A statistical technique used to support a new class of Alzheimer's drugs can inflate the perceived benefit by a staggering 29 times, according to a research letter published in JAMA Neurology by scientists at Brown University School of Public Health.
The Research
Led by senior author Sarah Ackley, the team investigated quantile aggregation, a method that groups patients, averages their outcomes, and looks for trends across clusters. This technique was originally used in a reanalysis of Eli Lilly's donanemab trial. Using computational simulations that mirrored real clinical trials, the researchers found that quantile aggregation hides individual patient variability and can exaggerate the connection between clearing amyloid plaques and slowing cognitive decline by 29 times its true strength.
To demonstrate the flaw, they applied the method to data from a failed 2014–2023 trial of solanezumab—a drug that showed no benefit—and found that quantile aggregation fabricated a strong, false link between amyloid reduction and cognitive improvement. "By combining large groups and averaging their results, the process hides variability, making a weak relationship appear really strong and important," Ackley explained.
Why It Matters
This discovery has huge implications for anyone following Alzheimer's research. If statistical methods overstate drug benefits, patients and doctors may have unrealistic expectations about treatment outcomes. The method also breaks clinical trial randomization by mixing drug and placebo groups, making it impossible to determine if amyloid removal truly causes cognitive benefits. Independent academic scrutiny is essential to ensure that drug evaluations remain accurate and trustworthy.
What You Can Do
While you can't change how scientists analyze data, you can stay informed by reading original research and looking for independent replications. For your own cognitive health, focus on evidence-based lifestyle factors like regular exercise, a balanced diet, mental stimulation, and social engagement—these have strong support for maintaining brain function.
Source: Neuroscience News
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