Figure 1.

A rational approach to design a future SELECT. A concerted multidirectional effort with simultaneous in vitro, in vivo preclinical and in vivo clinical studies is needed to design an ultimate final clinical trial with vitamin E and/or selenium. The in vitro studies need to be conducted to understand the biology and mechanism(s) of vitamin E and selenium. In vivo preclinical studies in appropriate animal models with relevance to human PCa should be carried out to study the best formulations, most effective doses and most appropriate disease stages. These studies should also be directed to study the mechanism of action of the agents and their in vivo pharmacokinetics and bioavailability. The outcome of these studies should feed into novel but initially smaller clinical trials. The small trial, either arising from the known knowledge or from the new preclinical studies, should be conducted with specific agents and in specific populations. The results from these studies should form the basis of a large clinical trial with best agent(s).