Statistics, Ethics, and Probiotica

A randomized clinical trial comparing an experimental new treatment to a standard therapy for a life-threatening medical condition should be stopped early on ethical grounds, in either of the following scenarios: (1) it has become overwhelmingly clear that the new treatment is better than the standard ; (2) it has become overwhelmingly clear that the trial is not going to show that the new treatment is any better than the standard. The trial is continued in the third scenario: (3) there is a reasonable chance that the new treatment will finally turn out to be better than the standard, but we arent sure yet. However, the (blinded) data monitoring committee in the “PROPATRIA” trial of an experimental probiotica treatment for patients with acute pancreatitis allowed the trial to continue at the half way interim analysis, in effect because there was still a good chance of proving that the probiotica treatment was very harmful to their patients. The committee did not know whether treatment A was the probiotica treatment or the placebo. In itself this should not have caused a problem, since it could easily have determined the appropriate decision under both scenarios. Were the decisions in the two scenarios different, then the data would have to be de-blinded, in order to determine the appropriate decision. And the decisions in this trial were indeed different: were A the probiotica treatment, the monitoring committee would have found themselves in scenario (2) and would have stopped the trial; were A the placebo, the monitoring committee would have found themselves in scenario (3) and would have let the trial continue.