Statistics, ethics, and probiotica

TL;DR

This paper discusses ethical and statistical considerations in clinical trial monitoring, highlighting a case where misinterpretation of data led to continued testing of a harmful treatment, risking patient lives.

Contribution

It analyzes the implications of data monitoring errors in clinical trials, emphasizing the importance of correct statistical interpretation and ethical decision-making.

Findings

Misinterpretation of p-values can lead to unethical trial continuation.

Approximately five lives were potentially lost due to trial mismanagement.

The importance of clear statistical communication in clinical decision-making.

Abstract

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 aren't 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. The committee mis-read the output of SPSS, which reports the smaller of two one-sided p-values, without informing the user what it is doing. It seems that about 5 lives were sacrificed to the chance of getting a significant result that the probiotica treatment was bad for the patients in the trial.