Statistics , ethics , and probiotica ∗ Richard

Ethical issues involved in the design of the “PROPATRIA” probiotica trial are discussed. This randomized clinical trial appeared to be well conducted according to accepted good practices. The finding that the treatment was actually rather harmful, and that despite this, and despite a built-in interim analysis, the trial was not stopped earlier, led to strong criticism in the media. I argue that “accepted good practices” need to be reconsidered in the light of this experience. Firstly, a much stronger distinction needs to be recognized between the immediate interests of the patients being treated in the trial, and the interests of future patients of future doctors elsewhere. Secondly, it is in the interests of future patients that well conducted clinical trials are accepted by society. Since it is unavoidable that an occasional trial will result in an unpredicted severely negative outcome, ethical screening committees must ensure that those performing a trial can never be accused of putting the interest of “science” above the interest of their own patients when such “accidents” happen. There are two consequences of this. Firstly, the design of a trial should also explicitly minimize the number of patients who are treated by the researchers with a potentially seriously harmful medicine. Secondly, the disadvantages of triple-blinding far outweigh the advantages. Though it might at best only have saved a few lives if the PROPATRIA trial been re-designed with these issues in mind, I argue that the scientific value of the trial would not have been significantly ∗Statistica Neerlandica (2009) Vol. 63, nr. 1, pp. 1–12