Institute of Medical Biometry and Statistics (IMBI)

Funding: Since 2012

Summary

This project refers to two active research areas of evidence synthesis in medicine, meta-analysis of diagnostic test accuracy studies and network meta-analysis. The final objective is to combine both areas.In standard approaches of meta-analysis of diagnostic accuracy studies, each study is assumed to contribute one pair of sensitivity and specificity. In the first period of the project, we investigated two more general approaches, which account for multiple thresholds of the underlying biomarker, `Modelling biomarker distributions' and `Averaging ROC curves'.The first approach is based on the idea of estimating the distribution functions of an underlying biomarker within the non-diseased and diseased individuals. Based on a distributional assumption, we estimate the distribution parameters in the two groups applying a linear mixed effects model to the appropriately transformed data. The model accounts for both the within-study dependence of sensitivity and specificity and between-study heterogeneity. We obtain a summary receiver operating characteristic (SROC) curve as well as the pooled sensitivity and specificity at every specific threshold. Furthermore, the determination of an optimal threshold across studies is possible through maximization of the Youden index.In the second approach, originally introduced by Martinez-Camblor (2014), the summary ROC curve is determined as a weighted average of the ROC curves of the primary studies by averaging in `vertical' direction (i.e., averaging sensitivities, conditional on specificity). We extended this method by (1) exchanging the roles of sensitivity and specificity, i.e., averaging specificities conditional on sensitivity (horizontal averaging), and (2) averaging the differences of true positive rates and false positive rates (i.e., the Youden indices) conditional on their sum (diagonal averaging).Another area of research was network meta-analysis (NMA). In four publications, we investigated (1) the relation between NMA and electrical network theory, (2) an alternative method of adjusting for multi-arm studies by appropriately inflating the standard errors, (3) methods of automated visualisation of networks, and (4) frequentist treatment ranking, based on a network-meta-analysis.In the second project period we want to refine and extend all these approaches, with a special focus on knowledge translation. There is a more and more increasing spectrum of advanced methods on the one hand and their restricted accessibility for non-statistical users on the other hand. We want to bridge this gap and continue to follow this aim by writing a new R package for implementation of the `Modelling biomarker distributions' and `Averaging ROC curves' approaches and extending our existing R package netmeta for network meta-analysis, for example by meta-regression. The final objective is to combine meta-analysis of DTA studies and NMA to network meta-analysis of DTA studies.

Publications

• Gerta Rücker, Susanne Schmitz, and Guido Schwarzer, "Component network meta-analysis compared to a matching method in a disconnected network: a case study", 2020 [Conference: Basel Biometric Section, Basel, Switzerland].
• Orestis Efthimiou, Gerta Rücker, Guido Schwarzer, Julian P. T. Higgins, Matthias Egger, and Georgia Salanti, "Network meta-analysis of rare events using the Mantel-Haenszel method", Statistics in Medicine, vol. 38, no. 16, pp. 2992-3012, Jul 20 2019. [Published online]
• Sung Ryul Shim, Seong-Jang Kim, Jonghoo Lee, and Gerta Rücker, "Network Meta-analysis: Application and Practice using R software", Epidemiology and Health, vol. 41, April 8 2019. [Published online]
• Gerta Rücker, Maria Petropoulou, and Guido Schwarzer, "Network meta-analysis of multicomponent interventions", Biometrical Journal, April 25 2019. [Published online]
• Gerta Rücker, Ulrike Krahn, Jochem König, Orestis Efthimiou, and Guido Schwarzer, "netmeta: Network Meta-Analysis using Frequentist Methods", 2019.
• Orestis Efthimiou, Dimitris Mavridis, Adriani Nikolakopoulou, Gerta Rücker, Sven Trelle, Matthias Egger, and Georgia Salanti, "A model for meta-analysis of correlated binary outcomes: The case of split-body interventions", Statistical Methods in Medical Research, vol. 28, no. 7, pp. 1998-2014, 2019.
• Guido Schwarzer, Hiam Chemaitelly, Laith J Abu-Raddad, and Gerta Rücker, "Seriously Misleading Results Using Inverse of Freeman-Tukey Double Arcsine Transformation in Meta-Analysis of Single Proportions", Research Synthesis Methods, vol. 10, pp. 476-483, 2019. [Published online]
• Lukas Schwingshackl, Guido Schwarzer, Gerta Rücker, and Joerg J Meerpohl, "Perspective: Network Meta-analysis Reaches Nutrition Research: Current Status, Scientific Concepts, and Future Directions", Advances in Nutrition, vol. 10, no. 5, pp. 739-754, 2019. [Published online]
• Gerta Rücker, Susanne Schmitz, and Guido Schwarzer, "Comparing component network meta-analysis to a matching method in a disconnected network: A case study", 2019 [Conference: ISCB Conference, Leuven (Belgium)].
• Sara Balduzzi, Gerta Rücker, and Guido Schwarzer, "How to perform a meta-analysis with R: a practical tutorial", Evidence-Based Mental Health, vol. 22, no. 4, pp. 153-160, 2019.
• Gerta Rücker and Guido Schwarzer, "Network meta-analysis of treatment combinations", July 2018 [Conference: SRSM (Society for Research Synthesis Methods) Conference, Bristol (UK)].
• Areti Angeliki Veroniki, Sharon E. Straus, Gerta Rücker, and Andrea C. Tricco, "Is providing uncertainty intervals in treatment ranking helpful in a network meta-analysis?", Journal of Clinical Epidemiology, 2018.
• Gerta Rücker, Srinath Kolampally, Guido Schwarzer, and Susanne Steinhauser, "Meta-analysis of diagnostic test accuracy studies with multiple cutoffs: The R package diagmeta", 2018 [Conference: MEMTAB Conference (Methods for evaluation of medical prediction models, tests and biomarkers), Utrecht (NL)].
• Gerta Rücker and Guido Schwarzer, "Contribution to the discussion of 'When should meta-analysis avoid making hidden normality assumptions'", Biometrical Journal, 2018.
• Harriet Sommer, Gerta Rücker, Gerd Antes, and Valérie Labonté, "Netzwerkmetaanalysen als Instrument für Evidenzsynthese und Therapiebewertung", Deutsche Zahnärztliche Zeitschrift , vol. 73, no. 1, 2018.
• Theodoros Papakonstantinou, Adriani Nikolakopoulou, Gerta Rücker, Anna Chaimani, Guido Schwarzer, Matthias Egger, and Georgia Salanti, "Estimating the contribution of studies in network meta-analysis: paths, flows and streams", F1000Research, vol. 7, no. 610, 2018.
• Gerta Rücker, "Network meta-analysis of diagnostic test accuracy studies," in Diagnostic Meta-Analysis, (Giuseppe Biondi-Zoccai, ed.), pp. 183-197, 2018.
• Gerta Rücker, Susanne Steinhauser, Srinath Kolampally, and Guido Schwarzer, "diagmeta: Meta-Analysis of Diagnostic Accuracy Studies with Several Cutpoints", 2018.
• Gerta Rücker, "The R package diagmeta-Meta-analysis of diagnostic test accuracy studies with multiple cutoffs", 2018 [Conference: GMDS Conference, Osnabrück].
• Gerta Rücker and Guido Schwarzer, "Network meta-analysis of multi-component treatments", 2018 [Conference: Cochrane Colloquium, Edinburgh (UK)].
• Gerta Rücker and Guido Schwarzer, "Differences in the placebo response between trials do not necessarily preclude network meta-analysis", Acta Psychiatrica Scandinavica, vol. 138, no. 6, pp. 615-615, 2018.
• Antonius Schneider, Klaus Linde, Johannes B. Reitsma, Susanne Steinhauser, and Gerta Rücker, "A novel statistical model for analyzing data of a systematic review generates optimal cut-off values for fractional exhaled nitric oxide for asthma diagnosis ", Journal of Clinical Epidemiology, pp. pii: S0895-4356(17)30278-0, Sep 12 2017. [Published online]
• Gerta Rücker, "Issues in meta-analysis of diagnostic accuracy tests", November 06./07. 2017 [Conference: Workshop on flexible designs for diagnostic studies - from diagnostic accuracy to personalized medicine, Göttingen].
• Gerta Rücker, Susanne Steinhauser, and Martin Schumacher, "Re: "Selective cutoff reporting in studies of diagnostic test accuracy: A comparison of conventional and individual-patient-data meta-analyses of the Patient Health Questionnaire-9 Depression Screening Tool", American Journal of Epidemiology, 23 August 2017. [Published online]
• Gerta Rücker and Guido Schwarzer, "Resolve conflicting rankings of outcomes in network meta-analysis: Partial ordering of treatments ", Research Synthesis Methods, vol. 8, no. 4, pp. 526-536 , 2017.
• Gerta Rücker, "Connecting the disconnected: new statistical methodology or new clinical research? ", 2017 [Conference: Workshop "Methods for Generalized Evidence Synthesis" at the annual conference of the GMDS, Oldenburg].
• Gerta Rücker and Guido Schwarzer, "Resolve conflicting rankings of outcomes in Network meta-analysis: Partial ordering of treatments", 2017 [Conference: CEN-ISBS Conference, Vienna].
• Gerta Rücker and Guido Schwarzer, "Resolve conflicting rankings of outcomes in network meta-analysis: Partial ordering of treatments ", 2017 [Conference: Methods in Meta-analysis Meeting, Birmingham].
• Gerta Rücker, Christopher J. Cates, and Guido Schwarzer, "Methods for including information from multi-arm trials in pairwise meta-analysis", Research Synthesis Methods, vol. 8, no. 4, pp. 392-403 , 2017.
• Harriet Sommer, Gerta Rücker, and Valérie Labonté, "Netzwerkmetaanalysen: Wie man vergleichen kann, was nie verglichen wurde ", 2017.
• Susanne Steinhauser, Martin Schumacher, and Gerta Rücker, "Modelling multiple thresholds in meta-analysis of diagnostic test accuracy studies", BMC Medical Research Methodology, vol. 16:97, 2016.
• Gerta Rücker, "Network meta-analysis," in Wiley StatsRef: Statistics Reference Online, (Paolo Brandimarte, Marie Davidian, Brian Everitt, Geert Molenberghs, Walter Piegorsch, and Fabrizio Ruggeri, eds.), pp. 1-8, 2016.
• Gerta Rücker and Guido Schwarzer, "Automated drawing of network plots in meta-analysis", Research Synthesis Methods, vol. 7, no. 1, pp. 94-107, 2016.
• Gerta Rücker and Guido Schwarzer, "Ranking treatments in frequentist network meta-analysis works without resampling methods", BMC Medical Research Methodology, vol. 15, 2015.
• Guido Schwarzer, James R. Carpenter, and Gerta Rücker, Meta-Analysis with R, Springer International Publishing, 2015.
• Gerta Rücker and Guido Schwarzer, "Reduce dimension or reduce weights? Comparing two approaches to multi-arm studies in network meta-analysis", Statistics in Medicine, vol. 33, pp. 4353-4369, 2014.
• Gerta Rücker and Martin Schumacher, "Procalcitonin as a diagnostic marker for sepsis", Lancet Infectious Diseases, vol. 13, pp. 1012-1013, 2013.
• Gerta Rücker, "Network meta-analysis, electrical networks and graph theory", Research Synthesis Methods, vol. 3, no. 4, pp. 312-324, 2012.
• Gerta Rücker and Martin Schumacher, "Summary ROC curve based on the weighted Youden index for selecting an optimal cutpoint in meta-analysis of diagnostic accuracy", Statistics in Medicine, vol. 29, pp. 3069-3078, 2010.
• Gerta Rücker and Martin Schumacher, "Letter to the editor", Biostatistics, vol. 10, no. 4, pp. 806-807, July 6 2009.