title: Can We Predict Individual Combined Benefit and Harm of Therapy? Warfarin Therapy for Atrial Fibrillation as a Test Case.
abstract: OBJECTIVE
  To construct and validate a prediction model for individual combined benefit and harm outcomes (stroke with no major bleeding, major bleeding with no stroke, neither event, or both) in patients with atrial fibrillation (AF) with and without warfarin therapy.
  
  
  METHODS
  Using the Kaiser Permanente Colorado databases, we included patients newly diagnosed with AF between January 1, 2005 and December 31, 2012 for model construction and validation. The primary outcome was a prediction model of composite of stroke or major bleeding using polytomous logistic regression (PLR) modelling. The secondary outcome was a prediction model of all-cause mortality using the Cox regression modelling.
  
  
  RESULTS
  We included 9074 patients with 4537 and 4537 warfarin users and non-users, respectively. In the derivation cohort (n = 4632), there were 136 strokes (2.94%), 280 major bleedings (6.04%) and 1194 deaths (25.78%) occurred. In the prediction models, warfarin use was not significantly associated with risk of stroke, but increased the risk of major bleeding and decreased the risk of death. Both the PLR and Cox models were robust, internally and externally validated, and with acceptable model performances.
  
  
  CONCLUSIONS
  In this study, we introduce a new methodology for predicting individual combined benefit and harm outcomes associated with warfarin therapy for patients with AF. Should this approach be validated in other patient populations, it has potential advantages over existing risk stratification approaches as a patient-physician aid for shared decision-making.
authors: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON, Canada.|St. Joseph's Hospital, McMaster University, Hamilton, ON, Canada.
authors: Guowei
authors: G
authors: Li
authors: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON, Canada.|St. Joseph's Hospital, McMaster University, Hamilton, ON, Canada.
authors: Lehana
authors: L
authors: Thabane
authors: Kaiser Permanente Colorado Clinical Pharmacy Research Team, Aurora, CO, United States of America.|University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Denver, CO, United States of America.
authors: Thomas
authors: T
authors: Delate
authors: Department of Pharmacotherapy, University of Utah, Salt Lake City, Utah, United States of America.
authors: Daniel M
authors: DM
authors: Witt
authors: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON, Canada.|St. Joseph's Hospital, McMaster University, Hamilton, ON, Canada.|Division of Clinical Pharmacology & Toxicology, Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors: Mitchell A H
authors: MA
authors: Levine
authors: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON, Canada.|St. Joseph's Hospital, McMaster University, Hamilton, ON, Canada.
authors: Ji
authors: J
authors: Cheng
authors: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON, Canada.|St. Joseph's Hospital, McMaster University, Hamilton, ON, Canada.|Division of Clinical Pharmacology & Toxicology, Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors: Anne
authors: A
authors: Holbrook
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D016208:Databases, Factual; D005260:Female; D006801:Humans; D008297:Male; D011379:Prognosis; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin