title: Prediction of individual combined benefit and harm for patients with atrial fibrillation considering warfarin therapy: a study protocol.
abstract: BACKGROUND
  Clinical prediction rules have been validated and widely used in patients with atrial fibrillation (AF) to predict stroke and major bleeding. However, these prediction rules were not developed in the same population, and do not provide the key information that patients and prescribers need at the time anticoagulants are being considered-what is the individual patient-specific risk of both benefit (decreased stroke) and harm (increased major bleeding). In this study, our primary objective is to develop and validate a prediction model for patients' individual combined benefit and harm outcomes (stroke, major bleeding and neither event) with and without warfarin therapy. Our secondary outcome is all-cause mortality.
  
  
  METHODS
  We will use data from the Kaiser Permanente Colorado (KPCO) anticoagulation management databases and electronic medical records. Patients with a primary or secondary diagnosis during an ambulatory KPCO medical office visit, emergency department visit, or inpatient stay between 1 January 2005 and 31 December 2012 with no AF diagnosis in the previous 180 days will be included. Patients' demographic characteristics, laboratory data, comorbidities, warfarin medication data and concurrent use of medication will be used to construct the prediction model. For primary outcomes (stroke with no major bleeding, and major bleeding with no stroke), we will perform polytomous logistic regression to develop a prediction model for patients' individual combined benefit and harm outcomes, taking neither event group as the reference group. As regards death, we will use Cox proportional hazards regression analysis to build a prediction model for all-cause mortality.
  
  
  BACKGROUND
  This study has been approved by the KPCO Institutional Review Board and the Hamilton Integrated Research Ethics Board. Results from this study will be published in a peer-reviewed journal electronically and in print. The prediction models may aid in patient-physician shared decision-making when they are considering warfarin therapy.
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Guowei
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada St. Joseph's Hospital, McMaster University, Hamilton, Ontario, Canada Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Anne
authors.initials: A
authors.lastname: Holbrook
authors.affiliation: Kaiser Permanente Colorado Clinical Pharmacy Research Team, Aurora, Colorado, USA University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Denver, Colorado, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Delate
authors.affiliation: Department of Pharmacotherapy, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Witt
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada St. Joseph's Hospital, McMaster University, Hamilton, Ontario, Canada Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Mitchell Ah
authors.initials: MA
authors.lastname: Levine
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada St. Joseph's Hospital, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Lehana
authors.initials: L
authors.lastname: Thabane
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications* / Q000188:drug therapy / Q000401:mortality*; D003120:Colorado / Q000453:epidemiology; D016208:Databases, Factual; D057286:Electronic Health Records; D005260:Female; D006470:Hemorrhage / Q000175:diagnosis*; D006801:Humans; D016015:Logistic Models; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D012107:Research Design; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis* / Q000517:prevention & control; D016896:Treatment Outcome; D054928:Validation Studies as Topic; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: EPIDEMIOLOGY