(253 days)
The BD GeneOhm™ StaphSR Assay is a qualitative in vitro diagnostic test for the rapid detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) directly from positive blood culture. The assay utilizes polymerase chain reaction (PCR) for the amplification of specific targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The assay is performed on Gram positive cocci, identified by Gram stain, from positive blood cultures. The BD GeneOhm™ StaphSR Assay is not intended to monitor treatment for MRSA/SA infections. Subculturing of positive blood cultures is necessary for further susceptibility testing.
The BD GeneOhm™ StaphSR Assay is a qualitative in vitro diagnostic test for the rapid detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) directly from positive blood culture. The assay utilizes polymerase chain reaction (PCR) for the amplification of specific targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The assay is performed on Gram positive cocci, identified by Gram stain, from positive blood cultures. To test a positive blood culture, an aliquot of the culture media is transferred into a sample buffer tube and lysed. Following specimen lysis, amplification of the targets (MRSA: a S. aureus specific target and a sequence near the insertion site of the Staphylococcal Cassette Chromosome mec (SCCmec); SA: another S. aureus specific sequence] occurs in the presence of either or both targets. Amplification of the IC, a DNA fragment of 335-bp including a 277-bp sequence not found in S. aureus or MRSA, also takes place unless PCR inhibitory substances are present. The amplified DNA targets are detected with molecular beacon probes, hairpin-forming single-stranded oligonucleotides labelled at one end with a quencher and at the other end with a fluorescent reporter dye (fluorophore). In the absence of target, the fluorescence is quenched. In the presence of target, the hairpin structure opens upon beacon/target hybridization, resulting in emission of fluorescence. For the detection of MRSA amplicon, the molecular beacon probe contains the fluorophore FAM at the 5' end and the non-fluorescent quencher moiety DABCYL at the opposite end of the oligonucleotide. For the detection of S. aureus amplicon, the molecular beacon probe is labelled with the fluorophore TexasRed at the 5' end and the quencher DABCYL at the 3' end. For the detection of the IC amplicon, the molecular beacon probe contains the fluorophore TET at the 5' end and the quencher DABCYL at the 3' end, Each beacon-target hybrid fluoresces at a wavelength characteristic of the fluorophore used in the particular molecular beacon probe. The amount of fluorescence at any given cycle, or following cycling, depends on the amount of specific amplicon present at that time. The SmartCycler software simultaneously monitors the fluorescence emitted by each beacon probe, interprets all data, and provides a final result at the end of the cycling program.
Acceptance Criteria and Device Performance for BD GeneOhm™ StaphSR Assay
This document describes the acceptance criteria and study proving the BD GeneOhm™ StaphSR Assay meets these criteria, as presented in the 510(k) Summary K071026.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the BD GeneOhm™ StaphSR Assay are implicitly established through the comparison to predicate devices, where the assay is deemed "substantially equivalent in performance." While specific numerical performance targets are not explicitly stated as "acceptance criteria" in the provided text, the clinical trial results demonstrate the performance achieved. Based on the analysis of the provided tables, the reported device performance for both MRSA and S. aureus detection consistently achieves high levels of positive and negative agreement with reference methods across multiple sites.
| Metric (Implicit Acceptance Criteria based on Predicate Device Performance) | BD GeneOhm™ StaphSR Assay Performance (Across 5 Sites) |
|---|---|
| MRSA Detection: | |
| Positive Agreement (Sensitivity) | 100% (Range: 100% across all sites) |
| Negative Agreement (Specificity) | 98.2% - 100% (Lowest: 98.2% at Site 2, Highest: 100% at Sites 3 & 5) |
| Overall Agreement | 98.5% - 100% (Lowest: 98.5% at Site 2, Highest: 100% at Sites 3 & 5) |
| S. aureus Detection: | |
| Positive Agreement (Sensitivity) | 98.8% - 100% (Lowest: 98.8% at Site 4, Highest: 100% at Sites 1, 2, 3, 5) |
| Negative Agreement (Specificity) | 96.5% - 100% (Lowest: 96.5% at Site 4, Highest: 100% at Sites 1, 3, 5) |
| Overall Agreement | 97.2% - 100% (Lowest: 97.2% at Site 4, Highest: 100% at Sites 1, 3, 5) |
| Unresolved Results | Low (Range: 0.0% - 0.3% initially; 0.0% - 0.0% on repeat) |
| Invalid Assays | Low (Range: 1.8% - 8.9% initially; 0.0% - 0.0% on repeat) |
Note: The "acceptance criteria" are implied by the claim of "substantial equivalence in performance" to established predicate devices (Remel Staphaurex Latex Agglutination Test, BBL (BD) Oxacillin Screen Agar, and BD Phoenix Automated ID/AST System). The reported device performance demonstrates a high degree of concordance with these reference methods.
2. Sample Size Used for the Test Set and Data Provenance
The clinical trials were performed at five sites. The total sample sizes for the test set across all sites are calculated from the provided tables:
- For MRSA:
- Site 1: 446 samples
- Site 2: 133 samples
- Site 3: 232 samples
- Site 4: 286 samples
- Site 5: 86 samples
- Total MRSA Test Set: 1183 samples
- For S. aureus:
- Site 1: 446 samples
- Site 2: 133 samples
- Site 3: 232 samples
- Site 4: 286 samples
- Site 5: 86 samples
- Total S. aureus Test Set: 1183 samples
(The sample sizes for MRSA and S. aureus appear to be derived from the same set of positive blood cultures.)
Data Provenance: The document states that the "Clinical trials were performed at five sites." While specific countries of origin for these sites are not explicitly mentioned, it is highly probable that the data were collected in the United States or Canada, given the submitter and contact information (BD Diagnostics, GeneOhm Sciences Canada Inc., with a US Agent in San Diego, CA). The study is prospective in nature, as it is a "clinical trial" evaluating the performance of a new diagnostic assay.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The ground truth was established by "reference methods" in clinical laboratories. These reference methods are listed as:
- Remel Staphaurex Latex Agglutination Test (for S. aureus)
- BBL (BD) Oxacillin Screen Agar (for MRSA)
- BD Phoenix Automated ID/AST System (for both S. aureus and MRSA)
- Culture/PBP2' Latex (for MRSA at Site 5)
The document does not specify the number of individual experts (e.g., microbiologists, lab technologists) who interpreted these reference methods at each site, nor their specific qualifications (e.g., years of experience). However, it is implied that these interpretations were performed by qualified laboratory personnel following standard laboratory protocols for these established diagnostic tests.
4. Adjudication Method for the Test Set
The document does not describe a formal adjudication method (like 2+1 or 3+1 consensus) for discrepancies between the test device and the reference methods. The tables present a direct comparison of the BD GeneOhm™ StaphSR results against the respective reference method results at each site. Any disagreements would have been considered false positives or false negatives against the established reference standard.
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 done. This study evaluates the performance of a diagnostic assay (BD GeneOhm™ StaphSR) against established laboratory reference methods, not the performance of human readers with or without AI assistance. Therefore, there is no effect size reported for human reader improvement with AI vs. without AI assistance.
6. If a Standalone Study (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, this was a standalone study in the context of a diagnostic test kit. The BD GeneOhm™ StaphSR Assay is a PCR-based molecular diagnostic test. The "performance" tables directly compare the output of the "BD GeneOhm™ StaphSR" assay (which includes the entire PCR and detection process interpreted by the SmartCycler software) against the reference culture/ID-AST systems. While human technicians perform the sample preparation and run the assay, the "result" generated by the device itself is interpreted by the SmartCycler software providing a final result at the end of the cycling program. This means the reported performance is the "algorithm only" or "device only" performance in its intended use.
7. The Type of Ground Truth Used
The ground truth used was established by standard microbiological culture and identification/antimicrobial susceptibility testing (ID/AST) methods, which are considered the gold standard for identifying bacterial species and their resistance patterns in clinical microbiology. Specifically, these included:
- Culture/ID-AST System 1, 2, 3
- Culture/Oxacillin Screen Agar
- Culture/PBP2' Latex
These are laboratory reference standards, often supported by expert interpretation of growth characteristics and biochemical or molecular profiles.
8. The Sample Size for the Training Set
The document does not provide information on the sample size for the training set. This is common for diagnostic assays of this type, where the "training" (development and optimization) often involves laboratory strains and characterized clinical isolates during the assay design phase, rather than a distinct, formally reported "training set" of patient samples in the same manner as machine learning models might have. The clinical trials described here represent the validation or test set.
9. How the Ground Truth for the Training Set Was Established
As no specific training set is detailed, the method for establishing its ground truth is also not provided. However, during the development of such assays, ground truth for optimization and development samples would typically be established using well-characterized clinical isolates and reference strains confirmed by extensive phenotypic and genotypic methods, including sequencing, to ensure accurate target and non-target differentiation.
§ 866.1640 Antimicrobial susceptibility test powder.
(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).