(422 days)
The BD GeneOhm™ VanR Assay is a qualitative in vitro test for the rapid detection of vancomycin-resistance (vanA and vanB) genes directly from perianal or rectal swabs. The BD GeneOhm™ VanR Assay detects the presence of the vanA and vanB genes that can be associated with vancomycin-resistant enterococci (VRE). The assay is performed on an automated real-time PCR instrument with perianal or rectal swabs from individuals at risk for VRE colonization. The BD GeneOhm™ VanR Assay can be used as an aid to identify, prevent and control vancomycin-resistant colonization in healthcare settings. The BD GeneOhm™ VanR Assay is not intended to diagnose VRE infections nor to guide or monitor treatment for VRE infections. Concomitant cultures are necessary to recover organisms for epidemiological typing, susceptibility testing and for further confirmatory identification.
Following specimen lysis, the vanA and vanB genetic targets, if present, are amplified. Amplification of the Internal Control (IC), a DNA fragment of 294-bp including a 254-bp sequence not found in VRE, will also take 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 the vanA amplicon, the molecular beacon probe contains the fluorophore FAM at the 5' end and the nonfluorescent quencher moiety DABCYL at the opposite 3' end of the oligonucleotide. For the detection of the vanB amplicon, the molecular beacon probe contains the fluorophore Texas Red 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 molecular beacon probe, interprets all data, and provides a final result at the end of the cycling program.
Here's a summary of the acceptance criteria and study details for the BD GeneOhm™ VanR Assay, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of specific performance thresholds (e.g., "Sensitivity must be >X%"). Instead, the study aims to demonstrate substantial equivalence to the predicate device. The performance is reported in terms of observed sensitivity and specificity (or Positive Percent Agreement and Negative Percent Agreement). The tables below summarize the overall clinical performance across all sites.
| Metric (for VanR detection) | Acceptance Criteria (Implicit: Demonstrate substantial equivalence) | Reported Device Performance (Overall) - Perianal Specimens | Reported Device Performance (Overall) - Rectal Specimens |
|---|---|---|---|
| Sensitivity (using Direct/Enriched Culture) | Sufficiently High (to be equiv. to predicate) | 92.9% (87.7% - 96.4% CI) | 93.1% (87.4% - 96.8% CI) |
| Specificity (using Direct/Enriched Culture) | Sufficiently High (to be equiv. to predicate) | 86.0% (83.8% - 87.9% CI) | 82.2% (79.2% - 85.0% CI) |
| Positive Percent Agreement (using Direct Culture) | Sufficiently High (to be equiv. to predicate) | 95.0% (89.3%-98.1% CI) | 95.5% (89.9%-98.5% CI) |
| Negative Percent Agreement (using Direct Culture) | Sufficiently High (to be equiv. to predicate) | 83.9% (81.7%-86.0% CI) | 81.0% (77.9%-83.8% CI) |
| Unresolved Rate (final) | Low | 0.3% (0.1% - 0.6% CI) | 0.3% (0.1% - 0.6% CI) (Overall study rate) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Test Set):
- Direct/Enriched Culture Comparison: 2156 specimens (1316 perianal and 834 rectal specimens). 2150 reportable results.
- Direct Culture Comparison: 2152 specimens (1314 perianal and 832 rectal specimens). 2146 reportable results.
- Data Provenance: The study was a "multisite prospective investigational study" conducted across "Five (5) medical centers." The country of origin is not explicitly stated, but the submission is to the US FDA, implying US-based or internationally accepted clinical trial standards. The study design is prospective.
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 or qualifications of experts involved in establishing the ground truth. The reference method involved a multi-step microbiological process. While it implicitly requires expert laboratory personnel to perform and interpret these complex tests, no specific "expert" panel for ground truth adjudication is mentioned.
4. Adjudication Method for the Test Set
No explicit adjudication method (like 2+1 or 3+1) is described for the test set. The ground truth (Reference Method) was established through a defined laboratory protocol involving direct culture, enriched culture, phenotypic identification of Enterococcus colonies, vancomycin resistance testing (MIC method), and genotypic characterization of vanA or vanB genes using alternative PCR. This is a sequential, algorithm-driven process rather than an independent expert adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study was not done. This device is a molecular diagnostic assay, not an imaging-based diagnostic tool that typically involves human reader interpretation. The comparison is between the automated PCR assay and a laboratory reference method.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was Done
Yes, the performance characteristics presented are for the standalone algorithm (BD GeneOhm™ VanR Assay). The device is a "qualitative in vitro test for the rapid detection of vancomycin-resistance (vanA and vanB) genes directly from perianal or rectal swabs" performed on "an automated real-time PCR instrument." The reported performance metrics (sensitivity, specificity etc.) are the direct output of this automated system compared to the reference method.
7. The Type of Ground Truth Used
The ground truth used was a "Reference Method" consisting of:
- Direct Culture complemented by Enriched Culture.
- Inoculation onto Bile Esculin Azide agar supplemented with 6 µg/mL vancomycin (BEAV).
- Phenotypic identification of presumptive Enterococcus colonies (PYR test, commercial tests for species identification).
- Vancomycin resistance determined using an MIC method.
- Genotypic characterization of vanA and vanB genes using alternative PCR for confirmed vancomycin-resistant enterococcal isolates.
A "vanA- and/or vanB-containing VRE positive specimen" was defined as a specimen with vancomycin-resistant enterococci from culture with vanA and/or vanB genes identified by alternative PCR. A negative specimen was defined as negative by both direct and enriched culture methods.
8. The Sample Size for the Training Set
The document provided (510(k) summary) does not specify a separate "training set" for the BD GeneOhm™ VanR Assay. Clinical performance studies typically involve a "test set" to evaluate the device against a reference method. For molecular assays, assay development involves extensive internal validation and optimization with various samples, but these are generally not described as a "training set" in the same way machine learning models would have one. The focus here is on the performance of the developed assay on a clinical validation cohort.
9. How the Ground Truth for the Training Set Was Established
As no specific "training set" is described for this type of device in the provided document, the method for establishing its ground truth is not detailed. However, the ground truth for the clinical validation (test set), as described in point 7, involved a comprehensive microbiological and molecular reference method. This rigorous reference method would implicitly guide the development and optimization of the assay during its pre-clinical phase.
§ 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).