Interim analyses {21b}
SAEs
There will be no interim analysis for efficacy. The DSMB will monitor the trial for safety purposes. To detect safety signals in a timely manner, the board members of the DSMB will be instructed to perform safety analyses after 65 and 130 included patients (if there are safety issues, the DSMB may ask for a higher frequency). SAEs and the primary outcome will be analysed according to the randomisation sequence. The DSMB may suggest stopping the trial if the overall pattern of related SAEs supports a major safety signal. For this trial, no statistical stopping rules will be used. The clinical trial is embedded in an EU Horizon2020-sponsored project (TTVguideTX). Thus, premature termination of the clinical trial will first be discussed by the project’s core team (project steering committee including the sponsor of the TTVguideIT study) and has to be decided on in the general assembly including all project partners. In case of premature termination of trial therapy according to the active group for a patient, the patient will continue the study following the protocol of the control arm. Further visits and trial-specific procedures will be continued. The documentation of all subsequent visits should still be pursued. Should the study be discontinued prematurely for a patient, all study materials will be retained. Data will be collected to the point of withdrawal and used for the intention-to-treat analysis if the subject consents. There will be no replacement of withdrawn subjects. For subjects withdrawing prematurely from the clinical trial, a final visit should be sought.