Meta-analysis and meta-modelling for diagnostic problems.
BACKGROUND
A proportional hazards measure is suggested in the context of analyzing SROC curves that arise in the meta-analysis of diagnostic studies. The measure can be motivated as a special model: the Lehmann model for ROC curves. The Lehmann model involves study-specific sensitivities and specificities and a diagnostic accuracy parameter which connects the two.


METHODS
A study-specific model is estimated for each study, and the resulting study-specific estimate of diagnostic accuracy is taken as an outcome measure for a mixed model with a random study effect and other study-level covariates as fixed effects. The variance component model becomes estimable by deriving within-study variances, depending on the outcome measure of choice. In contrast to existing approaches - usually of bivariate nature for the outcome measures - the suggested approach is univariate and, hence, allows easily the application of conventional mixed modelling.


RESULTS
Some simple modifications in the SAS procedure proc mixed allow the fitting of mixed models for meta-analytic data from diagnostic studies. The methodology is illustrated with several meta-analytic diagnostic data sets, including a meta-analysis of the Mini-Mental State Examination as a diagnostic device for dementia and mild cognitive impairment.


CONCLUSIONS
The proposed methodology allows us to embed the meta-analysis of diagnostic studies into the well-developed area of mixed modelling. Different outcome measures, specifically from the perspective of whether a local or a global measure of diagnostic accuracy should be applied, are discussed as well. In particular, variation in cut-off value is discussed together with recommendations on choosing the best cut-off value. We also show how this problem can be addressed with the proposed methodology.
Suphada
S
Charoensawat
Walailuck
W
Böhning
Southampton Statistical Sciences Research Institute, Mathematics and Medical Statistics, University of Southampton, Southampton SO17 1BJ, UK. d.a.bohning@soton.ac.uk.
Dankmar
D
Böhning
Heinz
H
Holling
D000465:Algorithms; D060825:Cognitive Dysfunction / Q000175:diagnosis*; D003704:Dementia / Q000175:diagnosis*; D003866:Depressive Disorder / Q000175:diagnosis*; D003951:Diagnostic Errors; D003955:Diagnostic Tests, Routine / Q000379:methods*; D006333:Heart Failure / Q000175:diagnosis*; D006801:Humans; D008603:Mental Health; D015233:Models, Statistical; D020097:Natriuretic Peptide, Brain / Q000032:analysis; D017063:Outcome Assessment, Health Care; D016016:Proportional Hazards Models; D012372:ROC Curve; D012680:Sensitivity and Specificity
D020097:Natriuretic Peptide, Brain