title: Evaluating the Importance of Heterogeneity of Treatment Effect: Variation in Patient Utilities Can Influence Choice of the "Optimal" Oral Anticoagulant for Atrial Fibrillation.
abstract: To investigate heterogeneity of treatment effect (HTE) for anticoagulants in atrial fibrillation across subgroups defined by 1) clinical characteristics and 2) variation in patient utilities for benefits and harms of treatment.
  
  
  
  We reanalyzed aggregate data from a published network meta-analysis that compared four anticoagulants for atrial fibrillation (apixaban, dabigatran, edoxaban, and rivaroxaban) as well as warfarin. Event rates for stroke/systemic embolism (SE) and major bleeding were generated for each agent across seven subgroups, and rankings were developed on the basis of clinical performance. Utilities were derived from a national catalog and then applied to generate summary measures of benefit. The choice between any two agents was examined across a range of plausible utility values, defined as the interquartile range for stroke/SE and major bleeding.
  
  
  
  Little HTE was apparent in clinical and utility-adjusted analyses. Dabigatran 150 mg produced the lowest rates of stroke/SE, and edoxaban 30 mg had the lowest rate of major bleeding. Greater HTE was observed when utilities were varied across a plausible utility range. For example, among patients 75 years and older, dabigatran 150 mg would be preferred over edoxaban 30 mg when mean utility estimates are used. The preferred agent, however, would change at plausible utility thresholds of 0.6 and 0.7 for major bleeding and stroke/SE, respectively. Nearly 25% of all possible comparisons would see a change in preferred treatment within the plausible utility range.
  
  
  
  The optimal choice of anticoagulant in atrial fibrillation differs across subgroups defined by clinical characteristics and reasonable ranges of utilities.
authors: Cornerstone Research Group, Burlington, ON, Canada.
authors: Christopher G
authors: CG
authors: Cameron
authors: Institute for Clinical and Economic Review, Boston, MA, USA.
authors: Patricia G
authors: PG
authors: Synnott
authors: Institute for Clinical and Economic Review, Boston, MA, USA.
authors: Steven D
authors: SD
authors: Pearson
authors: National Pharmaceutical Council, Washington, DC, USA.
authors: Robert W
authors: RW
authors: Dubois
authors: National Pharmaceutical Council, Washington, DC, USA.
authors: Michael
authors: M
authors: Ciarametaro
authors: Institute for Clinical and Economic Review, Boston, MA, USA. Electronic address: dollendorf@icer-review.org.
authors: Daniel A
authors: DA
authors: Ollendorf
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D005260:Female; D006304:Health Status; D006801:Humans; D008297:Male; D057240:Patient Preference; D011788:Quality of Life; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: atrial fibrillation; benefit-harm assessment comparative effectiveness research; efficacy; health-related quality of life; heterogeneity; network meta-analysis; new oral anticoagulants