Statistical controversies in clinical research: requiem for the 3 + 3 design for phase I trials.

@article{Paoletti2015StatisticalCI,
  title={Statistical controversies in clinical research: requiem for the 3 + 3 design for phase I trials.},
  author={Xavier Paoletti and Monia Ezzalfani and Christophe Le Tourneau},
  journal={Annals of oncology : official journal of the European Society for Medical Oncology},
  year={2015},
  volume={26 9},
  pages={1808-12}
}
BACKGROUND More than 95% of published phase I trials have used the 3 + 3 design to identify the dose to be recommended for phase II trials. However, the statistical community agrees on the limitations of the 3 + 3 design compared with model-based approaches. Moreover, the mechanisms of action of targeted agents strongly challenge the hypothesis that the maximum tolerated dose constitutes the optimal dose, and more outcomes including clinical and biological activity increasingly need to be taken… CONTINUE READING