Bacteriophage assays for rifampicin resistance detection in Mycobacterium tuberculosis: updated meta-analysis.
Bibliographic record
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.009 | 0.006 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".