(127 days)
The GIARDIA/CRYPTOSPORIDIUM CHEK™ test is an enzyme immunoassay for the qualitative detection of Giardia cyst and Cryptosporidium oocyst antigen in human fecal specimens. It is indicated for use as an aid in the diagnosis of patients with diarrhea suspected of Giardia and/or Cryptosporidium gastrointestinal infections.
The GIARDIA/CRYPTOSPORIDIUM CHEK™ test uses monoclonal and polyclonal antibodies to cell-surface antigens of Giardia and an oocyst antigen of Cryptosporidium. The Microassay Plate in the kit contains immobilized monoclonal antibodies against the antigens and the Conjugate consists of polyclonal antibodies against the antigens. In the assay, an aliquot of a diluted fecal specimen is transferred to a microassay well. The immobilized monoclonal antibodies bind the Giardia and Cryptosporidium antigens if the antigens are present. Upon addition, Conjugate then binds to the antigen/antibody complex. Any unbound materials are removed during the washing steps. Following the addition of substrate, a color is detected due to the enzyme-antibody-antigen complexes that formed in the presence of Giardia or Cryptosporidium antigens and Conjugate.
Here's a summary of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Acceptance Criteria and Device Performance
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of clinical performance thresholds. Instead, it presents the device's performance in comparison to predicate devices (ELISA) and microscopy. The implication is that the performance must be demonstrably comparable or superior to these established methods.
Here's the reported device performance:
| Performance Metric | Target/Comparison | Reported Device Performance (GIARDIA/CRYPTOSPORIDIUM CHEK™) |
|---|---|---|
| Comparison to Commercial ELISA | Agreement with ProSpecT® Giardia/Cryptosporidium Microplate Assay | |
| Positive Agreement | - | 98.6% (95% CI: 96.2% - 99.6%) |
| Negative Agreement | - | 98.7% (95% CI: 96.4% - 99.6%) |
| Overall Agreement | - | 98.6% (95% CI: 98.4% - 98.8%) |
| Comparison to Microscopy (IFA-confirmed) | Performance against Microscopic Analysis | |
| Sensitivity | - | 97.6% (95% CI: 92.6% - 99.4%) |
| Specificity | - | 100% (95% CI: 95.1% - 100%) |
| Predictive Positive Value | - | 100% (95% CI: 96.2% - 100%) |
| Predictive Negative Value | - | 96.9% (95% CI: 90.5% - 99.2%) |
| Correlation | - | 98.6% (95% CI: 98.2% - 98.9%) |
| Reproducibility | Consistent results across labs and trials | 100% correlation across 3 sites and 3 trials |
| Analytical Sensitivity | Detection limit for Giardia cysts and Cryptosporidium oocysts | 375 Giardia cysts/mL, 6250 Cryptosporidium oocysts/mL |
| Analytical Specificity | No cross-reactivity with common intestinal pathogens | No cross-reactivity observed |
| Interfering Substances | No effect on assay performance at tested concentrations | No effect on positive or negative results |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Clinical Evaluation compared to ELISA): n = 590 fecal specimens.
- Sample Size (Clinical Evaluation compared to Microscopy): n = 217 fecal specimens.
- Data Provenance: The samples were collected from "three clinical study sites" (Table 1) and specifically "Site 1" for the microscopy comparison (Table 2). The country of origin is not explicitly stated, but the submission is to the U.S. FDA, suggesting the studies were likely conducted in the U.S. The data appears to be prospective clinical evaluation data, as it describes "clinical evaluations" and samples "used in the clinical evaluation of the test."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number of experts or their qualifications for establishing the ground truth.
- For the comparison to the commercially available ELISA (ProSpecT® Giardia/Cryptosporidium Microplate Assay), the ELISA itself served as a reference.
- For the comparison to microscopy, the ground truth was established by "IFA-confirmed microscopy results." The individuals performing or confirming these IFA microscopy results are not described.
4. Adjudication Method for the Test Set
The document does not describe an explicit adjudication method. The comparisons are made directly against the results of the reference methods (commercial ELISA or IFA-confirmed microscopy).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
This device is an enzyme immunoassay (ELISA), not an AI-powered image analysis or diagnostic tool that involves human readers interpreting results with or without AI assistance. Therefore, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study of human readers with AI assistance is not applicable and was not performed.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the studies presented are for the device (GIARDIA/CRYPTOSPORIDIUM CHEK™) in a standalone capacity. The device itself performs the qualitative detection of antigens. The performance metrics (sensitivity, specificity, agreement) are for the assay's ability to detect the target antigens directly, without explicit human-in-the-loop interpretation that would significantly alter its performance.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The ground truth for the clinical evaluations was established by:
- Predicate Device Performance: Comparison to a "commercially available ELISA" (ProSpecT® Giardia/Cryptosporidium Microplate Assay) which itself is an established diagnostic method.
- IFA-Confirmed Microscopy: This is a laboratory diagnostic method where trained personnel visualize parasites in samples, and the "IFA-confirmed" implies an additional, highly specific immunological staining technique to confirm the identity of Giardia cysts and Cryptosporidium oocysts. This can be considered a form of expert-driven laboratory confirmation.
8. The Sample Size for the Training Set
This document describes a diagnostic test kit (ELISA), not a machine learning or AI algorithm. Therefore, the concept of a "training set" in the context of AI development is not applicable. The device's components (antibodies, reagents) are developed and optimized through laboratory research, but not via training on a data set in the same manner as an AI model.
9. How the Ground Truth for the Training Set Was Established
As noted above, the concept of a "training set" is not applicable for this type of device. The ground truth for the analytical studies (sensitivity, specificity, cross-reactivity) was established using known positive and negative controls, spiked samples with quantified antigen levels, and samples positive for other specific pathogens.
§ 866.3220
Entamoeba histolytica serological reagents.(a)
Identification. Entamoeba histolytica serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies toEntamoeba histolytica in serum. Additionally, some of these reagents consist of antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identifyEntamoeba histolytica directly from clinical specimens. The identification aids in the diagnosis of amebiasis caused by the microscopic protozoan parasiteEntamoeba histolytica and provides epidemiological information on diseases caused by this parasite. The parasite may invade the skin, liver, intestines, lungs, and diaphragm, causing disease conditions such as indolent ulcers, an amebic hepatitis, amebic dysentery, and pulmonary lesions.(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.