title: The FDA outlook of events reporting after ticagrelor or clopidogrel in the PLATO Trial: impact of sponsor censoring dates, drug discontinuation, and withdrawal of consent.
abstract: BACKGROUND
  Censoring by the study sponsor of clinical endpoint events in indication-seeking randomized trials represents a controversial approach since the reported data may be biased in favor of experimental agents due to the obvious conflict of interest. The frequency of drug discontinuation and rates of consent withdrawal may also impact the trial outcomes.
  
  
  OBJECTIVE
  To assess patterns of event reporting dependent on sponsor censoring dates, drug discontinuation and consent withdrawal in the PLATO trial.
  
  
  METHODS
  Analysis of the Food and Drug Administration Complete Response Review for ticagrelor.
  
  
  RESULTS
  Excluding adjudicated deaths, the distribution for clopidogrel appears more uniform while that for ticagrelor was skewed to the right, suggesting more events were reported after the sponsor censoring end date. PLATO investigators reported 16 unmatched primary endpoint events for ticagrelor immediately following the sponsor censoring date. Twenty-six out of 30 unreported events following early drug discontinuation occurred amongst patients using ticagrelor. More ticagrelor patients withdrew consent (Δ = 47), or were 'not willing' to complete the study (Δ = 87) when compared to clopidogrel.
  
  
  CONCLUSIONS
  Site-reported primary endpoints were unequally distributed for clopidogrel and ticagrelor in the PLATO trial. This pattern suggests the importance of questioning the impact of sponsor-mediated censoring on event reporting by investigators in indication-seeking trials. In PLATO, this pattern seems to have favored the experimental drug and may require further assessment.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Serebruany
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy; D000241:Adenosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic / Q000592:standards / Q000706:statistics & numerical data*; D000077144:Clopidogrel; D003627:Data Interpretation, Statistical; D030881:Disclosure; D006801:Humans; D007258:Informed Consent; D015337:Multicenter Studies as Topic / Q000592:standards / Q000706:statistics & numerical data*; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000592:standards / Q000706:statistics & numerical data*; D015203:Reproducibility of Results; D012107:Research Design / Q000592:standards; D012109:Research Support as Topic / Q000706:statistics & numerical data*; D015983:Selection Bias; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016312:Treatment Refusal / Q000706:statistics & numerical data; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine