Effects of the Endpoint Adjudication Process on the Results of a Randomised Controlled Trial: The ADVANCE Trial

Jun Hata, Hisatomi Arima, Sophia Zoungas, Greg Fulcher, Carol Pollock, Mark Adams, John Watson, Rohina Joshi, Andre Pascal Kengne, Toshiharu Ninomiya, Craig Anderson, Mark Woodward, Anushka Patel, Giuseppe Mancia, Neil Poulter, Stephen MacMahon, John Chalmers, Bruce Neal

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Article numbere55807
JournalPLoS One
Volume8
Issue number2
DOIs
Publication statusPublished - Feb 4 2013

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Blood pressure
endpoints
Screening
Randomized Controlled Trials
Research Personnel
committees
Medical problems
Myocardial Infarction
Clinical Trials
Blood Pressure
Blood Glucose
Lead
Risk Reduction Behavior
Glucose
Type 2 Diabetes Mellitus
Databases
Confidence Intervals
blood pressure
clinical trials
screening

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Hata, J., Arima, H., Zoungas, S., Fulcher, G., Pollock, C., Adams, M., ... Neal, B. (2013). Effects of the Endpoint Adjudication Process on the Results of a Randomised Controlled Trial: The ADVANCE Trial. PLoS One, 8(2), [e55807]. https://doi.org/10.1371/journal.pone.0055807

Effects of the Endpoint Adjudication Process on the Results of a Randomised Controlled Trial : The ADVANCE Trial. / Hata, Jun; Arima, Hisatomi; Zoungas, Sophia; Fulcher, Greg; Pollock, Carol; Adams, Mark; Watson, John; Joshi, Rohina; Kengne, Andre Pascal; Ninomiya, Toshiharu; Anderson, Craig; Woodward, Mark; Patel, Anushka; Mancia, Giuseppe; Poulter, Neil; MacMahon, Stephen; Chalmers, John; Neal, Bruce.

In: PLoS One, Vol. 8, No. 2, e55807, 04.02.2013.

Research output: Contribution to journalArticle

Hata, J, Arima, H, Zoungas, S, Fulcher, G, Pollock, C, Adams, M, Watson, J, Joshi, R, Kengne, AP, Ninomiya, T, Anderson, C, Woodward, M, Patel, A, Mancia, G, Poulter, N, MacMahon, S, Chalmers, J & Neal, B 2013, 'Effects of the Endpoint Adjudication Process on the Results of a Randomised Controlled Trial: The ADVANCE Trial', PLoS One, vol. 8, no. 2, e55807. https://doi.org/10.1371/journal.pone.0055807
Hata, Jun ; Arima, Hisatomi ; Zoungas, Sophia ; Fulcher, Greg ; Pollock, Carol ; Adams, Mark ; Watson, John ; Joshi, Rohina ; Kengne, Andre Pascal ; Ninomiya, Toshiharu ; Anderson, Craig ; Woodward, Mark ; Patel, Anushka ; Mancia, Giuseppe ; Poulter, Neil ; MacMahon, Stephen ; Chalmers, John ; Neal, Bruce. / Effects of the Endpoint Adjudication Process on the Results of a Randomised Controlled Trial : The ADVANCE Trial. In: PLoS One. 2013 ; Vol. 8, No. 2.
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AU - Watson, John

AU - Joshi, Rohina

AU - Kengne, Andre Pascal

AU - Ninomiya, Toshiharu

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