Data monitoring in the cardiac arrhythmia suppression trial.
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.
Friedman
L M
LM
National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
Bristow
J D
JD
Hallstrom
A
A
Schron
E
E
Proschan
M
M
Verter
J
J
DeMets
D
D
Fisch
C
C
Nies
A S
AS
Ruskin
J
J
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
D000889:Anti-Arrhythmia Agents