Dementia drug trials are based on flawed test

 The standard cognitive test used for trials of drugs for Alzheimer’s disease is not accurate, UK researchers have found.

The ADAS Cog test, which scores patients on an aggregate of 11 components (such as language use and naming objects), underestimates the progress of dementia and variance between patients.

The report suggests that some Alzheimer’s drugs, including ones that ‘failed’ clinical trials, may be more effective than was thought.

In particular, the test is unreliable as a means of tracking the early stages of dementia, where drug interventions are likely to have most impact.

Researchers from Plymouth University examined 675 ADAS Cog test results for people with mild Alzheimer’s disease at zero, six, 12, 18 and 24 months.

Analysis of the scores at component level revealed a ‘ceiling effect’ in relation to eight abilities: from 32–83% ‘passed’ the component with equivalent scores.

A follow-up study used Rasch analysis, a technique for evaluating aggregated tests, to confirm the flaw and suggest improvements: parts of the ADAS Cog need to be more difficult, and the overall scoring method needs reworking.

“It is impossible to say precisely the extent to which the ADAS Cog’s flaws have undermined the numerous clinical trials in which it has been used,” said study leader Professor Jeremy Hobart.

“It has been used, unchanged, for many years and its apparent contribution to suboptimal trials has led a number of drug companies to rethink their strategies.

“However, it is very clear that in its current form the ADAS Cog underestimates cognitive differences between people and changes over time.”

The test “is not working in people with mild Alzheimer’s disease,” he concluded.

The ADAS Cog was recently used in the ‘unsuccessful’ drug trials of Lilly’s solanezumab and Pfizer and J&J’s bapineuzumab.