Optimal design of clinical trials for drugs designed to slow the course of Alzheimer's disease.

Compounds now in clinical development are hypothesized to slow the clinical progression and pathogenesis of Alzheimer's disease (AD) by their effects to diminish production, increase clearance, or decrease aggregation of amyloid beta protein. Options for investigating the effects of these and other drugs on clinical progression and pathogenesis of AD were examined at a conference that included: (1) a review of experimental methods used to investigate disease-modifying drugs for multiple sclerosis, rheumatoid arthritis, cardiovascular disease, and osteoporosis; (2) discussion of possible study designs and outcome measures for trials in patients with AD; and (3) discussion of biomarkers available for AD. There is no uniformly best way to investigate a drug's impact on AD progression but characteristics of studies supportive of a disease-slowing effect can be specified. Relevant clinical outcomes in drug-treated patients versus placebo-treated patients should be compared over at least 1 and possibly as long as 2 years with biomarkers reflective of pathogenesis and of the drug's mechanistic effects measured concurrently.