Delays of event adjudication in the TRITON trial.
BACKGROUND
Central adjudication of clinical events in randomized controlled trials represents an attractive but still controversial approach since the adjudicated data usually match well with the investigator-reported event rates but increase affiliated costs.


OBJECTIVE
The aim was to assess the timing of clinical event adjudication in the TRITON trial.


METHODS
A review of the FDA action package for prasugrel was conducted.


RESULTS
Adjudications for deaths and strokes were distributed evenly throughout the study period. Bleeding event adjudications were performed predominantly in the later stages of the study. Adjudications for myocardial infarction and especially stent thrombosis were significantly delayed.


CONCLUSIONS
Among all clinical events, only deaths and strokes in TRITON were adjudicated without delays. Late adjudication of myocardial infarction and stent thrombosis are uncommon but at least can be explained by lack or change of event definitions. However, the delays with adjudications of revascularization procedures and especially timely recording of bleeding complications lack reasonable explanation. The regulatory authorities should consider independent audits when there is a major disagreement between centrally adjudicated and site-reported events influencing the results of a major clinical trial.
Serebruany
Victor L
VL
D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality*; D015906:Angioplasty, Balloon, Coronary / Q000401:mortality; D002544:Cerebral Infarction / Q000401:mortality / Q000517:prevention & control; D000077144:Clopidogrel; D023903:Coronary Restenosis / Q000401:mortality / Q000517:prevention & control; D003625:Data Collection / Q000706:statistics & numerical data*; D018572:Disease-Free Survival; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality; D009203:Myocardial Infarction / Q000401:mortality / Q000517:prevention & control; D015588:Observer Variation; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D015203:Reproducibility of Results; D012107:Research Design / Q000706:statistics & numerical data*; D015607:Stents; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine