Statistical Method May Overstate Alzheimer’s Drugs’ Cognitive Benefits By 29 Times

Writing in the JAMA Neurology journal, these researchers raise serious concerns about a statistical technique known as ‘quantile aggregation’, which has been used to analyze the effectiveness of newer Alzheimer’s drugs such as Eli Lilly’s donanemab. The method groups patients together, averages their outcomes, and searches for patterns between reductions in brain amyloid levels and improvements in cognition. The researchers describe how employing this approach can make the relationship between amyloid reduction and cognitive benefits appear to be much stronger than it actually is.

Using computer simulations designed to mimic recent Alzheimer’s trials, the research team found that quantile aggregation exaggerated the apparent connection between amyloid reduction and cognitive improvement by as much as 29 times. They say that averaging results across large patient groups masks important differences between individuals and can create misleading associations. The researchers also note that the method mixes data from treated patients and placebo recipients, therefore weakening the ability to determine whether amyloid reduction really causes cognitive benefits.

To test their concerns, the researchers applied the approach to data from a previous trial of solanezumab, a drug already shown not to slow cognitive decline. Worryingly, using the statistical technique still made the drug appear to be effective. The authors say their findings highlight the need for more rigorous methods to be used when analyzing these drugs.

To read how a major independent review published earlier this year cast serious doubt on the effectiveness of the latest so-called ‘breakthrough’ Alzheimer’s drugs, see this news story on our website.