Assessment of the End Point Adjudication Process on the Results of the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial : A Secondary Analysis
Farrant, Mary (University of California)
Easton, J.Donald (University of California)
Adelman, Eric E. (University of Wisconsin)
Cucchiara, Brett L. (University of Pennsylvania)
Barsan, Willian G. (University of Michigan)
Tillman, Holly J. (Medical University of South Carolina)
Elm, Jordan J. (Medical University of South Carolina)
Kim, Anthony S. (University of California)
Lindblad, Anne S. (Emmes Corporation)
Palesch, Yuyo Y. (Medical University of South Carolina)
Zhao, Wenle (Medical University of South Carolina)
Pauls, Keith (Medical University of South Carolina)
Walsh, Kyle B. (University of Cincinnati)
Martí-Fàbregas, Joan (Institut d'Investigació Biomèdica Sant Pau)
Bernstein, Richard A. (Northwestern University)
Johnston, Claiborne (University of Texas at Austin)
Universitat Autònoma de Barcelona

Data:	2019
Resum:	Debate continues about the value of event adjudication in clinical trials and whether independent centralized assessments improve reliability and validity of study results in masked randomized trials compared with local, investigator-assessed end points. To assess the results of the adjudicated end point process in the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial by comparing end points assessed by local site investigators with centrally adjudicated end points. This is an ad hoc secondary analysis of a randomized, double-blind clinical trial comparing safety and effectiveness of clopidogrel bisulphate plus aspirin vs placebo plus aspirin. Patients received either 600 mg of clopidogrel bisulphate on day 1, then 75 mg per day through day 90 plus 50 to 325 mg of aspirin per day, or the same range of dosages of placebo plus aspirin. Investigators reported all potential end points; independent masked adjudicators were randomly assigned to review using definitions specified in the study protocol. This was a multicenter study; 269 international sites in 10 countries enrolled from May 28, 2010, to December 19, 2017. The study enrolled 4881 patients 18 years or older with transient ischemic attack or minor acute ischemic stroke within 12 hours of symptom onset and followed for 90 days from randomization; last follow-up was completed in March 2018. Independent adjudicators external to the study and masked to study treatment assignment adjudicated 467 primary and secondary effectiveness outcomes and major and minor bleeding events, including the primary composite end point, which was the risk of a composite of major ischemic events at 90 days, defined as ischemic stroke, myocardial infarction, or death from an ischemic vascular event. The primary safety end point was major hemorrhage. All components of the primary and safety outcomes were adjudicated. In this secondary analysis of an international randomized clinical trial, a total of 269 sites worldwide randomized 4881 patients (median age, 65. 0 years; interquartile range, 55-74 years); 55. 0% were male. The primary results have been published previously. The hazard ratios for clopidogrel plus aspirin vs placebo plus aspirin for the primary composite end point were 0. 75 (95% CI, 0. 59-0. 95) for adjudicator-assessed events and 0. 76 (95% CI, 0. 60-0. 95) for investigator-assessed events. Agreement between adjudicator and investigator assessments was 90. 7%. The hazard ratios for clopidogrel plus aspirin vs placebo plus aspirin for the primary safety end point were 2. 32 (95% CI, 1. 10-4. 87) for adjudicator-assessed events and 2. 58 (95% CI, 1. 19-5. 58) for investigator-assessed events, with an agreement rate of 77. 5%. Conclusions and Relevance: Independent end point adjudication did not substantially alter estimates of the primary treatment effectiveness in the POINT trial.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	JAMA network open, Vol. 2 Núm. 9 (june 2019) , p. e1910769, ISSN 2574-3805

DOI: 10.1001/jamanetworkopen.2019.10769
PMID: 31490536

10 p, 790.0 KB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Recerca Sant Pau
Articles > Articles de recerca
Articles > Articles publicats