Abstract
BackgroundPrimary studies examining the accuracy of a continuous test evaluate its sensitivity and specificity at one or more thresholds. Meta-analysts then usually perform a separate meta-analysis for each threshold. However, the number of studies available for each threshold is often very different, as primary studies are inconsistent in the thresholds reported. Furthermore, of concern is selective reporting bias, because primary studies may be less likely to report a threshold when it gives low sensitivity and/or specificity estimates. This may lead to biased meta-analysis results. We developed an exploratory method to examine the potential impact of missing thresholds on conclusions from a test accuracy meta-analysis.MethodsOur method identifies studies that contain missing thresholds bounded between a pair of higher and lower thresholds for which results are available. The bounded missing threshold results (two-by-two tables) are then imputed, by assuming a linear relationship between threshold value and each of logit-sensitivity and logit-specificity. The imputed results are then added to the meta-analysis, to ascertain if original conclusions are robust. The method is evaluated through simulation, and application made to 13 studies evaluating protein:creatinine ratio (PCR) for detecting proteinuria in pregnancy with 23 different thresholds, ranging from one to seven per study.ResultsThe simulation shows the imputation method leads to meta-analysis estimates with smaller mean-square error. In the PCR application, it provides 50 additional results for meta-analysis and their inclusion produces lower test accuracy results than originally identified. For example, at a PCR threshold of 0.16, the summary specificity is 0.80 when using the original data, but 0.66 when also including the imputed data. At a PCR threshold of 0.25, the summary sensitivity is reduced from 0.95 to 0.85 when additionally including the imputed data.ConclusionsThe imputation method is a practical tool for researchers (often non-statisticians) to explore the potential impact of missing threshold results on their meta-analysis conclusions. Software is available to implement the method. In the PCR example, it revealed threshold results are vulnerable to the missing data, and so stimulates the need for advanced statistical models or, preferably, individual patient data from primary studies.Electronic supplementary materialThe online version of this article (doi:10.1186/2046-4053-4-12) contains supplementary material, which is available to authorized users.
Highlights
Primary studies examining the accuracy of a continuous test evaluate its sensitivity and specificity at one or more thresholds
The imputation method is a practical tool for researchers to explore the potential impact of missing threshold results on their meta-analysis conclusions
In the protein:creatinine ratio (PCR) example, it revealed threshold results are vulnerable to the missing data, and so stimulates the need for advanced statistical models or, preferably, individual patient data from primary studies
Summary
Primary studies examining the accuracy of a continuous test evaluate its sensitivity and specificity at one or more thresholds. Of concern is selective reporting bias, because primary studies may be less likely to report a threshold when it gives low sensitivity and/or specificity estimates This may lead to biased meta-analysis results. In an evaluation of the spot protein:creatinine ratio (PCR) for detecting significant proteinuria in pregnancy, Morris et al [5] extracted tables for 23 different thresholds across 13 studies; eight of the thresholds were considered by just one study, but the other 15 thresholds were considered in two or more studies (Table 1), with a maximum of six studies for any threshold In this situation, meta-analysts generally either utilise the results for just one of the thresholds per study or utilise results for all reported thresholds but perform a separate meta-analysis for each of the thresholds independently [6]. An approach that considers meta-analysis for each threshold independently will omit any studies that do not report the threshold of interest and ignore information from other thresholds that are available in those studies
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