title: Interpreting trial results following use of different intention-to-treat approaches for preventing attrition bias: a meta-epidemiological study protocol.
abstract: BACKGROUND
  When participants drop out of randomised clinical trials, as frequently happens, the intention-to-treat (ITT) principle does not apply, potentially leading to attrition bias. Data lost from patient dropout/lack of follow-up are statistically addressed by imputing, a procedure prone to bias. Deviations from the original definition of ITT are referred to as modified intention-to-treat (mITT). As yet, the impact of the potential bias associated with mITT has not been assessed. Our objective is to investigate potential bias and disadvantages of performing mITT and evaluate possible concerns when executing different mITT approaches in meta-analyses.
  
  
  METHODS
  Using meta-epidemiology on randomised trials considered less prone to bias (ie, good internal validity) and assessing biological or targeted agents in patients with rheumatoid arthritis, we will meta-analyse data from 10 biological and targeted drugs based on collections of trials that would correspond to 10 individual meta-analyses.
  
  
  BACKGROUND
  This study will enhance transparency for evaluating mITT treatment effects described in meta-analyses. The intended audience will include healthcare researchers, policymakers and clinicians. Results of the study will be disseminated by peer-review publication.
  
  
  BACKGROUND
  In PROSPERO CRD42013006702, 11. December 2013.
authors.affiliation: Musculoskeletal Statistics Unit, Department of Rheumatology, The Parker Institute, Copenhagen University Hospitals, Bispebjerg and Frederiksberg, Denmark Department of Clinical Medicine, Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anna
authors.initials: A
authors.lastname: Dossing
authors.affiliation: Musculoskeletal Statistics Unit, Department of Rheumatology, The Parker Institute, Copenhagen University Hospitals, Bispebjerg and Frederiksberg, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Tarp
authors.affiliation: University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Beyene
authors.affiliation: Musculoskeletal Statistics Unit, Department of Rheumatology, The Parker Institute, Copenhagen University Hospitals, Bispebjerg and Frederiksberg, Denmark.
authors.forename: Bjarke B
authors.initials: BB
authors.lastname: Hansen
authors.affiliation: Musculoskeletal Statistics Unit, Department of Rheumatology, The Parker Institute, Copenhagen University Hospitals, Bispebjerg and Frederiksberg, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Bliddal
authors.affiliation: Musculoskeletal Statistics Unit, Department of Rheumatology, The Parker Institute, Copenhagen University Hospitals, Bispebjerg and Frederiksberg, Denmark.
authors.forename: Robin
authors.initials: R
authors.lastname: Christensen
mesh_terms: D015982:Bias; D003627:Data Interpretation, Statistical; D016021:Epidemiologic Studies; D006801:Humans; D057194:Intention to Treat Analysis / Q000706:statistics & numerical data*; D010352:Patient Dropouts / Q000706:statistics & numerical data*
keywords: CLINICAL PHARMACOLOGY; EPIDEMIOLOGY; RHEUMATOLOGY