1. ELISA BETTER THAN WE THOUGHT Dr Direk Limmathurotsakul, MD MSc PhD

2. Introduction: problems and solutions of imperfect Gold Standard

3. Introduction: culture is an imperfect gold standard for melioidosis

4. ParametersCulture as a gold standard Final Bayesian LCM Prevalence37 %62 % Culture Sensitivity100 %60 % Specificity100 % ELISA Sensitivity82 %76 % Specificity73 %98 % Limmathurotsakul et al (2010) PLoS ONE 5(8) e12485

5. Next Step: What is the proper cutoff for ELISA

6. LCM estimate that true Se and Sp of ELISA were 76% and 98% Cut-off used was previously determined by conventional ROC Next Step: What is the proper cutoff for ELISA

7. METHOD Bayesian latent class models (LCM) were applied to all possible cut-off values Sensitivity and specificity estimated from each cut-off value was used to plot unbiased ROC curves

9. ParametersBayesian LCM using biased cut-off Bayesian LCM using optimal cut-off ELISA Se76 %81 % Sp98 %96 % RESULT

10. SUMMARY Cut-off determined by conventional method was biased towards misclassification of imperfect gold standard LCMs should be used to determine optimal cut-off ELISA could be furthered developed for use in the clinical setting with a reasonably high degree of accuracy Further evaluation of new diagnostic tests for melioidosis should be done with a carefully selected set of diagnostic tests and appropriate statistical models

11. How can general researchers apply Bayesian LCM to their own datasets http://mice.tropmedres.ac More information: PPI-37 (WMC2013)

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