Timely Detection of Adverse Advents in Therapeutic Trials Series
- Dr. Giard effectively summarizes the difficulties a Data Safety Monitoring Committee (DSMC) faces when deciding whether or not to terminate a trial early. We can comply with the suggested decision matrix by Knottnerus and Spigt, but feel that this matrix should be predefined in the study protocol. Furthermore, we and many others feel that a DSMC should take additional information into account as well. Pocock stated: “Negative stopping decisions cannot simply be based on statistical guidelines. For instance, if negative interim data are in contradiction with previous, more positive evidence, then the quality, extent, and relevance of that evidence will influence one's judgment” .
- The outcome of a therapeutic trial may be frustrating. In a recent Dutch randomized, double-blind, placebo-controlled multicenter trial, the effects of probiotics were studied to investigate their potential to diminish infectious complications in patients with predicted severe acute pancreatitis . Desolately, the results of this study were quite contrary to expectations: there was no diminution of infectious complications, and furthermore, patients taking the probiotics had more than double the relative mortality risk.
- When designing a trial, an interim analysis of the trial results may be considered, for example, halfway to the maximal follow-up time, or after a prespecified number of inclusions or events. The objectives of such an analysis include (1) avoiding exposure of further patients to harm if detected in the interim analysis; (2) not continuing exposure of further patients to the trial if unneeded for answering the study question; (3) avoiding unnecessary research costs; (4) providing an answer to the study question as soon as possible.