Table 2.

Requirements for demonstrating disease modification by a candidate agent for the treatment of Alzheimer’s disease (AD).

Preclinical evidence of disease modification

The candidate treatment impacts the pathologic and clinical aspects of an animal model that closely mimics AD

Supportive clinical trial observations

Randomized double-blinded placebo controlled trials establish a drug-placebo difference; parallel group designs with increasing drug-placebo divergence or staggered start designs are the most feasible approaches to conducting such trials

Supportive biomarker data

A biomarker that reflects the basic disease mechanism is incorporated into the clinical trial

There is a drug-placebo difference between the groups at the end of the trial on the surrogate measures

There is a correlation between the effects on the surrogate marker and the clinical effects of the compound in the trial