I was convinced from the beginning, and even more so after all of John’s marvelous mathematical scenarios and contortions, that such a trial would be too risky, too expensive and would expose too many patients to an unknown drug that might well still be unknown at the end of the study. I made the statement that no one would run such a trial. Jeff Lowtit from the Medicines Company then promptly jumped up and said that he would run such a trial! Nevertheless, it was clear to all in the room what the costs and risks of such a trial would be and what the prospects for funding and for return on investment in such a scenario would be. It was not a pretty picture. One caveat – could a Bayesian approach substantially de-risk the NI venture?