Effects of the end point adjudication process on the results of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS).
OBJECTIVE
End point adjudication committees (EPAC) are widely used in large-scale clinical trials to ensure the robustness of diagnosis for end points.


METHODS
The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a double-blind randomized trial of blood pressure lowering in 6105 participants with pre-existing cerebrovascular disease. Separate estimates of the effects of randomized treatment were determined using Cox regression models that were based on the unadjudicated events initially reported by the investigator and on the final events assigned by the EPAC.


RESULTS
There were 992 strokes initially reported by the investigators and 894 (90%) retained these diagnoses after adjudication by the EPAC. The hazard ratios (95% CIs) for the effect of randomized treatment on stroke were 0.74 (0.64 to 0.85) based on the investigator diagnoses and 0.72 (0.62 to 0.83) based on the EPAC diagnoses (P homogeneity=0.7). For each stroke subtype reported, the corresponding numbers of diagnoses (investigators/EPAC) were ischemic (593/565), hemorrhagic (124/111), and unknown (124/93) with no impact of the EPAC review on the estimates of treatment effects (all P homogeneity >0.3). There was likewise no detectable effect of reclassification of diagnoses for the effect estimates calculated for myocardial infarction or the main causes of death (all P homogeneity >0.5).


CONCLUSIONS
The EPAC process had no discernible impact on the trial conclusions. Very large trials powered to detect effects on stroke subtypes might obtain real scientific gain from an EPAC, but in the case of PROGRESS, the value of the EPAC was in the reassurance it provided.
The George Institute for International Health, University of Sydney, Sydney, Australia.
Toshiharu
T
Ninomiya
Geoff
G
Donnan
Neil
N
Anderson
Chris
C
Bladin
Brian
B
Chambers
Gary
G
Gordon
Norman
N
Sharpe
John
J
Chalmers
Mark
M
Woodward
Bruce
B
Neal
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000150:complications; D002543:Cerebral Hemorrhage / Q000150:complications; D004311:Double-Blind Method; D023381:Endpoint Determination; D006801:Humans; D020913:Perindopril / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012044:Regression Analysis; D055502:Secondary Prevention; D020521:Stroke / Q000175:diagnosis / Q000473:pathology / Q000517:prevention & control*; D009626:Terminology as Topic
D000806:Angiotensin-Converting Enzyme Inhibitors; D020913:Perindopril