What lessons can be learned from failed Alzheimer's disease trials?

Trials missing primary efficacy end points raise the question of whether the choice of drug or the limitations of disease biology were at fault. In some trials, drugs appear not to have achieved biochemical effect thresholds sufficient for clinical benefit. This suggests the need for improved drugs that are more active at tolerated doses. In other trials, it is unclear how the observed biomarker changes are related to potential efficacy. However, hints of efficacy from exploratory analyses support the idea that starting treatment earlier in the course of the disease might be more effective. A closer look at the failed trials will help de-risk future trials.