important questions about the mechanical role of amyloid and highlight issues related to limiting access to clinical trial data. Both have a major impact on research, regulation and treatment. Two meta-analyses of amyloid-targeted drugs (British Medical Journal2021; Alzheimer's disease and dementia2024), I showed a small but statistically significant effect of amyloid removal on cognitive decline, only in aggregated treatment group data. However, such group-level analyses may obscure the true mechanical link between amyloid reduction and cognitive outcomes. Could participants who experienced the greatest amyloid reduction have seen the greatest cognitive benefits? Or can participants with minimal amyloid experience the greatest benefits regardless of the amount removed?

Using already existing data to answer this type of mechanistic question, would be strong evidence of the causal role of amyloid. Skeptic biologists have proposed alternative mechanisms for the effects of anti-amyloid agents, suggesting that the effects on cognitive decline may be attributed to immunological effects rather than amyloid removal. Masu. Meanwhile, skeptical methodologists assume that even minor side effects may not blind caregivers, and distorted test results support treatment. Access to individual-level data allows us to test the true mechanisms behind the cognitive effects of these agents. Demonstrating the causal role of amyloid in treatment is more than just an academic exercise. Amyloid removal is used as a proxy for the trial as the basis for accelerated approval of adcanumab and lecanemab. Establishing a strong link between the reduction in amyloid and the benefits of cognitive is essential to assess whether amyloid is in fact a valid surrogate for cognition. If amyloid removal promotes cognitive changes, this evidence can be used to advocate for full approval of future agents based solely on biomarker changes.

On the other hand, if amyloid is not a critical driver, acceleration approval based on reduced amyloid is not guaranteed. Excellent mechanical questions continue to fuel the controversy over anti-amyloid therapy. But the answer may be within our reach. The required data are already present in individual-level results from recent trials of adcanumab, lecanemab, and donanemab, if they can be made available to researchers with the necessary expertise.

– Sarah Ackley of Brown University School of Public Health

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“What my sister's life and death taught me about NIHAriel reinishes

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The similarities between this experience and myself are creepy. Ten years ago, in the early days of Car-T, I was also at the National Cancer Institute to treat my siblings. The 12-year-old brother Samuel was re-run/sailing away everything. For months, my family and I crossed the street from the NIH to the pediatric wing, a children's accommodation in 10, in which Sam's hospital room is located. The constant critical headlines are heartbreaking and angry with the equal parts, and likewise do not reflect any NIH I know at all. Thank you, Dr. Reinish, for submitting this article. What a lovely tribute, it captures the critical yet missing perspective of me still struggling with words.

– Claire Wetzel, American Society of Hematology

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As a doctor for 35 years and now a patient with metastatic kidney cancer, I have experienced two aspects of my life. As an MD, I have always introduced hundreds of people to NIH, MD Anderson, and more, often prolonging my life and reducing my suffering. As a patient, my treatment has kept me alive and I have been suppressing symptoms for over 8 years. These institutions are very necessary and give hope to the desperate. Let's continue to help our anxiety and desperation with their research and treatment. Their staff are one of the best people and are trying to heal despair. Saving money by reducing these institutions is cruel and ignorant.

– Alberto Garcia Romeu retired internal medicine physics

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“Misguided belief in health policy cult governmentCharles M. Silver, David A. Heyman, Michael F. Cannon.

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Charles M. Silver, David A. Hyman and Michael F. Cannon urged regulators to robustly enforce existing medical price transparency rules and laws. '' criticizes patients' rights and vision. However, the authors want to “treat healthcare like the ordinary services people buy and sell through normal market mechanisms.” They miss the most basic market mechanisms that consumers need to shop to seek profits from affordable care and competition. Price transparency is the keystone of the free market health care system of all of us who are looking for and deserves proper government enforcement.

– Cynthia Fisher, PatientRightsadvocate.org

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“Will PBM reforms prevent pharmacies from closing?”

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The authors stated, “Today, the largest portion of traditional pharmacies' prescription drug revenue is related to insurance, with three largest PBMs paying nearly 80% of all prescriptions in the US. A network of pharmacies that provide savings for health plans supported by will ultimately come from the revenue of the pharmacies. The payer is either a US for-profit organization or a single payer government agency in France or the UK. Whether or not, trying to secure the best price for prescription drugs hurts most retail pharmacies.”

However, the dynamics of single payer systems (such as France and the UK) are made up of different ways. There, the government sets reimbursement rates and often includes fixed dispensing fees to protect the viability of pharmacies. Both models aim to ensure the highest price for drugs, but in a single payer system, negotiation and reimbursement mechanisms usually ensure cost reductions and pharmacies remain solvent. It is designed. In contrast, the fragmented nature of the US system and its reliance on private insurance companies and PBMs can make pharmacies more vulnerable to pressure.

– Tom Mchugh, Optum Rx