title: The current practice of handling and reporting missing outcome data in eight widely used PROMs in RCT publications: a review of the current literature.
abstract: Patient-reported outcome measures (PROMs) are designed to assess patients' perceived health states or health-related quality of life. However, PROMs are susceptible to missing data, which can affect the validity of conclusions from randomised controlled trials (RCTs). This review aims to assess current practice in the handling, analysis and reporting of missing PROMs outcome data in RCTs compared to contemporary methodology and guidance.
  
  
  
  This structured review of the literature includes RCTs with a minimum of 50 participants per arm. Studies using the EQ-5D-3L, EORTC QLQ-C30, SF-12 and SF-36 were included if published in 2013; those using the less commonly implemented HUI, OHS, OKS and PDQ were included if published between 2009 and 2013.
  
  
  
  The review included 237 records (4-76 per relevant PROM). Complete case analysis and single imputation were commonly used in 33 and 15 % of publications, respectively. Multiple imputation was reported for 9 % of the PROMs reviewed. The majority of publications (93 %) failed to describe the assumed missing data mechanism, while low numbers of papers reported methods to minimise missing data (23 %), performed sensitivity analyses (22 %) or discussed the potential influence of missing data on results (16 %).
  
  
  
  Considerable discrepancy exists between approved methodology and current practice in handling, analysis and reporting of missing PROMs outcome data in RCTs. Greater awareness is needed for the potential biases introduced by inappropriate handling of missing data, as well as the importance of sensitivity analysis and clear reporting to enable appropriate assessments of treatment effects and conclusions from RCTs.
authors.affiliation: Health Economics Research Centre (HERC), Nuffield Department of Population Health, University of Oxford, Oxford, UK. ines.rombach@ndorms.ox.ac.uk.|RCS Surgical Intervention Trials Unit (SITU), Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. ines.rombach@ndorms.ox.ac.uk.
authors.forename: Ines
authors.initials: I
authors.lastname: Rombach
authors.affiliation: National Perinatal Epidemiology Unit (NPEU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Rivero-Arias
authors.affiliation: Health Economics Research Centre (HERC), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
authors.forename: Alastair M
authors.initials: AM
authors.lastname: Gray
authors.affiliation: Health Services Research Unit (HSRU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
authors.forename: Crispin
authors.initials: C
authors.lastname: Jenkinson
authors.affiliation: Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
authors.forename: Órlaith
authors.initials: Ó
authors.lastname: Burke
mesh_terms: D003627:Data Interpretation, Statistical; D006801:Humans; D000071066:Patient Reported Outcome Measures; D016032:Randomized Controlled Trials as Topic / Q000592:standards*; D015203:Reproducibility of Results
keywords: Missing data; Patient-reported outcomes measures (PROMs); Quality of life (QoL); Randomised controlled trials (RCTs); Sensitivity analysis
references.citation: J Bone Joint Surg Br. 2007 Aug;89(8):1010-4
references.pmid: 17785736
references.citation: Pain. 2014 Oct;155(10):1996-2004
references.pmid: 25020004
references.citation: Ann Intern Med. 1993 Apr 15;118(8):622-9
references.pmid: 8452328
references.citation: Pharmacoeconomics. 1995 May;7(5):403-15
references.pmid: 10155328
references.citation: Stat Med. 2012 Dec 10;31(28):3433-43
references.pmid: 22829439
references.citation: BMJ. 2013 Jan 28;346:f167
references.pmid: 23358487
references.citation: Epidemiology. 2012 Sep;23(5):729-32
references.pmid: 22584299
references.citation: Qual Life Res. 2015 Apr;24(4):805-15
references.pmid: 25471286
references.citation: Health Policy. 1996 Jul;37(1):53-72
references.pmid: 10158943
references.citation: J Neurol. 1998 May;245 Suppl 1:S10-4
references.pmid: 9617716
references.citation: Crit Care. 2013 Feb 25;17(2):R58
references.pmid: 23531324
references.citation: CMAJ. 2008 Oct 7;179(8):751-3
references.pmid: 18838445
references.citation: BMC Med Res Methodol. 2014 Nov 19;14:118
references.pmid: 25407057
references.citation: Health Econ. 2012 Feb;21(2):187-200
references.pmid: 22223561
references.citation: BMC Med Res Methodol. 2013 Jul 16;13:92
references.pmid: 23855337
references.citation: Arthritis Care Res (Hoboken). 2011 Nov;63 Suppl 11:S200-7
references.pmid: 22588745
references.citation: Qual Life Res. 2013 Aug;22(6):1161-75
references.pmid: 22987144
references.citation: J Natl Cancer Inst. 1993 Mar 3;85(5):365-76
references.pmid: 8433390
references.citation: J Bone Joint Surg Br. 1996 Mar;78(2):185-90
references.pmid: 8666621
references.citation: Qual Life Res. 2009 Feb;18(1):99-107
references.pmid: 19034690
references.citation: Clin Pharmacol Ther. 2012 Mar;91(3):550-4
references.pmid: 22318615
references.citation: Open Med. 2009 May 12;3(2):e51-3
references.pmid: 19946393
references.citation: Am J Kidney Dis. 2011 Sep;58(3):349-55
references.pmid: 21778004
references.citation: Health Policy. 1990 Dec;16(3):199-208
references.pmid: 10109801
references.citation: BMJ. 2010 Mar 23;340:c723
references.pmid: 20332510
references.citation: Evid Based Med. 2014 Oct;19(5):161-2
references.pmid: 24778412
references.citation: J Sch Psychol. 2010 Feb;48(1):5-37
references.pmid: 20006986
references.citation: N Engl J Med. 2012 Oct 4;367(14):1355-60
references.pmid: 23034025
references.citation: Age Ageing. 1997 Sep;26(5):353-7
references.pmid: 9351479
references.citation: Clin Rehabil. 2012 Oct;26(10):945-51
references.pmid: 22324057
references.citation: JAMA. 1996 Aug 28;276(8):637-9
references.pmid: 8773637
references.citation: Health Qual Life Outcomes. 2003 Oct 16;1:54
references.pmid: 14613568
references.citation: J Public Health Med. 1997 Jun;19(2):179-86
references.pmid: 9243433
references.citation: Contemp Clin Trials. 2012 May;33(3):461-9
references.pmid: 22265924
references.citation: JAMA. 2013 Feb 27;309(8):814-22
references.pmid: 23443445
references.citation: Stat Med. 2011 Nov 30;30(27):3192-207
references.pmid: 21948462
references.citation: Clin Trials. 2004;1(4):368-76
references.pmid: 16279275
references.citation: Lancet Oncol. 2013 Mar;14(3):236-43
references.pmid: 23333117
references.citation: BMC Med Res Methodol. 2012 Jul 11;12:96
references.pmid: 22784200
references.citation: Health Qual Life Outcomes. 2008 Aug 04;6:57
references.pmid: 18680574
references.citation: Arthritis Care Res (Hoboken). 2011 Nov;63 Suppl 11:S208-28
references.pmid: 22588746
references.citation: J Clin Epidemiol. 2014 Jan;67(1):15-32
references.pmid: 24262770
references.citation: Qual Life Res. 2013 Oct;22(8):1889-905
references.pmid: 23288613
references.citation: Value Health. 2007 Nov-Dec;10 Suppl 2:S125-37
references.pmid: 17995471
references.citation: Stat Med. 1998 Mar 15-Apr 15;17(5-7):667-77
references.pmid: 9549815
references.citation: J Biopharm Stat. 2009 Sep;19(5):872-88
references.pmid: 20183449
references.citation: Trials. 2008 Aug 11;9:51
references.pmid: 18694492
references.citation: BMJ. 2011 Feb 07;342:d40
references.pmid: 21300711
references.citation: Qual Life Res. 2011 Mar;20(2):287-300
references.pmid: 20882358
references.citation: Trials. 2014 Jun 19;15:237
references.pmid: 24947664
references.citation: J Bone Joint Surg Br. 1998 Jan;80(1):63-9
references.pmid: 9460955