The detection of adverse events in randomized clinical trials: can we really say new medicines are safe?
Trials are insufficiently powered to detect the majority of adverse events that are reported in clinical trials, even for common adverse events. Observations other than primary efficacy endpoints such as AEs that are not prespecified with adequate power should be treated as hypothesis generating only and not justification of evidence. Claims of safety based on trial evidence not designed for the safety endpoint are often premature.
In this cohort of patients treated in a comprehensive postarrest care pathway that included TH, absence of neurologic function on initial ED presentation was not reliable for prognostication. Given these findings, clinicians should refrain from using the initial ED neurological examination to guide the aggressiveness of care or in counseling of family members regarding anticipated outcome.