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The Aptiva CTD Essential Reagent consists of 10 multiplexed immunoassays utilizing particle-based multi-analyte technology for the quantitative determination of IgG autoantibodies against dsDNA, and semi-quantitative determination of IgG autoantibodies against RNP, Sm, Ro52, Ro60, SS-B, Scl-70, Jo-1, centromere, and Ribo-P in human serum:

· The presence of dsDNA antibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the diagnosis of systemic lupus erythematosus.

· The presence of RNP antibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the diagnosis of mixed connective tissue disease and systemic lupus erythematosus.

· The presence of Sm antibodies, in conjunction with clinical findings and other laboratory tests, is an ad in the diagnosis of systemic lupus erythematosus.

· The presence of Ro52 antibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the

diagnosis of systemic lupus erythematosus, Sjögren's systemic scleross, and idiopathic inflammatory myositis. · The presence of Ro60 antibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the

diagnosis of systemic lupus erythematosus and Sjögren's syndrome.

· The presence of SS-B antibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the diagnosis of systemic lupus erythematosus and Sjögren's syndrome.

· The presence of Scl-70 antibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the diagnosis of systemic sclerosis.

· The presence of Jo-1 antibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the diagnosis of idiopathic inflammatory myositis.

· The presence of centromere antibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the diagnosis of systemic sclerosis.

· The presence of Ribo-P antibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the diagnosis of systemic lupus erythematosus.

The individual assays included in the Aptiva CTD Essential Reagent are intended for use with the Inova Diagnostics Aptiva System.

The Aptiva CTD Essential reagent utilizes particle based multi-analyte technology (PMAT) in a cartridge format. Each analyte (dsDNA, RNP, Sm, Ro60, Ro52, SS-B, Scl-70, Jo-1, Centromere and Ribo-P) in the Aptiva CTD Essential reagent is a solid phase immunoassay utilizing fluorescent microparticles. This technology allows each of the ten analytes, along with a human anti-lgG capture antibody (IgG Control Microparticle), to be coated onto eleven uniquely recognizable paramagnetic microparticles, which are combined into one tube.

The Aptiva Multi-Analyte Instrument is a fully automated, random-access analyzer. This platform is a closed system with continuous load and random-access capabilities that processes the samples, runs the reagent, and reports results. It includes liquid handling hardware, optical module (OM), and integrated computer with proprietary software and touch screen user interface.

The ten unique populations of microparticles coated with dsDNA, RNP, Sm, Ro60, Ro52, SS-B, Scl-70, Jo-1, Centromere and Ribo-P, along with the one for the control microparticle, are stored in the reagent cartridge under conditions that preserve the autoantigens in their reactive states. When the assay cartridge is ready to be used for the first time, the reagent tube seals are pierced using the cartridge lid. The reagent cartridge is then loaded onto the Aptiva Multi-Analyte Instrument, where the microparticles are automatically rehydrated using buffer located within the cartridge.

A patient's serum is diluted 1:44.4 fold with Aptiva system rinse by the instrument in a disposable cuvette. A small amount of the diluted sample is combined with assay buffer and the microparticle suspension in a second cuvette, and mixed (final serum dilution: 1:230). This reaction cuvette is incubated for 9 ½ minutes at 37°C. The cuvette is then exposed to a magnet that retains the microparticles in place. The liquid is aspirated, and the microparticles are resuspended as system rinse is added to the cuvette and the magnet is removed. This wash cycle is repeated. During the third wash, no system rinse is added after the aspiration step. After the third wash, phycoerythrin conjugated polyclonal anti-human lgG (known as PE Tracer IgG) is added to the cuvette with microparticles, and mixed. Again, the cuvette is incubated for 9 ½ minutes at 37°C. Three wash steps, as described above, are performed on the microparticles. Following the wash steps, the microparticles are transferred to the optical module of the instrument, where a charge coupled device (CCD) camera takes multiple images to identify and count the twelve unique microparticle regions, as well as determine the amount of conjugate on the microparticles. A twelfth particle, coated with goat anti-human IgG, is present in the reagent as a control to flag low concentrations of IgG in the patient serum sample as an assay verification step. The median fluorescent intensity (MFI) is proportional to the amount of PE Tracer that is bound to the human IgG, which is proportional to the amount of IgG antibodies bound to the corresponding microparticle regions.

For quantitation, the ten assays (together as part of the Aptiva CTD Essential Reagent) each utilizes a predefined lot specific Master Curve that is uploaded onto the instrument through the RFID tag on the reagent cartridge. The first time a reagent cartridge of a new lot of Aptiva CTD Essential is placed in the instrument, it must be calibrated. The Aptiva CTD Essential Calibrators are sold separately. The calibration process utilizes the 6 Calibrators that are included in the Calibrators kit to adjust the predefined lot specific dsDNA, RNP, Sm, Ro60, Ro52, SS-B, Scl-70, Jo-1, Centromere and Ribo-P Master Curves into instrument specific Working Curves. These Working Curves are used to calculate FLU (or IU/mL for dsDNA) values from the measured MFI. The Working Curves are lot and instrument specific and stored in the system for use with any reagent cartridge from that lot. The lot specific calibration expires 6 months from the last time the calibration was performed, and re-calibration is required.

Aptiva CTD Essential Calibrators and Aptiva CTD Essential Controls are sold separately.

The Aptiva CTD Essential Reagent kit contains the following materials:

One (1) Aptiva CTD Essential Reagent Cartridge contains the following materials to process 250 determinations:

• a. dsDNA, RNP, Sm, Ro60, Ro52, SS-B, Scl-70, Jo-1, Centromere and Ribo-P, and Control paramagnetic particles, preserved.
• b. Assay Buffer clear liquid, containing protein stabilizers and preservatives.
• c. PE Tracer IgG PE labeled anti-human IgG antibody, containing buffer, protein stabilizers and preservative.
• d. Rehydration Buffer containing protein stabilizers and preservatives.

This document describes the analytical and clinical performance characteristics of the Aptiva CTD Essential Reagent, a multiplexed immunoassay system, and its comparison to predicate devices.

Here's an analysis of the acceptance criteria and study proving device performance:

1. A table of acceptance criteria and the reported device performance

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The ZEUS IFA™ nDNA Test System is an indirect immunofluorescence assay utilizing Crithidia luciliae for the qualitative and semi-quantitative determination of anti-native DNA (nDNA) IgG antibodies to DNA in human serum by manual fluorescence microscopy or with ZEUS dIFine®. The presence of nDNA antibodies in conjunction with other serological and clinical findings can be used to aid in the diagnosis of systemic lupus erythematosus (SLE).

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This document is an FDA clearance letter for the ZEUS IFA nDNA Test System. It does not contain information about the acceptance criteria or a study proving the device meets those criteria. The provided text is a standard FDA 510(k) clearance letter, confirming the device's substantial equivalence to a predicate device and outlining regulatory obligations.

Therefore, I cannot provide the requested information based on the provided input. The details about acceptance criteria, study design, sample sizes, expert involvement, and ground truth establishment are not present in this regulatory document.

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The Immuno Concepts IgG Anti-nDNA Fluorescent Test System is for in vitro diagnostic use for the qualitative detection and semi-quantitation of anti-nDNA antibodies of the IgG class in human serum by manual fluorescent microscopy or with the Image Navigator® Fluorescence Semiautomated Microscope. The Immuno Concepts IgG Anti-IDNA Fluorescent Test System is to be used as an aid in the diagnosis of Systemic Lupus Erythematosus (SLE) in conjunction with other clinical and laboratory findings. A trained operator must confirm results generated with the Image Navigator® semi-automated device and software.

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The provided text is a 510(k) premarket notification clearance letter from the FDA for the "Immuno Concepts IgG Anti-nDNA Fluorescent Test System" and the "Image Navigator® Fluorescence Semiautomated Microscope." It details the device's indications for use and general regulatory information but does not contain the specific acceptance criteria, study details, or performance data that would allow for a complete answer to your request.

Therefore, I cannot extract the following information from the provided text:

• A table of acceptance criteria and the reported device performance
• Sample size used for the test set and the data provenance
• Number of experts used to establish the ground truth for the test set and the qualifications of those experts
• Adjudication method for the test set
• Whether a multi-reader multi-case (MRMC) comparative effectiveness study was done, or the effect size
• Whether a standalone (algorithm only) performance study was done
• The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
• The sample size for the training set
• How the ground truth for the training set was established

The document primarily states that the FDA has determined the device is substantially equivalent to legally marketed predicate devices. To find the detailed study information, one would typically need to review the full 510(k) summary or the pivotal study report submitted by the manufacturer to the FDA, which is not included in this clearance letter.

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EliA Ro52 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Ro52 in human serum as an aid in the diagnosis of Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM) in conjunction with other laboratory and clinical findings. EliA Ro52 uses the EliA IgG method.

EliA Ro60 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Ro60 in human serum as an aid in the diagnosis of Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA Ro60 uses the EliA IgG method.

The EliA Ro52 and EliA Ro60 Immunoassays are semi-quantitative solid-phase fluoroenzyme immunoassays, for the determination of autoantibodies against SS-A/Ro 52 kDa and 60 kDa proteins. The EliA Ro52 and EliA Ro60 test System is a fully integrated and automated system composed of assay-specific reagents, EliA method-specific reagents, and general reagents.

The provided document describes the EliA Ro52 and EliA Ro60 Immunoassays, which are intended for the semi-quantitative measurement of IgG antibodies directed to Ro52 and Ro60 in human serum, respectively. These devices aid in the diagnosis of specific autoimmune diseases. The document includes detailed analytical and clinical performance data to support the substantial equivalence claim.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal "acceptance criteria" in a tabulated format. Instead, it presents various analytical and clinical performance metrics, implying that these metrics, when compared to the predicate device and established clinical utility, are deemed acceptable for the device's intended use. Based on the provided performance data, the implicit acceptance criteria would likely be related to aspects like precision, linearity, detection limits, specificity (interference), and clinical sensitivity/specificity.

Below is a table summarizing key performance indicators reported in the document:

Table 1: Key Performance Metrics for EliA Ro52 and EliA Ro60

The acceptance of these performance metrics is implicitly based on comparison with the predicate devices (QUANTA Flash Ro52 and QUANTA Flash Ro60) and the established clinical utility in diagnosing the mentioned autoimmune diseases. The FDA's substantial equivalence determination (K210902) confirms that the submitted data supports the claim that the new devices perform comparably to the predicate devices.

2. Sample Size Used for the Test Set and Data Provenance

The document describes several test sets for different performance characteristics:

• Precision/Reproducibility:
  • Phadia 250: 5 samples, each with 252 replicate determinations (across 3 instruments, 7 days, 21 runs).
  • Within-lab Imprecision: Samples in 80 replicates on 1 instrument over 20 days (40 runs).
  • Phadia 2500 and Phadia 5000 series (E-module): 5 samples, each with 84 replicates (across 3 instruments, 7 days, 21 runs).
• Linearity/Assay Reportable Range: 3 patient serum samples serially diluted in at least 9 dilution steps, tested in quadruplicates.
• Detection Limit: 4 blank and 4 low-level samples, tested in 5-fold determination, across 2 different reagent sets (totaling 120 combined observations for blank and low-level per instrument type).
• Analytical Specificity (Interference): 3 serum samples (negative, equivocal, high positive), spiked with interfering substances, tested in triplicates.
• Method Comparison with Predicate Device:
  • EliA Ro52: 208 patient serum samples (only 181 used in agreement calculations due to samples outside measuring range).
  • EliA Ro60: 208 patient serum samples (only 104 used in agreement calculations due to samples outside measuring range).
• Clinical Sensitivity and Specificity:
  • EliA Ro52: 755 clinically and ethnically defined serum samples. These include:
    • Diagnostic group: SLE (n=120), Sjögren's syndrome (n=60), IIM (n=94), SSc (n=91) - total 365.
    • Disease control group: 390 samples (various autoimmune and infectious diseases).
  • EliA Ro60: 713 clinically and ethnically defined serum samples. These include:
    • Diagnostic group: SLE (n=120), Sjögren's syndrome (n=60) - total 180.
    • Disease control group: 533 samples (various autoimmune and infectious diseases, excluding SSc).

Data Provenance:
The document states that the clinical samples used for sensitivity and specificity determination were from "clinically and ethnically defined serum samples, including those of US origin." This indicates a mix of retrospective (clinically defined, likely banked samples) and potentially prospective (if US origin implies some form of fresh collection for the study) data. It is not explicitly stated whether it was purely retrospective or involved prospective collections, but the description "clinically and ethnically defined serum samples" strongly suggests retrospective use of samples with established diagnoses.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

The document does not provide information on the number of experts used to establish the ground truth for the test sets (e.g., for diagnoses of SLE, SS, IIM, SSc). It only states that samples were "clinically and ethnically defined." This typically implies that patient diagnoses were established through standard clinical practice by medical professionals, but the specifics of these experts' qualifications or the consensus process are not detailed in this submission summary.

4. Adjudication Method for the Test Set

The document does not specify an adjudication method for establishing the ground truth for the test set. It refers to diagnoses as "clinically defined," which generally suggests diagnosis was made by treating physicians following clinical guidelines, but no adjudication process like 2+1 or 3+1 by independent experts is mentioned for the study.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This document describes an in vitro diagnostic (IVD) device, specifically an immunoassay for measuring antibody levels. MRMC studies are typically performed for imaging devices or other diagnostic tools where human interpretation is involved and needs to be compared with and/or augmented by AI. This device is an automated laboratory test, and its performance is evaluated directly through analytical measurements and comparison to a predicate device, as well as clinical sensitivity and specificity against established clinical diagnoses.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, this is a standalone device. The EliA Ro52 and EliA Ro60 Immunoassays are "automated semi-quantitative solid phase fluoroenzymeimmunoassays" run on "Phadia 250 instrument and the Phadia 5000 instrument series (E-modules)." The results are automatically converted to EliA U/mL. The performance characteristics described (precision, linearity, detection limit, analytical specificity, clinical sensitivity, specificity) are all based on the output of the automated instrument and reagents, independent of human interpretation during the actual test process itself. The interpretation of results (negative, equivocal, positive) is based on defined cut-off values.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

For the clinical sensitivity and specificity studies, the ground truth was clinical diagnosis. The samples were "clinically and ethnically defined serum samples" with established diagnoses of various autoimmune diseases (SLE, SS, IIM, SSc) and control conditions. This implies that the diagnosis was based on the standard clinical criteria and medical records established by healthcare professionals, rather than a separate expert consensus panel or specific pathology results for the study.

8. The Sample Size for the Training Set

The document does not describe a "training set" in the context of machine learning or AI models, as this is an immunoassay and not an AI/ML-based device.

However, if "training set" is generally interpreted as samples used for assay development, optimization, or establishing parameters like cut-offs, the relevant information is:

• Cut-off definition: A cohort of 69 healthy blood donors, 19 SLE patients, and 9 Sjögren's syndrome (SS) patients for EliA Ro52, and 70 healthy blood donors, 22 SLE patients, and 6 Sjögren's syndrome patients for EliA Ro60, were used to define the cut-off values. This can be considered the 'development' or 'calibration' set for determining the interpretive thresholds.

9. How the Ground Truth for the Training Set Was Established

As noted above, this device does not utilize a machine learning "training set" in the conventional sense. For the samples used to establish the cut-off values (which could be considered analogous to determining a 'decision boundary' in an ML context), the ground truth was established based on the clinical diagnoses of the patient samples (healthy blood donors, SLE patients, Sjögren's syndrome patients). The document states that the initial cut-off for EliA Ro52, set using SLE and SS patients, was later verified with additional IIM and SSc patient sera. This indicates clinical diagnosis as the gold standard.

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Assay:

ZEUS IFA™ ANA HEp-2 Test System is an indirect immunofluorescence assay for the qualitative detection and semiquantitative determination of IgG anti-nuclear antibodies in human serum by manual fluorescence microscopy or with ZEUS dlFine®. The presence of anti-nuclear antibodies can be used in conjunction with other serological tests and clinical findings to aid in the diagnosis of systemic lupus erythematosus and other systemic rheumatic diseases. All suggested results obtained with ZEUS dIFine® must be confirmed by a trained operator.

Instrument:

ZEUS dIFine® is an automated instrument consisting of a fluorescent microscope and software that acquires, interprets, stores and displays digital images of stained indirect immunofluorescence slides. ZEUS dlFine can only be used with FDA cleared or approved ZEUS in vitro diagnostic assays that are indicated for use on this instrument. All suggested results obtained with ZEUS dIFine must be confirmed by a trained operator

ZEUS dIFine® is an automated instrument consisting of a fluorescent microscope and software that acquires, interprets, stores and displays digital images of stained indirect immunofluorescence slides.

The provided text is an FDA 510(k) clearance letter for the Zeus IFA ANA HEp-2 Test System and Zeus dIFine. While it states the device is "substantially equivalent" and outlines its indications for use, it does not contain the detailed study information required to answer your specific questions about acceptance criteria and performance data.

The FDA 510(k) summary, often referred to as the 510(k) "Premarket Notification Summary" or "Special 510(k) Notification Summary," would contain the information you are seeking regarding acceptance criteria and performance data. This document is typically publicly available on the FDA's website alongside the 510(k) clearance letter.

Therefore, I cannot provide the requested information based solely on the text you provided. To answer your questions, I would need access to the 510(k) summary document for K201956.

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EliA Rib-P is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Rib-P in human serum as an aid in the diagnosis of systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA Rib-P uses the EliA IgG method.

EliA Rib-P is a semi-quantitative solid-phase fluoroenzymeimmunoassay, for the determination of autoantibodies against Rib-P. The EliA Rib-P test System is fully integrated and automated system which comprises of assay-specific reagents, EliA method-specific reagents, and general reagents.

Assav-Specific Reagents include:

• EliA Rib-P Wells: coated with human recombinant ribosomal P-proteins P0, P1 . and P2 - 2 carriers (12 wells each), ready to use;
• . EliA ANA 3 Positive Control 250 or 2500/5000: Human monoclonal antibodies in Tris buffer containing IgG antibodies to Ro52, Rib-P and RNA Pol III – 6 single use vials, 0.3 mL each, ready to use;
• . EliA IgG/IgM/IgA Negative Control 250 or 2500/5000: Human blood preparation from healthy donors in PBS containing BSA, detergent and 0.095% sodium azide - 6 single-use vials, 0.3 mL each, ready to use;

EliA Method-Specific Reagents include:

• EliA Sample Diluent: PBS containing BSA, detergent and 0.095% sodium azide . - 6 bottles, 48 mL each, ready to use; or 6 bottles, 400 mL each, ready to use;
• I EliA IqG Conjuqate 50 or 200: ß-Galactosidase labeled anti-lgG (mouse monoclonal antibodies) in PBS containing BSA and 0.06% sodium azide - 6 wedge shaped bottles, 5 mL each, ready to use; or 6 wedge shaped bottles, 19 mL each, ready to use:
• . EliA IgG Calibrator Strips: Human IqG (0, 4, 10, 20, 100, 600 uq/L) in PBS containing BSA, detergent and 0.095% sodium azide - 5 strips, 6 single-use vials per strip, 0.3 mL each, ready to use;
• EliA IgG Curve Control Strips: Human IgG (20 ug/L) in PBS containing BSA, . detergent and 0.095% sodium azide - 5 strips, 6 single-use vials per strip, 0.3 mL each, ready to use:
• EliA IgG Calibrator Well: coated with mouse monoclonal antibodies 4 carriers . (12 wells each), ready to use;

General Reagents include:

• Development Solution: 0.01% 4-Methylumbelliferyl-β-D-galactoside, 110, 6x >170, or 6x >1165 determinations;
• I Stop Solution: 4% Sodium Carbonate - 6 bottles (65 mL, 119 mL, or 2800 mL each), sufficient for 6x >292, 6x >560, or 6x >13100 determinations;
• 트 Washing Solution Additive: detergent, preservative

The provided document is a 510(k) Summary for the EliA Rib-P device, an in vitro semi-quantitative immunoassay for detecting IgG antibodies directed to Rib-P as an aid in diagnosing Systemic Lupus Erythematosus (SLE). This document does not describe a study involving an AI-enabled device or human-in-the-loop performance. Instead, it focuses on the analytical and clinical performance of a standalone laboratory diagnostic device and its substantial equivalence to a predicate device.

However, I can extract and structure the information related to acceptance criteria and the performance study of this specific diagnostic device in the format requested, even without AI-specific parameters.

Acceptance Criteria and Device Performance Study for EliA Rib-P

The EliA Rib-P device is an automated semi-quantitative solid phase fluoroenzymeimmunoassay for the measurement of IgG antibodies directed to Rib-P in human serum. This summary outlines the performance characteristics tested to demonstrate its substantial equivalence to a legally marketed predicate device, the Quanta Lite Ribosome P ELISA.

1. Table of Acceptance Criteria and the Reported Device Performance

• Range of Total Imprecision %CV across 5 samples: 4.0% - 13.3%
• Within-lab Imprecision %CV across 4 samples: 3.5% - 13.8%
  Phadia 2500/5000:
• Range of Total Imprecision %CV across 5 samples: 5.7% - 18.4% (one sample had high CV, 18.4%) |
  | Linearity/Reportable Range| Coefficient of determination (R²) close to 1.00, and slopes close to 1.00, across the measuring range. CLSI EP6-A guidelines followed. | Phadia 250:
• R² values: 1.00 for all three dilution ranges.
• Slopes: 0.95, 1.00, 1.00.
  Phadia 2500E:
• R² values: 0.99, 1.00, 0.99 for the three dilution ranges.
• Slopes: 1.03, 1.00, 1.02.
  "Linearity was shown for the entire measuring range." |
  | Detection Limit | LoB, LoD, and LoQ to be established according to CLSI EP17-A2 guidelines (false positives and false negatives 10 EliA U/mL |
  | Comparison Studies | | |
  | Method Comparison (vs. Predicate Device) | High Positive Percent Agreement (PPA), Negative Percent Agreement (NPA), and Total Agreement with the predicate device. CLSI EP09c-ED3 followed. | EliA Rib-P (equivocal considered negative):
• PPA: 94.7% (95% CI: 82.3% - 99.4%)
• NPA: 98.6% (95% CI: 96.4% - 99.6%)
• Total Agreement: 98.1% (95% CI: 96.0% - 99.3%)
  EliA Rib-P (equivocal considered positive):
• PPA: 100% (95% CI: 90.7% - 100%)
• NPA: 88.1% (95% CI: 83.7% - 91.6%)
• Total Agreement: 89.5% (95% CI: 85.6% - 92.6%) |
  | Instrument Comparison | Strong correlation and agreement between different Phadia instrument series. | Regression analysis showed a slope of 0.94 (95% CI: 0.93 - 0.98) and an intercept of -0.76 (95% CI: -1.20 - -0.48) between Phadia 250 and Phadia 2500E. |
  | Clinical Studies | | |
  | Clinical Sensitivity and Specificity | Acceptable sensitivity for SLE and high specificity against other autoimmune and infectious diseases. | EliA Rib-P (equivocal considered positive):
• Sensitivity (for SLE): 34.9% (95% CI: 27.2% - 43.3%)
• Specificity (against disease controls): 99.3% (95% CI: 97.9% - 99.9%)
  EliA Rib-P (equivocal considered negative):
• Sensitivity (for SLE): 28.1% (95% CI: 21.0% - 36.1%)
• Specificity (against disease controls): 99.8% (95% CI: 98.7% - 100%) |

2. Sample Size Used for the Test Set and Data Provenance

• Precision/Reproducibility:
  • Phadia 250: 5 samples, tested in 252 replicates each across 3 lots and 3 instruments over 7 days.
  • Within-Lab Imprecision: 4 samples, tested in 80 replicates each on 1 instrument over 20 days.
  • Phadia 2500/5000 (E-module): 5 samples, tested in 84 replicates each on 3 instruments over 7 days.
  • Provenance: Not explicitly stated, typically laboratory-prepared controls or banked human serum samples.
• Linearity/Assay Reportable Range: 3 serum samples (diluted). Provenance not explicitly stated.
• Detection Limit: 4 blank and 4 low-level samples (depleted IgG sera and prepared low-level samples) tested in 5-fold determination across 3 runs on Phadia 250 and Phadia 2500E.
• Analytical Specificity (Interference): 3 serum samples (one negative, one equivocal, one high positive) spiked with interfering substances. Provenance not explicitly stated.
• Assay Cut-Off: A cohort of 70 apparently healthy blood donors and 30 samples from SLE patients. Provenance not explicitly stated.
• Method Comparison with Predicate Device: 323 patient samples. Provenance not explicitly stated, but implies diverse clinical samples covering the measuring range.
• Instrument Comparison: 47 positive, 10 equivocal, and 28 negative samples. Provenance not explicitly stated.
• Clinical Sensitivity and Specificity: 560 clinically defined serum samples from various diagnostic groups (146 SLE, 414 disease controls). Provenance not explicitly stated, but these are patient samples with confirmed diagnoses.
• Expected Values/Reference Range: 638 apparently healthy subjects, equally distributed by age and gender from Caucasian, African American, Hispanic, and Asian populations obtained from a blood bank.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not mention the use of experts to establish ground truth for the analytical performance characteristics. For clinical studies, the "ground truth" for patient samples was based on "clinically defined serum samples with a diagnosis" (e.g., systemic lupus erythematosus, Celiac disease, etc.). This typically implies diagnosis by medical professionals (e.g., rheumatologists, gastroenterologists, etc.) based on established diagnostic criteria, but the number and specific qualifications of these experts are not explicitly stated in this summary.

4. Adjudication Method (e.g. 2+1, 3+1, none) for the Test Set

No explicit adjudication method is mentioned. The ground truth for clinical samples appears to be based on pre-existing clinical diagnoses.

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 section is not applicable as the device is a standalone in vitro diagnostic immunoassay, not an AI-enabled device or an assist device for human readers. No MRMC study was conducted.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done

This device is a standalone algorithm/device in the sense that it performs automated semi-quantitative measurement of antibodies without real-time human interpretation impacting the measurement result. The assay directly measures the amount of antibody via fluorescence. The interpretation of results (negative, equivocal, positive) is based on predefined cut-offs.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc)

• Analytical ground truth: Based on reference materials, spiked samples, and dilution series with known concentrations or characteristics.
• Clinical ground truth: "Clinically defined serum samples with a diagnosis" (e.g., SLE patients, various disease controls). This implies established clinical diagnoses, likely based on standard diagnostic criteria, which could involve expert clinical assessment, pathology, and other laboratory findings.

8. The Sample Size for the Training Set

This document does not specify a separate "training set" in the context of machine learning or AI. For a traditional immunoassay, method development and optimization would involve various experiments and sample sets, but these are not explicitly termed "training sets" here. The "Assay Cut-Off" study used 70 healthy blood donors and 30 SLE patients to define the cut-off, which could be considered a form of "training" for the interpretive criteria.

9. How the Ground Truth for the Training Set Was Established

As noted above, a formal "training set" in the AI sense is not described. For the cut-off determination, the ground truth was established by using "apparently healthy blood donors" and "samples from SLE patients," indicating that these samples had known clinical statuses (healthy or diagnosed with SLE).

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EliA RNA Pol III is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to RNA polymerase III (RNA Pol III) in human serum as an aid in the diagnosis of systemic sclerosis (diffuse form) in conjunction with other laboratory and clinical findings. EliA RNA Pol III uses the EliA IgG method.

EliA RNA Pol III is a semi-quantitative solid-phase fluoroenzymeimmunoassay, for the determination of autoantibodies against RNA polymerase III. The EliA RNA Pol III test System is fully integrated and automated system which comprises of assay-specific reagents, EliA method-specific reagents, and general reagents.

Here's a breakdown of the acceptance criteria and study information for the EliA RNA Pol III device, based on the provided text:

Acceptance Criteria and Device Performance

Study Details

2. Sample Size and Data Provenance for the Test Set:

• Test Set (Method Comparison with Predicate Device):
  • Sample Size: 193 patient serum samples.
  • Data Provenance: Not explicitly stated, but includes 126 samples with a diagnosis of SSc. The context suggests these are clinical samples.
• Test Set (Clinical Sensitivity and Specificity):
  • Sample Size: 596 clinically defined serum samples.
  • Data Provenance: Clinically defined samples from patients with various diagnoses, including Systemic Sclerosis (diffuse and limited forms), and various control diseases/conditions (e.g., Celiac disease, Crohn's disease, SLE, RA, bacterial/viral infections). The text does not specify country of origin or if prospective/retrospective; however, "clinically defined serum samples" typically implies retrospective collection with known diagnoses.
• Test Set (Assay Cut-Off):
  • Sample Size: 70 apparently healthy blood donor samples and 17 target disease (Systemic Sclerosis, diffuse) samples.
  • Data Provenance: "apparently healthy blood donor samples" and "target disease samples" (Systemic Sclerosis, diffuse). The text explicitly mentions "sera from Caucasian, African American, Hispanic and Asian population obtained from a blood bank" for the frequency distribution, which likely overlaps with the "apparently healthy blood donor samples" used for cut-off establishment.

3. Number of Experts and Qualifications for Ground Truth (Test Set):

• Number of Experts: Not specified.
• Qualifications of Experts: Not specified. The wording "clinically defined serum samples with a diagnosis" implies that the diagnoses used as ground truth were established clinically by medical professionals, but their specific roles, number, or years of experience are not detailed.

4. Adjudication Method (Test Set):

• Adjudication Method: Not specified. The diagnostic labels for the clinical samples are presented as established fact without mention of an adjudication process.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

• Was an MRMC study done? No. This device is an in-vitro diagnostic (IVD) assay designed for automated measurement of antibodies, not for interpretation by human readers. Therefore, an MRMC comparative effectiveness study regarding human reader improvement with AI assistance is not applicable.

6. Standalone (Algorithm Only) Performance:

• Was a standalone study done? Yes. The entire performance evaluation, including analytical performance, method comparison, and clinical sensitivity/specificity, evaluates the performance of the EliA RNA Pol III assay itself (the "algorithm only" in this context, as it's an automated system) without human interpretation as part of the primary measurement. The results are generated directly by the instrument.

7. Type of Ground Truth Used:

• For Method Comparison: The ground truth was the results from the predicate device, QUANTA LITE RNA POL III ELISA.
• For Clinical Sensitivity and Specificity: The ground truth was clinical diagnosis ("clinically defined serum samples with a diagnosis from patients with systemic sclerosis, diffuse," etc.).
• For Assay Cut-Off: The ground truth was based on apparently healthy blood donors and clinically diagnosed Systemic Sclerosis, diffuse patients.

8. Sample Size for the Training Set:

• Training Set (Assay Cut-Off establishment): This involved 70 apparently healthy blood donor samples and 17 target disease (Systemic Sclerosis, diffuse) samples. While not explicitly called a "training set," these samples were used to "define the cut-off," which is a form of model training/optimization for classification.
• Other "training" data: The document mentions that "New batches of IgG calibrators are compared to a secondary standard (standardized with the IRP) or the IRP directly and adjusted accordingly to meet the correct concentration." This implies a continuous process of calibration and standardization, where previous data/standards (IRP) could be considered a form of "training" for the calibrators. However, a distinct, large-scale training set for an AI/algorithm in the conventional sense is not detailed as this is a chemical assay.

9. How the Ground Truth for the Training Set was Established:

• For Assay Cut-Off establishment: The ground truth for the 70 apparently healthy blood donors means they were confirmed healthy (presumably through standard screening). For the 17 Systemic Sclerosis (diffuse) samples, the ground truth was their clinical diagnosis.
• For Calibrators: The ground truth for calibrators is established through their traceability to the International Reference Preparation (IRP) 67/86 of Human Serum Immunoglobulins A, G and M from WHO.

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EliA SmDP-S is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Sm in human serum and EDTA-plasma as an aid in the diagnosis of systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA SmDP-S uses the EliA IgG method.

The EliA SmD -S is a semi-quantitative solid-phase fluoroimmunoassay, for the determination of autoantibodies against Sm. The EliA SmDP-S test System is fully integrated and automated system which comprises of assay-specific reagents, EliA method-specific reagents, and general reagents.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the EliA SmDP-S device are not explicitly stated as distinct criteria with numerical targets in the provided document. Instead, the document presents performance characteristics that implicitly serve as acceptance criteria by demonstrating that the device is substantially equivalent to a predicate device. Below is a summary of the reported device performance for key analytical and clinical characteristics.

2. Sample Sizes and Data Provenance

• Test Set (Method Comparison):
  • Sample Size: A total of 628 patient samples were initially tested in the method comparison study with the predicate device. For statistical analyses, 460 samples were used after excluding 168 values outside the measuring range.
  • Data Provenance: Not explicitly stated, but typically such studies involve samples collected from various clinical sites. It is implied to be clinical patient samples, likely retrospective given they were previously collected for comparison.
• Test Set (Clinical Sensitivity and Specificity):
  • Sample Size: 328 clinically defined samples: 104 with Systemic Lupus Erythematosus (SLE) and 224 disease controls (Mixed connective tissue disease, Sjögren's syndrome, Scleroderma, Polymyositis/Dermatomyositis, Rheumatoid arthritis, Graves' disease, Hashimoto's disease, Bacterial infections, Viral infections).
  • Data Provenance: Not explicitly stated, but implied to be from clinical settings for diagnosed patients and controls. Likely retrospective.
• Reference Range/Expected Values:
  • Sample Size: 632 apparently healthy subjects.
  • Data Provenance: Sera obtained from a blood bank, equally distributed by age and gender, from Caucasian, African American, Hispanic and Asian populations.

3. Number of Experts and their Qualifications for Ground Truth

• Number of Experts: Not specified.
• Qualifications of Experts: The ground truth for clinical sensitivity and specificity was based on "clinically defined samples with a diagnosis". This implies that the diagnosis was established by medical professionals (e.g., rheumatologists, infectious disease specialists) based on a comprehensive clinical assessment, which would include other laboratory and clinical findings. The document does not provide details on the number or specific qualifications (e.g., years of experience) of these clinicians or specialists.

4. Adjudication Method for the Test Set

The document does not describe an explicit adjudication method (like 2+1 or 3+1 consensus) for establishing the ground truth of the test set samples. The samples were "clinically defined with a diagnosis" or "apparent healthy subjects," implying that their disease status or health status was established through standard clinical practice/diagnostic criteria rather than a specific expert adjudication process for the purpose of this study.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was mentioned. The device is an in vitro diagnostic (IVD) immunoassay, which typically does not involve human readers interpreting results in the same way imaging devices do. The performance evaluation focuses on the analytical and clinical accuracy of the assay itself compared to a predicate device and clinical diagnoses, not on human reader improvement with AI assistance.

6. Standalone (Algorithm Only) Performance

Yes, a standalone performance study was done. The entire document describes the performance of the EliA SmDP-S device as an in vitro diagnostic assay, which functions independently (algorithm only) to measure IgG antibodies. There is no human-in-the-loop component described for its operation or result generation. The device produces a semi-quantitative measurement (EliA U/mL) that is then interpreted based on defined cut-offs.

7. Type of Ground Truth Used

• For Method Comparison: The ground truth was the result obtained from the predicate device (EliA SmDP assay) for common patient samples.
• For Clinical Sensitivity and Specificity: The ground truth was based on "clinically defined diagnoses" of patients with Systemic Lupus Erythematosus (SLE) and various disease controls. This implies a diagnosis established through standard clinical criteria, which would include medical history, physical examination, other laboratory tests, and imaging findings (i.e., clinical diagnosis/outcomes data).
• For Reference Range: The ground truth was a group of "apparently healthy subjects."

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of device development or algorithm training. For IVD devices like this, the development process usually involves internal validation and optimization batches, but not typically a formally labeled "training set" in the sense of machine learning. The studies described are primarily for validation and verification of the final device performance.

9. How Ground Truth for Training Set was Established

As no explicit "training set" is mentioned, the method for establishing its ground truth is also not detailed. However, for the development and optimization of such assays, ground truth for sample panels would typically be established using confirmed clinical diagnoses, reference methods, or well-characterized reference materials, similar to how the validation samples' ground truth was established using clinical diagnoses and predicate device comparisons.

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NOVA Lite® DAPI dsDNA Crithidia luciliae is an indirect immunofluorescent assay for the qualitative and/or semi-quantitative determination of anti-double stranded DNA (dsDNA) IgG antibodies in human serum by NOVA View Automated Fluorescence Microscope or manual fluorescence microscopy. The presence of anti-dsDNA can be used in conjunction with other serological and clinical findings to aid in the diagnosis of systemic lupus erythematosus (SLE). All results generated with NOVA View device must be confirmed by a trained operator.

The NOVA Lite DAPI dsDNA Crithidia luciliae Kit is an indirect immunofluorescence assay for the qualitative detection and semi-quantitative determination of Anti-dsDNA Antibodies (IgG) in human serum. Samples are diluted 1:10 in PBS and incubated with the antigen substrate (dsDNA on glass microscope slides). After incubation, unbound antibodies are washed off. The substrate is then incubated with antihuman IgG-FITC conjugate. The conjugate contains a DNA-binding blue fluorescent dye, 4',6-diamidino-2phenylindole (DAPI) that is required for NOVA View use. The blue dye is not visible by traditional fluorescence microscope at the wavelength where FITC fluorescence is viewed. Unbound reagent is washed off. Stained slides are read by manual fluorescence microscope or scanned with the NOVA View Automated Fluorescence Microscope. The resulting digital images are reviewed and interpreted from the computer monitor. dsDNA positive samples exhibit an apple green fluorescence corresponding to areas of the substrate where autoantibody has bound.

Here's a breakdown of the acceptance criteria and study details for the NOVA Lite DAPI dsDNA Crithidia luciliae Kit, based on the provided text:

Acceptance Criteria and Reported Device Performance

Study Details:

1. Sample sizes used for the test set and the data provenance:

   • Precision Study: 6 samples (2 negative, 2 borderline, 2 positive), each processed in triplicate across 14 runs (2 runs/day for 7 days), resulting in 42 data points per sample.
   • Reproducibility Studies (Between sites/instruments): 10 samples (3 negative, 7 positive), each tested in triplicate, twice a day for 5 days at each of 3 sites. This results in 30 data points per sample per site, or 90 data points per sample across all sites. Total data points for this study: 10 samples * 30 data points/sample * 3 sites = 900 data points.
   • Reproducibility (Between lots): 20 clinically and/or analytically characterized samples, tested in duplicate.
   • Linearity Study: 3 positive samples (high, medium, low), serially diluted from 1:10 up to 1:5120. (Number of replicates not specified for this part, but results are given for each dilution).
   • Interference Study: 3 specimens (one negative, one positive, one strong positive) for each interferent, with interfering substances spiked at three different concentrations in 10% of total specimen volume. Samples assessed in triplicates.
   • Sample Stability and Handling: 3 samples (negative, cut-off, positive), tested in duplicates for various conditions (up to 21 days at 2-8°C, up to 48 hours at room temperature, up to 3 freeze/thaw cycles).
   • Reagent Stability (Shelf-life): 3 lots of the kit, tested over 4 weeks accelerated stability (each week = 6 months real time). Real-time stability data was available up to 24, 15, and 19 months for the respective lots at the time of submission.
   • Reagent Stability (In-use/Open Vial): Not detailed how many units/tests were performed each week for 8 weeks.
   • Clinical Performance (Initial Study): 766 clinically characterized serum samples (391 SLE, 375 other diseases). No explicit country of origin is stated, but given this is an FDA submission for Inova Diagnostics, Inc. in San Diego, California, it is reasonable to infer a US-centric data provenance. The study appears to be retrospective based on "clinically characterized serum samples."
   • Clinical Performance (3 Sites Study): 269 clinically characterized samples tested at three sites. Total for reporting: 100 positive (SLE) and 169 negative (non-SLE) per site. The samples comprise 300 SLE and 507 non-SLE clinical diagnoses in total across the three sites. The data provenance is likely multi-center, potentially within the US. The description "clinically characterized samples" suggests these were collected and diagnosed prior to the study, implying a retrospective nature.
   • Expected Values: 120 samples from apparently healthy subjects (60 females, mean age 41, range 18-73).
   • Comparison with Predicate Device: The same 744 serum samples used in the initial clinical study (391 SLE, 353 other diseases).
   • SWT Validation: 31 positive samples for initial validation. 7 positive samples in the between-sites reproducibility study.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • For clinical studies: The ground truth for the clinical studies is stated as "clinically characterized serum samples" and "clinical diagnosis." This implies that the samples were obtained from patients with established diagnoses, likely made by medical professionals (e.g., rheumatologists for SLE patients). The text does not specify the number of experts or their exact qualifications (e.g., "Radiologist with 10 years of experience" is not mentioned, as this is an immunoassay, but rather "clinicians" or "diagnosticians").
   • For analytical studies (Precision, Reproducibility, Linearity, Interference, Stability): The ground truth (Expected Result/Expected Grade) for the control samples or known samples was established by the manufacturer, often based on previous characterization or established laboratory practices. The interpretation of "Manual Reading" and "Digital Reading" results are performed by "trained operators."

3. Adjudication method for the test set:

   • For analytical results (Precision, Reproducibility, Linearity, Interference, Stability): The text mentions that "Digital images were interpreted and confirmed" in multiple sections (e.g., Linearity, Interference, Sample Stability). For the "Reproducibility Studies (Between sites/instruments)", manual and digital reading was performed by "two operators at each site, to assess between operator reproducibility." The acceptance criteria then focus on agreement percentages between operators. This implies that if disagreements occurred, they were likely adjudicated to reach the "Summary" percentages. However, a specific formal adjudication method like "2+1" or "3+1" is not explicitly stated.
   • For clinical results: The clinical samples were "clinically characterized," meaning their diagnosis served as the ground truth. There's no indication of an adjudication process for these clinical diagnoses within the context of this device study.

4. 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 a traditional MRMC comparative effectiveness study involving AI assistance improving human readers. The study compares three modes of interpretation:
     • Manual Reading: Human interpretation using a traditional fluorescence microscope.
     • Digital Reading: Human interpretation of NOVA View generated images on a computer monitor.
     • NOVA View (Software): Automated interpretation by the device's software (algorithm only), which is then confirmed by a trained operator.
   • Therefore, the setup is more of a comparison between manual microscopy, human interpretation of digital images, and the device's automated output. The device itself (NOVA View) is not presented as an AI-assistance tool for human readers but as an alternative interpretation method that still requires human confirmation.
   • The "effect size of how much human readers improve with AI vs without AI assistance" is not directly measured in this context because the "NOVA View" results are the algorithm's output, not a human reader assisted by the algorithm. The "Digital Reading" is human interpretation of the images produced by the NOVA View device, which might be considered an "assisted" or "different modality" reading but not in the typical AI-driven improvement sense.

   Let's look at sensitivity/specificity to show the comparison between manual, digital (human on digital images), and NOVA View (algorithm):

   Initial Clinical Study (N=766)

   • Sensitivity (on SLE):
     • Manual: 48.1% (43.2-53.0)
     • Digital: 48.1% (43.2-53.0)
     • NOVA View: 57.0% (52.1-61.8)
   • Specificity:
     • Manual: 91.2% (87.9-93.7)
     • Digital: 92.3% (89.1-94.6)
     • NOVA View: 88.8% (85.2-91.6)

   Clinical Studies 3 Sites (N=807)

   • Sensitivity (on SLE):
     • Manual Reading: 32.7% (27.6-38.2)
     • Digital Reading: 34.0% (28.9-39.5)
     • NOVA View: 40.0% (34.6-45.6)
   • Specificity:
     • Manual Reading: 95.5% (93.3-97.0)
     • Digital Reading: 95.5% (93.3-97.0)
     • NOVA View: 85.4% (82.1-88.2)

   In both clinical studies, the NOVA View algorithm demonstrates higher sensitivity for SLE detection compared to manual or digital human readings, but lower specificity. This highlights a performance difference, not an improvement of human readers with AI assistance.

5. If a standalone (i.e. algorithm only without human-in-the loop performance) was done:

   • Yes, the "NOVA View" performance reported in the tables (e.g., sensitivity, specificity, qualitative agreements in reproducibility studies) represents the standalone algorithm's performance.
   • The text explicitly states: "All results generated with NOVA View device must be confirmed by a trained operator." This indicates that while the software generates automated classifications, the final clinical interpretation includes a human-in-the-loop for confirmation. The reported performance metrics for "NOVA View" specifically reflect the device's automated output.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

   • Clinical Ground Truth: "Clinical diagnosis" for patient-derived samples (e.g., Systemic Lupus Erythematosus (SLE), Drug Induced Lupus, Infectious Disease, etc.). This is likely based on a combination of clinical findings and serological tests by clinicians. It is stated as "clinically characterized serum samples."
   • Analytical Ground Truth: For the precision, reproducibility, linearity, interference, and stability studies, the "Expected Result" or "Expected Grade" for the tested samples serves as the ground truth. These are typically reference materials or well-characterized samples with known positive/negative status or reactivity grades established by the manufacturer.

7. The sample size for the training set:

   • The document does not explicitly state the sample size of a training set for the NOVA View algorithm. It describes validation studies (test sets) for the kit and the performance of the NOVA View device, but not how the algorithm itself was developed or trained.
   • What is mentioned is that for the SWT (Single Well Titer) feature, "The SWT function was established using 22 dsDNA positive samples that represent various levels of antibodies." However, this refers to establishing the intensity curves for titer determination, not necessarily a broad 'training set' for the overall positive/negative classification logic or image analysis.

8. How the ground truth for the training set was established:

   • As the training set size is not stated, neither is the method for establishing its ground truth.
   • For the 22 dsDNA positive samples used to establish SWT intensity curves, it is implied that manual and digital readings (human interpretations) served as comparison points for establishing the LIU (Light Intensity Units) to titer relationship. The validation of SWT compares its output to manual and digital end-point titers.

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EliA SymphonyS is intended for the in vitro, qualitative measurement of antibodies in human serum and plasma (Li-heparin, EDTA). EliA SymphonyS is based on human recombinant U1RNP (RNP 70, A, C), SS-A/Ro (60 kDa, 52 kDa), SSB/La, Centromere B, Scl-70, Jo-1 proteins and a synthetic SmD3 peptide as antigen and is useful as an aid in the clinical diagnosis of patients with systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), Sjögren's syndrome, scleroderna and polymyositis, in conjunction with other laboratory and clinical findings. EliA SymphonyS uses the EliA IgG method on the instrument Phadia 250.

EliA SymphonyS is intended for the in vitro, qualitative measurement of antibodies in human serum and plasma (Li-heparin, EDTA). EliA SymphonyS is based on human recombinant U1RNP (RNP 70, A, C), SS-A/Ro (60 kDa, 52 kDa), SSB/La, Centromere B, Scl-70, Jo-1 proteins and a synthetic SmD3 peptide as antigen and is useful as an aid in the clinical diagnosis of patients with systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), Sjögren's syndrome, scleroderma and polymyositis, in conjunction with other laboratory and clinical findings. EliA SymphonyS uses the EliA IgG method on the instrument Phadia 2500/5000.

The method specific reagents on Phadia® 250 and Phadia® 2500/5000 are identical; they are only filled in different containers. Each device consists of:

• EliA Symphony® Wells are coated with human recombinant U1RNP (RNP70, A. -C). SS-A/Ro (60 kDa. 52 kDa). SS-B/La. Centromere B. Scl-70. Jo-1 proteins and synthetic SmD3 peptide - 4 carriers (16 wells each), ready to use;
• EliA Sample Diluent: PBS containing BSA, detergent and 0.095% sodium azide --6 bottles, 48 mL each, ready to use; or 6 bottles, 400 mL each, ready to use;
• EliA IgG Conjugate 50 or 200: ß-Galactosidase labeled anti-IgG (mouse monoclonal antibodies) in PBS containing BSA and 0.06% sodium azide -6 wedge shaped bottles, 5 mL each, ready to use; or 6 wedge shaped bottles, 19 mL each, ready to use
• EliA ANA Positive Control 250 or 2500/5000: Human serum containing lgG antibodies to dsDNA, RNP, Sm, Ro. La. Scl-70. CENP and Jo-1 in PBS containing BSA, detergent and 0.095% sodium azide - 6 single use vials, 0.3 mL each, ready to use;
• -EliA Negative Control 250 or 2500/5000: Human sera from healthy donors in PBS containing BSA, detergent and 0.095% sodium azide - 6 single-use vials, 0.3 mL each, ready to use;
• EliA IgG Calibrator Strips: Human IgG (0, 4, 10, 20, 100, 600 µg/L) in PBS containing BSA, detergent and 0.095% sodium azide - 5 strips, 6 single-use vials per strip, 0.3 mL each, ready to use;
• -EliA IgG Curve Control Strips: Human IgG (20 µg/L) in PBS containing BSA, detergent and 0.095% sodium azide - 5 strips, 6 single-use vials per strip, 0.3 mL each, ready to use;
• EliA IgG Calibrator Well: Coated with mouse monoclonal antibodies 4 carriers (12 wells each), ready to use.

The Phadia EliA Immunodiagnostic System is an automated system for immunodiagnostic testing. The EliA reagents are available as modular packages, each purchased separately. Apart from the EliA ANA Positive Control 250 or 2500/5000 and the EliA IqG/IqM/IgA Neqative Control 250 or 2500/5000, all packages listed above are required to carry out an EliA SymphonyS Test.

Here's a breakdown of the acceptance criteria and study information for the EliA SymphonyS Immunoassay, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

Study Details:

2. Sample Size and Data Provenance (Test Set)

• Precision Study (Phadia 250): 5 samples, 252 replicates per sample (totaling 1260 determinations). Data provenance not explicitly stated, but clinical samples are generally used for such studies.
• Precision Study (Phadia 2500/5000): 7 samples, 84 replicates per sample (totaling 588 determinations). Data provenance not explicitly stated.
• Interference Study: 3 serum samples (negative, cut-off, high positive), analyzed in triplicates, repeated twice. Spiked with specific interfering substances. Data provenance not explicitly stated.
• Cut-off Study: 70 apparently healthy blood donor samples from Caucasian individuals (equally distributed by sex and age). 30 ANA positive samples with known reactivities. Data provenance not explicitly stated.
• Method Comparison Study: 633 serum samples from patients with various diagnoses (Mixed Connective Tissue Disease, Poly-/Dermatomyositis, Systemic Sclerosis, SLE, Sjögren's Syndrome, Bacterial Infection, HIV Infection, HCV Infection, HBV Infection, Rheumatoid Arthritis, Cancer). Data provenance not explicitly stated (likely retrospective clinical samples from diverse sources).
• Matrix Comparison Study: 62 patients, serum, lithium heparin plasma, and EDTA plasma collected from the same patients. Data provenance not explicitly stated.
• Instrument Comparison Study: 110 samples (81 positive, 10 equivocal, 19 negative). Data provenance not explicitly stated.
• Clinical Sensitivity and Specificity Study: 444 clinically defined samples with a diagnosis from patients with various autoimmune diseases and control conditions (Mixed Connective Tissue Disease, Poly-/Dermatomyositis, Systemic Sclerosis, SLE, SLE/Lupus nephritis, Sjögren's Syndrome, Bacterial Infection, Viral Infection, Rheumatoid Arthritis, Celiac Disease, Crohn's Disease, Ulcerative Colitis, Graves' Disease, Hashimoto's Disease, primary Antiphospholipid Syndrome, PBC, Autoimmune hepatitis, Granulomatosis with Polyangiitis). Data provenance not explicitly stated (likely retrospective clinical samples from diverse sources).
• Expected Values/Reference Range Study: 558 apparently healthy subjects (Caucasian, African American, Hispanic and Asian population) obtained from a blood bank. This suggests diverse geographic and demographic provenance for the "normal" population.

Most of the studies likely used retrospective clinical samples, given the disease-specific grouping. No specific country of origin is mentioned for individual studies, but the applicant is Phadia AB from Sweden, and the 510(k) contact is in the USA, implying potential multi-site studies or data collection.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not explicitly state the number or qualifications of experts used to establish ground truth for the test set.

• For the "clinically defined samples" in the clinical sensitivity/specificity study, the "diagnosis from patients" would be considered the ground truth, presumably established by treating physicians based on clinical findings and other laboratory tests, but not by a specific panel of experts for the purpose of this device's validation.
• Reference sera (CDC and AMLI) have "target" values, which are established by their respective institutions (Centers for Disease Control and Prevention, and Association of Medical Laboratory Immunologists) and represent a consensus or assigned value, but not necessarily a specific "number of experts" for this study.

4. Adjudication Method for the Test Set

The document does not mention any explicit adjudication method (e.g., 2+1, 3+1) for establishing the ground truth for the test set. Clinical diagnoses are typically made by single treating physicians, and reference materials have predefined target values.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This device is an in vitro diagnostic immunoassay, which does not involve human readers interpreting results in the same way an imaging AI might. Its performance is measured directly through analytical and clinical studies against predicate devices or known clinical statuses.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance)

Yes, the device performance described is standalone (algorithm only). The EliA SymphonyS Immunoassay is an automated system that measures antibody levels and provides a qualitative result (negative, equivocal, positive) based on predefined cut-offs, without direct human-in-the-loop interpretation during the measurement process. The "aid in clinical diagnosis" part implies that clinicians interpret the results in conjunction with other findings, but the device itself operates in a standalone manner.

7. Type of Ground Truth Used

The types of ground truth used include:

• Clinical Diagnoses: For the clinical sensitivity/specificity study, the "diagnosis from patients with" various diseases (e.g., SLE, MCTD, Sjögren's syndrome) served as the ground truth. This is based on established clinical criteria for each disease.
• Reference Material Targets: For the evaluation of CDC and AMLI sera, the "Target" reactivity/results defined by these external institutions were used as ground truth.
• Expected Behavior: For precision, interference, carry-over, and cut-off studies, the ground truth is often the expected behavior of the assay (e.g., negative sample should be negative, spiked sample should show no interference, etc.) or statistically derived values from healthy populations.
• Predicate Device Results: For the method comparison study, the results from the legally marketed predicate device (EliA Symphony) served as a comparative ground truth to demonstrate substantial equivalence.

8. Sample Size for the Training Set

The document does not explicitly describe a "training set" in the context of machine learning. This is an immunoassay, which typically relies on established biochemical reactions, calibration curves, and empirically determined cut-offs rather than a machine learning model that requires a discrete training phase with labeled data. The calibration curve is established using calibrator strips (human IgG at known concentrations).

9. How the Ground Truth for the Training Set Was Established

As noted above, there isn't a "training set" in the machine learning sense for this immunoassay.

• The calibration curve is established using EliA IgG Calibrator Strips, which contain human IgG at known concentrations (0, 4, 10, 20, 100, 600 µg/L). The "ground truth" for these calibrators is their precisely defined IgG concentrations, which are traceable to the International Reference Preparation (IRP) 67/86 of Human Serum Immunoglobulins A, G and M from WHO.
• The cut-off values (0.7 Ratio and 1.0 Ratio) were established by evaluating 70 apparently healthy blood donor samples and taking into account the 95th percentile, along with testing 30 ANA positive samples with known reactivities. This is a form of empirical ground truth setting based on biological distribution and known positive/negative samples.

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