title: Documentation of study medication dispensing in a prospective large randomized clinical trial: experiences from the ARISTOTLE Trial.
abstract: BACKGROUND
  In ARISTOTLE, apixaban resulted in a 21% reduction in stroke, a 31% reduction in major bleeding, and an 11% reduction in death. However, approval of apixaban was delayed to investigate a statement in the clinical study report that "7.3% of subjects in the apixaban group and 1.2% of subjects in the warfarin group received, at some point during the study, a container of the wrong type."
  
  
  METHODS
  Rates of study medication dispensing error were characterized through reviews of study medication container tear-off labels in 6,520 participants from randomly selected study sites. The potential effect of dispensing errors on study outcomes was statistically simulated in sensitivity analyses in the overall population.
  
  
  RESULTS
  The rate of medication dispensing error resulting in treatment error was 0.04%. Rates of participants receiving at least 1 incorrect container were 1.04% (34/3,273) in the apixaban group and 0.77% (25/3,247) in the warfarin group. Most of the originally reported errors were data entry errors in which the correct medication container was dispensed but the wrong container number was entered into the case report form. Sensitivity simulations in the overall trial population showed no meaningful effect of medication dispensing error on the main efficacy and safety outcomes.
  
  
  CONCLUSIONS
  Rates of medication dispensing error were low and balanced between treatment groups. The initially reported dispensing error rate was the result of data recording and data management errors and not true medication dispensing errors. These analyses confirm the previously reported results of ARISTOTLE.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC. Electronic address: john.h.alexander@duke.edu.
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.forename: Elliott
authors.initials: E
authors.lastname: Levy
authors.forename: Jack
authors.initials: J
authors.lastname: Lawrence
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Waclawski
authors.forename: Junyuan
authors.initials: J
authors.lastname: Wang
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
mesh_terms: D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D004282:Documentation; D004311:Double-Blind Method; D004348:Drug Labeling / Q000706:statistics & numerical data*; D006470:Hemorrhage / Q000188:drug therapy / Q000453:epidemiology*; D006801:Humans; D008508:Medication Errors / Q000009:adverse effects / Q000706:statistics & numerical data*; D011446:Prospective Studies; D011720:Pyrazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D011728:Pyridones / Q000008:administration & dosage* / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D020521:Stroke / Q000188:drug therapy / Q000453:epidemiology*; D015996:Survival Rate; D013923:Thromboembolism / Q000188:drug therapy / Q000453:epidemiology*; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin