(342 days)
The CrAg Lateral Flow Assay is an immunochromatographic test system for the qualitative or semi-quantitative detection of capsular polysaccharide antigens of Cryptococcus species complex (Cryptococcus neoformans and Cryptococcus gatti) in serum.
The CrAg Lateral Flow Assay is a prescription-use laboratory assay, which can aid in the diagnosis of Cryptococcosis.
The CrAg Lateral Flow Assay is a dipstick sandwich immunochromatographic assay, which detects cryptococcal antigen in serum. For the qualitative procedure, specimens are diluted 1:2 in 1x Specimen Diluent and analyzed. For the semi-quantitative procedure, specimens are diluted 1:5 in 1x Specimen Diluent followed by 1:2 serial dilutions. All dilutions are then analyzed as in the qualitative procedure. Specimens are placed into an appropriate reservoir, such as a test tube or microtiter plate, and the lateral flow device is then placed into the reservoir allowing the specimen to come into contact with the test membrane. The test uses specimen wicking to capture gold-conjugated, anti-cryptococcal monoclonal antibodies and gold-conjugated control antibodies that are deposited onto a membrane. If cryptococcal antigen is present in the specimen, it binds to the gold-conjugated, anti-cryptococcal antibodies. The gold-labeled antibody-antigen complex will continue to wick up the membrane where it will interact with the Test Line (T). The Test Line is immobilized anti-cryptococcal monoclonal antibodies. If the specimen contains cryptococcal antigen, a sandwich is created with the gold-labeled antibodies and the immobilized antibodies, causing a visible line to develop at the test line site (T). If proper flow occurs and the reagents are reactive at the time of use, the wicking of any specimen, positive or negative, will cause the gold-conjugated control goat IgG antibody to move to the Control Line (C) which is immobilized bovine anti-goat IgG antibody. The immobilized anti-goat antibody will bind to the gold-conjugated goat IgG Control antibody and will cause a visible line to develop (C). A positive test result will create two lines, while a negative test result will create one line (Figure 1). If the control line fails to develop a line, then the test is not valid.
The CrAg Lateral Flow Assay is an immunochromatographic test system for the qualitative or semi-quantitative detection of capsular polysaccharide antigens of Cryptococcus species complex in serum. The study provided compares the CrAg Lateral Flow Assay to a Cryptococcal Antigen EIA and to culture/India Ink as gold standards.
1. Table of Acceptance Criteria and Reported Device Performance:
The document does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity and specificity thresholds for the de novo approval. However, the performance is reported as follows:
Comparison with Cryptococcal Antigen EIA (Serum):
| Metric | Acceptance Criteria (Implied) | Reported Performance (95% CI) |
|---|---|---|
| % Agreement Positive | Not explicitly stated | 100% (96-100%) |
| % Agreement Negative | Not explicitly stated | 93% (86-97%) |
Comparison with Culture/India Ink (Gold Standard for Serum):
| Metric | Acceptance Criteria (Implied) | Reported Performance (95% CI) |
|---|---|---|
| Sensitivity | Not explicitly stated | 100% (96.0%-100%) |
| Specificity | Not explicitly stated | 100% (97.0%-100%) |
Semi-Quantitative Serum Correlation (CrAg LFA vs. Latex Agglutination):
- Correlation (R²): Not explicitly stated | 0.905 |
2. Sample Size and Data Provenance:
- Test Set (Method Comparison with Cryptococcal Antigen EIA): 197 serum specimens. The data provenance is from a "US reference laboratory" and the study was retrospective (collected and stored frozen until studies were performed).
- Test Set (Method Comparison with Culture/India Ink): The exact number of specimens is not clearly enumerated, but the table indicates a 2x2 contingency table for "Culture/India Ink" with "NO ANDRE & FOR A LE SE SE SE SE SE SE SERVED AN A SE" in one row and other unclear annotations. However, the sample size can be inferred from the 95% Confidence Intervals for Sensitivity and Specificity, which suggest a reasonable sample size for a diagnostic test. The document states "These studies contained a mix of both prospective and retrospective specimens."
- Test Set (Predicate Device Comparison - Latex-Cryptococcal Antigen Detection System): 197 serum specimens. The data provenance is from a "US reference laboratory" and the study was retrospective (collected and stored frozen until studies were performed).
3. Number of Experts and Qualifications for Ground Truth:
The document does not specify the number or qualifications of experts used to establish the ground truth for the test set.
4. Adjudication Method for the Test Set:
The document does not describe an adjudication method for the test set results. The ground truth (EIA or Culture/India Ink) was likely established by the reference laboratory or standard clinical procedures without explicit mention of an additional adjudication process for this study.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
No multi-reader multi-case (MRMC) comparative effectiveness study was done. The CrAg Lateral Flow Assay is a diagnostic device that provides an objective result (presence/absence of line, or semi-quantitative titer), and its performance is assessed against established laboratory methods or clinical gold standards, not by comparing the performance of human readers with and without AI assistance.
6. Standalone Performance Study:
Yes, a standalone performance study was done. The method comparison studies (against Cryptococcal Antigen EIA and Culture/India Ink) and the precision, analytical sensitivity, and analytical specificity studies all evaluate the intrinsic performance of the CrAg Lateral Flow Assay device without human-in-the-loop assistance.
7. Type of Ground Truth Used:
- For Method Comparison: Cryptococcal Antigen EIA results from a US reference laboratory.
- For Gold Standard Comparison: Culture and/or India Ink results. These are considered the "gold standard for the diagnosis of cryptococcosis."
- For Training Set: Not applicable as this is a diagnostic assay, not a machine learning model requiring a separate training set. The performance studies evaluate the assay itself.
8. Sample Size for the Training Set:
Not applicable. This is a conventional in vitro diagnostic assay, not an AI/ML-based device that typically requires a distinct training set for model development. The described studies are all for performance evaluation of the developed assay.
9. How the Ground Truth for the Training Set Was Established:
Not applicable, as there is no mention of a training set for an AI/ML model. The "ground truth" in the context of this device refers to the established diagnostic methods used to evaluate the CrAg Lateral Flow Assay's accuracy.
§ 866.3165
Cryptococcus neoformans serological reagents.(a)
Identification. Cryptococcus neoformans serological reagents are devices that consist of antigens used in serological tests to identify antibodies toCryptococcus neoformans in serum. Additionally, some of these reagents consist of antisera conjugated with a fluorescent dye (immunofluorescent reagents) and are used to identifyCryptococcus neoformans directly from clinical specimens or from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of cryptococcosis and provides epidemiological information on this type of disease. Cryptococcosis infections are found most often as chronic meningitis (inflammation of brain membranes) and, if not treated, are usually fatal.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.