[Monitoring the safety of participants in randomised clinical trials: basis and methods]

--Prior to conducting a randomised trial, permission must be obtained from the medical ethics committee (METC). The METC assesses the relevance of the trial and the appropriateness of the chosen study methods. It also weighs the clinical/scientific relevance against the potential benefits, risks and burdens for participants. --Monitoring interim data is the responsibility of an independent data monitoring committee (DMC), comprised of experts in the relevant field. The DMC provides recommendations to the study directors regarding the continuation, amendment or possibly early stopping of the study (when participant safety becomes an issue or when the trial aims are achieved earlier than expected). --Reported adverse events are interpreted clinically by the DMC in the context of available safety data. A statistical protocol for this process cannot be defined prospectively. --A strict statistical protocol can be defined prospectively for the interim analysis of the efficacy of the investigational intervention. In some cases, the results can be so convincing that the study can be stopped early. In other cases, the differences between groups may be smaller than expected, and increasing the size of the study groups can be considered. --In a blinded study, only an independent statistician is aware of the treatment codes. The chair of the DMC also possesses a sealed envelope containing the codes. The envelope can be opened at the request of the entire DMC.