Reporting, handling and assessing the risk of bias associated with missing participant data in systematic reviews: a methodological survey

Objectives To describe how systematic reviewers are reporting missing data for dichotomous outcomes, handling them in the analysis and assessing the risk of associated bias. Methods We searched MEDLINE and the Cochrane Database of Systematic Reviews for systematic reviews of randomised trials published in 2010, and reporting a meta-analysis of a dichotomous outcome. We randomly selected 98 Cochrane and 104 non-Cochrane systematic reviews. Teams of 2 reviewers selected eligible studies and abstracted data independently and in duplicate using standardised, piloted forms with accompanying instructions. We conducted regression analyses to explore factors associated with using complete case analysis and with judging the risk of bias associated with missing participant data. Results Of Cochrane and non-Cochrane reviews, 47% and 7% (p<0.0001), respectively, reported on the number of participants with missing data, and 41% and 9% reported a plan for handling missing categorical data. The 2 most reported approaches for handling missing data were complete case analysis (8.5%, out of the 202 reviews) and assuming no participants with missing data had the event (4%). The use of complete case analysis was associated only with Cochrane reviews (relative to non-Cochrane: OR=7.25; 95% CI 1.58 to 33.3, p=0.01). 65% of reviews assessed risk of bias associated with missing data; this was associated with Cochrane reviews (relative to non-Cochrane: OR=6.63; 95% CI 2.50 to 17.57, p=0.0001), and the use of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology (OR=5.02; 95% CI 1.02 to 24.75, p=0.047). Conclusions Though Cochrane reviews are somewhat less problematic, most Cochrane and non-Cochrane systematic reviews fail to adequately report and handle missing data, potentially resulting in misleading judgements regarding risk of bias.

[1]  Gordon H Guyatt,et al.  Addressing continuous data measured with different instruments for participants excluded from trial analysis: a guide for systematic reviewers. , 2014, Journal of clinical epidemiology.

[2]  G. Guyatt,et al.  A methodological survey of the analysis, reporting and interpretation of Absolute Risk ReductiOn in systematic revieWs (ARROW): a study protocol , 2013, Systematic Reviews.

[3]  Xin Sun,et al.  Addressing continuous data for participants excluded from trial analysis: a guide for systematic reviewers. , 2013, Journal of clinical epidemiology.

[4]  Sally Hopewell,et al.  Incorporation of assessments of risk of bias of primary studies in systematic reviews of randomised trials: a cross-sectional study , 2013, BMJ Open.

[5]  Matthias Briel,et al.  Addressing Dichotomous Data for Participants Excluded from Trial Analysis: A Guide for Systematic Reviewers , 2013, PloS one.

[6]  Gordon H Guyatt,et al.  Potential impact on estimated treatment effects of information lost to follow-up in randomised controlled trials (LOST-IT): systematic review , 2012, BMJ : British Medical Journal.

[7]  R Brian Haynes,et al.  Sensitive Clinical Queries retrieved relevant systematic reviews as well as primary studies: an analytic survey. , 2011, Journal of clinical epidemiology.

[8]  G. Guyatt,et al.  GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. , 2011, Journal of clinical epidemiology.

[9]  G. Guyatt,et al.  GRADE guidelines: 4. Rating the quality of evidence--study limitations (risk of bias). , 2011, Journal of clinical epidemiology.

[10]  D. Moher,et al.  CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials , 2010, BMJ : British Medical Journal.

[11]  J. Higgins Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration , 2011 .

[12]  Mark van der Laan,et al.  Addressing missing data in clinical trials. , 2011, Annals of internal medicine.

[13]  D. Moher,et al.  CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials , 2011, BMJ : British Medical Journal.

[14]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. , 2010, International journal of surgery.

[15]  Catherine Sherrington,et al.  Cochrane reviews used more rigorous methods than non-Cochrane reviews: survey of systematic reviews in physiotherapy. , 2009, Journal of clinical epidemiology.

[16]  Jeremy Grimshaw,et al.  AMSTAR is a reliable and valid measurement tool to assess the methodological quality of systematic reviews. , 2009, Journal of clinical epidemiology.

[17]  G. Guyatt,et al.  LOST to follow-up Information in Trials (LOST-IT): a protocol on the potential impact , 2009, Trials.

[18]  Ian R White,et al.  Imputation methods for missing outcome data in meta-analysis of clinical trials , 2008, Clinical trials.

[19]  Nicky J Welton,et al.  Allowing for uncertainty due to missing data in meta‐analysis—Part 2: Hierarchical models , 2008, Statistics in medicine.

[20]  Ian R White,et al.  Allowing for uncertainty due to missing data in meta‐analysis—Part 1: Two‐stage methods , 2008, Statistics in medicine.

[21]  Carrol Gamble,et al.  Uncertainty method improved on best-worst case analysis in a binary meta-analysis. , 2005, Journal of clinical epidemiology.