(90 days)
The TECHLAB® TRI-COMBO PARASITE SCREEN test is an enzyme immunoassay for the simultaneous qualitative detection of Giardia spp., Cryptosporidium spp. and/or E. histolytica antigen in human fecal specimens. The test is indicated as an aid in the diagnosis of gastrointestinal infection when giardiasis, cryptosporidiosis and amebiasis is suspected. The test does not differentiate between the three parasites and follow-up testing is required for all positive results to confirm the specific diagnosis.
The TRI-COMBO PARASITE SCREEN test is an enzyme immunoassay for the simultaneous qualitative detection of Giardia spp., Cryptosporidium spp. and/or E. histolytica antigen in human fecal specimens. The test uses monoclonal and polyclonal antibodies to cell-surface antigens of Giardia, Cryptosporidium and E. histolytica. 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, Cryptosporidium and/or E. histolytica antigens if they 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 antigens and conjugate.
Here's an analysis of the provided text regarding the TECHLAB® TRI-COMBO PARASITE SCREEN test, structured according to your requested points:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state pre-defined acceptance criteria (e.g., "The device must achieve sensitivity of X% and specificity of Y%"). Instead, it presents performance data which implicitly serves as the basis for the FDA's substantial equivalence decision. Therefore, I will present the reported performance data from the prospective clinical study as the proxy for "acceptance criteria met." For the retrospective study, while providing higher values, the prospective study is generally weighted more heavily for regulatory approval as it reflects real-world conditions more closely. The document also provides "95% Confidence Limits" for sensitivity and specificity.
| Metric (Prospective Study vs. Microscopy) | Reported Device Performance | 95% Confidence Limits |
|---|---|---|
| Sensitivity | 92.9% | 68.5% - 98.7% |
| Specificity | 98.1% | 96.9% - 98.9% |
| Positive Percent Agreement (vs. Microscopy and Molecular) | 62.1% | 44.0% - 77.3% |
| Negative Percent Agreement (vs. Microscopy and Molecular) | 98.8% | 97.7% - 99.4% |
2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)
- Prospective Study:
- Sample Size: 754 (740 negative, 14 microscopy positive - 13 Giardia, 1 E. histolytica)
- Data Provenance: Conducted at 3 independent clinical sites. Specific country of origin is not explicitly stated, but the submission is to the U.S. FDA by a U.S. company, suggesting U.S. clinical sites. The data is prospective.
- Retrospective Study:
- Sample Size: 96 archived specimens (previously collected and frozen)
- Data Provenance: From one clinical site in an E. histolytica endemic area (not specified by country). The data is retrospective.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience)
The document primarily refers to "microscopy" and "molecular testing."
- Microscopy: It states that "accuracy of O&P results depends upon the skill of the technician." This implies trained laboratory technicians or medical technologists are performing microscopy. However, the exact number of experts or their specific qualifications (e.g., board certification, years of experience) are not provided in the document.
- Molecular Testing: The document mentions "molecular testing of a commercial FDA cleared device and PCR with sequencing." It does not specify the number or qualifications of experts involved in interpreting or performing these molecular tests.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set
The document does not describe a formal adjudication method (e.g., 2+1, 3+1) involving multiple human readers for discrepancies. Instead, discrepancies between the device and microscopy were resolved via further testing:
- For the prospective study, the 14 TRI-COMBO PARASITE SCREEN positives that were microscopy negative were "confirmed to be positive for Giardia with an alternate FDA cleared antigen test or by PCR with sequencing." This constitutes a form of resolution by a more definitive method rather than human adjudication.
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 is not an AI-assisted device for human readers. The device is an in vitro diagnostic (IVD) immunoassay for detecting antigens in fecal specimens. Therefore, an MRMC comparative effectiveness study involving human readers improving with AI assistance is not applicable to this device. The comparison is between the immunoassay and traditional methods (microscopy and molecular testing).
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the device is a standalone diagnostic test (an immunoassay). Its performance is evaluated directly against comparator methods (microscopy, PCR, other FDA-cleared antigen tests) without human interpretation of the device's generated data being a variable. The test results are "spectrophotometric" or "visual" interpretations of a color change, but the core performance data reflects the device's ability to detect the analytes by itself.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth for the test sets was established using a combination of:
- Microscopy: Primarily light microscopy for identification of Giardia, Cryptosporidium, and E. histolytica.
- Molecular Testing:
- For the prospective study, "composite results from multiple tests that consisted of light microscopy, molecular testing of a commercial FDA cleared device and PCR with sequencing for the identification of Giardia spp., Cryptosporidium spp., in addition to identification and subspeciation of E. histolytica." This "composite" is considered the ground truth.
- For discrepancies, "alternate FDA cleared antigen test or by PCR with sequencing" was used.
- Archived Specimen Characterization: For the retrospective study, specimens were characterized as "microscopy and PCR positive."
8. The sample size for the training set
The document describes performance studies for the device but does not mention a training set because this is an in vitro diagnostic (IVD) immunoassay, not a machine learning or AI-based device that requires a training set. The design of the assay (antibodies, reagents) is based on scientific principles and previous research, not on learning from a specific dataset.
9. How the ground truth for the training set was established
As there is no training set for this type of device, this question is not applicable.
§ 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.