J Donald Easton1, Hans Denison2, Scott R Evans3, Mikael Knutsson2, Pierre Amarenco4, Gregory W Albers5, Per Ladenvall2, Kazuo Minematsu6, Carlos A Molina7, Yongjun Wang8, Ks Lawrence Wong9, S Claiborne Johnston10. 1. Department of Neurology, University of California, San Francisco, USA. 2. Global Medicines Development, AstraZeneca, Gothenburg, Sweden. 3. Biostatistics Center, George Washington University, Washington, USA. 4. Department of Neurology and Stroke Centre, Bichat Hospital, Paris University, Paris, France. 5. Stanford Stroke Center, Stanford University, Stanford, USA. 6. Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan. 7. Stroke Unit, Hospital Vall d'Hebron, Barcelona, Spain. 8. Department of Neurology, Beijing Tiantan Hospital, Beijing, China. 9. Department of Medicine & Therapeutics, Chinese University of Hong Kong, Shatin, Hong Kong. 10. Dean's Office, Dell Medical School, University of Texas at Austin, Austin, USA.
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.
RCT Entities:
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.
Authors: Peter J Godolphin; Philip M Bath; Christopher Partlett; Eivind Berge; Martin M Brown; Misha Eliasziw; Per Morten Sandset; Joaquín Serena; Alan A Montgomery Journal: Eur Stroke J Date: 2020-02-26
Authors: S Claiborne Johnston; Pierre Amarenco; Hans Denison; Scott R Evans; Anders Himmelmann; Stefan James; Mikael Knutsson; Per Ladenvall; Carlos A Molina; Yongjun Wang Journal: Int J Stroke Date: 2019-02-12 Impact factor: 5.266
Authors: S Claiborne Johnston; Pierre Amarenco; Maria Aunes; Hans Denison; Scott R Evans; Anders Himmelmann; Marianne Jahreskog; Stefan James; Mikael Knutsson; Per Ladenvall; Carlos A Molina; Sven Nylander; Joachim Röther; Yongjun Wang Journal: Stroke Date: 2021-09-03 Impact factor: 7.914