(139 days)
The Copalis Treponemal Antibody Assay uses Coupled Particle Light Scattering (Copalis®) technology in a microparticle agglutination-based immunoassay for the qualitative detection of total antibodies (IgG and IgM) to recombinant Treponema pallidum antigens in human serum using the Copalis I Immunoassay System. The presence of antibodies is indicative of current or prior infection with T. pallidum. The assay is indicated as an aid in the confirmation of syphilis disease following a positive result with a nontreponemal screening test. This assay has not been FDA cleared or approved for the screening of blood or plasma donors.
The Copalis® Treponemal Antigen Total Antibody Assay is based on Coupled Particle Light Scattering (Copalis) technology which provides a rapid method for the measurement of antibodies to specific pathogens.
The assay is a microparticle agglutination test using the Copalis light scattering technology. Polystyrene microparticles are coated with recombinant antigen derived from T. pallidum and are contained within a special covered reaction well in the test cup. The dried reagent is reconstituted with a reaction buffer on the instrument at the start of the assay. Patient sample is added to the reaction mixture and incubated for 10 minutes. The presence of antibodies specific to T. pallidum in the patient sample results in agglutination of the monomer microparticles to form aggregrates. The reaction mixture is passed through a flow cell and the instrument uses light scattering technology to measure the monomer concentration. The decrease in the monomer population resulting from agglutination is related to the amount of antibody in the sample. The residual monomer concentration in each reaction mixture is compared to a cutoff value to determine sample reactivity and nonreactivity.
Here's a summary of the acceptance criteria and study details for the Copalis Treponemal Antigen Total Antibody Assay based on the provided text:
Acceptance Criteria and Device Performance
The document does not explicitly state pre-defined acceptance criteria with specific thresholds (e.g., "sensitivity must be >95%"). Instead, it presents the device's performance across various clinical scenarios and compares it to established predicate devices. The implicit acceptance criteria are the satisfactory performance across these categories benchmarked against the predicate devices (FTA-ABS and TP-PA).
The reported device performance, which implies the acceptance criteria were met by these reported values, are:
| Metric / Stage | Treatment Status | Copalis Performance (with 95% CI where provided) | Notes |
|---|---|---|---|
| Clinical Sensitivity: RPR + FTA + | Primary (Untreated) | 100% (15.8-100%) | |
| Primary (Treated) | 100% (75.3-100%) | ||
| Secondary (Untreated) | 100% (86.3-100%) | ||
| Secondary (Treated) | 100% (88.1-100%) | ||
| Latent (Treated) | 97.8% (92.2-99.7%) | ||
| Late, Cardiovascular | 100% (29.2-100%) | ||
| Congenital | 100%* (15.8-100%) | *Excludes 1 equivocal result | |
| Clinical Sensitivity: RPR - FTA + | Primary (Treated) | 66.7% (22.2-95.7%) | |
| Secondary (Treated) | 100% (2.5-10%) | Note the narrow confidence interval, likely due to a very small sample size in this specific sub-category. | |
| Latent (Treated) | 100% (66.4-100%) | ||
| Late, Cardiovascular | 100% (2.5-100%) | ||
| Congenital | 100% (15.8-100%) | ||
| Clinical Specificity: RPR +/- FTA - | Primary (Untreated) | 100% (2.5-100%) | |
| Primary (Treated) | 100% (2.5-100%) | ||
| Agreement - RPR positive samples | N/A | 96.3% (944/980) | 25 samples were equivocal. These were RPR positive samples sent to hospital laboratories for confirmation. |
| Prevalence - Apparently healthy adults | Copalis | 3.2% (32/1002) | Compared to FTA = 2.2% (22/1002) |
| Agreement - Obstetric; Pediatric >18 months | N/A | 100% (34/34) | 1 Copalis equivocal/FTA negative sample |
| Agreement - CDC Panel | N/A | 90% (18/20) | |
| Agreement - Commercial syphilis mixed titer panel | N/A | 100% (25/25) | |
| Reproducibility: Total %CV (across sites) | Negative Control | 1.4 | Tested in duplicate once a day for 5 days using 6 samples spanning the assay's CTRs at 3 sites. |
| Positive Control | 8.7 | ||
| RP1 | 1.9 | ||
| RP2 | 18.0 | ||
| RP3 | 1.8 | ||
| RP4 | 16.7 | ||
| RP5 | 16.7 | ||
| RP6 | 13.3 |
Study Details:
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Sample sizes used for the test set and the data provenance:
- Syphilis Patients: 188 samples from patients with a diagnosis of syphilis.
- Other disease/health states:
- RPR positive samples for confirmation: 1005 samples
- Apparently healthy adults: 1002 samples
- Obstetric; Pediatric (>18 months old): 35 samples
- CDC Panel: 20 samples
- Commercial syphilis mixed titer panel: 25 samples
- Data Provenance: Clinical trials were conducted at four sites: 2 clinical laboratories, 1 reference laboratory, and DiaSorin Inc.'s laboratory. The origin of the patient samples (e.g., country) is not specified, but the diverse site locations suggest a possible mix of sources within the US. The data appears to be prospective in nature, as it describes a clinical trial process to evaluate the assay's performance.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document implies ground truth was established by comparison to predicate devices (Zeus Scientific Inc. FTA-ABS assay and FUJIREBIO Inc. TP-PA), which are described as confirmatory tests for syphilis.
- For the "Samples from patients with diagnosis of syphilis," the diagnosis itself would typically be made by medical professionals, likely physicians, based on a combination of clinical symptoms and laboratory results (including RPR and FTA-ABS). However, the number and qualifications of these specific "experts" (e.g., infectious disease specialists or pathologists) who established the original patient diagnoses are not explicitly stated in the provided text. The study primarily uses the results of existing confirmatory tests as its gold standard for evaluating the new device.
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Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- The document does not detail an adjudication method beyond referencing the results of the predicate confirmatory tests (FTA-ABS and TP-PA) and RPR. There's no mention of multiple experts independently reviewing cases and then adjudicating discrepancies.
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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:
- No. This is an immunoassay device, not an imaging AI diagnostic. Therefore, an MRMC study and human reader improvement with AI assistance are not applicable in this context. The device directly measures antibodies, and human "readers" (in the sense of interpreting images) are not involved in its primary function.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this is a standalone device. The Copalis Treponemal Antigen Total Antibody Assay is an automated immunoassay that uses Coupled Particle Light Scattering technology to detect antibodies. It generates a result (reactive/non-reactive) based on its intrinsic algorithm and measurement. While a human interprets the final result, the assay performance itself is standalone in generating the raw data and comparison to a cutoff value. It does not involve human users actively interpreting complex patterns that AI might augment.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The primary ground truth appears to be based on results from predicate confirmatory tests (Zeus Scientific Inc. FTA-ABS assay and FUJIREBIO Inc. TP-PA), which are established methods for confirming syphilis. For the "diagnosis of syphilis" patient group, this would represent a form of expert consensus implicitly, as the diagnosis would have been made by clinicians using established diagnostic criteria and confirmatory testing. For the panels, the ground truth was "characterized commercial syphilis mixed titer panel" and CDC panel, indicating pre-determined reference results.
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The sample size for the training set:
- The document does not explicitly state a dedicated "training set" sample size. For immunoassay development, there isn't typically a distinct "training set" in the same way an AI model would have. The assay's parameters (like cutoff values) are established during the development and optimization phases, which would involve testing a variety of samples, but these are not usually quantified or presented as a formal "training set" within a 510(k) summary for such a device. The data provided focuses on the validation (test) set performance.
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How the ground truth for the training set was established:
- As no formal training set is described, the method for establishing its ground truth is also not described. The assay's design and cutoff values would have been determined through internal validation and optimization against known positive and negative samples, but the specifics are not provided in this regulatory document.
§ 866.3830
Treponema pallidum treponemal test reagents.(a)
Identification. Treponema pallidum treponemal test reagents are devices that consist of the antigens, antisera and all control reagents (standardized reagents with which test results are compared) which are derived from treponemal sources and that are used in the fluorescent treponemal antibody absorption test (FTA-ABS), theTreponema pallidum immobilization test (T.P.I.), and other treponemal tests used to identify antibodies toTreponema pallidum directly from infecting treponemal organisms in serum. The identification aids in the diagnosis of syphilis caused by bacteria belonging to the genusTreponema and provides epidemiological information on syphilis.(b)
Classification. Class II (performance standards).