(143 days)
IDI-MRSA™ assay is a qualitative in vitro diagnostic test for the direct detection of nasal colonization by methicillin-resistant Staphylococcus aureus (MRSA) to aid in the prevention and control of MRSA infections in healthcare settings. The test performed on the Smart Cycler® instrument with a nasal swab specimen from patients at risk for colonization, utilizes polymerase chain reaction (PCR) for the amplification of MRSA DNA and fluorogenic target-specific hybridization probes for the detection of the amplified DNA.
IDI-MRSA is not intended to diagnose MRSA infections nor to guide or monitor treatment for Concomitant cultures are necessary only to recover organisms for MRSA infections. epidemiological typing or for further susceptibility testing.
IDI-MRSA™ assay is a qualitative in vitro diagnostic test for the direct detection of nasal colonization by methicillin-resistant Staphylococcus aureus (MRSA). A nasal specimen is collected and transported to the laboratory using the Copan Venturi Transystem®. For testing, the swab is placed in sample preparation buffer. The specimen is concentrated and lysed. An aliquot of the lysate is added to PCR reagents which contain the MRSA-specific primers used to amplify the genetic target [a sequence near the insertion site of Staphylococcal Cassette Chromosome mec (SCCmec)], if present. The assay also includes an internal control (IC) used to detect PCR inhibitory specimens and to confirm the integrity of an internal of the PC (C is a DNA fragment of 335-bp including a 277-bp assay reagents in hogative optionnel to targets are detected with hybridization probes labeled sequence fluorophores (rnolecular beacons). For the detection of MRSA amplicons, the with quencher beacon contains the fluorophore 5-carboxyfluorescein (amine reactive ester of molocally beader commonly called FAM) at the 5' end and the non-fluorescent quencher carboxy-liderooooin bonneeriy on the opposite end of the oligonucleotide. For the detection moley daboy onlorido (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) ( fluorescein (TET) at the 5' end and the non-fluorescent quencher moiety DABCYL at the 3' end. The test is performed on the Smart Cycler® instrument which monitors simultaneously the fluorescence emitted by each beacon, interprets all data and at the end of the cycling program provides a final result.
1. Table of Acceptance Criteria and Reported Device Performance:
| Acceptance Criteria (Implied) | Reported Device Performance (IDI-MRSA™ Assay) |
|---|---|
| Ability to detect MRSA-positive specimens (Sensitivity) | 92.5% (95% CI: 86.9-96.2%) |
| Ability to correctly identify MRSA-negative specimens (Specificity) | 96.4% (95% CI: 94.6-97.7%) |
| Consistent performance across different clinical sites | Individual site sensitivities ranged from 86.8% to 100%; specificities ranged from 90.8% to 99.6% |
| Low rate of unresolved/invalid test results | 35 unresolved out of 786 specimens (4.5%); 3 invalid runs out of 89 total runs (3.4%) |
Note: The document does not explicitly state "acceptance criteria." The criteria listed above are inferred from the performance metrics presented in the clinical study results and are typical for diagnostic device submissions.
2. Sample Size and Data Provenance for the Test Set:
- Sample Size: 786 nasal swab specimens.
- Data Provenance: The data was collected as part of a multi-center study. The specific countries are not mentioned, but the submitting company is based in Canada. The study was prospective in nature, as indicated by the collection of specimens for the study.
3. Number of Experts and Qualifications for Ground Truth Establishment (Test Set):
- The document does not specify the number of individual experts or their qualifications (e.g., radiologists with X years of experience) used to establish the ground truth.
- Instead, the ground truth was established using a "reference method" which consisted of a culture-based approach. This method involved:
- Initial analysis with oxacillin screen agar (OxaMSA) after selective growth on mannitol salt agar.
- For specimens negative by OxaMSA, an additional analysis included an enrichment step in trypticase soy broth (OxaTSB) followed by oxacillin screen agar test.
- An MRSA-positive specimen was defined as positive by either culture technique, and an MRSA-negative specimen was negative by both.
- Further investigation was conducted for discrepant results where IDI-MRSA was positive but culture-negative, which involved "more enhanced culture techniques" (details not provided) and mecA-specific PCR of isolates. This implies expert judgment and advanced laboratory techniques were involved in clarifying these specific cases.
4. Adjudication Method for the Test Set:
- The document does not describe a traditional "adjudication method" involving multiple human readers for interpreting the ground truth.
- The ground truth was established by a defined laboratory methodology (culture techniques) which inherently serves as a reference standard.
- For discrepant results (IDI-MRSA positive, culture negative), "further investigation" was conducted, leading to a reclassification of some specimens. This suggests a form of expert review for these specific cases, but not a full-scale multi-reader adjudication process.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed.
- This study evaluates a diagnostic assay (IDI-MRSA™ assay) against a laboratory reference standard (culture method), not the improvement of human readers with AI assistance.
6. Standalone Performance Study:
- Yes, a standalone performance study was done. The entire "Clinical Performance" section describes the performance of the IDI-MRSA™ assay on its own, directly comparing its results to the established culture reference method. The reported sensitivity, specificity, positive predictive value, and negative predictive value are all measures of the algorithm's standalone performance.
7. Type of Ground Truth Used:
- The primary ground truth used was expert consensus pathology/culture results. This involved a multi-step culture-based reference method (oxacillin screen agar, enrichment in trypticase soy broth, and follow-up mecA-specific PCR for discrepant results).
8. Sample Size for the Training Set:
- The document does not explicitly state the sample size for a training set. The study described is a clinical performance study using a test set of 786 specimens.
- As this is a molecular diagnostic assay (PCR-based), it is likely that the "training" (development and optimization) would have involved laboratory experiments with characterized strains and clinical samples, but a formal clinical "training set" in the context of machine learning is not applicable or described here.
9. How the Ground Truth for the Training Set Was Established:
- Since a formal "training set" is not explicitly mentioned or applicable in the context of this analytical device, the method for establishing ground truth for such a set is not described.
- Presumably, the development of the assay (including primer and probe design) would have been based on known MRSA strains with established genetic characteristics (e.g., presence of SCCmec and mecA gene), and preliminary testing would have involved well-characterized clinical isolates and control samples with confirmed MRSA status via standard microbiological and genetic methods.
§ 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).