Discussion
Bleeding, bleeding
BLEEDING, EVENTS, BLEEDING, BLEEDS
In these analyses from the ASCENDFor major bleeding events, ASCEND is one of the first published studies to compare relative and absolute treatment effects from a large-scale randomised trial using adjudicated direct follow-up versus the hypothetical scenario that follow-up had been solely through routinely collected data. A previous study assessing routine data ascertained major bleeding events in EnglandOur analysis of the ASCEND trial highlights the challenges of ensuring complete follow-up for major bleeding outcomes when using either adjudicated direct-participant mail-based follow-up or routinely collected data. When comparing these two methods of follow-up, we found that although there was moderate agreement, over 200 major bleeding events were either reported in adjudicated direct-participant follow-up alone or routine data only. Importantly, in ASCEND, despite these discrepancies, relative and absolute treatment effects were similar between both data sources. However, if a trial must ensure complete follow-up for major bleeding outcomes, then this will likely require a combined approach of direct participant and routine data follow-up.For the major bleeding events only identified in adjudicated direct-participant follow-up, the majority had a corresponding routinely collected hospitalisation record, but either the record gave no indication of bleeding severity or no bleeding code was recorded. Although there has been an expansion in sources of routine data available for UK clinical trials,A number of studies have reported on the impact of clinical adjudication on investigator-reported and participant-reported cardiovascular events.There are some limitations of the current analyses. First, the ASCEND mail-based follow-up reports appeared to miss some major bleeding events and did not have the associated medical notes to verify or refute major bleeds identified in routine data only; thus, there are challenges to interpreting the agreement statistics presented. Second, ASCEND used innovative mail-based methods, so comparisons with traditional methods of site-investigator reported major bleeding were not possible. Third, findings are based on the particular definition of major bleeding used in ASCEND; these definitions were an adaptation of the Bleeding Academic Research Consortium (BARC)