Update in methodology and conduct of cancer clinical trials

RECIST guidelines were published five yeas ago and have since then been largely implemented and used in clinical trials. Although the criteria were initially designed for screening phase II trials they have been used also in most phase III studies aiming at determining the efficacy of new treatments. Problems have been identified some of which require further clarifications and others deserve further research which is being undertaken. Overall RECIST is well accepted and a revised version is being considered for 2007. Interim analysis is also an important issue revealed recently through many large adjuvant or advanced trials being prematurely discontinued at the time of an interim analysis. In most instances trials were stopped because of evidence of superiority of the investigational treatment over the standard treatment. Premature discontinuation of trial poses a number of challenges addressed in this paper. Finally, the consequences of the implementation of the EU clinical trial directive are being discussed. The conclusions are without equivoque. There is much less academic research conducted in Europe, there is a lot of discrepancy and inconsistency in the implementation of the directive across member states and there is no apparent direct benefit for the patients.