Background: Endpoint adjudication committees (EPAC) are widely used in clinical trials. The aim of the present analysis is to
assess the effects of the endpoint adjudication process on the main findings of the ADVANCE trial (Trial registration:
Methods and Findings: The ADVANCE trial was a multicentre, 262 factorial randomised controlled trial of blood pressure
lowering and intensive blood glucose control in 11140 patients with type 2 diabetes. Primary outcomes were major
macrovascular (nonfatal myocardial infarction, nonfatal stroke and cardiovascular death) and microvascular (new or
worsening nephropathy and retinopathy) events. Suspected primary outcomes were initially reported by the investigators
at the 215 sites with subsequent adjudication by the EPAC. The EPAC also adjudicated upon potential events identified
directly by ongoing screening of all reported events. Over a median follow-up of 5 years, the site investigators reported one
or more primary outcomes among 2443 participants. After adjudication these events were confirmed for 2077 (85 ) with 48
further events added through the EPAC-led database screening process. The estimated relative risk reductions (95
confidence intervals) in the primary outcome for the blood pressure lowering comparison were 8 (21 to 15 ) based on
the investigator-reported events and 9 (0 to 17 ) based on the EPAC-based events (P for homogeneity = 0.70). The
corresponding findings for the glucose comparison were 8 (1 to 15 ) and 10 (2 to 18 ) (P for homogeneity = 0.60).
The effect estimates were also highly comparable when studied separately for macrovascular events and microvascular
events for both comparisons (all P for homogeneity.0.6).
Conclusions: The endpoint adjudication process had no discernible impact on the main findings in ADVANCE. These data
highlight the need for careful consideration of the likely impact of an EPAC on the findings and conclusions of clinical trials
prior to their establishment.