Public trust is easily cracked and, once cracked, hard to repair
Originally published in MEDPAGETODAY
Systematic fraud — led by a “cabal of self-interested researchers, government accomplices, and corporate greed” in the words of the publisher’s promotional textopens in a new tab or window — has produced harmful and ineffective Alzheimer’s drugs.
This is the terrifying message of investigative journalist Charles Piller’s new book, Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer’s. It suggests that the FDA approvals of lecanemab (Leqembi) and donanemab (Kisunla) for the treatment of Alzheimer’s disease have allowed expensive, harmful drugs into practice, and that the massive investment of NIH funding and the efforts of patients and caregivers in research have all been a waste.
This message has enormous significance, and it’s getting attention.
The problem is that the facts don’t support Piller’s message. It’s sensational, and in my experience, it’s causing harm. One of my patients who plans to take one of these anti-amyloid drugs explained that the multiple scandals reported by Piller caused him to question his decision. My colleagues relay similar dispiriting conversations with their patients.
Meanwhile, I know from conversations with colleagues that participants are dropping out of studies testing anti-amyloid drugs. Notably, during his confirmation hearing testimony before the Senate Finance Committee, Robert F. Kennedy Jr. cited Piller’s reporting and suggested NIH hasn’t done meaningful Alzheimer’s research. HHS Secretary Kennedy now oversees the NIH, and in a recent interview he cited the “amyloid plaque scandals” and concluded NIH scientists “need to be moved.“
All of this undermines the successes we’ve made and the research we still have to do to accomplish the goals of our national Alzheimer’s plan, particularly goal number one: to prevent and effectively treat Alzheimer’s disease.
The anti-amyloid drugs lecanemab and donanemab aren’t cures — the drugs both target amyloid plaques, one of the pathologies that cause Alzheimer’s dementia – and they have risks. But the conclusion that they’re essentially useless and the product of a corrupt system is a vast overreach. Yes, Piller’s argument includes the case of FDA’s controversial decision to grant Biogen’s Alzheimer’s drug aducanumab (Aduhelm) accelerated approval. That approval was a mistake, but government investigations, free markets, free press, and open debate in the expert community pushed the drug from the market. It’s an inspiring example of the system purging misconduct and self-interests. The system worked.
Doctored highlights important examples of misconduct and self-interests. Piller and others — particularly brave junior researchers and vigilant, committed members of the public — have discovered bad scientists, sloppy medical journals, under-resourced NIH investigations, and universities dragging their feet to investigate their own faculty.
The cases are compelling. They show us that private self-interests of individuals and corporations are damaging the reputation of Alzheimer’s science and threatening essential public trust and support to sustain that science.
One stands out: PhD scientist Sylvain Lesne’s “discovery” (in genetically engineered Alzheimer’s mice models) of a toxic species of amyloid, a protein implicated as a cause of human Alzheimer’s — the very protein targeted by the drugs I prescribe. There was no discovery because he reportedly manipulated his data. He has recently resigned from his University of Minnesota position. But even before Piller uncovered Lesne’s alleged fraud, the field was skeptical of his results. Skeptical because efforts to reproduce them, a core process of science, kept falling flat.
In my opinion, Doctored doesn’t offer a convincing link between egregious fraud in basic science and the design and results of clinical studies that enroll human participants — in particular, the multi-center trials that developed donanemab and lecanemab. Notably, two of the biggest scandals he reported and detailed in his book — Cassava Sciences’ simufilam, which faced fraud allegations, and University of Southern California’s Berislav Zlokovic, MD, PhD, who faced whistleblower allegations of misconduct and data manipulation — have little to do with the amyloid hypothesis that supports drugs like lecanemab and donanemab. Doctored doesn’t uncover facts or re-analyze available facts that allow me to connect these allegedly fraudulent studies with the clinical science that guides the care of my patients.
Still, a skeptic might worry. Is it possible the Alzheimer’s clinical research enterprise is championing drugs whose foundation is fraudulent? That there are data to prove his unproven claim that donanemab and lecanemab are corrupted?
We should have faith the system will, in time, answer these questions, and even if the answers are a sad, dispiriting “yes,” the system will correct. It will correct itself because the system of clinical research is public and social. These are the foundations of trust. Scientists declare their interests, identify conflicts, and resolve them. They make data public and when they aren’t already public, they speak up and demand it. With these data, they debate important topics.
Doctored shows there’s corruption in the system, but that doesn’t mean that donanemab and lecanemab are inherently corrupt. As long as the system preserves and protects these public and social characteristics, scientists will rout out fraud and misconduct. What worries me is public trust in the system could break because trust is delicate, like porcelain: easily cracked and, once cracked, hard to repair.
