Department of Mathematics

Careless Statistics Cost Lives: the Utrecht probiotica trial

(Leiden University)

7 May 2008

I will explain the Snapinn (1992) rule for early stopping of a randomized clinical trial. This very cunning protocol preserves the standard analysis at the end of a not-early-terminated trial, by balancing the chances (under the null-hypothesis) of abandoning the trial early for expected futily when actually the final result would have been significant, and abandoning the trial early for expected signficance when actually the final result would not have been significant. Further cunning features allows the protocol to be extended from the primary setting of comparing two normal means with known variances to the general setting of, for instance, comparing two unknown Bernoulli probabilities. It appears that the famous PROPATRIA trial of probiotics treatment in acute pancreatits was allowed to run to completion because of a confusion between one-sided and two-sided testing. The fact that the monitoring committee was blinded to the actual treatments given to the two treatment groups made it possible for them to continue the trial in the expectation of finally obtaining a significant harmfull effect of the treatment, when they should have stopped it because there was almost no hope of proving a significant difference.

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Charlene Kalle