Phase III clinical trials should generally be simple affairs. The rule of thumb is that the standard of care should be compared with a promising intervention among reasonably well-defined patients and the proposed outcome should be readily measurable, generalizable, and clinically meaningful. Ideally, the results, if positive, should change practice and be implemented widely. As a generality, one (and only one) variable should be changed in the experimental group to facilitate understanding the intervention and its consequences.
Simplicity, though an oft-stated goal, is not always achieved. In prostate cancer trials, outcomes will always occur long after the trial was designed. Trial architects are forced to consider various future treatment approaches, and the potential future state of affairs is inherently uncertain. Speculating on future scenarios is interesting, but even well-informed investigators may have substantial discordance in their views.
Currently in nonmetastatic prostate cancer, the time to reach the most relevant clinical end points (metastases or overall survival) can take a decade or even more. Definitions of prognostic categories, biomarkers, and treatments are all subject to flux over time. How to anticipate these changes can determine the success or failure of a trial. Much is at stake because both research dollars and trial participants are limited.
Source: Journal of Clinical Oncology
