Search Results

The Great Basin Staph ID/R Blood Culture Panel is a qualitative, multiplex, nucleic acid-based in vitro diagnostic assay intended for the simultaneous identification of nucleic acid from Staphylococcus lugdumensis and various Staphylococcus species to the genus level and the detection of the mecA gene for methicillin resistance directly from patient positive blood culture specimens. The test utilizes automated hot-start enabled polymerase chain reaction (PCR) for the amplification of specific DNA targets detected by hybridization probes immobilized on a silicon chip surface. The assay is performed directly on positive blood culture specimens identified as positive by continuous monitoring blood culture system that demonstrates the presence of organisms as determined by Gram stain to contain gram-positive cocci in clusters (GPCC) or gram-positive cocci in singles (GPC). The test may be performed using blood culture bottles. The Staph ID/R Blood Culture Panel identifies Staphylococcus aureus (SA), and Staphylococcus lugdunensis, and detects other Staphylococcus species without identification to species level.

The Portrait Staph ID/R Blood Culture Panel is indicated for use in conjunction with other clinical or laboratory findings to aid in the diagnosis of bacterial bloodstream infections; however, it is not used to monitor these infections. Subculturing positive blood cultures is necessary to recover viable organisms for further identification, susceptibility testing, or epidemiological typing to identify organisms in the blood culture that are not detected by the Great Basin Staph ID/R Blood Culture Panel. If detected, mecA may or may not be associated with Staphylococcus spp. detected or the agent responsible for the disease. Negative results for mecA antimicrobial resistance gene assays do not always indicate susceptibility, as other mechanisms of resistance to methicillin exist.

The Great Basin PA500 Portrait™ Analyzer System is a fully automated system that includes the Portrait Analyzer, single-use Staph ID/R Blood Culture Panel Test Cartridges, and the Portrait data analysis software. The PA500 Portrait Analyzer System is designed to perform automated sample preparation, PCR, and optical chip-based detection with integrated data analysis in approximately 110 minutes.

The Great Basin Staph ID/R Blood Culture Panel is a qualitative, multiplex, nucleic acid-based in vitro diagnostic assay intended for the simultaneous identification of nucleic acid from Staphylococcus aureus, Staphylococcus lugdunensis, and various Staphylococcus species to the genus level, and the detection of the mecA gene for methicillin resistance directly from patient positive blood culture specimens. The device uses automated hot-start enabled PCR for amplification and hybridization probes on a silicon chip for detection.

Here's an analysis of its acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

• Staphylococcus positivity: 100% (540/540) for positive, 96.7% (87/90) for negative.
• Specific Staphylococcus detection: 99.6% (538/540) for positive, 99.3% (1341/1350) for negative.
• mecA detection (no organism): 99.7% (359/360) for present, 100% (270/270) for absent. |
  | Evaluation of Blood Culture Bottle Types | Compatibility with various bottle types. | All 13 tested blood culture bottle types were compatible with the Staph ID/R Blood Culture Panel, with no false negative results. One false positive S. aureus and one false positive Staphylococcus species OTHER than S. aureus or S. lugdunensis were observed in a single test run each, attributed to contamination. Nine invalid calls for E. faecalis. |
  | Prospective Clinical Performance - S. aureus | PPA ≥ 95%, NPA ≥ 95% (implied). | - PPA: 98.6% (211/214) (95% CI: 96.0 - 99.5%)
• NPA: 99.5% (548/551) (95% CI: 98.4 - 99.8%) |
  | Prospective Clinical Performance - S. lugdunensis | PPA ≥ 95%, NPA ≥ 95% (implied). | - PPA: 100.0% (3/3) (95% CI: 43.9 - 100%)
• NPA: 99.9% (761/762) (95% CI: 99.3 - 99.9%) |
  | Prospective Clinical Performance - Other Staphylococcus spp. | PPA ≥ 95%, NPA ≥ 95% (implied). | - PPA: 98.9% (444/449) (95% CI: 97.4 - 99.5%)
• NPA: 97.2% (307/316) (95% CI: 94.7 - 98.5%) |
  | Prospective Clinical Performance - mecA with S. aureus | PPA ≥ 90%, NPA ≥ 98% (implied). | - PPA: 94.4% (68/72) (95% CI: 86.6 - 97.8%)
• NPA: 98.8% (682/690) (95% CI: 97.7 - 99.4%) |
  | Prospective Clinical Performance - mecA with Other Staphylococcus spp. | PPA ≥ 90%, NPA ≥ 95% (implied). | - PPA: 92.7% (243/262) (95% CI: 88.1 - 97.1%)
• NPA: 96.2% (481/500) (95% CI: 92.4 - 98.0%) |
  | Invalid Rate - Clinical | Acceptable low rate, resolvable on retest. | Initial Invalid Rate: 1.39% (11/789). Final Invalid Rate: 0.00% after retest. |
  | Abort Rate - Clinical | Acceptable low rate, resolvable on retest. | Initial Abort Rate: 3.30% (26/789). Final Abort Rate: 0.00% after retest. |

2. Sample Size Used for the Test Set and Data Provenance

• Prospective Clinical Study:

  • Sample Size: A total of 762 prospective specimens were tested. Additionally, 69 archived frozen specimens were tested after the prospective study, making the overall clinical sample set significantly larger. A 'Low Prevalence' panel of 102 contrived or 'simulated' blood culture specimens was also tested.
  • Data Provenance: The prospective specimens were collected at three geographically diverse U.S. sites.

• Analytical Studies (LoD, Inclusivity, Exclusivity, Interference, Bottle Types, Reproducibility):

  • These studies used various numbers of cultured bacterial strains (ATCC, NCTC, CCUG, Clinical isolates where specified) and simulated blood culture specimens, often with multiple replicates per strain (ranging from 2 to 20+ replicates per strain for LoD, 2 replicates per strain for exclusivity, and 90 replicates per analyte for reproducibility). The specific number of unique strains and replicates varies per study as detailed in the tables (e.g., 22 strains for LoD, 116 off-panel strains for exclusivity, 7 simulated blood culture specimens for reproducibility).
  • Data Provenance: Not explicitly stated for each analytical study, but context suggests laboratory-controlled experiments. Strains were from recognized culture collections (ATCC, NCTC, CCUG) or clinical sources.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts

The document does not specify the number of experts or their qualifications used to establish the ground truth for the clinical or analytical test sets.

For the clinical study, the ground truth (Staphylococcus species identification and mecA gene presence) was established using "Reference Method(s)". While not explicitly defined, these reference methods typically involve conventional microbiology techniques such as:

• Sub-culturing of positive blood cultures.
• Phenotypic identification (e.g., Gram stain, catalase, coagulase tests, biochemical panels).
• Molecular methods (e.g., gene sequencing, PCR assays with a different target).
• Antimicrobial susceptibility testing (e.g., oxacillin MIC) to confirm methicillin resistance (though the device detects the mecA gene, not phenotypic resistance itself).

For analytical studies, bacterial strains from recognized collections (ATCC, NCTC, CCUG) and presumably well-characterized clinical isolates were used, implying their identity and mecA status were already established by standard microbiological and genetic methods.

4. Adjudication Method for the Test Set

The document does not explicitly describe an adjudication method (like 2+1 or 3+1) for the clinical test set. The comparison is made directly against "Reference Method(s)". For discrepant results in the exclusivity and microbial interference studies, repeat testing was performed (e.g., a minimum of six (6) repeat tests for 'Staphylococcus POSITIVE' calls in exclusivity, sometimes at higher CFU/mL input for interference studies to resolve miscalls).

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not conducted. This device is an automated in vitro diagnostic assay (algorithm only), not an AI-assisted human reading system. Therefore, there is no human-in-the-loop performance to measure improvement with AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done

Yes, the studies conducted demonstrate the standalone performance of the Great Basin Staph ID/R Blood Culture Panel. This device is an automated, qualitative, molecular diagnostic system, meaning its output is generated by the instrument itself (the Portrait Analyzer and its software) without direct human interpretation of complex images or data that would typically benefit from AI assistance. The performance metrics (PPA, NPA) directly reflect the device's accuracy against reference methods.

7. The Type of Ground Truth Used

The primary ground truth for both analytical and clinical performance studies was established through reference microbiology methods. This includes:

• Culture-based identification: Sub-culturing, Gram staining, and phenotypic tests for species identification.
• Molecular identification: Implied use of validated molecular techniques or genetic characterization (e.g., for mecA gene presence and confirmation of species for various strains).
• Antimicrobial Susceptibility Testing (AST): Specifically, oxacillin MIC was used in the Analytical Reactivity (Inclusivity) Challenge Panel to determine phenotypic resistance, which indirectly supports the genotypic mecA detection.
• For the analytical studies, well-characterized strains from culture collections (ATCC, NCTC, CCUG) served as a strong foundation for ground truth.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of device development or any specific AI/machine learning models. This is typical for traditional molecular diagnostic assays, where assay design (primer/probe sequences, reaction conditions) is based on known genetic targets and verified through extensive analytical validation rather than data-driven machine learning training. The analytical studies (LoD, inclusivity, exclusivity) serve to validate the analytical performance of the developed assay against a wide range of relevant organisms and conditions.

9. How the Ground Truth for the Training Set Was Established

As no explicit "training set" is described for an AI/ML model, this question is not directly applicable. If one considers the development of the assay (design of specific DNA targets and hybridization probes) as analogous to "training," then the ground truth would have been established through extensive molecular biology research, genetic sequencing, and characterization of Staphylococcus species and the mecA gene. This would involve identifying conserved and variable regions of target genes across a broad collection of known Staphylococcus strains to ensure specificity and sensitivity.

Ask a specific question about this device

The Verigene® Gram Negative Blood Culture Nucleic Acid Test (BC-GN), performed using the sample-to-result Verigene System, is a qualitative multiplexed in vitro diagnostic test for the simultaneous detection and identification of selected gram-negative bacteria and resistance markers. BC-GN is performed directly on blood culture media using blood culture bottles identified as positive by a continuous monitoring blood culture system and which contain gram-negative bacteria as determined by gram stain.

BC-GN detects and identifies the following:

BC-GN will not distinguish Escherichia coli from Shigella spp. (S. dysenteriae, S. flexneri, S. boydii, and S. sonnei)

BC-GN is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial bloodstream infections; however. is not used to monitor these infections. Sub-culturing of positive blood cultures is necessary to recover organisms for antimicrobial susceptibility testing (AST), for identification of organisms not detected by BC-GN, to detect mixed infections that may not be detected by BC-GN, for association of antimicrobial resistance marker genes to a specific organism, or for epidemiological typing.

The Verigene Gram Negative Blood Culture Nucleic Acid Test (BC-GN) is a molecular assay which relies on detection of specific nucleic acid targets in a microarray format. For each of the bacterial nucleic acid sequences detected by the BC-GN test, unique Capture and Mediator oligonucleotides are utilized, with gold nanoparticle probe-based endpoint detection. The Capture oligonucleotides are covalently bound to the microarray substrate and hybridize to a specific portion of the nucleic acid targets. The Mediator oligonucleotides have regions which bind to a different portion of the same nucleic acid targets and also have sequences which allow binding of gold nanoparticle probes. Specific silver enhancement of the bound gold nanoparticle probes at the capture sites results in gold-silver aggregates that scatter light with high efficiency and provide accurate detection of target capture.

The BC-GN test is performed on the Verigene System, a sample-to-result, fully automated. bench-top molecular diagnostics workstation consisting of two components: the Verigene Reader and the Verigene Processor SP. For the BC-GN test, the Verigene System allows automated nucleic acid extraction from positive bacteria-containing blood culture specimens and target detection of bacteria-specific DNA. The BC-GN test utilizes single-use disposable test consumables and a self-contained Verigene Test Cartridge for each sample tested.

The Reader is the Verigene System's central control unit and user interface, and, with a touch-screen control panel and barcode scanner, guides the user through test processing. imaging, and test result generation. The Verigene Processor SP executes the test procedure. automating the steps of (1) Sample Preparation- cell lysis and magnetic bead-based bacterial DNA isolation from blood culture samples, and (2) Hybridization-- detection and identification of bacterial-specific DNA in a microarray format by using gold nanoparticle probe-based technology. Once the specimen is loaded by the operator, all other fluid transfer steps are performed by an automated pipette that transfers reagents between wells of the trays and loads the specimen into the Test Cartridge for hybridization. Single-use disposable test consumables and a self-contained Verigenc Test Cartridge are utilized for each sample tested with the BC-GN test.

To obtain the test results after processing is complete. the user removes the Test Cartridge from the Processor SP, and inserts the substrate holder into the Reader for analysis. Light scatter from the capture spots is imaged by the Reader and intensities from the microarray spots are used to make a determination regarding the presence (Detected) or absence (Not Detected) of a bacterial nucleic acid sequence/analyte. This determination is made by means of software-based decision algorithm resident in the Reader.

The Nanosphere Verigene® Gram Negative Blood Culture Nucleic Acid Test (BC-GN) is a qualitative multiplexed in vitro diagnostic test designed for the simultaneous detection and identification of selected gram-negative bacteria and resistance markers directly from positive blood culture media.

Here's an analysis of its acceptance criteria and the supporting studies:

1. Table of Acceptance Criteria (Performance Goals) and Reported Device Performance (Method Comparison Study)

The document does not explicitly state "acceptance criteria" as a set of predefined thresholds for performance metrics. However, the "Method Comparison" study presents the device's performance against reference methods, which implicitly serve as the comparison points for its effectiveness. The reported performance metrics are Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA), along with their 95% Confidence Intervals.

Note: The document does not explicitly state numerical acceptance criteria. The "implied acceptance criterion" section is a general interpretation based on typical regulatory expectations for diagnostic accuracy.

2. Sample Size Used for the Test Set and Data Provenance

• Sample Size for Test Set: A total of 1412 specimens were analyzed in the method comparison study.
  • 604 prospectively-collected fresh specimens
  • 272 prospectively-collected frozen specimens
  • 239 selected frozen specimens
  • 297 simulated frozen specimens
• Data Provenance: The study was conducted at thirteen (13) investigational sites. The document does not specify the countries of origin for these sites or the data itself, but such clinical trials for FDA submissions are typically conducted in the US or under comparable regulatory frameworks. The inclusion of "prospectively-collected fresh specimens" and "prospectively-collected frozen specimens" indicates prospective data collection, while "selected frozen specimens" and "simulated frozen specimens" indicate retrospective or artificially prepared samples. This suggests a mixed approach to sample collection.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications

The document does not explicitly state the number of experts used to establish ground truth or their specific qualifications (e.g., "radiologist with 10 years of experience"). Instead, it describes the methods used to establish ground truth:

• For bacterial organisms: "standard culture-based automated phenotypic bacterial identification reference methods." This implies that the ground truth was established by clinical microbiology laboratories following established protocols, likely interpreted by qualified clinical microbiologists or medical laboratory scientists.
• For resistance markers: "the combination of PCR amplification and bidirectional sequencing confirmation." This indicates molecular biology techniques, which would also be performed and interpreted by appropriately trained laboratory personnel.

4. Adjudication Method for the Test Set

The document does not mention an explicit "adjudication method" involving multiple human readers for the test set results. The ground truth was established using standard reference laboratory methods, not through an adjudication process of human interpretations of the device's output. The device's results were directly compared to these reference methods.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not reported. This device is an in vitro diagnostic test (an algorithm-only device without human-in-the-loop performance being evaluated in the clinical study presented) rather than an imaging or interpretive AI device where human reader performance is typically assessed and compared to AI-assisted performance. The study focuses on the agreement of the device's output with standard reference methods. Therefore, an effect size of human readers improving with AI vs. without AI assistance is not applicable here.

6. Standalone (Algorithm-Only Without Human-in-the-Loop Performance) Study

Yes, the method comparison study directly assesses the standalone performance of the Verigene BC-GN test (algorithm only). The device's results are automatically generated by the Verigene System (Reader and Processor SP) and then compared to the ground truth established by reference laboratory methods, without human intervention in the interpretation of the device's output that would then be compared to human interpretation.

7. Type of Ground Truth Used

The ground truth used was:

• Culture-based automated phenotypic bacterial identification reference methods for bacterial organisms.
• PCR amplification and bidirectional sequencing confirmation for resistance markers.

8. Sample Size for the Training Set

The document does not explicitly specify a "training set" in the context of machine learning model development. This device appears to be a molecular diagnostic assay using a microarray and a software-based decision algorithm, rather than a system heavily reliant on a continuously learning or adaptable AI model that would typically have a distinct training phase with a specific dataset.

However, analytical studies involved extensive testing that could be considered analogous to developing and refining the device's performance characteristics:

• Analytical Sensitivity (LOD): Tested 12 bacterial strains.
• Analytical Reactivity (Inclusivity): Tested 195 strains of 44 different organisms (including 79 with resistance markers).
• Analytical Specificity (Exclusivity): Tested 172 "non-BC-GN panel" organisms.
• Competitive Inhibition / Mixed Growth: Multiple studies involving combinations of bacterial organisms.
• Precision/Repeatability: 18-member panel tested for 864 replicates.
• Reproducibility: 18-member panel tested for 1620 replicates across 3 external sites.

These studies contribute to the design and validation of the test's targets, probes, and decision algorithm, but a "training set" in the context of statistical machine learning for inferential models is not presented.

9. How the Ground Truth for the Training Set Was Established

As noted in point 8, a distinct "training set" with ground truth in the typical machine learning sense is not explicitly described. For the analytical studies (e.g., LOD, inclusivity, exclusivity), the ground truth for bacterial identification and resistance marker presence would have been established using well-characterized laboratory strains and standard microbiological and molecular identification techniques. These involve:

• Pure cultures: For LOD and inclusivity, known bacterial strains are used.
• Conventional identification methods: Such as cell morphology, growth characteristics, biochemical tests, and potentially 16S rRNA sequencing for difficult or novel strains.
• Molecular techniques for resistance markers: Such as PCR and sequencing to confirm the presence and identity of specific resistance genes.

These methods are the gold standards in microbiology for characterizing bacteria and their genetic elements, forming the basis of the device's design and analytical performance evaluation.

Ask a specific question about this device