Effects of the end point adjudication process on the results of the perindopril protection against recurrent stroke study (PROGRESS)

Toshiharu Ninomiya, Geoff Donnan, Neil Anderson, Chris Bladin, Brian Chambers, Gary Gordon, Norman Sharpe, John Chalmers, Mark Woodward, Bruce Neal

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)2111-2115
Number of pages5
JournalStroke
Volume40
Issue number6
DOIs
Publication statusPublished - Jun 1 2009

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Perindopril
Stroke
Research Personnel
Cerebrovascular Disorders
Preexisting Condition Coverage
Advisory Committees
Proportional Hazards Models
Cause of Death
Myocardial Infarction
Clinical Trials
Blood Pressure

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

Cite this

Effects of the end point adjudication process on the results of the perindopril protection against recurrent stroke study (PROGRESS). / Ninomiya, Toshiharu; Donnan, Geoff; Anderson, Neil; Bladin, Chris; Chambers, Brian; Gordon, Gary; Sharpe, Norman; Chalmers, John; Woodward, Mark; Neal, Bruce.

In: Stroke, Vol. 40, No. 6, 01.06.2009, p. 2111-2115.

Research output: Contribution to journalArticle

Ninomiya, T, Donnan, G, Anderson, N, Bladin, C, Chambers, B, Gordon, G, Sharpe, N, Chalmers, J, Woodward, M & Neal, B 2009, 'Effects of the end point adjudication process on the results of the perindopril protection against recurrent stroke study (PROGRESS)', Stroke, vol. 40, no. 6, pp. 2111-2115. https://doi.org/10.1161/STROKEAHA.108.539601
Ninomiya, Toshiharu ; Donnan, Geoff ; Anderson, Neil ; Bladin, Chris ; Chambers, Brian ; Gordon, Gary ; Sharpe, Norman ; Chalmers, John ; Woodward, Mark ; Neal, Bruce. / Effects of the end point adjudication process on the results of the perindopril protection against recurrent stroke study (PROGRESS). In: Stroke. 2009 ; Vol. 40, No. 6. pp. 2111-2115.
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AU - Ninomiya, Toshiharu

AU - Donnan, Geoff

AU - Anderson, Neil

AU - Bladin, Chris

AU - Chambers, Brian

AU - Gordon, Gary

AU - Sharpe, Norman

AU - Chalmers, John

AU - Woodward, Mark

AU - Neal, Bruce

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N2 - 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.

AB - 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.

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