title: Effects of the endpoint adjudication process on the results of a randomised controlled trial: the ADVANCE trial.
abstract: 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: ClinicalTrials.gov NCT00145925).
  
  
  RESULTS
  The ADVANCE trial was a multicentre, 2 × 2 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% (-1 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.
authors: The George Institute for Global Health, University of Sydney, Sydney, New South Wales, Australia.
authors: Jun
authors: J
authors: Hata
authors: Hisatomi
authors: H
authors: Arima
authors: Sophia
authors: S
authors: Zoungas
authors: Greg
authors: G
authors: Fulcher
authors: Carol
authors: C
authors: Pollock
authors: Mark
authors: M
authors: Adams
authors: John
authors: J
authors: Watson
authors: Rohina
authors: R
authors: Joshi
authors: Andre Pascal
authors: AP
authors: Kengne
authors: Toshiharu
authors: T
authors: Ninomiya
authors: Craig
authors: C
authors: Anderson
authors: Mark
authors: M
authors: Woodward
authors: Anushka
authors: A
authors: Patel
authors: Giuseppe
authors: G
authors: Mancia
authors: Neil
authors: N
authors: Poulter
authors: Stephen
authors: S
authors: MacMahon
authors: John
authors: J
authors: Chalmers
authors: Bruce
authors: B
authors: Neal
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D003657:Decision Making; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003929:Diabetic Neuropathies / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003930:Diabetic Retinopathy / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D020521:Stroke / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents
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