title: Data monitoring in the cardiac arrhythmia suppression trial.
abstract: OBJECTIVE
  This report discusses practical aspects of data monitoring in a clinical trial which stopped ahead of schedule due to adverse findings.
  
  
  METHODS
  A review of the considerations and decisions made by the data-monitoring committee of the Cardiac Arrhythmia Suppression Trial (CAST), a randomized, double-blind clinical trial.
  
  
  METHODS
  CAST consisted of men and women with a recent myocardial infarction, asymptomatic or minimally symptomatic ventricular arrhythmias, and reduced left ventricular ejection fraction.
  
  
  METHODS
  In CAST, 3 antiarrhythmic agents, encainide, flecainide, and moricizine, were compared against placebo.
  
  
  METHODS
  The main outcome measures in CAST were arrhythmic death and total mortality.
  
  
  RESULTS
  CAST found the 3 agents to be harmful. Encainide and flecainide were stopped first. Subsequently, moricizine was discontinued ahead of schedule.
  
  
  CONCLUSIONS
  The complexity of the study design and a midcourse protocol modification raise several data-monitoring issues not previously discussed. These include how to handle apparently dramatic yet unexpected results, the need for flexibility in modifying study design and goals, and the conflict between existing study data and both conventional wisdom and medical practice.
authors.affiliation: National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
authors.forename: L M
authors.initials: LM
authors.lastname: Friedman
authors.forename: J D
authors.initials: JD
authors.lastname: Bristow
authors.forename: A
authors.initials: A
authors.lastname: Hallstrom
authors.forename: E
authors.initials: E
authors.lastname: Schron
authors.forename: M
authors.initials: M
authors.lastname: Proschan
authors.forename: J
authors.initials: J
authors.lastname: Verter
authors.forename: D
authors.initials: D
authors.lastname: DeMets
authors.forename: C
authors.initials: C
authors.lastname: Fisch
authors.forename: A S
authors.initials: AS
authors.lastname: Nies
authors.forename: J
authors.initials: J
authors.lastname: Ruskin
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D003627:Data Interpretation, Statistical; D003657:Decision Making; D005260:Female; D006801:Humans; D008297:Male; D015337:Multicenter Studies as Topic; D009203:Myocardial Infarction / Q000150:complications; D011367:Professional Staff Committees; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
chemical_list: D000889:Anti-Arrhythmia Agents