Diagnostic criteria and adjudication process both determine published event-rates: the ACTION trial experience.
OBJECTIVE
Few trials report event-adjudication procedures in detail. Using data from the ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) study, we compared the impact on event-rates of an adjudication strategy based on systematic screening of all reported serious adverse events (SAEs) with a strategy based on investigator diagnoses. The final diagnosis was always made by a critical events committee (CEC) using standard criteria.


METHODS
ACTION randomized 7665 patients with stable angina to either nifedipine or placebo. Pre-specified events included acute or procedural myocardial infarction (MI), refractory angina, heart failure and debilitating stroke. Clinically related SAEs including in-hospital procedures were combined into episodes independent from the investigator diagnoses entered on SAE reports. All fatal episodes and those episodes suggestive of pre-specified events were adjudicated by the CEC.


RESULTS
During follow-up, 17,081 episodes were reported in 5312 patients. The SAE descriptions ruled out the occurrence of a pre-specified event in 28%. The remaining 72% were adjudicated by the CEC and 616 cases of MI, 361 of refractory angina, 275 of heart failure and 190 of debilitating stroke were diagnosed (total=1442). Had adjudication by the CEC been limited to the 3924 episodes (2397 patients) that were fatal or for which the investigator had reported any of the diagnoses mentioned, 98 cases of MI, 35 of refractory angina, 81 of heart failure and 14 of debilitating stroke would have been missed (total=228).


CONCLUSIONS
Both the diagnostic criteria used and the adjudication process determine event-rates and conclusions about treatment effects in clinical trials. Published trial reports should always state if event-adjudication was independent of the diagnoses of investigators, and if all events of interest were adjudicated or only the first one.
Kirwan
Bridget-Anne
BA
SOCAR Research, PO Box 2564, CH-1260 Nyon, Switzerland.
Lubsen
Jacobus
J
de Brouwer
Sophie
S
Danchin
Nicolas
N
Battler
Alexander
A
Bayes de Luna
Antonio
A
Dunselman
Peter H J M
PH
Glasser
Stephen
S
Koudstaal
Peter J
PJ
Sutton
George
G
van Dalen
Frederik J
FJ
Poole-Wilson
Philip A
PA
D000328:Adult; D003324:Coronary Artery Disease / Q000188:drug therapy*; D006801:Humans; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010919:Placebos; D018571:Sentinel Surveillance; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D010919:Placebos; D014665:Vasodilator Agents; D009543:Nifedipine