Effects of the endpoint adjudication process on the results of a randomised controlled trial: the ADVANCE trial.

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  • Additional Information
    • Corporate Authors:
      ADVANCE Collaborative Group
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Decision Making*; Antihypertensive Agents/*therapeutic use ; Diabetes Mellitus, Type 2/*drug therapy ; Diabetic Neuropathies/*drug therapy ; Diabetic Retinopathy/*drug therapy ; Hypertension/*drug therapy ; Hypoglycemic Agents/*therapeutic use ; Myocardial Infarction/*drug therapy ; Stroke/*drug therapy; Aged ; Antihypertensive Agents/pharmacology ; Blood Glucose/analysis ; Blood Pressure/drug effects ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/complications ; Diabetic Neuropathies/blood ; Diabetic Neuropathies/complications ; Diabetic Retinopathy/blood ; Diabetic Retinopathy/complications ; Drug Therapy, Combination ; Female ; Humans ; Hypertension/blood ; Hypertension/complications ; Hypoglycemic Agents/pharmacology ; Male ; Middle Aged ; Myocardial Infarction/blood ; Myocardial Infarction/etiology ; Stroke/blood ; Stroke/etiology ; Treatment Outcome
    • 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).
      Methods and Findings: 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.
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    • Molecular Sequence:
      ClinicalTrials.gov NCT00145925
    • Accession Number:
      0 (Antihypertensive Agents)
      0 (Blood Glucose)
      0 (Hypoglycemic Agents)
    • Publication Date:
      Date Created: 20130208 Date Completed: 20130719 Latest Revision: 20220330
    • Publication Date:
      20221213
    • Accession Number:
      PMC3563633
    • Accession Number:
      10.1371/journal.pone.0055807
    • Accession Number:
      23390553