Key result
End point adjudication has no impact on the estimated effect of blood pressure lowering on stroke.
Why the study?
End point adjudication committees are widely used in large-scale clinical trials to ensure robustness of diagnosis for end points, but their impact on trial results is unclear.
Does the use of an End Point Adjudication Committee (EPAC) alter the estimated treatment effects of blood pressure lowering on stroke in patients with pre-existing cerebrovascular disease?
RCT (n=6,105)
Double-blind
Does the use of an End Point Adjudication Committee (EPAC) alter the estimated treatment effects of blood pressure lowering on stroke in patients with pre-existing cerebrovascular disease?
Hazard Ratio: 0.72 (95% CI 0.62–0.83)
p-value: P homogeneity=0.7
The use of an End Point Adjudication Committee in the PROGRESS trial had no discernible impact on the trial's conclusions regarding treatment effects on stroke, myocardial infarction, or death.
Investigator adjudication produces equivalent BP-lowering effects on stroke versus EPAC; confirms trial robustness and supports simplified endpoint assessment in future cerebrovascular RCTs.
BACKGROUND AND PURPOSE: 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.
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A 2009 study conducted an RCT in pre-existing cerebrovascular disease (n=6,105). Blood pressure lowering was evaluated on stroke (HR 0.72, 95% CI 0.62 to 0.83, p=P homogeneity=0.7). End point adjudication committee review had no impact on the estimated effect of blood pressure lowering on stroke (HR 0.72 for EPAC vs HR 0.74 for investigators; P homogeneity=0.7).
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