An Overview of Clinical Trials

To date, no clinical trials have successfully demonstrated an ability to arrest, or significantly retard the progression of Alzheimer Disease (AD). The challenges of demonstrating disease modification in a slowly progressive neurodegenerative disease like AD are daunting, but a number of strategies offer clear advantages: Five  strategies are discussed:  1. Outcome measures for cognition are limited by striking variability across subjects. Use of cognitively homogeneous patient subgroups (such as anomic or impaired in executive function) can decrease this variability and increase signal to noise ratio. 2.  Change in rate of decline (as opposed to increase in cognitive markers) improves sensitivity. 3) Use of sensitive imaging biomarkers – functional imaging and anatomic imaging – reduces sample size. Some -but by no means all of these - have now been defined in large groups in the AD Neuroimaging Initiative. 4) Focussing on earlier subjects increases likelihood of effective disease modification. The development of studies of “prodromal AD / Mild Cognitive Impairment  due to AD”(MCI plus biomarkers) offers one way foreward in developing such trials. 5) Use of internet evaluation of cognition and reaction time measures may radically decrease the cost of large scale studies. Large scale trials involving many hundreds of subjects need to be augmented by smaller, pilot trials investigating new agents identified by basic scientists that have been tested in transgenic mouse models.