Game behind, premature termination of Random Control trials for extraordinary benefits.

These days increasing number of clinical trials (RCT) are terminated prematurely for claim of extraordinary benefit of experimental drug, procedure or investigation. Such prematurely terminated trials usually are published in high impact journal and get immediate recognation and acceptance of experimental drug, procedure or investigation by practicing clinicians. So makers of the new mode of treatment get huge profits.
In cardio exchange Victor Montori, MD, MSc has scrutinized results PRAMI trial.  This trial was also terminated prematurely due to benefit in experimental group. In this trial total outcomes were just 74. Further he says nonfatal MI of just three more in control arm is sufficient tilt balance to opposite side. If this trial were to continue, who knows results with a larger group could be much different. Like all premature terminated trials PRAMI trial is published in NEJM which is a high impact journal, as expected because of extraordinary benefit it has become a breaking news, and funding agencies have terminated the study, so this has reduced cost of conducting study also.
Number of events or outcomes which lead decision of termination of study has greater impact on validity of the study. If number of events are too less, then it could be just a random chance, either in experimental or control arm, which can tilt the balance to either side. If total number events are more than 500 then it may be fair estimate, if number of events are between 200 to 499 then it is moderate estimation of outcome, if number events are less than 200 then one has be very careful in believing the results
For any investigational agent which is still not an accepted modality, responsibility of organizers or funding agenesis of clinical trial, owe greater responsibility to the general public who will be exposed their new modality then the control arm which may not get their treatment modality. From past history we have seen many investigational agents came with a big bang and have disappeared later due to harmful side effects.
One can read this article on JAMA which discuss the detail of premature termination of clinical trials

Author: Dr Umesh Bilagi

MBBS, MD, DM (cardiology). I am Interventional cardiologist. Blogging is my passion. Associate professor of cardiology KIMS Hubli. Director and consultant at Tatwadarsha Hospital Hubli. Owner of Jeevan Jyoti Hospital Hubli. Mobile +91 9343403620.

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