Two problems in trials of psychotropic medications are the use of placebos and the high placebo response. Both lead to ethical concerns and a number of failed trials. The ethical issue with regard to use of placebos has been well addressed for trials in depression and panic disorders where the risk with the placebo arm is small and there is a need for placebos to demonstrate that a drug has efficacy. Another issue is the potential use of surrogate markers in designing trials. In this presentation, I will discuss the use of novel trial designs to minimize placebo exposure and the use of surrogates in Alzheimer disease. I will discuss "play the winner" as an example of a design that could be used to reduce the number of subjects exposed to placebo and also its potential as a design for proof of concept. The limitations and problems with this type of design will be discussed. The use of magnetic resonance imaging and spectroscopy as a surrogate in Alzheimer disease trials will be discussed. Results from clinical trials will be presented to illustrate their use.
Krishnan KRR. Advances in Neuropsychiatry. Arch Neurol. 2002;59(2):327. doi: