(261 days)
The cobas vivoDx MRSA test performed on the cobas vivoDx System is an automated qualitative in vitro diagnostic test for the direct detection of live methicillin-resistant Staphylococcus aureus (MRSA) cells in nasal swab samples from patients who are at risk for nasal colonization by MRSA. The test utilizes selective agents and bioparticles (Smarticles technology) to introduce a luciferase gene into targeted bacteria to create an amplified luminescent signal in only viable (live) MRSA cells. The cobas vivoDx MRSA test is intended to aid in the prevention and control of MRSA infections in healthcare settings. It is not intended to diagnose MRSA infections, nor to guide, or monitor treatment. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.
The cobas vivoDx MRSA Collection and Transport Kit is used to collect, transport and store human nasal swab specimens for use with the cobas vivoDx MRSA test.
The cobas vivoDx MRSA test, performed on the cobas vivoDx Instrument, is an automated, phenotypic assay for the direct, qualitative detection of MRSA in nasal swab specimens that are collected and transported to the testing laboratory using the cobas vivoDx MRSA Collection and Transport Kit.
Upon receipt in the laboratory, the test operator vortexes the specimen to elute the target organisms (if present) and transfers an aliquot of the transport medium to an MRSA Test Tube containing a dried bead of a selective reagent (cefoxitin) that is solubilized with the sample. The operator then applies a MRSA Reagent Cap to the Test Tube, briefly vortexes the assembled cartridge and loads it onto the cobas vivoDx Instrument for automated processing.
The MRSA Reagent Cap comprises two reagent-filled blisters, one containing Staphylococcus aureus-specific bacteriophage-based Smarticles that encode the enzyme luciferase, and the other, a luminescent substrate. The cobas vivoDx Instrument automatically completes incubation of the cartridge, addition of the Smarticles and substrate to the test sample, as well as measurement and analysis of the luminescent signal. Results are reported as "Positive" (MRSA detected) or "Negative" (no MRSA detected).
Here's a detailed breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:
Acceptance Criteria and Device Performance for cobas vivoDx MRSA
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" but rather presents a clinical study evaluating the device's performance against a reference method (culture). The implied acceptance criteria are the target sensitivity and specificity values.
| Performance Metric | Acceptance Criterion (Implied/Target) | Reported Device Performance (vs. Direct & Enriched Culture) | Reported Device Performance (vs. Direct Culture alone) |
|---|---|---|---|
| Sensitivity | High | 90.0% (189/210); 85.2-93.4% CI | N/A (term used: Positive Percent Agreement) |
| Specificity | High | 98.6% (3702/3753); 98.2-99.0% CI | N/A (term used: Negative Percent Agreement) |
| Positive Predictive Value | (Not explicitly stated) | 78.8% (189/240) | N/A |
| Negative Predictive Value | (Not explicitly stated) | 99.4% (3702/3723) | N/A |
| Positive Percent Agreement (PPA) | (Not explicitly stated for primary comparison) | N/A | 96.7% (176/182); 93.0-98.5% CI |
| Negative Percent Agreement (NPA) | (Not explicitly stated for primary comparison) | N/A | 98.3% (3717/3781); 97.8-98.7% CI |
2. Sample Size for the Test Set and Data Provenance
- Test Set Sample Size: 3,963 evaluable subjects (from 4,198 paired specimens enrolled).
- Data Provenance: Prospective Clinical Study conducted at seven geographically diverse locations in the U.S.
3. Number of Experts Used to Establish Ground Truth and Qualifications
The document refers to a "reference culture method" and "direct culture on chromogenic medium" with subsequent confirmation steps for the ground truth. It does not explicitly state the number or qualifications of experts involved in interpreting these culture results. The process for identifying MRSA colonies on chromogenic medium and confirming identity is described, but not in terms of expert involvement.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method involving experts for cases of discordance between the cobas vivoDx MRSA test and the reference culture. It appears that the reference culture method (direct and enriched culture) was considered the definitive ground truth.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study involving human readers improving with AI vs. without AI assistance was not explicitly described or presented in this document. The cobas vivoDx MRSA is an automated diagnostic test, and the evaluation focuses on its standalone performance compared to culture, not its impact on human reader performance.
6. Standalone (Algorithm Only) Performance
Yes, a standalone performance study was done. The entire clinical study described in Section L(3)(a) evaluates the performance of the cobas vivoDx MRSA test (an automated system) against culture methods, without human-in-the-loop assistance. The results presented in Table 15 and 16 directly reflect the standalone performance of the device.
7. Type of Ground Truth Used
The primary ground truth used was reference culture method, specifically "direct and enriched culture" for MRSA. The process involved:
- Direct culture on chromogenic medium.
- "Further 28 subjects were positive by (b) (4) (D) (4)" which implies an additional confirmation or enrichment step.
- Identity of suspected colonies of MRSA on (b) (4) was confirmed following (b) (4), suggesting further laboratory testing for definitive identification.
8. Sample Size for the Training Set
The document does not specify the sample size for the training set. It mentions that "The algorithm was developed using data from known MRSA positive and negative analytical and clinical samples," but no numbers are provided for these training data.
9. How the Ground Truth for the Training Set Was Established
The document states, "The result algorithm for the cobas vivoDx MRSA test uses a series of decision trees to evaluate features of the kinetic luminescent curve obtained after addition of substrate to the test sample. The algorithm was developed using data from known MRSA positive and negative analytical and clinical samples..." This implies that the ground truth for the training set was established through known analytical and clinical samples that were already characterized as MRSA positive or negative, likely via culture or other gold standard methods similar to those used for the clinical study ground truth. However, the exact methods for establishing the ground truth for the training set are not detailed.
§ 866.1655 System for detection of microorganisms and antimicrobial resistance using reporter expression.
(a)
Identification. A system for detection of microorganisms and antimicrobial resistance using reporter expression is an in vitro diagnostic device intended for the detection and identification of live microorganisms and the detection of associated antimicrobial drug susceptibility or resistance in specimens from patients at risk of colonization or suspected of infection.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use for the device in the labeling required under § 809.10 of this chapter must include a detailed description of the targets the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended.
(2) Any device used for specimen collection and transport must be FDA-cleared, approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of the specimen types claimed by this device and for the maintenance of viability of the targeted microorganisms; alternatively, the specimen collection device must be cleared in a premarket submission as a part of this device.
(3) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed description of the device, including reagents, instruments, ancillary materials, applicable specimen collection and transport device(s) and control elements, and a detailed explanation of the methodology, including all pre-analytical methods for handling and processing of specimens and controls to maintain organism viability;
(ii) Detailed descriptions of the test procedure, including the preparation and maintenance of quality controls and the interpretation of test results;
(iii) Detailed discussion of the performance characteristics of the device for all claimed organisms and specimen types based on analytical studies, including evaluation of analytical sensitivity, inclusivity, cross-reactivity, potentially interfering substances and microorganisms, contamination, specimen stability, precision, and reproducibility;
(iv) Detailed discussion of the performance characteristics of the device observed in a clinical study performed on a population that is consistent with the intended use population in comparison to the results obtained by a reference or comparator method determined to be acceptable by FDA, for microbial detection, identification, and antimicrobial susceptibility testing; and
(v) A limiting statement indicating that a negative test result does not preclude colonization or infection with organisms that do not express detectable levels of the reporter that is identified by the device.
(4) Design verification and validation must include:
(i) A detailed description of the device, including an explanation of the technology, hardware, software, and consumables, as well as an explanation of the result algorithms and method(s) of data processing from signal acquisition to result assignment;
(ii) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions;
(iii) Detailed documentation of the analytical and clinical studies required in paragraphs (b)(3)(iii) and (iv) of this section, including the study protocols containing descriptions of the test methods, prescribed methods of data analysis and acceptance criteria, final study reports, and data line listings;
(iv) Detailed documentation of quality control procedures, including an explanation of how quality control materials were selected, the recommended frequency of testing, methods of control preparation, acceptance criteria for performance and the results from quality control testing performed during the analytical and clinical studies required under paragraphs (b)(3)(iii) and (iv) of this section;
(v) Detailed documentation of studies performed to establish onboard and in-use reagent stability, including the test method(s), data analysis plans, acceptance criteria, final study reports, and data line listings;
(vi) Detailed documentation of studies to establish reagent shelf-life for the assay kit and each applicable specimen collection and transport device, including study protocols containing descriptions of the test method(s), data analysis plans, and acceptance criteria; and
(vii) Documentation of an appropriate end user device training program that will be offered as part of efforts to assure appropriate conduct of the assay and to mitigate the risk associated with false results, including failure to use the device correctly or correctly interpret results.