CHICAGO, July 28 /PRNewswire-USNewswire/ -- Lack of measureable decline in memory and thinking processes among placebo groups in Alzheimer's disease clinical trials might reduce the ability to show the effectiveness of new Alzheimer therapies, according to new research reported today at the 2008 Alzheimer's Association International Conference on Alzheimer's Disease (ICAD 2008) in Chicago.
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Alzheimer clinical trials seek to show that those who received the treatment improved over the course of the study when compared to those who received the placebo, or that they got worse to a lesser degree. A complication that is emerging in Alzheimer clinical trials is the perception that participants with Alzheimer's in the placebo arms of the trials are showing less worsening over the time period of current studies. It has been speculated that this may be due to:
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-- Inadequate sensitivity of the standard scales used for measuring cognition in these trials.
-- Differences in disease severity and co-existing medical conditions between the populations being recruited now compared with previous trials.
-- The relatively common use of the currently approved Alzheimer drugs (cholinesterase inhibitors and memantine) by populations involved in the clinical trials.
"In Alzheimer trials, if the placebo group does not worsen over the course of the trial then it might be very difficult, or even impossible, to show that a drug is effective," said William Thies, PhD, vice president for Medical & Scientific Relations at the Alzheimer's Association.
Two scientific presentations from ICAD 2008 address the issue head on -- one through a review of 87 Alzheimer clinical trials conducted between 1991 and 2005, and the second by specifically looking at trials of the drug donepezil from 1990 to 1999.
Analysis of Multiple Studies Reveals Process to Ensure Placebo Group Decline
Lon S. Schneider, MD, professor of psychiatry and neurology at the University of Southern California Keck School of Medicine, and professor of gerontology at the USC Leonard Davis School of Gerontology and colleagues searched published and unpublished sources for six months or longer randomized, double-blind, placebo-controlled Alzheimer clinical trials. They found 103 trials conducted between 1991 and 2005 and obtained information from 87. From these they extracted information about trial size, countries, number of sites, treatment allocation ratios, enrollment dates, age, gender, and scores on two standard measures of cognition -- the Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog).
The researchers found no changes in amounts of cognitive decline across the 15-year time period of the trials. They found that smaller placebo groups were associated with less likelihood of cognitive worsening over the course of the trial. Placebo group sample sizes less than 100 had a 37 percent chance of not showing significant change, while samples greater then 200 all showed significant worsening at six months. In 12-month studies, 95 percent of placebo group sample sizes greater then 100 showed significant decline.
Several other factors were found to be associated with whether or not there was cognitive decline in the placebo group. Studies with non-English speaking trial sites were associated with less cognitive worsening over the course of the clinical trial. Use of more frequent cognitive assessments reduced the amount of variance in the amount of worsening. Use of cholinesterase inhibitors was not associated with less cognitive decline during clinical trials.
"Experts have no need to worry that people with Alzheimer's in clinical trials are less likely to worsen than
