(116 days)
The Diamedix Is-Toxoplasma IgG Test Kit is an Enzyme Immunoassay (EIA) for the qualitative and quantitative determination of IgG antibodies in human serum to aid in the assessment of the patient's immunological response to infection with Toxoplasma gondii and in the determination of the immune status of individuals, including females of child-bearing age. The evaluation of acute and convalescent sera can aid in the diagnosis of primary or reactivated infection with Toxoplasma gondii. These reagents can be used either manually or in conjunction with the MAGO® Plus Automated EIA Processor. This product is not FDA cleared for use in screening blood and plasma donors.
The Is-Toxoplasma IgG Test System is an enzyme-linked immunosorbent assay (ELISA) for the qualitative and quantitative detection of IgG to Toxoplasma gondii in human serum
Here's an analysis of the provided text regarding the acceptance criteria and study for the Is-Toxoplasma IgG Test System:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" in a quantitative, pre-defined manner for the comparison studies. Instead, it presents the results of these comparisons and implicitly suggests that these results were deemed acceptable for market clearance. For the purpose of this table, I will infer the "acceptance criteria" based on common expectations for such devices and the reported "predicate device performance" as the target. The "reported device performance" will be the "Is-Toxoplasma IgG" results.
| Metric | Assumed/Inferred Acceptance Criterion (Based on Predicate Performance) | Is-Toxoplasma IgG Test System Reported Performance (Range across sites) |
|---|---|---|
| Qualitative Detection | ||
| Relative Sensitivity | High (e.g., >85-90%) | 87.5% - 93.3% (manual), 92.2% - 92.5% (Diamedix, manual & MAGO+) |
| Relative Specificity | High (e.g., >95%) | 98.7% - 100.0% (manual), 99.5% (Diamedix, manual & MAGO+) |
| Overall Agreement | High (e.g., >90%) | 92.1% - 99.4% (manual), 97.5% - 97.9% (Diamedix, manual & MAGO+) |
| Precision (Interassay CV%) | Low (e.g., typically 0.95 or >0.98) | 0.9969 (Manual), 0.9973 (MAGO Plus) |
| Correlation to WHO Standard (R-squared) | High (e.g., >0.95 or >0.98) | 0.9932 |
| Cross-Reactivity | No significant cross-reactivity with common interfering analytes | 0 positive results out of 50 samples positive for various viruses/ANA |
2. Sample Sizes and Data Provenance:
- Test Set for Comparison Studies:
- Site #1 (Miami, FL): 200 samples (37% fresh, 73% frozen). Samples from the S. Florida area. Purposefully selected for equal positive/negative results. Retrospective/Prospective status not explicitly stated for individual samples, but likely a mix.
- Site #2 (Salt Lake City, Utah): 179 samples (all fresh). Samples from the West region. Submitted for ToRCH screening. Prospective.
- Site #3 (Diamedix Corp., Miami, FL): 242 samples (all frozen) for manual testing, 241 for MAGO Plus testing. Samples from S. Florida blood donors. Retrospective.
- Total for comparison studies: 200 + 179 + 242 (manual) / 241 (MAGO Plus) = 621-622 samples total across all sites/methods.
- Test Set for Cross-Reactivity: 50 sera, negative for T. gondii IgG, but positive for one or more of VZV, HSV, CMV, Rubella, EBV, anti-DNA, ANA. Provenance not specified, but implied to be human serum samples.
- Test Set for Precision: 6 serum samples, 50 IU/ml kit Standard, Low Positive Control, and Negative Control. Tested in triplicate across 3 days at 3 sites (Site #1, Site #2, Site #3).
- Test Set for Linearity: Several strongly positive serum samples (number not specified).
- Test Set for WHO Standard Correlation: Several dilutions of the WHO 3rd International Standard for Anti-Toxoplasma Serum (code TOXM).
- Test Set for Quantitative Data/Serum Pairs: Multiple two-fold dilutions of several strongly positive sera (number not specified).
- Test Set for Expected Values (Prevalence): 100 healthy South Florida donors (52 female, 48 male). 37 female donors of child-bearing age (18-45 years) from this group. 45 sera from pregnant females (15 from each trimester) (separate from above 100, but unclear if they overlap with the "outside and in-house clinical studies" mentioned later). 216 samples from females of childbearing age identified in "outside and in-house clinical studies" (includes the 45 pregnant females).
3. Number of Experts and Qualifications for Ground Truth:
- The document does not explicitly state that experts were used to establish the ground truth for the entire test set in the primary comparison studies.
- Instead, comparison was done against "their currently used testing method" or "another marketed EIA method." The performance of these comparator assays served as the initial "relative ground truth."
- For discordant samples, "further resolution" was performed by testing them in a "referee EIA method." The qualifications of the individuals running or interpreting this referee method are not specified, nor is the number of experts.
4. Adjudication Method for the Test Set:
- For the comparison studies, there wasn't a formal adjudication method of multiple independent readers or experts establishing a primary ground truth against which both devices were judged.
- Instead, for discordant results between the Is-Toxoplasma IgG Test Kit and the comparator EIA, a "referee EIA method" was used for resolution (essentially a third-party tie-breaker). For example:
- Site #1: 12 Is-Toxoplasma IgG negative, Other EIA positive -> referee negative. 1 Is-Toxoplasma IgG positive, Other EIA negative -> referee negative.
- Site #2: 1 Is-Toxoplasma IgG negative, Other EIA positive -> referee negative.
- Site #3 (manual): 5 Is-Toxoplasma IgG negative, Other EIA positive -> referee negative. 1 Is-Toxoplasma IgG positive, Other EIA negative -> referee positive.
- Site #3 (MAGO Plus): 4 Is-Toxoplasma IgG negative, Other EIA positive -> referee negative. 1 Is-Toxoplasma IgG positive, Other EIA negative -> referee positive.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No. This document describes the performance of a diagnostic assay (ELISA) which typically does not involve human "readers" interpreting images or complex data in the same way an MRMC study would apply to an AI for image analysis. The device itself is designed to provide a result (qualitative or quantitative IU/ml), not to assist human interpretation of complex medical cases. Therefore, the concept of "how much human readers improve with AI vs without AI assistance" is not applicable here.
6. Standalone (Algorithm Only) Performance:
- Yes, in essence. The entire evaluation focuses on the performance of the "Is-Toxoplasma IgG Test System" itself, both in manual operation and when integrated with an automated EIA processor (MAGO Plus). This is a standalone device providing diagnostic results. Human involvement is in plate loading, reagent addition (for manual), and result interpretation (based on established cut-offs), but the "algorithm" (the ELISA's chemical reactions and spectrophotometric reading) is what determines the result. The comparison studies directly assess this standalone performance against predicate devices.
7. Type of Ground Truth Used:
- For the primary comparison studies, the "ground truth" was established by comparison to "another marketed EIA method" (predicate devices).
- For discordant results, a "referee EIA method" was used.
- The document explicitly states: "NOTE: Please be advised that 'relative' refers to the comparison of the assay's results to that of a similar assay. There was not an attempt to correlate the assay's results with disease presence or absence. No judgment can be comparison assay's accuracy to predict disease." This clarifies that the ground truth was based on agreement with other laboratory tests, not clinical outcomes or pathology data directly.
- For the WHO Correlation study, the ground truth was the WHO International Standard for Anti-Toxoplasma Serum.
8. Sample Size for the Training Set:
- The document does not specify a separate "training set" in the context of machine learning. This is a traditional in vitro diagnostic device (ELISA).
- The manufacturer would have performed internal development and validation studies, which involve implicitly "training" the assay (e.g., optimizing reagents, establishing cut-offs) based on a broad range of samples, but these are not explicitly termed "training sets" with a specific sample size in the context of this 510(k) summary. The clinical studies described are for validation, not training.
9. How the Ground Truth for the Training Set Was Established:
- As there's no explicitly defined "training set" in the machine learning sense, this question isn't directly applicable.
- For the development of the assay, the manufacturer would have used various characterized samples (positive, negative, equivocal) to establish assay parameters and cut-offs. The characterization of these samples would have likely relied on a combination of known clinical status and/or results from established reference assays, similar to how the ground truth for the validation studies was approached (i.e., using predicate devices and a referee method).
§ 866.3780
Toxoplasma gondii serological reagents.(a)
Identification. Toxoplasma gondii serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies toToxoplasma gondii in serum. Additionally, some of these reagents consist of antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identifyToxoplasma gondii from clinical specimens. The identification aids in the diagnosis of toxoplasmosis caused by the parasitic protozoanToxoplasma gondii and provides epidemiological information on this disease. Congenital toxoplasmosis is characterized by lesions of the central nervous system, which if undetected and untreated may lead to brain defects, blindness, and death of an unborn fetus. The disease is characterized in children by inflammation of the brain and spinal cord.(b)
Classification. Class II (performance standards).