Estimated treatment effect of ticagrelor versus aspirin by investigator-assessed events compared with judgement by an independent event adjudication committee in the SOCRATES trial

for the SOCRATES Steering Committee and Investigators

Research output: Contribution to journalArticle

Abstract

Background: Adjudication of endpoints is a standard procedure in cardiovascular clinical trials. However, several studies indicate that the benefit of adjudication in estimating treatment effect may be limited. Aims: This post hoc analysis of SOCRATES (NCT01994720) compared the treatment effects and investigated the agreement of clinical event assessment by site investigators and independent adjudicators. Methods: SOCRATES compared ticagrelor and aspirin in 13,199 patients with acute minor stroke or high-risk transient ischemic attack. The primary endpoint was stroke, myocardial infarction, or death. Stroke was the major component of the primary endpoint and a secondary endpoint. The endpoints were adjudicated by a blinded independent committee. We compared the treatment effect on the primary endpoint and stroke alone based on the investigators' and adjudicators' assessments, and investigated the agreement rate on the stroke endpoint and major hemorrhages. Results: The hazard ratios (95% confidence interval) for ticagrelor versus aspirin therapy for the primary endpoint were 0.89 (0.78–1.01) when calculated on adjudicator-assessed events and 0.88 (0.78–1.00) for investigator-assessed events. The hazard ratios (95% confidence intervals) for stroke were 0.86 (0.75–0.99) based on the adjudicators' diagnoses and 0.85 (0.75–0.97) based on the investigators' diagnoses. The overall agreement between adjudicator- and investigator-diagnosed stroke was 91%, and for major hemorrhages was 88%. Conclusions: In SOCRATES, there was no clinically meaningful difference in the estimated treatment effect, on either the primary endpoint or stroke, by using investigator- or adjudicator-assessed events. Double-blind treatment outcome studies with stroke endpoints may not benefit from adjudication. Trial Registration: ClinicalTrials.gov Identifier: NCT01994720.

Original languageEnglish (US)
Pages (from-to)908-914
Number of pages7
JournalInternational Journal of Stroke
Volume14
Issue number9
DOIs
StatePublished - Dec 1 2019

Fingerprint

Aspirin
Stroke
Research Personnel
Therapeutics
Confidence Intervals
Hemorrhage
Ticagrelor
Transient Ischemic Attack
Myocardial Infarction
Outcome Assessment (Health Care)
Clinical Trials

Keywords

  • Stroke
  • adjudication
  • aspirin
  • clinical trials
  • ticagrelor
  • transient ischemic attack

ASJC Scopus subject areas

  • Neurology

Cite this

Estimated treatment effect of ticagrelor versus aspirin by investigator-assessed events compared with judgement by an independent event adjudication committee in the SOCRATES trial. / for the SOCRATES Steering Committee and Investigators.

In: International Journal of Stroke, Vol. 14, No. 9, 01.12.2019, p. 908-914.

Research output: Contribution to journalArticle

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abstract = "Background: Adjudication of endpoints is a standard procedure in cardiovascular clinical trials. However, several studies indicate that the benefit of adjudication in estimating treatment effect may be limited. Aims: This post hoc analysis of SOCRATES (NCT01994720) compared the treatment effects and investigated the agreement of clinical event assessment by site investigators and independent adjudicators. Methods: SOCRATES compared ticagrelor and aspirin in 13,199 patients with acute minor stroke or high-risk transient ischemic attack. The primary endpoint was stroke, myocardial infarction, or death. Stroke was the major component of the primary endpoint and a secondary endpoint. The endpoints were adjudicated by a blinded independent committee. We compared the treatment effect on the primary endpoint and stroke alone based on the investigators' and adjudicators' assessments, and investigated the agreement rate on the stroke endpoint and major hemorrhages. Results: The hazard ratios (95{\%} confidence interval) for ticagrelor versus aspirin therapy for the primary endpoint were 0.89 (0.78–1.01) when calculated on adjudicator-assessed events and 0.88 (0.78–1.00) for investigator-assessed events. The hazard ratios (95{\%} confidence intervals) for stroke were 0.86 (0.75–0.99) based on the adjudicators' diagnoses and 0.85 (0.75–0.97) based on the investigators' diagnoses. The overall agreement between adjudicator- and investigator-diagnosed stroke was 91{\%}, and for major hemorrhages was 88{\%}. Conclusions: In SOCRATES, there was no clinically meaningful difference in the estimated treatment effect, on either the primary endpoint or stroke, by using investigator- or adjudicator-assessed events. Double-blind treatment outcome studies with stroke endpoints may not benefit from adjudication. Trial Registration: ClinicalTrials.gov Identifier: NCT01994720.",
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author = "{for the SOCRATES Steering Committee and Investigators} and Easton, {J. Donald} and Hans Denison and Evans, {Scott R.} and Mikael Knutsson and Pierre Amarenco and Albers, {Gregory W.} and Per Ladenvall and Kazuo Minematsu and Molina, {Carlos A.} and Yongjun Wang and Wong, {KS Lawrence} and Johnston, {S. Claiborne}",
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AU - Easton, J. Donald

AU - Denison, Hans

AU - Evans, Scott R.

AU - Knutsson, Mikael

AU - Amarenco, Pierre

AU - Albers, Gregory W.

AU - Ladenvall, Per

AU - Minematsu, Kazuo

AU - Molina, Carlos A.

AU - Wang, Yongjun

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