(102 days)
The artus C. difficile QS-RGQ MDx Kit is an in vitro polymerase chain reaction (PCR) assay for use on the QIAsymphony RGQ MDx system for the qualitative detection of toxigenic Clostridium difficile toxin A and toxin B genes in human liquid or soft stool specimens from patients suspected of having Clostridium difficile associated disease. The test is intended to be used directly on patient samples.
The artus C. difficile QS-RGQ MDx Kit is intended to be used to aid in diagnosis of Clostridium difficile infection.
The artus C. difficile QS-RGQ MDx Kit assay uses PCR to generate an amplified product from the tcdA and tedB/tedBv genes of toxigenic C. difficile DNA in clinical specimens. Samples are extracted and prepared using the Q1Asymphony SP instrument with the QIAsymphony DSP Virus/Pathogen Mini Kit, followed by assay setup on the OIAsymphony AS. Amplification and detection are carried out using the artus C. difficile OS-RGQ MDx Kit with the Rotor-Gene Q MDx (RGQ MDx) and Rotor-Gene AssayManager software. The presence of a toxigenic C. difficile target sequence is indicated by the fluorescent signal generated through the use of fluorescently labeled oligonucleotide probes. The probes do not generate a signal unless they are specifically bound to the amplified product. The amplification cycle at which fluorescent signal is detected by the RGQ MDx is inversely proportional to the toxigenic C. difficile DNA target concentration present in the original specimen. A bacterial species unrelated to toxigenic C. difficile is introduced into each specimen during sample preparation to serve as an internal control. The internal control bacteria are lysed simultaneously with toxigenic C. difficile in the specimen. and amplified in the same reaction as the C. difficile targets using PCR, and serve to demonstrate that the entire assay process has proceeded correctly for each specimen.
Here's a summary of the acceptance criteria and study details for the QIAGEN artus® C. difficile QS-RGQ MDx Kit, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria (e.g., "Sensitivity must be >X%", "Specificity must be >Y%"). Instead, it reports the device's performance against a comparative method (enriched toxigenic culture and direct toxigenic culture) for the purpose of demonstrating substantial equivalence to a predicate device.
However, based on the provided clinical performance tables, we can present the reported performance:
| Metric | Performance vs. Enriched Toxigenic Culture (95% CI) | Performance vs. Direct Toxigenic Culture (95% CI) |
|---|---|---|
| Sensitivity | 90% (83% - 94%) | 99% (94% - 100%) |
| Specificity | 97% (96% - 98%) | 97% (95% - 98%) |
| Positive Predictive Value (PPV) | 87% (80% - 92%) | 80% (71% - 87%) |
| Negative Predictive Value (NPV) | 98% (96% - 99%) | 100% (99% - 100%) |
| Prevalence | 17% (15% - 20%) | 12% (10% - 15%) |
2. Sample Size and Data Provenance for the Test Set
- Sample Size (for clinical evaluation):
- Initially, 759 liquid or soft stool specimens were collected.
- 10 specimens were withdrawn due to missing results.
- 16 specimens reported an invalid result with the artus kit (8 became valid upon retesting as negative, 8 remained invalid).
- The final dataset for performance analysis included 741 specimens (for comparison against enriched culture).
- For comparison against direct culture, 699 specimens were available.
- Data Provenance: The specimens were collected from 5 geographically diverse locations within the United States in 2013. The study was prospective as it involved collecting specimens from patients suspected of having Clostridium difficile-associated disease for concurrent testing.
3. Number of Experts and Qualifications for Ground Truth
The document does not mention the use of "experts" in the sense of clinicians or radiologists establishing ground truth. The "ground truth" for the clinical study was established by laboratory methods: enriched toxigenic culture and direct toxigenic culture. For discordant results, alternative PCR followed by bi-directional sequencing was used to resolve discrepancies. The qualifications of the personnel performing these laboratory tests are not specified, but it can be inferred they were trained laboratory technicians.
4. Adjudication Method for the Test Set
For discordant results in the clinical comparison studies:
- Discordant Analysis: An "alternative PCR followed by bi-directional sequencing" was used.
- Enriched Culture Comparison:
- For 17 specimens that were artus Positive/Enriched Culture Negative, 12 were found positive by alternative PCR, agreeing with artus.
- For 12 specimens that were artus Negative/Enriched Culture Positive, 10 were found negative by alternative PCR, agreeing with artus. One specimen was unavailable for testing.
- Direct Culture Comparison:
- For 19 specimens that were artus Positive/Direct Culture Negative, 14 were found positive by alternative PCR, agreeing with artus. Two specimens were unavailable for testing.
- The 1 specimen that was artus Negative/Direct Culture Positive was unavailable for testing.
This method resembles a third-party arbitration/adjudication (2+1 or similar logic) where an additional, more definitive test (alternative PCR + sequencing) was used to resolve disagreements between the index test (artus kit) and the primary comparator (culture).
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not conducted. This device is an in vitro diagnostic (IVD) assay that provides a quantitative or qualitative result, not an image-based diagnostic read by human observers. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable here.
6. Standalone Performance
Yes, the studies reported demonstrate the standalone performance of the algorithm (the artus C. difficile QS-RGQ MDx Kit). The clinical performance tables compare the kit's results directly against culture methods, without human interpretation for the artus kit's output.
7. Type of Ground Truth Used
The primary ground truth for the clinical studies was laboratory culture results, specifically:
- Enriched Toxigenic Culture
- Direct Toxigenic Culture
- For discordant cases, a more definitive molecular method, alternative PCR followed by bi-directional sequencing, was used as a confirmatory "reference standard" to resolve discrepancies.
8. Sample Size for the Training Set
The document does not specify the sample size used for any training set. This information is typically proprietary to the manufacturer's algorithm development process and is not always disclosed in 510(k) summaries for IVD devices. The studies described are performance validation studies, not algorithm training studies.
9. How Ground Truth for the Training Set Was Established
As the sample size for a training set is not provided, the method for establishing its ground truth is also not described.
§ 866.3130 Clostridium difficile toxin gene amplification assay.
(a)
Identification. AClostridium difficile toxin gene amplification assay is a device that consists of reagents for the amplification and detection of target sequences inClostridium difficile toxin genes in fecal specimens from patients suspected of havingClostridium difficile infection (CDI). The detection of clostridial toxin genes, in conjunction with other laboratory tests, aids in the clinical laboratory diagnosis of CDI caused byClostridium difficile. (b)
Classification. Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Toxin Gene Amplification Assays for the Detection ofClostridium difficile; Guideline for Industry and Food and Drug Administration Staff.” See § 866.1(e) for information on obtaining this document.