title: Missing data in randomized controlled trials testing palliative interventions pose a significant risk of bias and loss of power: a systematic review and meta-analyses.
abstract: To assess the risk posed by missing data (MD) to the power and validity of trials evaluating palliative interventions.
  
  
  
  A systematic review of MD in published randomized controlled trials (RCTs) of palliative interventions in participants with life-limiting illnesses was conducted, and random-effects meta-analyses and metaregression were performed. CENTRAL, MEDLINE, and EMBASE (2009-2014) were searched with no language restrictions.
  
  
  
  One hundred and eight RCTs representing 15,560 patients were included. The weighted estimate for MD at the primary endpoint was 23.1% (95% confidence interval [CI] 19.3, 27.4). Larger MD proportions were associated with increasing numbers of questions/tests requested (odds ratio [OR], 1.19; 95% CI 1.05, 1.35) and with longer study duration (OR, 1.09; 95% CI 1.02, 1.17). Meta-analysis found evidence of differential rates of MD between trial arms, which varied in direction (OR, 1.04; 95% CI 0.90, 1.20; I(2) 35.9, P = 0.001). Despite randomization, MD in the intervention arms (vs. control) were more likely to be attributed to disease progression unrelated to the intervention (OR, 1.31; 95% CI 1.02, 1.69). This was not the case for MD due to death (OR, 0.92; 95% CI 0.78, 1.08).
  
  
  
  The overall proportion and differential rates and reasons for MD reduce the power and potentially introduce bias to palliative care trials.
authors.affiliation: Hull York Medical School, University of York, Heslington, York YO10 5DD, UK. Electronic address: jah553@york.ac.uk.
authors.forename: Jamilla A
authors.initials: JA
authors.lastname: Hussain
authors.affiliation: MRC Biostatistics Unit, Cambridge Institute for Public Health, Forvie Site, Robinson Way, Cambridge CB2 0SR, UK.
authors.forename: Ian R
authors.initials: IR
authors.lastname: White
authors.affiliation: Centre for Reviews and Dissemination, University of York, Heslington, York YO10 5DD, UK.
authors.forename: Dean
authors.initials: D
authors.lastname: Langan
authors.affiliation: SEDA, Hertford Building, University of Hull, Hull HU6 7RX, UK.
authors.forename: Miriam J
authors.initials: MJ
authors.lastname: Johnson
authors.affiliation: Hull York Medical School, University of York, Heslington, York YO10 5DD, UK; Palliative and Supportive Services, Flinders University, 216 Daws Road, Daw Park, South Australia 5041, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: Currow
authors.affiliation: York Trials Unit, University of York, Heslington, York YO10 5DD, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Torgerson
authors.affiliation: Health Sciences Department, University of York, Heslington, York YO10 5DD, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Bland
mesh_terms: D015982:Bias; D000068598:Data Accuracy; D003627:Data Interpretation, Statistical; D006801:Humans; D010166:Palliative Care / Q000379:methods / Q000706:statistics & numerical data*; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000706:statistics & numerical data*; D015203:Reproducibility of Results; D012306:Risk
keywords: Differential mortality; Meta-analysis; Missing data; Palliative care; Randomized controlled trials; Systematic review