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The T2Bacteria Panel run on the T2Dx Instrument is a qualitative T2 Magnetic Resonance (T2MR) test for the direct detection of bacterial species in K2EDTA human whole blood specimens with suspected bacteremia. The T2Bacteria Panel identifies six species of bacter baumannii, Enterococus faccium, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus.

The T2Bacteria Panel is indicated as an aid in the diagnosis of bacteremia and results should be used in conjunction with other clinical and laboratory data. Concomitant blood cultures are necessary to recover organisms for susceptibility testing or further identification and for organisms not detected by the T2Bacteria Panel.

Results from the T2Bacteria Panel are not intended to be used as for diagnosis, treatment, or other patient management decisions in patients with suspected bacteremia.

The T2Bacteria Panel detects and identifies six bacterial target species directly from whole blood specimens and independent of blood culture using nucleic acid amplification and proprietary T2MR detection technology. The assay is performed on the proprietary T2Dx platform. The whole blood specimen, drawn into a blood collection tube containing K₂EDTA is used for the test. The blood collection tube containing a minimum of 3 mL of blood is loaded directly onto the T2Dx instrument as part of the assembled Cartridge, a single use self-contained unit that contains all of the reagents and disposables required to run a single test. Fully automated on the T2Dx, the blood specimen is mixed with the Lysis Reagent to lyse the red blood cells and the bacterial cells are concentrated by centrifygation. The Internal Control is added to the concentrated bacterial cells, which then undergo a bead beating step to lyse the bacteria cells. The supernatant containing the DNA from the lysed bacterial cells and the Internal Control are amplified with the target and Internal Control specific primers. The generated amplicon is then aliquoted into individual tubes containing target specific conjugated particles for Acinetobacter baumannii, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and the Internal Control. These individual tubes are read in the MR reader and a signal is generated.

Up to seven specimens can be loaded onto the T2Dx Instrument in parallel. When running a single specimen, the first result is reported in 3.5 hours from the specimen is loaded onto the instrument. The results are interpreted using the T2Dx applications software as valid or invalid, and if valid, target specific results are reported as Positive or Target not Detected. For one target, the Escherichia coli channel, results are reported as Positive, Indeterminate, or Target not Detected. An Indeterminate result is a valid result, but the presence or absence of Escherichia coli cannot be definitively assessed, and the indeterminate status applies only to the Escherichia coli channel. Results are displayed on the T2Dx touchscreen and can be printed. Raw T2MR data are not available to the end user.

Here's a summary of the acceptance criteria and study details for the T2Bacteria Panel, specifically concerning the addition of Acinetobacter baumannii detection:

Acceptance Criteria and Device Performance for Acinetobacter baumannii

Study Details for Acinetobacter baumannii Performance

1. Test Set Sample Size and Data Provenance:

   • Clinical Performance Study (Prospective Arm): 1,427 subjects were enrolled prospectively.
     • Provenance: US (indicated by "evaluated at eleven sites within the US").
     • Type: Prospective.
   • Clinical Performance Study (Contrived Arm):
     • 50 contrived specimens directly for A. baumannii.
     • 300 blood samples not spiked with A. baumannii members (250 of these spiked with other T2Bacteria Panel organisms).
     • Provenance: Healthy donor whole blood, prepared at internal/external lab.
     • Type: Contrived (spiked samples).
   • Reproducibility Study: Total of 108 replicates (36 replicates per sample per site) for each test concentration and negative control, conducted across three sites.
   • Analytical Reactivity (Inclusivity) Study: 14 strains tested, 3 replicates each (20 replicates if initial false negative).
   • Analytical Specificity (Exclusivity) Study: 128 different organisms tested.
   • Interfering Substances Study: 3 replicates for each substance tested.
   • Evaluation of False Positive Results (Retrospective): 980 valid samples (98 replicates for each of 10 reagent lots).
   • Additional A. baumannii Contrived Samples: 33 unique strains tested.

2. Number of Experts and Qualifications for Ground Truth (Clinical Study):

   • The document implies that species identification for positive blood cultures was performed by standard laboratory methods (Gram stain, bioMerieux Vitek® 2, bioMerieux or Bruker MALDI TOF, and PCR). It does not specify the number of individual experts or their years of experience for establishing the ground truth from blood cultures. The ground truth relies on conventional microbiology techniques as the reference method.

3. Adjudication Method for Test Set:

   • The document does not explicitly describe an adjudication method for the clinical study results in terms of conflict resolution between multiple reviewers. The primary comparison is the T2Bacteria Panel results against the blood culture reference method.
   • For potential false positive analyses, there was a hierarchy: "Other Blood Culture positive," "Sequencing positive," "Strong evidence of infection," "Other evidence of infection," and "No evidence of infection" were used to re-evaluate T2+/BC- cases. This acts as a form of retrospective adjudication or re-classification of discrepant results.

4. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

   • No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) test, not an AI-assisted interpretation tool for human readers. It provides a direct result (Positive/Negative for specific bacteria), so there's no "human readers improve with AI vs without AI assistance" effect size to be measured. The output is from the device itself.

5. Standalone (Algorithm Only) Performance:

   • Yes, the performance metrics (PPA, NPA, LoD, Reproducibility, Specificity, Inclusivity) reported are for the standalone device (T2Bacteria Panel on the T2Dx Instrument) without human input for result interpretation other than loading the sample and reading the final result from the instrument's display or printout. The "algorithm" here refers to the instrument's internal processing and detection logic.

6. Type of Ground Truth Used:

   • Clinical Study: Gold Standard for bacteremia was blood culture (with species identification by Gram stain, Vitek® 2, MALDI TOF, and PCR). For some discrepant cases (T2+/BC-), gene sequencing from blood samples and clinical outcomes/other culture positives were used for further analysis.
   • Analytical Studies (LoD, Reproducibility, Inclusivity, Exclusivity, Interference, Competitive Inhibition): Ground truth was established by known concentrations of spiked bacterial strains (confirmed by colony count where applicable).

7. Training Set Sample Size:

   • The document does not explicitly state the sample size for a "training set" in the context of machine learning. This device uses T2 Magnetic Resonance (T2MR) technology and nucleic acid amplification, which points towards a rule-based or signal-processing algorithm rather than a typical machine learning model that would require a distinct "training set" for model development. The development and optimization of the assay would have involved numerous experiments, but these are generally referred to as assay development or verification, rather than a "training set" for AI.

8. How Ground Truth for Training Set was Established:

   • As there isn't a traditional "training set" in the AI/ML sense, the concept of ground truth establishment for it doesn't directly apply. The assay development would have involved extensive analytical studies using well-characterized bacterial strains at known concentrations, with confirmation by standard microbiological methods (e.g., colony counting) to establish the true presence and quantity of targets. These analytical studies ensure the robust performance of the underlying molecular and T2MR detection principles.

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