First Opinion is STAT’s platform for fascinating, illuminating, and provocative articles concerning the life sciences writ massive, written by biotech insiders, well being care employees, researchers, and others.
To encourage strong, good-faith dialogue about points raised in First Opinion essays, STAT publishes chosen Letters to the Editor obtained in response to them. You may submit a Letter to the Editor right here, or discover the submission type on the finish of any First Opinion essay.
The story
“How the ‘amyloid mafia’ took over Alzheimer’s analysis,” by Charles Piller
The response
Dennis Selkoe has already responded to this text. He was too form. Piller describes the advantages of Leqembi as “minute” and “minimal.” My spouse has been on lecanemab since August 2023. She stays an energetic and glad 59-year-old. Lecanemab has given us extra years collectively. That’s not “minute” nor “minimal” to me. Piller permits that there are “tragic, uncommon instances of youthful individuals featured within the media.” 2 hundred thousand People develop Alzheimer’s earlier than age 65. Possibly the media ought to ignore them. Piller is vital of the monetary motives of the drug firms. But, he makes use of patent sensationalism to advertise his guide, with monikers of “amyloid mafia,” “cabal,” and “Church of the Holy Amyloid.” The hypocrisy is profound.
— Fred Haberle
The response
Lastly an essay on the unbelievable “non secular” like fervor surrounding the amyloid delusion! As I learn the article, what struck me was the usage of the phrase “science” talked about so many instances by the “scientists” who had develop into so enamored with this speculation, that they believed it regardless of the overwhelming knowledge that rejected it. The info, in fact, is the variety of amyloid-targeted trials which have been carried out over time (at huge price) which have failed! Lots of them demonstrating some impact on the amyloid buildup, with no demonstrable scientific profit for the affected person. The first final result should be the scientific enchancment of the affected person, each by validated devices over particular timeframes in contrast with placebo controls in addition to patient-reported outcomes between the teams within the trials. Observing and measuring biomarkers has a task, however this should be secondary to the scientific enchancment of the affected person.
— Brian Levy, InflammX Therapeutics
The response
Charles Piller, by way of exhaustive efforts and dogged adherence to reproducible information, lays naked a disturbing though decades-old function of Alzheimer’s illness analysis, which is the promotion and in some instances fabrication of information to suit a pre-ordained narrative. In doing so, Piller highlights a scientific disaster in a wider sense, which is the abandonment of scientific ideas. Based on scientific philosophy, it’s not as much as journalists or so-called sleuths to query scientific concept. It’s as much as the scientists themselves. As an alternative, trendy Alzheimer’s illness analysis has cultivated advocates for a trigger. Letter-writing campaigns from the very best ranges of academia, opinion articles in scientific journals and mainstream retailers, and group posturing in a fashion of cheerleaders on social media are all 180 levels out of part with the scientific mode of inquiry. But every of those are embedded within the material of recent Alzheimer’s illness analysis.
The considerate, science-minded shopper has no alternative however to wonder if the info being introduced to them are a part of a broader technique pushed by secondary achieve, that’s each superficially unassailable and an obstacle to progress. Piller, in impact, is doing the work of scientists. He’s difficult orthodoxy and offering transparency to a public that’s largely underwriting the efforts. It reads as clarion name to medical science for a return to primary problem, somewhat than promotion, of 1’s personal observations, so vital to the scientific technique and to scientific progress. If medical science thrives by way of salesmanship and advocacy, questionable knowledge and affirmation bias will discover their method into excessive affect journals, the one query being the extent. Within the meantime, Alzheimer’s illness sufferers and their households will proceed to be victimized by false hope, paying for it with their time, their pocketbook, and their lives in some instances.
— Rudy Castellani, Northwestern College Feinberg Faculty of Drugs
The response
Charles Piller’s current opinion in STAT raises necessary questions concerning the mechanistic function of amyloid and highlights points associated to restricted entry to scientific trial knowledge, each of which have profound implications for analysis, regulation, and therapy. In two meta-analyses on amyloid-targeting medication (British Medical Journal, 2021; Alzheimer’s & Dementia, 2024), I’ve demonstrated a small however statistically vital impact of amyloid removing on cognitive decline, although solely in aggregated treatment-group knowledge. Nevertheless, such group-level analyses might obscure a real, mechanistic hyperlink between amyloid discount and cognitive outcomes: May individuals who skilled the best amyloid discount even have seen the best cognitive profit? Or might individuals with the least residual amyloid expertise the best profit, regardless of the quantity eliminated?
Answering this sort of mechanistic query, with knowledge that exist already, could be robust proof of a causal function for amyloid. Skeptical biologists have proposed various mechanisms for the results of anti-amyloid brokers, suggesting that their affect on cognitive decline might stem from immunologic results somewhat than amyloid removing. Skeptical methodologists, in the meantime, posit that even minor unwanted side effects might unblind caregivers, skewing trial ends in favor of therapy. Entry to individual-level knowledge would allow testing the true mechanisms behind these brokers’ cognitive results. Demonstrating a causal function for amyloid in therapy is just not merely a tutorial train. Amyloid removing has been used as a surrogate final result in trials as the premise for accelerated approval of aducanumab and lecanemab. Establishing a powerful hyperlink between amyloid discount and cognitive profit is crucial for evaluating whether or not amyloid is in truth a legitimate surrogate for cognition. If amyloid removing is driving cognitive adjustments, this proof may very well be used to advocate for full approval of future brokers based mostly on biomarker adjustments alone.
Alternatively, if amyloid is just not the important thing driver, accelerated approval based mostly on lowered amyloid is just not warranted. Excellent mechanistic questions proceed to drive controversy round anti-amyloid therapies. However the solutions could also be inside our attain. The required knowledge exist already, in individual-level outcomes from current trials of aducanumab, lecanemab, and donanemab — if solely it may very well be made accessible to researchers with the required experience.
— Sarah Ackley, Brown College Faculty of Public Well being
The story
“What my sister’s life and loss of life taught me concerning the NIH,” by Ariel Reinish
The response
The similarities between this expertise and my very own are uncanny. A decade in the past, within the earlier days of CAR-T, I used to be additionally on the Nationwide Most cancers Institute for a sibling’s therapy — my then-12-year-old brother, Samuel, who had relapsed/refractory ALL. For months, my household and I crossed the road from the Kids’s Inn at NIH to the pediatric wing in Constructing 10, the place Sam’s hospital room was, and the place he in the end died. The incessant, vital headlines have been equal elements heartbreaking and infuriating, and equally, do under no circumstances mirror the NIH that I do know. Thanks, Dr. Reinish, for submitting this piece. What a beautiful tribute, one which captures the vital, but lacking, perspective that I’m nonetheless struggling to place into phrases.
— Claire Whetzel, American Society of Hematology
the response
As a health care provider for 35 years and now a affected person with metastatic kidney most cancers, I’ve skilled two sides of life. As an M.D. I all the time stored up with the very best analysis outcomes, referring lots of to NIH, MD Anderson, and others, which frequently extended life and decreased struggling. As a affected person, my therapy has stored me alive and symptom-free for over eight years. These establishments are very crucial and provides hope to the determined. Allow them to proceed to assist the anxious and determined with their analysis and coverings. Their employees are among the many greatest individuals, attempting to heal the hopeless. It’s merciless and ignorant to economize by shrinking these establishments.
— Alberto Garcia-Romeu, retired inside drugs doctor
The story
“The well being coverage cult’s misplaced religion in authorities,” by Charles M. Silver, David A. Hyman, and Michael F. Cannon
The response
Charles M. Silver, David A. Hyman, and Michael F. Cannon criticize PatientRightsAdvocate.org for “a misplaced religion in authorities” when calling on regulators to robustly implement current well being care value transparency guidelines and legal guidelines. However later, the authors name for “treating well being care like an abnormal service that folks purchase and promote by way of abnormal market mechanisms.” They miss how essentially the most basic market mechanism wanted to empower shoppers to buy reasonably priced care and profit from competitors is upfront costs. Value transparency is the keystone of the pro-consumer, free-market healthcare system all of us search, and it deserves ample authorities enforcement.
— Cynthia Fisher, PatientRightsAdvocate.org
The story
“Will PBM reform save pharmacies from closing?” by T. Joseph Mattingly II and Kelly E. Anderson
The response
The authors state, “Right this moment, the biggest portion of prescription drug income for conventional pharmacies is tied to insurance coverage, and the three largest PBMs pay for practically 80% of all prescriptions within the U.S. Which means any value concessions PBMs attempt to extract out of their pharmacy networks to ship financial savings to employer- or government-sponsored well being plans would ultimately come out of pharmacies’ backside traces. Whether or not the payer is a for-profit PBM within the U.S. or a single-payer authorities entity in France or the U.Ok., trying to safe the very best costs for pharmaceuticals will harm most retail pharmacies.”
Nevertheless, the dynamics in single-payer techniques (like in France or the U.Ok.) are structured in another way. There, the federal government units reimbursement charges and sometimes contains mounted dishing out charges to guard pharmacies’ viability. Whereas each fashions goal to safe the very best costs for medication, in single-payer techniques the negotiation and reimbursement mechanisms are often designed to steadiness price financial savings with guaranteeing pharmacies stay solvent. In distinction, the U.S. system’s fragmented nature and heavy reliance on non-public insurers and PBMs could make pharmacies extra susceptible to squeezing.
— Tom McHugh, Optum Rx