You know - this is a subject that has been discussed by people much more knowledgeable than I am. Novel agents and molecules that have specific molecular targets are rewriting the standards protocol we're all used to. Even in cancer trials - many of the new agents tested are very, very low in toxicity. The idea that phI trials may need to consider different measurement criterion is an idea that is thrown about in the research circles. Because it very well may happen. New agents, which often have focus on maximizing very specific genetic expression, no longer fit tidily into the research criteria we're used to with chemotoxic agents. It is a situation that will be a conundrum as this wave of novel agent targeted medicine continues.  Given the animal data on Kevetrin - we will reach a toxic endpoint from which we can retreat to measure maximum tolerated dose. So the protocol won't have to be rewritten this time. : )   But it is likely we'll be around to see the day when such revision is necessary.