The median and the mode as robust meta-analysis methods in the presence of small study effects

Meta-analyses based on systematic literature reviews are commonly used to obtain a quantitative summary of the available evidence on a given topic. Despite its attractive simplicity, and its established position at the summit of the evidence-based medicine hierarchy, the reliability of any meta-analysis is largely constrained by the quality of its constituent studies. One major limitation is small study effects, whose presence can often easily be detected, but not so easily adjusted for. Here, robust methods of estimation based on the median and mode are proposed as tools to increase the reliability of findings in a meta-analysis. By re-examining data from published meta-analyses, and by conducting a detailed simulation study, we show that these two simple methods offer notable robustness to a range of plausible bias mechanisms, without making any explicit modelling assumptions. In conclusion, when performing a meta-analysis with suspected small study effects, we recommend reporting the mean, median and modal pooled estimates as a simple but informative sensitivity analyses.

[1]  John P A Ioannidis,et al.  The Mass Production of Redundant, Misleading, and Conflicted Systematic Reviews and Meta-analyses. , 2016, The Milbank quarterly.

[2]  George Davey Smith,et al.  Meta-analysis: Principles and procedures , 1997, BMJ.

[3]  M. Pittler Systematic Reviews in Health Care: Meta‐analysis in Context , 2010 .

[4]  G. Davey Smith,et al.  Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator , 2016, Genetic epidemiology.

[5]  Y. Ohtsuki,et al.  ISOLATION OF HTLV-I FROM CEREBROSPINAL FLUID OF A PATIENT WITH MYELOPATHY , 1986, The Lancet.

[6]  Gordon H Guyatt,et al.  GRADE guidelines: 5. Rating the quality of evidence--publication bias. , 2011, Journal of clinical epidemiology.

[7]  J. Copas What works?: selectivity models and meta‐analysis , 1999 .

[8]  R. Collins,et al.  Intravenous and intracoronary fibrinolytic therapy in acute myocardial infarction: overview of results on mortality, reinfarction and side-effects from 33 randomized controlled trials. , 1985, European heart journal.

[9]  Fernando Pires Hartwig,et al.  Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption , 2017, bioRxiv.

[10]  J. Sterne,et al.  The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials , 2011, BMJ : British Medical Journal.

[11]  Gruppo Italiano per lo Studio della Soprawivenza nell'Inf Miocardico.,et al.  EFFECTIVENESS OF INTRAVENOUS THROMBOLYTIC TREATMENT IN ACUTE MYOCARDIAL INFARCTION , 1986, The Lancet.

[12]  Julian P T Higgins,et al.  Commentary: Heterogeneity in meta-analysis should be expected and appropriately quantified. , 2008, International journal of epidemiology.

[13]  G. Smith,et al.  Bias in meta-analysis detected by a simple, graphical test , 1997, BMJ.

[14]  P. Wiffen,et al.  Single dose oral aspirin for acute pain. , 1999, The Cochrane database of systematic reviews.

[15]  Stephen Burgess,et al.  Improving on a modal-based estimation method: model averaging for consistent and efficient estimation in Mendelian randomization when a plurality of candidate instruments are valid , 2017, bioRxiv.

[16]  D. Bickel Robust and efficient estimation of the mode of continuous data: the mode as a viable measure of central tendency , 2003 .

[17]  J. Ioannidis,et al.  Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials , 2011, BMJ : British Medical Journal.

[18]  S Duval,et al.  Trim and Fill: A Simple Funnel‐Plot–Based Method of Testing and Adjusting for Publication Bias in Meta‐Analysis , 2000, Biometrics.

[19]  David R. Bickel,et al.  On a fast, robust estimator of the mode: Comparisons to other robust estimators with applications , 2005, Comput. Stat. Data Anal..

[20]  T. Lumley,et al.  Efficacy of antiseptic-impregnated central venous catheters in preventing catheter-related bloodstream infection: a meta-analysis. , 1999, JAMA.