title: Protecting the pipeline of science: openness, scientific methods and the lessons from ticagrelor and the PLATO trial.
abstract: Ticagrelor, a potent antiplatelet, has been shown to be beneficial in patients with acute coronary syndromes in a randomised controlled trial published in a highly ranked peer reviewed journal. Accordingly it has entered guidelines and has been approved for clinical use by authorities. However, there remains a controversy regarding aspects of the PLATO trial, which are not immediately apparent from the peer-reviewed publications. A number of publications have sought to highlight potential discrepancies, using data available in publicly published documents from the US Food and Drug Administration (FDA) leading to disagreement regarding the value of open science and data sharing. We reflect upon potential sources of bias present in even rigorously performed randomised controlled trials, on whether peer review can establish the presence of bias and the need to constantly challenge and question even accepted data.
authors.affiliation: Monash University, Australia; University of Warwick, UK; International Journal of Cardiology, Australia. Electronic address: ajscoats@aol.com.
authors.forename: Andrew J Stewart
authors.initials: AJ
authors.lastname: Coats
authors.affiliation: Imperial College London, UK.
authors.forename: Sukhjinder S
authors.initials: SS
authors.lastname: Nijjer
authors.affiliation: Imperial College London, UK.
authors.forename: Darrel P
authors.initials: DP
authors.lastname: Francis
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015982:Bias; D006801:Humans; D017712:Peer Review, Research; D011643:Publishing; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000592:standards*; D012107:Research Design; D015871:Scientific Misconduct; D000077486:Ticagrelor; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D000077486:Ticagrelor; D000241:Adenosine
keywords: Blinding; Clinical trial; Research misconduct; Ticagrelor