(249 days)
Lumipulse G TP-N Immunoreaction Cartridges Set For in vitro diagnostic use. WARNING: Lumipulse G TP-N is not intended for blood and tissue donor screening. United States federal law restricts this device to sale by or on the order of a physician. Lumipulse G TP-N is a Chemiluminescent Enzyme Immunoassay (CLEIA) for the qualitative determination of antibodies (1gG and 1gM) to Treponema pallidum in human serum and plasma (sodium citrate, or dipotassium EDTA) on the LUMIPULSE & System. Lumipulse G TP-N can be used as an initial diagnostic test or in conjunction with a nontreponemal laboratory test and clinical findings to aid in the diagnosis of syphilis infection.
The Lumipulse G TP-N is an assay system, including a set of immunoassay reagents, for the qualitative detection of anti-TP antibodies (IgG and IgM) in specimens based on CLEIA technology by a two-step sandwich immunoassay method on the LUMIPULSE G System.
Here's an analysis of the acceptance criteria and study detailed in the provided document:
Device: Lumipulse G TP-N Immunoreaction Cartridges Set (for qualitative determination of antibodies to Treponema pallidum)
Indications for Use: For in vitro diagnostic use. Can be used as an initial diagnostic test or in conjunction with a nontreponemal laboratory test and clinical findings to aid in the diagnosis of syphilis infection.
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" in a numerical, pre-defined format for PPA/NPA. Instead, it presents the performance results obtained and implicitly compares them to the predicate device's expected performance and clinical utility. For qualitative assays like this, the relevant performance metrics are Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA).
| Criteria / Performance Metric | Reported Device Performance (Lumipulse G TP-N) - Prospective Samples | Reported Device Performance (Lumipulse G TP-N) - Retrospective Samples |
|---|---|---|
| Positive Percent Agreement (PPA) vs. Final Comparator Result | 92.7% (95% CI: 88.6%, 95.4%) | 94.3% (95% CI: 92.0%, 96.0%) |
| Negative Percent Agreement (NPA) vs. Final Comparator Result | 99.6% (95% CI: 99.0%, 99.9%) | 98.1% (95% CI: 97.0%, 98.8%) |
Note: The document states, "The results of these analytical (nonclinical) and clinical studies demonstrate that the performance of the Lumipulse G TP-N assay is substantially equivalent to the performance of the ADVIA Centaur Syphilis (SYPH) assay." This implies that the observed PPA and NPA values were considered acceptable for demonstrating substantial equivalence to the predicate device.
2. Sample Size Used for the Test Set and Data Provenance
- Total Test Set Sample Size: 2,791 subjects were submitted for testing. After exclusions, 1,290 evaluable prospective samples and 1,472 evaluable retrospective samples were used.
- Data Provenance:
- Prospective Samples: Collected sequentially from patients prescribed a laboratory test for syphilis during a defined period. Collected from 7 sites representing different geographical regions of the US, including both low-prevalence and high-prevalence sites.
- Retrospective Samples: Pre-selected (enriched population) from various sources:
- 379 pregnant women (250 without syphilis, 129 with syphilis)
- 520 HIV positive subjects (298 remnant samples from reference laboratories, 222 collected at a research facility)
- 130 known to be T. pallidum (TP)-reactive by previous laboratory testing
- 68 samples from a research facility from patients clinically diagnosed with syphilis
- 375 samples consisting of remnants of specimens for routine syphilis testing
- 289 samples from subjects with well-characterized medically diagnosed syphilis (from Argentina (52%) and Florida (48%))
- 474 samples from apparently healthy subjects (75 pediatric, 399 adult/not pregnant).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The ground truth for the test set was not established by individual experts reviewing cases. Instead, it was based on an algorithmic combination of results from other FDA-cleared laboratory tests. Therefore, information regarding "number of experts" and their "qualifications" is not applicable in the traditional sense of image or clinical interpretation.
4. Adjudication Method for the Test Set
The adjudication method was a "2 out of 3 rule" based on the results of three FDA-cleared tests:
- A treponemal test (EIA)
- A non-treponemal Rapid Plasma Reagin (RPR) test
- A second treponemal test, Treponema pallidum particle agglutination (TP-PA)
The "Final Comparator Result" was determined as Positive or Negative if at least two of the three comparator tests yielded a consistent result.
- Example: Positive EIA + Positive RPR + Positive TP-PA = Positive Final Comparator Result.
- Example: Negative EIA + Negative RPR + Negative TP-PA = Negative Final Comparator Result.
- Example: Negative EIA + Positive RPR + Positive TP-PA = Positive Final Comparator Result.
- Indeterminate Results: Cases were considered "Indeterminate" if the EIA was "equivocal" and the TP-PA was "inconclusive". These were excluded from the final analysis.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic assay for qualitative determination of antibodies. Its performance is evaluated against a pre-established "ground truth" derived from other laboratory tests, not by comparing human reader performance with and without AI assistance in interpreting diagnostic images or clinical data.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, a standalone performance study was done. The entire clinical study presented (comparison against the "Final Comparator Result") represents the standalone performance of the Lumipulse G TP-N assay, as it is an automated laboratory test. There is no human interpretation or "in-the-loop" component in the direct output of this specific device.
7. The Type of Ground Truth Used
The ground truth used was a "Reference Comparator Algorithm" based on the consensus results of three established, FDA-cleared laboratory tests (EIA, RPR, and TP-PA), using a "2 out of 3 rule."
8. The Sample Size for the Training Set
The document describes performance characteristics and clinical comparison studies for the Lumipulse G TP-N. It does not explicitly mention a "training set" in the context of machine learning. For in-vitro diagnostic assays like this, the development typically involves:
- Internal studies for analytical performance (precision, interference, cross-reactivity).
- Clinical validation studies for method comparison to established comparator methods or reference standards.
The closest analogue to initial "training" or development data might be mentioned in the section on "Assay cut-off": "Lumipulse G TP-N was developed in 1997. 312 negative specimens, 99 positive specimens, and 6 intermediate specimens previously assigned using TP-PA were measured with Lumipulse G TP-N in order to establish its cut-off index."
- If this is considered the "training set" for cutoff establishment: 417 samples (312 negative, 99 positive, 6 intermediate).
9. How the Ground Truth for the Training Set Was Established
For the establishment of the assay cut-off, the "ground truth" for the 417 samples (312 negative, 99 positive, 6 intermediate) was established using TP-PA (Treponema pallidum particle agglutination), which is described as a previous method for assigning positivity/negativity.
§ 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).