(90 days)
The BioPlex Syphilis Total & RPR kit is a multiplex flow immunoassay intended for the qualitative detection of total (IgG/IgM) antibodies to Treponema pallidum and the qualitative detection and/or titer determination of non-treponemal reagin antibodies in human serum or plasma. The Syphilis Total or RPR assays may be used to supplement a previously determined reactive treponemal or non-treponemal test. The test system should be used in conjunction with other laboratory tests and clinical findings to aid in the diagnosis of syphilis infection.
The BioPlex 2200 Syphilis Total & RPR kit is not intended for use in screening blood or plasma donors
The BioPlex 2200 Syphilis Total & RPR kit is intended for use with the Bio-Rad BioPlex 2200 System.
The BioPlex 2200 Syphilis Total & RPR Control Set is intended for use as an assayed quality control to monitor the performance of the BioPlex 2200 Instrument and BioPlex 2200 Syphilis Total & RPR assay in the clinical laboratory. The performance of the BioPlex 2200 Syphilis Total & RPR Control Set has not been established with any other Syphilis Total & RPR assays.
The BioPlex 2200 Syphilis Total & RPR Calibrator Set is intended for the BioPlex 2200 Syphilis Total & RPR Reagent Pack.
BioPlex 2200 Syphilis Total & RPR kit includes the following components:
- One (1) 10 mL vial, containing dyed beads coated with recombinant Syphilis ● rTP47/rTP17 fusion protein, a cardiolipin antigen, an Internal Standard Bead (ISB) and a Serum Verification Bead (SVB) in MOPS (3-[N-Morpholino] propanesulfonic acid) buffer containing bovine proteins with protein stabilizers. ProClin 300 (≤ 0.3%), sodium benzoate (≤ 0.1%) and sodium azide (
Here's an analysis of the provided text, extracting the acceptance criteria and study details as requested:
BIO-RAD BioPlex 2200 Syphilis Total & RPR Kit Evaluation
1. Table of Acceptance Criteria and Reported Device Performance
The document describes internal precision and reproducibility acceptance criteria implicitly through the reported values for %CV within CLSI guidelines. For clinical performance, acceptance criteria are not explicitly stated as numerical thresholds (e.g., minimum sensitivity/specificity), but agreement percentages are reported. The provided tables are direct results from the studies and serve as the reported performance against assumed internal/regulatory acceptance ranges.
For Syphilis Total Assay (Treponemal Test):
| Performance Metric | Acceptance Criteria (Implicit from CLSI Guidelines/Observed Performance) | Reported Device Performance |
|---|---|---|
| Precision | ||
| Within Run %CV | Low %CV for various AI levels | Sample 1 (0.3 AI): 10.4% |
| Sample 6 (3.2 AI): 2.5% | ||
| Positive Control: 4.7% | ||
| Total Precision %CV | Low %CV for various AI levels | Sample 1 (0.3 AI): 13.4% |
| Sample 6 (3.2 AI): 4.1% | ||
| Positive Control: 5.1% | ||
| Reproducibility | ||
| Total %CV | Low %CV across sites for various AI levels | Sample 1 (0.5 AI): 18.2% |
| Sample 5 (6.8 AI): 4.4% | ||
| Positive Control: 7.0% | ||
| Matrix Comparison | Slope: 0.8-1.2, Intercept: -0.2-0.2, Correlation: >0.95 | Lithium Heparin: Slope: 0.8421, Intercept: 0.0316, r: 0.9899 |
| Sodium Heparin: Slope: 0.8333, Intercept: 0.0500, r: 0.9924 | ||
| K2EDTA: Slope: 1.1923, Intercept: -0.0923, r: 0.9943 | ||
| K3EDTA: Slope: 1.1667, Intercept: -0.0625, r: 0.9915 | ||
| Clinical Performance (Overall Prospective) | High Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) | PPA: 92.5% (147/159) [87.3% - 95.6% CI] |
| NPA: 97.9% (824/842) [96.6% - 98.6% CI] | ||
| Clinical Performance (Overall Retrospective - Known Positive) | High PPA and NPA (especially PPA for known positives) | PPA: 99.6% (486/488) [98.5% - 99.9% CI] |
| NPA: 100% (56/56) [93.6% - 100% CI] | ||
| Clinical Performance (Clinically Diagnosed Syphilis - Total) | High PPA (often referred to as sensitivity here) | PPA: 96.8% (151/156) [92.7% - 98.6% CI] |
| Cross-Reactivity (Negative Agreement) | High % Negative Agreement (e.g., >95%) | Overall: 99.7% (331/332) (One Anti-Cardiolipin IgG sample was reactive) |
For RPR Assay (Non-Treponemal Test):
| Performance Metric | Acceptance Criteria (Implicit from CLSI Guidelines/Observed Performance) | Reported Device Performance |
|---|---|---|
| Precision | ||
| Within Run %CV | Low %CV for various AI levels | Sample 1 (0.2 AI): 11.2% |
| Sample 6 (3.4 AI): 2.6% | ||
| Positive Control: 2.4% | ||
| Total Precision %CV | Low %CV for various AI levels | Sample 1 (0.2 AI): 20.7% |
| Sample 6 (3.4 AI): 6.5% | ||
| Positive Control: 7.1% | ||
| Reproducibility | ||
| Total %CV | Low %CV across sites for various AI levels | Sample 1 (0.8 AI): 9.1% |
| Sample 5 (7.4 AI): 6.9% | ||
| Positive Control: 4.7% | ||
| RPR Titer On-Board Dilution Reproducibility | High agreement within ± 1 titer (e.g., 100%) | Negative Control: 100% |
| Positive Control: 100% | ||
| Low Reactive (1:8): 100% | ||
| Moderately Reactive (1:16): 100% | ||
| High Reactive (>1:64): 100% | ||
| Matrix Comparison | Slope: 0.8-1.2, Intercept: -0.2-0.2, Correlation: >0.95 | Lithium Heparin: Slope: 0.8684, Intercept: 0.0908, r: 0.9893 |
| Sodium Heparin: Slope: 0.8353, Intercept: 0.1147, r: 0.9849 | ||
| K2EDTA: Slope: 1.0930, Intercept: -0.0314, r: 0.9864 | ||
| K3EDTA: Slope: 1.0776, Intercept: -0.0233, r: 0.9810 | ||
| Clinical Performance (Overall Prospective) | High PPA and NPA compared to predicate RPR | PPA: 81.5% (75/92) [72.4% - 88.1% CI] |
| NPA: 96.5% (877/909) [95.1% - 97.5% CI] | ||
| Clinical Performance (Overall Retrospective - Known Positive) | High PPA and NPA compared to predicate RPR | PPA: 98.1% (422/430) [96.4% - 99.1% CI] |
| NPA: 80.7% (92/114) [72.5% - 86.9% CI] | ||
| Clinical Performance (Clinically Diagnosed Syphilis - Total) | High PPA (referred to as sensitivity here) | PPA: 84.0% (131/156) [77.4% - 88.9% CI] |
| Cross-Reactivity (Negative Agreement) | High % Negative Agreement (e.g., >95%) | Overall: 99.4% (330/332) (One Anti-Cardiolipin IgA and one Systemic Lupus Erythematosus sample were reactive) |
2. Sample Size and Data Provenance for Test Set
- Total Samples for Clinical Studies: 2008 samples.
- Test Set Breakdown:
- Prospective Samples: 1001 samples.
- Country of Origin: Approximately 91% US (23.6% Northeast, 18.7% Southwest, 28.4% Southeast, 9.2% Midwest, 10.8% Unknown), 9% outside US (3.5% Argentina, 3.2% France/Europe, 1.4% China, 1.2% Others).
- Retrospective Samples: 661 samples.
- Country of Origin: Not explicitly broken down for retrospective samples, but generally stated to be from "multiple commercial suppliers" with the 91% US / 9% outside US split likely encompassing both.
- Clinically Diagnosed Individuals: 160 individuals (separate cohort from prospective/retrospective samples with specific diagnoses).
- Prospective Samples: 1001 samples.
- Data Provenance: Both prospective and retrospective samples were used. Prospectively collected samples were from apparently healthy subjects, syphilis/RPR test ordered patients, pregnant women, and HIV positive individuals. Retrospective samples were from known RPR/VDRL positive, clinically diagnosed syphilis, pregnant syphilis positive, and HIV/Syphilis dual positive individuals.
3. Number of Experts and Qualifications for Ground Truth
The document does not explicitly state the number or qualifications of "experts" used for establishing the ground truth directly. Instead, it relies on a "Final Comparator Algorithm Result" for the Syphilis Total assay, which is derived from multiple commercially available syphilis assays (predicate devices). For the RPR assay, the ground truth is primarily based on a commercially available RPR Card Test (Predicate).
- No specific number of human experts is mentioned for adjudicating individual cases or establishing the final ground truth. The "ground truth" seems to be established algorithmically or through established predicate diagnostic tests.
4. Adjudication Method
- For BioPlex 2200 Syphilis Total assay: The ground truth was established using a "2 out of 3" rule from three commercially available syphilis assays:
- Treponemal chemiluminescent immunoassay (primary predicate)
- RPR Card Test (non-treponemal assay)
- Treponema Pallidum Particle Agglutination (TP-PA) (second treponemal assay)
If at least two of these predicate assays agreed, that was considered the final comparator result. If there was no agreement (e.g., 1 positive, 1 negative, 1 inconclusive), the result was deemed "indeterminate" and excluded from analysis.
- For BioPlex 2200 RPR assay: The ground truth was established by comparing directly to a commercially available RPR Card Test (Predicate). No explicit "adjudication" among multiple assays is described here.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC or human-in-the-loop study is described in this document. The device is an automated immunoassay system, and its performance is compared to other diagnostic assays (predicate devices), not to human readers. Therefore, there is no effect size reported for human readers improving with or without AI assistance.
6. Standalone Performance Study
- Yes, a standalone performance study was done. The entire document describes the standalone performance of the BioPlex 2200 Syphilis Total & RPR kit. The device is an algorithm only (automated immunoassay) without a human-in-the-loop component in the diagnostic process itself. The clinical performance tables explicitly show the agreement of the BioPlex 2200 with the "Final Comparator Algorithm Result" (for Syphilis Total) or the "Predicate RPR Result" (for RPR).
7. Type of Ground Truth Used
- For Syphilis Total assay: A composite comparator algorithm based on the results of three commercially available diagnostic assays (predicate Treponemal CIA, RPR Card Test, TP-PA). This could be categorized as a form of expert consensus using established diagnostic tests rather than pathology or direct outcomes data for every individual case.
- For RPR assay: A single predicate diagnostic assay (RPR Card Test).
8. Sample Size for Training Set
- The document does not explicitly state the sample size used for the training set. It mentions the "feasibility phase of BioPlex 2200 Syphilis Total & RPR assay development" where cutoff values were established using "native human samples from apparently healthy subjects, patients sent to the laboratory for syphilis testing and patients diagnosed with syphilis infection." However, specific numbers for this development/training phase are not provided.
9. How Ground Truth for Training Set Was Established
- The cutoff values for the Syphilis Total and RPR assays were established "in the feasibility phase" using Native human samples from:
- Apparently healthy subjects
- Patients sent to the laboratory for syphilis testing
- Patients diagnosed with syphilis infection
- The establishment involved Receiver Operating Characteristics (ROC) analysis using "predicate results as standard". This indicates that the ground truth for establishing the cutoffs was derived from existing, legally marketed assays (predicates). Calibrator values were then adjusted based on this analysis to align with the 1.0 AI cutoff. Further confirmation of cutoff values involved comparing BioPlex results from patient samples to commercially available assays, and ultimately, clinical studies validated the cutoff.
§ 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).