(223 days)
The IMDx VanR for Abbott m2000 assay is an in vitro diagnostic assay that uses polymerase chain reaction (PCR) amplification for the qualitative detection of nucleic acids encoding the vancomycin resistance genes vanA and/or vanB. The assay is performed directly on human perirectal swabs, rectal swabs, or stool specimens from patients at risk for Vancomycin Resistant Enterococcus (VRE) colonization. The IMDx VanR for Abbott m2000 assay detects the presence of vanA and vanB genes that can be associated with vancomycin-resistant enterococci. The IMDx VanR for Abbott m2000 assay can be used as an aid to identify. prevent and control vancomycin-resistant colonization in healthcare settings. The IMDx VanR for Abbott m2000 assay is not intended to diagnose VRE infection nor to guide or monitor treatment of infection. Culture methods are necessary to recover organisms for epidemiology typing and confirmation testing.
The IMDx VanR for Abbott m2000 assay is a PCR-based assay that targets regions unique to the vanA and vanB vancomycin resistance genes that may be associated with vancomycin resistant Enterococcus (VRE). Detection of the vanA and vanB genes is measured by the presence of fluorescently-labeled oligonucleotide probes that generate a fluorescent signal when specifically bound to amplified vanA and/or vanB PCR products. Differentiation of vanA from vanB is attained by labeling the oligonucleotide probes with different colored fluorescent dyes. The amplification cycle at which fluorescent signal is detected by the Abbott m2000rt is inversely proportional to the vanA and vanB DNA target level present in the sample.
The IMDx VanR for Abbott m2000 assay includes reagents for the detection of the assay process control, which contains inactivated bacteria, unrelated to enterococci, and is introduced into each specimen during sample preparation. The process control (also acting as an internal control (IC)) is co-extracted with the specimen and co-amplified in the same PCR reaction as the vanA and vanB targets. The IC demonstrates that the entire assay process has proceeded within specification.
Here's an analysis of the provided information, focusing on the acceptance criteria and the study proving the device meets them:
Acceptance Criteria and Device Performance for IMDx VanR for Abbott m2000
The document provided, K123753, describes the IMDx VanR for Abbott m2000 assay, an in vitro diagnostic device for detecting vancomycin resistance genes. The acceptance criteria are implicitly derived from the performance goals demonstrated in the clinical studies, as explicit pre-defined acceptance criteria are not directly stated in the summary. The performance is reported as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) based on comparison to a "gold standard" method.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (95% CI) |
|---|---|---|
| Peri-rectal Swab Specimens | ||
| Sensitivity | High sensitivity for detecting vanA and/or vanB genes. | 94.0% (83.8% - 97.9%) |
| Specificity | High specificity for differentiating between detected vanA/vanB and negative samples. | 93.9% (91.5% - 95.6%) |
| Positive Predictive Value | Adequate PPV for indicating presence of vanA/vanB. | 58.8% (47.8% - 68.9%) |
| Negative Predictive Value | High NPV for ruling out vanA/vanB presence. | 99.4% (98.3% - 99.8%) |
| Rectal Swab Specimens (Prospective) | ||
| Sensitivity | High sensitivity for detecting vanA and/or vanB genes. | 96.8% (89.1% - 99.1%) |
| Specificity | High specificity for differentiating between detected vanA/vanB and negative samples. | 91.7% (88.3% - 94.2%) |
| Positive Predictive Value | Adequate PPV for indicating presence of vanA/vanB. | 68.5% (58.3% - 77.2%) |
| Negative Predictive Value | High NPV for ruling out vanA/vanB presence. | 99.4% (97.7% - 99.8%) |
| Rectal Swab Specimens (Retrospective) | ||
| Positive Percent Agreement | High agreement with the reference method for positive samples. | 100.0% (91.6% - 100.0%) |
| Negative Percent Agreement | High agreement with the reference method for negative samples. | 0.0% (0.0% - 65.8%) Note: This low NPA is due to the specific composition of the retrospective cohort, where all "negative" samples by the IMDx assay were also negative by the reference standard. The total NEG for the IMDx assay was 0, meaning no calculation was possible. This requires careful interpretation. |
| Stool Specimens | ||
| Sensitivity | High sensitivity for detecting vanA and/or vanB genes. | 87.0% (77.0% - 93.0%) |
| Specificity | High specificity for differentiating between detected vanA/vanB and negative samples. | 85.8% (82.0% - 88.8%) |
| Positive Predictive Value | Adequate PPV for indicating presence of vanA/vanB. | 51.3% (42.3% - 60.2%) |
| Negative Predictive Value | High NPV for ruling out vanA/vanB presence. | 97.4% (95.2% - 98.6%) |
Note on Acceptance Criteria: The document does not explicitly state numerical acceptance criteria (e.g., "Sensitivity must be >X%"). Instead, the clinical performance study aims to demonstrate that the device performs comparably and effectively for its intended use, implying that the reported percentages of sensitivity, specificity, PPV, and NPV are deemed acceptable for supporting substantial equivalence to the predicate device.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set (Clinical Performance Study):
- Peri-rectal swabs: 587 samples
- Rectal swabs: 444 samples (further broken down into prospective and retrospective collections)
- Prospective: 400 samples
- Retrospective: 44 samples
- Stool specimens: 469 samples
- Total Clinical Samples: 587 + 444 + 469 = 1500 samples
- Data Provenance: Samples were collected from "five geographically diverse test sites within the United States." The study included both prospective and retrospective collection for rectal swabs.
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 used to establish the ground truth. It states that the ground truth was "enriched culture combined with confirmation of the molecular basis of vancomycin resistance of isolates using an alternate PCR method." This implies laboratory personnel with expertise in microbiology and molecular diagnostics, but no specific number or detailed qualifications are provided.
4. Adjudication Method for the Test Set
The document does not describe a formal adjudication method (e.g., 2+1, 3+1, none) for the test set. The ground truth was established by a combination of enriched culture and an alternate PCR method, implying a direct comparison against these established laboratory techniques rather than a human consensus process.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This study focuses on the in vitro diagnostic performance of the assay itself (device vs. reference method) rather than evaluating human reader performance with and without AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the clinical performance study evaluates the IMDx VanR for Abbott m2000 assay in a standalone manner. The assay is an automated PCR-based diagnostic test, and its results are compared directly to the ground truth (enriched culture + alternative PCR). There is no human interpretation of images or other data being assisted by the algorithm; the assay itself generates the result.
7. The Type of Ground Truth Used
The ground truth used was a combination of enriched culture combined with confirmation of the molecular basis of vancomycin resistance of isolates using an alternate PCR method. This is a highly robust ground truth for detecting the presence of vanA and/or vanB genes and is considered a reference standard in microbiology.
8. The Sample Size for the Training Set
The document does not explicitly state the sample size for a "training set." This type of molecular diagnostic assay typically undergoes extensive analytical validation (e.g., LOD, reactivity, cross-reactivity) using characterized strains and spiked samples, and then its clinical performance is evaluated on a distinct clinical test set. It's possible that data from these extensive analytical studies could be considered analogous to training data for method optimization, but a defined "training set" in the context of machine learning is not applicable here as it's a rule-based PCR assay, not an AI/ML algorithm.
9. How the Ground Truth for the Training Set Was Established
As noted above, a traditional "training set" as understood in AI/ML is not described. However, for the analytical studies (e.g., Analytical Reactivity, Challenge Study), the ground truth was established using "well-characterized vancomycin-resistant Enterococcus strains and/or clinical isolates" and other organisms. These strains would have their vanA/vanB status, and other genetic characteristics, confirmed through standard microbiological and molecular methods (e.g., sequencing, biochemical tests, established PCR assays).
§ 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).