Current standards of clinical trials require that, whenever possible, the new therapy be compared with a standard of care, if one exists, and that all efforts be made to ensure that the two or more cohorts are similar in every respect. This latter point is essential if we are to be sure that any benefits are real and not a perception. Thus, to achieve the comparability of cohorts, it is essential to dictate inclusion and exclusion criteria to reduce the outlying cases that can confound the interpretation. In many clinical trials, the actual number of subjects enrolled is a fraction of those who are diagnosed with the same condition. Indeed, from personal experience, it is rare to observe recruitment of 30% to 40% of potential patients. Moreover, the number of evaluable cases diminishes even further as subjects fail to complete therapy or return for assessments or they drop out because of adverse events or death. The latter is perhaps something we cannot prepare for, but we must account for the other factors as we conduct sample size estimations. It is no surprise, therefore, that for a pharmaceutical company today to develop a new drug, it is estimated to cost more than $2.5 billion and take 8 to 10 years.