EXPERIMENTAL AND CLINICAL METHODS IN THE DEVELOPMENT OF ANTI-ALZHEIMER DRUGS

Methodology used for the development of anti-Alzheimer's disease (AD) drugs raises specific problems which are rarely examined in the litera ture. While the general development scheme is similar to that required for most drugs, some specific aspects must be analyzed, highly domina ted by the dual goal of pharmacology, ie, to obtain both symptomatic a nd etiopathogenic drugs. During preclinical studies, aged or lesioned animals are mainly useful for symptomatic drugs, whereas transgenic mo dels or neurodegeneration-induced techniques would probably lead to et iopathogenic drugs potentially slowing down the process of AD. The fir st administrations of a new compound to human beings raise the questio n of the activity measurement techniques. Psychometry remains the most informative procedure to detect and analyze the activity of the drugs on the different components of cognition. Electrophysiology and neuro imaging need some complementary studies before they can be proposed as surrogate criteria in phase III trials. At this stage of development, American and the recently published European guidelines are of great help while insisting on long-term (6 months) placebo controlled trials with the use of the triple efficacy criterion: an objective cognition scale, a global assessment, and the opinion of the caregiver. In the long term, pharmacoepidemiology and pharmacoeconomy will have to confi rm the rationale of this recent progress in the methodology of anti-AD drug development. (C) 1998 Elsevier, Paris.