This Article Full Text Full Text (PDF) All Versions of this Article: 40/6/2111    most recent STROKEAHA.108.539601v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ninomiya, T. Search for Related Content PubMed PubMed Citation Articles by Ninomiya, T. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Stroke Related Collections Clinical Studies Acute myocardial infarction Acute Cerebral Infarction

(Stroke. 2009;40:2111.)
© 2009 American Heart Association, Inc.

Original Contributions

Effects of the End Point Adjudication Process on the Results of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS)

Toshiharu Ninomiya, MD, PhD; Geoff Donnan, MD; Neil Anderson, MD, PhD; Chris Bladin, MD; Brian Chambers, MD; Gary Gordon, MD; Norman Sharpe, MD; John Chalmers, MD, PhD; Mark Woodward, PhD; Bruce Neal, MD, PhD for the PROGRESS Collaborative Group

From the The George Institute for International Health (T.N., J.C., M.W., B.N.), Sydney, Australia; the University of Melbourne (G.D., B.C.), Melbourne, Australia; Auckland City Hospital (N.A.), Auckland, New Zealand; Box Hill Hospital (C.B., G.G.), Melbourne, Australia; Monash University (C.B.), Melbourne, Australia; National Stroke Research Institute (G.D., B.C.), Melbourne, Australia; Austin Health (B.C.), Melbourne, Australia; University of Auckland (N.S.), Auckland, New Zealand; the University of Sydney (J.C., M.W., B.N.), Sydney, Australia; and Mount Sinai Medical Center (M.W.), New York, NY.

Correspondence to Bruce Neal, The George Institute for International Health, University of Sydney, Level 10, King George V Building, Royal Prince Alfred Hospital, Camperdown, Sydney NSW 2050, Australia. E-mail bneal{at}george.org.au

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).

Conclusion— 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.

Key Words: adjudication • clinical trial • outcomes

This article has been cited by other articles:

				D. R. Kerr and E. Nasco Value of Central Event Adjudication Stroke, November 1, 2009; 40(11): e638 - e638. [Full Text] [PDF]

				B. Neal, T. Ninomiya, G. Donnan, N. Anderson, C. Bladin, B. Chambers, G. Gordon, N. Sharpe, J. Chalmers, and M. Woodward Response to Letter by Kerr and Nasco Stroke, November 1, 2009; 40(11): e639 - e640. [Full Text] [PDF]