High failure rate observed in the conventional well-controlled phase III clinical trials has prompted critical root-cause analyses for seeking possible improvement on the conventional design approaches and analytical tools. In 2004, recognizing the stagnation, the U.S. FDA critical path initiative has called for innovations for clinical drug development program. One proposal pertains to the role of adaptive/flexible clinical trial designs in the drug development program. In this talk, I shall present some practical strategies for alternative design considerations and analysis approaches in clinical trials that allow flexible learning versus limited learning/confirming while maintaining statistical validity. In particular, a unique paradigm that comes with the features of scientific integrity and trial infrastructures allowing the assessment of trial conduct integrity will be highlighted