Clinical trials: the past, a lesson for the future

Numerous drugs have been tested in amyotrophic lateral sclerosis with the e xpectations both that they will treat patients and improve our understandin g of some of the basic mechanisms of the disease. Most of these trials were considered to be negative. Careful analysis of the trials does not allow u s to clearly discard any of the tested drugs, or any of the suspected mecha nisms. Expectations for the future are that: a) we need to be realistic abo ut what to expect; b) we have to define clearly our end-points; c) we have to calculate the expected power before the trials, not after; and d) we hav e to improve our understanding of the pharmacology.