title: Applying the intention-to-treat principle in practice: Guidance on handling randomisation errors.
abstract: BACKGROUND
  The intention-to-treat principle states that all randomised participants should be analysed in their randomised group. The implications of this principle are widely discussed in relation to the analysis, but have received limited attention in the context of handling errors that occur during the randomisation process. The aims of this article are to (1) demonstrate the potential pitfalls of attempting to correct randomisation errors and (2) provide guidance on handling common randomisation errors when they are discovered that maintains the goals of the intention-to-treat principle.
  
  
  METHODS
  The potential pitfalls of attempting to correct randomisation errors are demonstrated and guidance on handling common errors is provided, using examples from our own experiences.
  
  
  RESULTS
  We illustrate the problems that can occur when attempts are made to correct randomisation errors and argue that documenting, rather than correcting these errors, is most consistent with the intention-to-treat principle. When a participant is randomised using incorrect baseline information, we recommend accepting the randomisation but recording the correct baseline data. If ineligible participants are inadvertently randomised, we advocate keeping them in the trial and collecting all relevant data but seeking clinical input to determine their appropriate course of management, unless they can be excluded in an objective and unbiased manner. When multiple randomisations are performed in error for the same participant, we suggest retaining the initial randomisation and either disregarding the second randomisation if only one set of data will be obtained for the participant, or retaining the second randomisation otherwise. When participants are issued the incorrect treatment at the time of randomisation, we propose documenting the treatment received and seeking clinical input regarding the ongoing treatment of the participant.
  
  
  CONCLUSIONS
  Randomisation errors are almost inevitable and should be reported in trial publications. The intention-to-treat principle is useful for guiding responses to randomisation errors when they are discovered.
authors.affiliation: Women's & Children's Health Research Institute, The University of Adelaide, Adelaide, SA, Australia School of Population Health, The University of Adelaide, Adelaide, SA, Australia lisa.yelland@adelaide.edu.au.
authors.forename: Lisa N
authors.initials: LN
authors.lastname: Yelland
authors.affiliation: School of Population Health, The University of Adelaide, Adelaide, SA, Australia.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Sullivan
authors.affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Merryn
authors.initials: M
authors.lastname: Voysey
authors.affiliation: Murdoch Children's Research Institute, Parkville, VIC, Australia Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK Surgical Intervention Trials Unit, University of Oxford, Oxford, UK.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Cook
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Forbes
mesh_terms: D015982:Bias; D017408:Guidelines as Topic; D006801:Humans; D057194:Intention to Treat Analysis; D011897:Random Allocation
keywords: Randomisation error; guidelines; ineligible participant; intention to treat; randomised controlled trial