J Minion1, M Pai. 1. Department of Epidemiology, McGill University, Montreal, Quebec, Canada. madhukar.pai@mcgill.ca
Abstract
OBJECTIVE: To update a previously reported meta-analysis of evidence regarding the diagnostic accuracy and performance characteristics of commercial and non-commercial phage-based assays for the detection of rifampicin (RMP) resistant tuberculosis (TB). DESIGN AND OUTCOMES: We conducted a systematic review and meta-analysis of test accuracy using bivariate random effects regression and hierarchical summary receiver operating characteristics (HSROC) analysis. Tests included the commercial FASTPlaque assays, luciferase reporter phage (LRP) assays, and in-house phage amplification tests. Sensitivity and specificity for RMP resistance were the main outcomes. RESULTS: By updating previous literature searches, a total of 31 studies (with 3085 specimens) were included in this meta-analysis. Evaluations of commercial phage amplification assays yielded more variable estimates of sensitivity (range 81-100%) and specificity (range 73-100%) compared to evaluations of in-house amplification assays (sensitivity range 88-100%, specificity range 84-100%). LRP evaluations yielded the most consistent estimates of diagnostic accuracy, with seven of eight studies reporting 100% sensitivity and four of eight reporting 100% specificity. Estimates of accuracy failed to capture a major failing of the commercial assay, i.e., the rate of contaminated and indeterminate results. These ranged from 3% to 36% in studies looking at direct detection of RMP resistance from patient specimens (mean 20%). CONCLUSION: Phage-based assays will require further development to maximise interpretable results and reduce technical failures. Once technical issues are resolved, impact on patient-important outcomes and cost-effectiveness need to be determined to inform policy for widespread use.
OBJECTIVE: To update a previously reported meta-analysis of evidence regarding the diagnostic accuracy and performance characteristics of commercial and non-commercial phage-based assays for the detection of rifampicin (RMP) resistant tuberculosis (TB). DESIGN AND OUTCOMES: We conducted a systematic review and meta-analysis of test accuracy using bivariate random effects regression and hierarchical summary receiver operating characteristics (HSROC) analysis. Tests included the commercial FASTPlaque assays, luciferase reporter phage (LRP) assays, and in-house phage amplification tests. Sensitivity and specificity for RMP resistance were the main outcomes. RESULTS: By updating previous literature searches, a total of 31 studies (with 3085 specimens) were included in this meta-analysis. Evaluations of commercial phage amplification assays yielded more variable estimates of sensitivity (range 81-100%) and specificity (range 73-100%) compared to evaluations of in-house amplification assays (sensitivity range 88-100%, specificity range 84-100%). LRP evaluations yielded the most consistent estimates of diagnostic accuracy, with seven of eight studies reporting 100% sensitivity and four of eight reporting 100% specificity. Estimates of accuracy failed to capture a major failing of the commercial assay, i.e., the rate of contaminated and indeterminate results. These ranged from 3% to 36% in studies looking at direct detection of RMP resistance from patient specimens (mean 20%). CONCLUSION: Phage-based assays will require further development to maximise interpretable results and reduce technical failures. Once technical issues are resolved, impact on patient-important outcomes and cost-effectiveness need to be determined to inform policy for widespread use.
Authors: Liliana Rondón; Mariana Piuri; William R Jacobs; Jacobus de Waard; Graham F Hatfull; Howard E Takiff Journal: J Clin Microbiol Date: 2011-02-23 Impact factor: 5.948
Authors: Paras Jain; David S Thaler; Mamoudou Maiga; Graham S Timmins; William R Bishai; Graham F Hatfull; Michelle H Larsen; William R Jacobs Journal: J Infect Dis Date: 2011-11-15 Impact factor: 5.226