title: Post-trial follow-up methodology in large randomized controlled trials: a systematic review protocol.
abstract: Clinical trials typically have a relatively short follow-up period, and may both underestimate potential benefits of treatments investigated, and fail to detect hazards, which can take much longer to emerge. Prolonged follow-up of trial participants after the end of the scheduled trial period can provide important information on both efficacy and safety outcomes. This protocol describes a systematic review to qualitatively compare methods of post-trial follow-up used in large randomized controlled trials.
  
  
  
  A systematic search of electronic databases and clinical trial registries will use a predefined search strategy. All large (more than 1000 adult participants) randomized controlled trials will be evaluated. Two reviewers will screen and extract data according to this protocol with the aim of 95% concordance of papers checked and discrepancies will be resolved by a third reviewer. Trial methods, participant retention rates and prevalence of missing data will be recorded and compared. The potential for bias will be evaluated using the Cochrane Risk of Bias tool (applied to the methods used during the in-trial period) with the aim of investigating whether the quality of the post-trial follow-up methodology might be predicted by the quality of the methods used for the original trial.
  
  
  
  Post-trial follow-up can provide valuable information about the long-term benefits and hazards of medical interventions. However, it can be logistically challenging and costly. The aim of this systematic review is to describe how trial participants have been followed-up post-trial in order to inform future post-trial follow-up designs.
  
  
  
  Not applicable for PROSPERO registration.
authors.affiliation: Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford, OX3 7LF, UK. rebecca.llewellyn-bennett@ndph.ox.ac.uk.
authors.forename: Rebecca
authors.identifier: 0000-0002-9708-9923
authors.initials: R
authors.lastname: Llewellyn-Bennett
authors.affiliation: Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford, OX3 7LF, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Bowman
authors.affiliation: Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford, OX3 7LF, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Bulbulia
mesh_terms: D005500:Follow-Up Studies; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D000078202:Systematic Reviews as Topic
keywords: Cost; Effective; Follow-up; Long term; Methodology; Post-trial; Randomized controlled trial; Retention