title: A systematic review of randomised controlled trials in rheumatoid arthritis: the reporting and handling of missing data in composite outcomes.
abstract: Most reported outcome measures in rheumatoid arthritis (RA) trials are composite, whose components comprise single measures that are combined into one outcome. The aims of this review were to assess the range of missing data rates in primary composite outcomes and to document the current practice for handling and reporting missing data in published RA trials compared to the Consolidated Standards of Reporting Trials (CONSORT) recommendations.
  
  
  
  A systematic search for randomised controlled trials was conducted for RA trials published between 2008 and 2013 in four rheumatology and four high impact general medical journals.
  
  
  
  A total of 51 trials with a composite primary outcome were identified, of which 38 (75 %) used the binary American College of Rheumatology responder index and 13 (25 %) used the Disease Activity Score for 28 joints (DAS28). Forty-four trials (86 %) reported on an intention-to-treat analysis population, while 7 trials (14 %) analysed according to a modified intention-to-treat population. Missing data rates for the primary composite outcome ranged from 2-53 % and were above 30 % in 9 trials, 20-30 % in 11 trials, 10-20 % in 18 trials and below 10 % in 13 trials. Thirty-eight trials (75 %) used non-responder imputation and 10 (20 %) used last observation carried forward to impute missing composite outcome data at the primary time point. The rate of dropout was on average 61 % times higher in the placebo group compared to the treatment group in the 34 placebo controlled trials (relative rate 1.61, 95 % CI: 1.29, 2.02). Thirty-seven trials (73 %) did not report the use of sensitivity analyses to assess the handling of missing data in the primary analysis as recommended by CONSORT guidelines.
  
  
  
  This review highlights an improvement in rheumatology trial practice since the revision of CONSORT guidelines, in terms of power calculation and participant's flow diagram. However, there is a need to improve the handling and reporting of missing composite outcome data and their components in RA trials. In particular, sensitivity analyses need to be more widely used in RA trials because imputation is widespread and generally uses single imputation methods, and in this area the missing data rates are commonly differentially higher in the placebo group.
authors.affiliation: Academic Department of Rheumatology, Faculty of Life Sciences and Medicine, King's College London, Weston Education Centre, 10 Cutcombe Road, London, SE5 9RJ, UK. fowzia.ibrahim@kcl.ac.uk.
authors.forename: Fowzia
authors.initials: F
authors.lastname: Ibrahim
authors.affiliation: MRC Biostatistics Unit, Cambridge Institute of Public Health, Cambridge, UK.
authors.forename: Brian D M
authors.initials: BD
authors.lastname: Tom
authors.affiliation: Academic Department of Rheumatology, Faculty of Life Sciences and Medicine, King's College London, Weston Education Centre, 10 Cutcombe Road, London, SE5 9RJ, UK.
authors.forename: David L
authors.initials: DL
authors.lastname: Scott
authors.affiliation: Imperial Clinical Trials Unit, Imperial College London, Stadium House, 68 Wood Lane, London, W12 7RH, UK.
authors.forename: Andrew Toby
authors.initials: AT
authors.lastname: Prevost
mesh_terms: D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000628:therapy*; D000068598:Data Accuracy; D003625:Data Collection / Q000379:methods* / Q000706:statistics & numerical data; D003627:Data Interpretation, Statistical; D006801:Humans; D057194:Intention to Treat Analysis; D015233:Models, Statistical; D010352:Patient Dropouts / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data; D012107:Research Design / Q000706:statistics & numerical data; D018401:Sample Size; D016896:Treatment Outcome
keywords: Composite outcomes; Imputation; Missing data; RA; Sensitivity analysis