(346 days)
The Directigen® Meningitis Test Kits are a presumptive latex agglutination test for the direct qualitative detection of antigens to H. influenzae type b, S. pneumoniae, group B Streptococcus, N. meningitidis groups A, B, C, Y or W135 and E. coli K1 in cerebrospinal fluid (CSF), serum, urine, or blood culture media. Visible agglutination occurs when a sample containing any of these bacterial antigens is reacted with its respective antibody-coated latex beads. This 510(k) was submitted to add colony confirmation and serotyping claims to the Intended Use Statement.
Specific antibodies are bound to the surface of latex beads. In the presence of specific antigens, latex particle aggregation becomes large enough to allow visualization of positive agglutination These specific soluble polysaccharide antigens accumulate in CSF, serum, urine or blood as a result of infection by H. influenzae type b, S. pneumoniae, group B Streptococcus, N. meningitidis groups A, B, C, Y or W135 and E. coli K1.
Here's a breakdown of the acceptance criteria and the study details for the Directigen® Meningitis Test Kits, based on the provided text:
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for this device appear to be tied directly to achieving high Relative Sensitivity and Relative Specificity values, as demonstrated by the study results. While specific pre-defined numeric thresholds for acceptance are not explicitly stated as "acceptance criteria" in a separate section, the FDA's acceptance of these results implies they met an internal standard for clinical utility for diagnostic devices of this type. The reported performance is summarized below:
| Suspected Organism | Acceptance Criteria (Implied) | Reported Performance (Relative Sensitivity) | Reported Performance (Relative Specificity) |
|---|---|---|---|
| H. influenzae type b | High Sensitivity & Specificity | 100% (92-100% CI) | 98.5% (92-100% CI) |
| S. pneumoniae | High Sensitivity & Specificity | 93% (84-98% CI) | 79% (66-88% CI) |
| Group B Streptococcus | High Sensitivity & Specificity | 100% (95-100% CI) | 90.5% (80-96% CI) |
| Neisseria meningitidis Grp A/Y | High Sensitivity & Specificity | 100% (83-100% CI) | 100% (96-100% CI) |
| Neisseria meningitidis Grp C/W135 | High Sensitivity & Specificity | 96% (82-100% CI) | 98.5% (92-100% CI) |
| Neisseria meningitidis Grp B | High Sensitivity & Specificity | 85% (55-98% CI) | 100% (96-100% CI) |
2. Sample Size and Data Provenance (Test Set)
- Sample Size (Test Set):
- H. influenzae type b: 112
- S. pneumoniae: 124
- Group B Streptococcus: 129
- Neisseria meningitidis Group A/Y: 106
- Neisseria meningitidis Group C/W135: 94
- Neisseria meningitidis Group B: 106
- Data Provenance: The studies were described as "Two external studies." The country of origin is not specified but generally for FDA submissions, these would be US-based or international studies conducted under US regulatory standards. The data is prospective, as it involves testing the device on suspected colony growth in a clinical correlation study.
3. Number of Experts and Qualifications (Ground Truth for Test Set)
The document does not explicitly state the "number of experts" or their specific qualifications for establishing the ground truth. However, for a test like this, the ground truth would be established by standard microbiological culture and identification methods, which are typically performed by trained microbiologists or laboratory personnel.
4. Adjudication Method (Test Set)
No specific adjudication method (e.g., 2+1, 3+1) is mentioned. For this type of diagnostic test, especially one comparing against established culture methods, adjudication often involves confirming discrepancies through re-testing or review by a senior microbiologist if there are unexpected results between the investigational device and the gold standard.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study focuses on the device's performance directly against established microbiological methods for colony identification and serogrouping, not on human readers' improvement with or without AI assistance. The device is a latex agglutination test, not an AI-assisted diagnostic tool for human interpretation.
6. Standalone Performance
Yes, this study represents a standalone performance evaluation. The latex agglutination test is performed directly on suspected colony growth to determine the presence of specific antigens. Its performance (sensitivity and specificity) is measured independently against the presumed "ground truth" standard microbiological methods. It is not evaluating human-in-the-loop performance but the diagnostic accuracy of the kit itself.
7. Type of Ground Truth Used
The ground truth used for the test set was standard microbiological culture and identification methods (e.g., Gram stain, biochemical tests, traditional serogrouping methods, or molecular methods) that would definitively identify the bacterial species and serogroup of the cultured colonies. This is implied by the study's objective to add "colony confirmation and serogrouping capabilities from suspected colony growth." The "Relative Sensitivity" and "Relative Specificity" are calculated against this established truth.
8. Sample Size for the Training Set
The document does not provide information on a separate "training set" or its sample size. This type of device (latex agglutination kit) is not typically "trained" in the same way an AI/machine learning model would be. Development of such a kit involves antibody selection and reagent optimization, but there isn't a "training set" in the computational sense. The provided data is for the validation/test set used to demonstrate performance.
9. How the Ground Truth for the Training Set Was Established
Since there is no "training set" in the context of this device type, this question is not applicable. The design and validation of the device components (antibodies, latex beads) would have relied on well-characterized bacterial strains and established immunoassay principles during the product development phase, but these wouldn't constitute a "training set" for the final device performance validation.
§ 866.3390
Neisseria spp. direct serological test reagents.(a)
Identification. Neisseria spp. direct serological test reagents are devices that consist of antigens and antisera used in serological tests to identifyNeisseria spp. from cultured isolates. Additionally, some of these reagents consist ofNeisseria spp. antisera conjugated with a fluorescent dye (immunofluorescent reagents) which may be used to detect the presence ofNeisseria spp. directly from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genusNeisseria, such as epidemic cerebrospinal meningitis, meningococcal disease, and gonorrhea, and also provides epidemiological information on diseases caused by these microorganisms. The device does not include products for the detection of gonorrhea in humans by indirect methods, such as detection of antibodies or of oxidase produced by gonococcal organisms.(b)
Classification. Class II (performance standards).