Late clinical testing of cognition enhancers: demonstration of efficacy.

The major difference between clinical trials for efficacy and Phase I trials is their duration; clinical trials of cognition enhancers, for example in senile dementia, require at least 6 months. Because no widely accepted treatment is available, the methodology for these trials is still in a the process of refinement. Double blind placebo-controlled trials are considered to be mandatory particularly by the FDA. Parallel group designs seem preferable and the so-called "enriched design" seems to possess advantages over more classical procedures. Outcome measures should include ratings by clinicians and family members. Self-reports are considered to be unreliable in Alzheimer patients but may be less problematic in AAMI. Psychometric tests of cognition and motor skill should also be included. An essential and pragmatic outcome criterion is, however, the quality of daily life.