Interim analyses {21b}
STEC
EVENTS
The study’s Data and Safety Monitoring Board (DSMB), whose purpose is to protect the safety of participants and promote the scientific integrity of the study, will include five members. The DSMB will monitor study participant accrual, protocol adherence, data quality, site performance, SAEs and other subject safety issues and will review formal interim statistical analyses of treatment efficacy. The EDC will send reports relating to DSMB members prior to each meeting. The EDC will attend DSMB meetings; each meeting will have summary recommendations that will be provided to the principal investigators who will be responsible for responding to all recommendations. The EDC will distribute the final signed recommendation within 3 business days to the investigators, DSMB members, and the federal funding agency and will post the final signed recommendations to the EDC Document Library.The DSMB had its inaugural pre-launch meeting on June 17, 2022, and an additional meeting was convened on July 29, 2022, to address outstanding concerns prior to study launch. The DSMB will hold two planned meetings to review formal interim analyses to examine treatment efficacy and patient safety. The first formal efficacy analysis will occur prior to the intervention switch (i.e., crossover). This analysis will test the primary hypothesis by using the model described for the analysis of the primary outcome but without a period effect term. In the second intervention phase, a formal interim efficacy analysis will occur after the seasonal peak of STEC incidence. Early stopping of the trial will be considered if efficacy has been established. One-sided Haybittle–Peto boundaries will be used for efficacy monitoring. The trial may be stopped for harm and such analyses will be performed as part of our interim analysis. The DSMB will review accumulating AE data and weigh the potential risks and benefits at each meeting. If there is a perceived increase in risk of AEs with little indication of benefit, the DSMB has the ability to recommend stopping the trial. In addition, they will meet every 12 months to review the protocol, study procedures, monitoring, participant safety, enrollment, and loss to follow-up.This study may be suspended or prematurely terminated if there is sufficient reasonable cause at an ad hoc DSMB meeting. The following events will trigger a notification to the DSMB chair to determine whether an ad hoc DSMB meeting is warranted to review AEs and to make recommendations to the principal investigators:Mortality frequency > 1% of participantsRRT frequency > 15% of participantsIntubation frequency > 5% of participants (minimum duration > 24 h)When considering such AE data, the DSMB will be encouraged to consider the number of participants enrolled to date.Written notification, documenting the reason for study suspension or termination, will be provided by the EDC to investigators, funding agencies, the central IRB, and local REBs. The notification will include the reason(s) for the termination or suspension. The study may resume once the identified concerns are addressed to the satisfaction of the sponsor, IRB/REBs, and the DSMB.