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Abstract
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BACKGROUND: The PLATO trial data set reported to the FDA (DRFDA) revealed that some primary deaths causes (PDC) were inaccurately reported favoring ticagrelor. Trial Investigators (DRTI) received different data set with more ticagrelor mortality advantage. We compared these two death lists for the match in PDC.
METHODS and Results: The DRFDA contains 938 deaths, while the DRTI contains 905. We matched "vascular", "non-vascular", "unknown", "missed", and "other" causes of death between DRFDA and DRTI. The DRFDA used 14 vascular, 9 non-vascular, 1 unknown and 1 other PDC codes, while the DRTI used 14 but different vascular, 14 non-vascular but no unknown or other PDC codes. We observed a significant mismatch for the PDC codes between the DRFDA and DRTI data sets. Most DRFDA deaths were vascular (n = 677), fewer non-vascular (n = 159) and unexpectedly many unknown (n = 95) or other (n = 7) PDC. Surprisingly, the shorter DRTI contains more vascular (n = 795), fewer non-vascular (n = 110), but no unknown, other, or missed causes. There were more sudden deaths in DRTI than in DRFDA (161 vs. 138; p < 0.03), twice as many post-myocardial infarction deaths (373 vs. 178; p < 0.001) but fewer heart failure deaths (73 vs. 109; p = 0.02). The reported non-vascular PDC match better except for 2 extra suicides in the clopidogrel arm of the DRTI.
CONCLUSIONS: Over 100 "unknown", "missed", or "other" PDC events reported by the trial sponsor to the FDA were omitted from the investigator data set contributing to the inflated differences in vascular mortality benefit of ticagrelor reported in numerous PLATO publications. Synchronization of PDC reporting between regulatory agencies and investigators was lacking in PLATO but remains mandatory to ensure quality for future indication-seeking trials. Copyright: © 2022 The Author(s).
Language: en |