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The Aptiva APS IgG Reagent is an immunoassay utilizing particle-based multi-analyte technology for the semiquantitative determination of anti-cardiolipin (aCL) and anti-beta 2 glycoprotein 1 (all2GPI) IgG autoantibodies in human serum as an aid in the diagnosis of primary antiphospholipid syndrome (APS), when used in conjunction with other laboratory findings.

The Aptiva APS IgG Reagent is intended for use with the Aptiva System.

The Aptiva APS IgM Reagent is an immunoassay utilizing particle-based multi-analyte technology for the semiquantitative determination of anti-cardiolipin (aCL) and anti-beta 2 glycoprotein 1 (aß2GPI) IgM autoantibodies in human serum as an aid in the diagnosis of primary and secondary antiphospholipid syndrome (APS), when used in conjunction with other laboratory findings.

The Aptiva APS IgM Reagent is intended for use with the Aptiva System.

The Aptiva APS IgG and Aptiva APS IgM reagent utilize particle based multi-analyte technology (PMAT) in a cartridge format. Each analyte (anti-cardiolipin [aCL] and anti-B2-Glycoprotein I [aB2GPI]) in the Aptiva APS IgG and Aptiva APS IgM reagent is a solid phase immunoassay utilizing fluorescent microparticles. This technology allows each of the two analytes, along with a human IgG or human IgM capture antibody (IgG or IgM Control Microparticle), to be coated onto three uniquely recognizable paramagnetic microparticles, which are combined into one tube.

The Aptiva 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 two analyte microparticles, along with the control microparticle, are stored in the reagent cartridge under conditions that proteins 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 instrument, where the microparticles are automatically rehydrated using a buffer located within the cartridge.

The Aptiva System dilutes the sample 1:8, then combines an aliquot of diluted sample, and reagent into a cuyette. The mixture is incubated at 37°C. After a wash cvcle, conjugated antihuman IgG or IdM antibodies are added to the particles and this mixture is incubated at 37°C. Excess conjugate is removed in another wash cycle, and the particles are re-suspended in system fluid.

Multiple images are generated by the system to identify and count the two (2) unique analyte particles, as well as determine the amount of coniugate on each particle. Coated with goat anti-human lgG or IdM antibodies, is present as a control to flaq low concentrations of IgG or IgM in the sample as an assay verification step. The median fluorescent intensity (MFI) for each analyte is proportional to the concentration of conjugate bound to human IgG or IgM, which is proportional to the concentration of IgG or IgM antibodies bound to the corresponding particle population. The system uses the MFI from at least 50 particles of each population. The identity of the particles is determined by the unique signature of the particles.

Each analyte in the Aptiva APS IgG Reagent and the Aptiva APS IgM Reagent is assigned a predefined lot specific master curve. The analyte specific master curve is stored on the reagent cartridge RFID label. Based on results obtained by running calibrators (supplied separately), the system creates individual working curves. Working curves are used by the software to calculate Fluorescent Light Units (FLU) for each analyte from the MFI values obtained for each sample.

Aptiva APS IgG and Aptiva APS IgM Calibrators and Aptiva APS IgG and Aptiva APS IgM Controls are sold separately.

The provided text describes the analytical and clinical performance characteristics of the Aptiva APS IgG and Aptiva APS IgM Reagents, which are immunoassays for the semi-quantitative determination of anti-cardiolipin (aCL) and anti-beta 2 glycoprotein 1 (aβ2GPI) IgG/IgM autoantibodies. This information is presented in the context of a 510(k) premarket notification for FDA clearance.

Here's a breakdown of the requested information based on the provided text:

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

The document does not explicitly state "acceptance criteria" as a separate, quantified set of thresholds for each performance metric. Instead, it presents the results of various analytical and clinical studies, implying that these results met the internal criteria for substantial equivalence to predicate devices and overall performance claims for an in vitro diagnostic (IVD) device.

However, we can infer performance targets based on the presented data and the overall context of an FDA submission for an IVD. The primary performance metrics presented are related to precision, detection limits, linearity, interference, and clinical sensitivity/specificity.

Inferred Acceptance Criteria and Reported Device Performance (Summary)

• aCL IgG: 5.6% - 9.5% (generally decreasing with higher FLU)
• aβ2GPI IgG: 6.9% - 11.7% (generally decreasing with higher FLU)
• aCL IgM: 4.3% - 9.7% (generally decreasing with higher FLU)
• aβ2GPI IgM: 5.5% - 10.2% (generally decreasing with higher FLU)

Between-Site Reproducibility CV% (3 sites):

• aCL IgG: 5.2% - 9.3%
• aβ2GPI IgG: 6.4% - 10.0%
• aCL IgM: 5.4% - 10.0%
• aβ2GPI IgM: 5.9% - 10.5%

Between-Lot Reproducibility CV% (3 lots):

• aCL IgG: 6.6% - 13.3%
• aβ2GPI IgG: 8.5% - 12.1%
• aCL IgM: 6.1% - 11.4%
• aβ2GPI IgM: 6.0% - 10.5% |
  | Limit of Blank (LoB) | Very low, close to zero, ensuring no signal from blank samples. | aCL IgG: 0.00 FLU
  aβ2GPI IgG: 0.02 FLU
  aCL IgM: 0.01 FLU
  aβ2GPI IgM: 0.03 FLU |
  | Limit of Detection (LoD)| Low, indicating ability to detect small amounts of analyte. | aCL IgG: 0.07 FLU
  aβ2GPI IgG: 0.09 FLU
  aCL IgM: 0.04 FLU
  aβ2GPI IgM: 0.06 FLU |
  | Limit of Quantitation (LoQ)| Low, defining the lowest concentration that can be reliably quantified. | aCL IgG: 0.29 FLU
  aβ2GPI IgG: 0.21 FLU
  aCL IgM: 0.06 FLU (set to 0.10 FLU for AMR lower limit)
  aβ2GPI IgM: 0.09 FLU (set to 0.10 FLU for AMR lower limit) |
  | Analytical Measuring Range (AMR)| Wide enough to cover relevant clinical concentrations, with demonstrated linearity. | aCL IgG: 0.29 - 328.94 FLU
  aβ2GPI IgG: 0.21 - 256.70 FLU
  aCL IgM: 0.10 – 114.68 FLU
  aβ2GPI IgM: 0.10 – 95.86 FLU

Linearity demonstrated across these ranges with R2 values mostly ≥ 0.98. |
| High Concentration Hook Effect| No hook effect within or above the AMR. | Confirmed no hook effect up to theoretically calculated values: aCL IgG: 2645.36 FLU, aβ2GPI IgG: 1790.48 FLU, aCL IgM: 167.25 FLU, aβ2GPI IgM: 126.13 FLU. |
| Interference | No significant interference from common endogenous or exogenous substances at specified concentrations. | No interference detected for aCL IgG, aβ2GPI IgG, aCL IgM, and aβ2GPI IgM with tested interferents (bilirubin, hemoglobin, triglycerides, cholesterol, RF IgM, human IgG, ibuprofen, warfarin, prednisone, acetaminophen, aspirin, hydroxychloroquine, omeprazole, simvastatin, heparin) at their respective tested concentrations. Percent recoveries or FLU differences were within acceptable ranges (generally close to 100% recovery for spiked samples, or low FLU difference for negative samples). |
| Sample Stability | Samples should be stable for specific storage conditions and freeze/thaw cycles. | Samples stable up to 48 hours at room temperature, up to 14 days at 2-8°C, and for up to 5 freeze/thaw cycles. |
| Reagent Stability | Reagent shelf-life and in-use stability should be established. | Shelf-life: 9 months for Aptiva APS IgG Reagent, 7 months for Aptiva APS IgM Reagent (based on accelerated stability, verified by ongoing real-time studies).
In-use (onboard) stability: 28 days for both, with 14-day recalibration. |
| Clinical Sensitivity & Specificity| High sensitivity to detect disease (APS) and high specificity to correctly identify non-disease states (controls/non-APS). | Aptiva APS IgG:

• aCL IgG: Sensitivity 54.1% (95% CI: 45.3–62.7%), Specificity 99.5% (95% CI: 98.2–99.9%)
• aβ2GPI IgG: Sensitivity 53.3% (95% CI: 44.5-61.9%), Specificity 99.0% (95% CI: 97.5-99.6%)

Aptiva APS IgM:

• aCL IgM: Sensitivity 27.5% (95% CI: 22.7–32.9%), Specificity 97.5% (95% CI: 95.4–98.6%)
• aβ2GPI IgM: Sensitivity 24.7% (95% CI: 20.1–30.0%), Specificity 98.5% (95% CI: 96.8–99.3%) |
  | Predicate Method Comparison (Percent Agreement)| High agreement with legally marketed predicate devices. | Aptiva APS IgG (aCL IgG) vs. QUANTA Flash aCL IgG: PPA: 81.6%, NPA: 95.7%, TPA: 93.1% (N=202)
  Aptiva APS IgG (aβ2GPI IgG) vs. QUANTA Lite Beta 2GP1 IgG ELISA: PPA: 88.0%, NPA: 89.7%, TPA: 88.9% (N=108)
  Aptiva APS IgM (aCL IgM) vs. QUANTA Flash aCL IgM: PPA: 87.0%, NPA: 90.2%, TPA: 89.8% (N=422)
  Aptiva APS IgM (aβ2GPI IgM) vs. QUANTA Flash β2GPI IgM: PPA: 88.9%, NPA: 84.3%, TPA: 84.8% (N=244) |

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Clinical Performance Test Set Sample Sizes:

  • Aptiva APS IgG (aCL IgG & aβ2GPI IgG): N=526 (122 APS combined, 404 controls/non-APS)
  • Aptiva APS IgM (aCL IgM & aβ2GPI IgM): N=689 (291 APS combined, 398 controls/non-APS)
  • Normal Population for Expected Values: N=200 apparently healthy blood donors.

• Method Comparison Test Set Sample Sizes:

  • Aptiva APS IgG (aCL IgG vs. QUANTA Flash aCL IgG): N=202
  • Aptiva APS IgG (aβ2GPI IgG vs. QUANTA Lite Beta 2GP1 IgG ELISA): N=108
  • Aptiva APS IgM (aCL IgM vs. QUANTA Flash aCL IgM): N=422
  • Aptiva APS IgM (aβ2GPI IgM vs. QUANTA Flash β2GPI IgM): N=244

• Analytical Performance Test Set Sample Sizes:

  • Precision: 7 samples for IgG, 7 samples for IgM (80 replicates each for within-lab; 75 replicates each for between-site/lot reproducibility from multiple sites/lots).
  • LoB/LoD/LoQ: Blanks (LoB: 4 samples, 60 data points/lot); Low-level samples (LoD/LoQ: 4 samples, 120 data points/assay/lot).
  • Interference: 6 human specimens (negative, cutoff, positive) for each analyte, spiked with various interferents and tested in 5 replicates.
  • Sample Stability: 5 serum samples (IgG), 5 serum samples (IgM) tested in duplicates over time/cycles.
  • In-use Stability: 11 samples (IgG), 7 samples (IgM) tested periodically.

• Data Provenance: The document states that a "cohort of characterized samples, none of which were used for establishing the reference range, was used to validate the clinical performance." It does not explicitly state the country of origin of the data or whether the studies were retrospective or prospective. However, for a 510(k) submission, clinical validation studies typically involve retrospective or prospectively collected clinical samples, but the exact nature (e.g., specific clinical sites, patient populations beyond disease groups) and geographic origin are not detailed here. The studies were likely conducted within a controlled laboratory setting by the manufacturer (Inova Diagnostics, Inc. in San Diego, CA) or its affiliates, using sourced human serum samples.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

The establishment of "ground truth" for IVD devices like these typically relies on well-characterized clinical samples and established diagnostic criteria for the disease (Antiphospholipid Syndrome - APS).

• The document states that the clinical performance validation was performed using "a cohort of characterized samples." The characterization of these samples (i.e., whether they definitively represent APS or control) would serve as the ground truth.
• However, the document does not specify the number of experts or their qualifications (e.g., rheumatologists, clinical immunologists/pathologists) who established the diagnostic status (ground truth) of the clinical samples (APS vs. control) used in the clinical sensitivity and specificity studies. It is implied that these were "characterized samples," meaning their disease status was determined by established clinical and laboratory criteria, likely involving clinical consensus or previous diagnoses.
• For cut-off establishment, the reference population included "apparently healthy subjects," and the "internal APS samples (data not provided)" and "distribution of result values of healthy controls" were used. This suggests clinical characterization of these samples.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

The concept of "adjudication method" (like 2+1 or 3+1) is typically relevant for interpretative tasks, such as reading medical images, where multiple human readers interpret the same data and their interpretations need to be reconciled to establish a ground truth.

For these types of IVD assays, ground truth for clinical performance is established based on the clinical diagnosis of the patient from whom the sample was collected. This diagnosis is usually a culmination of clinical findings, established criteria (e.g., the revised Sapporo criteria for APS), and other laboratory tests, rather than an "adjudication" of multiple independent interpretations of the test results themselves.

Therefore, the document does not mention any adjudication method in the context of establishing ground truth for the test samples, as it's not applicable in the same way it would be for an AI-medical imaging device. The "ground truth" for the samples (APS vs. non-APS) is assumed to be pre-established clinical diagnosis.

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

No MRMC study was conducted or is applicable here.

This device is an in vitro diagnostic (IVD) immunoassay, not an AI-powered image analysis or diagnostic aid that assists human readers (e.g., radiologists interpreting images). The device directly measures biomarker levels in a sample, and its output is a quantitative value (FLU) which then determines a semi-quantitative result (Positive/Negative/Indeterminate based on cut-offs). Human "readers" (laboratory personnel) operate the instrument and interpret the final quantitative results based on predefined cut-offs, but they are not subjectively interpreting complex data that AI would assist with, in the sense of an MRMC study.

Therefore, an MRMC comparative effectiveness study, and an effect size related to human reader improvement with AI assistance, are not relevant for this type of device and are not mentioned in the document.

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

This is a "standalone" device in terms of its core functionality, but the term "algorithm only" or "human-in-the-loop" isn't directly analogous.

• The Aptiva System is a fully automated, random-access analyzer (page 6). This means the instrument itself, with its integrated software and optical module, processes the samples, runs the reagents, and reports results independently after the sample is loaded and the assay initiated.
• The "performance" described here (sensitivity, specificity, precision, linearity, etc.) is the device's performance (including its internal algorithms and mechanics) in generating quantitative results. There isn't a separate "algorithm only" performance that needs to be differentiated from a "human-in-the-loop" performance, because the device is the automated system determining the FLU values. The human interaction is primarily in sample loading, reagent handling, and result review/reporting, not in interpreting raw data that the device itself would also interpret in an unassisted mode.

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

The ground truth for the clinical performance studies (sensitivity and specificity) was established based on "characterized samples" representing patients with Antiphospholipid Syndrome (APS) and various control groups (patients with other autoimmune/infectious diseases, apparently healthy subjects).

While the document doesn't explicitly state "expert consensus," it's highly implied that the "characterization" of these samples as APS or control would be based on:

• Clinical findings: Presenting symptoms, medical history.
• Other laboratory findings: Beyond the novel antibodies, other relevant diagnostic tests.
• Established diagnostic criteria: For APS, this would typically be the revised Sapporo classification criteria, which combine clinical and laboratory criteria.

So, it's a combination of established clinical diagnoses and potentially other laboratory data, which implicitly would involve the consensus or findings of medical experts involved in patient diagnosis. It is not based on pathology (e.g., tissue biopsy) or outcomes data (e.g., long-term disease progression as the sole ground truth).

8. The sample size for the training set

The document describes the submission of a "new device" and its performance characteristics. It does not explicitly mention or quantify a "training set" in the context of machine learning.

For IVD devices, a "training set" isn't a standard concept unless the device incorporates adaptive algorithms or AI that learns from data. In this case, the device is an immunoassay with predefined master curves and calibrated reagents. The master curves are generated "at Inova for each reagent lot, where in-house Master Curve Standards with assigned FLU values are run multiple times." These "in-house Master Curve Standards" could be considered analogous to a "training" or calibration process, but it's not a dataset for training a generalized AI model but rather for calibrating each reagent lot of a classical assay.

The sample sizes provided in the document are for:

• Analytical performance (precision, LoB/LoD/LoQ, linearity, interference, stability).
• Clinical validation (sensitivity/specificity studies).
• Method comparison studies.
• Reference range establishment.

None of these are explicitly labeled as a "training set."

9. How the ground truth for the training set was established

As there is no explicitly defined "training set" for a machine learning model, the concept of establishing ground truth for such a set is not applicable here.

However, if we consider the "Master Curve Standards" as analogous to calibration/training data for the assay, their "ground truth" (assigned FLU values) would be established through a rigorous internal process by the manufacturer (Inova Diagnostics) based on:

• Carefully prepared and characterized aliquots (standards) with known or assigned concentrations of the target antibodies.
• Repeat measurements and statistical analysis for consistent and accurate assignment of FLU values.
• This is a standard practice for calibrating quantitative IVD assays, ensuring the device outputs accurate and traceable results.

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EliA Cardiolipin IgA is intended for the in vitro semi-quantitative measurement of IgA antibodies directed to cardiolipin in human serum and plasma (heparin, EDTA, citrate) to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA Cardiolipin IgA uses the EliA IgA method on the instruments Phadia 100.

EliA Cardiolipin IgA is intended for the in vitro semi-quantitative measurement of IgA antibodies directed to cardiolipin in human serum and plasma (heparin, EDTA, citrate) to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA Cardiolipin IgA uses the EliA IgA method on the instruments Phadia 250.

The new device belongs to a fully integrated and automated system for immunodiagnostic testing. It comprises a Fluorescence-Immunoassay test system using EliA single wells as the solid phase and is intended to be performed on the instruments Phadia 100 and Phadia 250.

The conjugate for the EliA IgA method is mouse anti-human IgA beta-galactosidase, which uses 4-Methylumbelliferyl-BD-Galactoside as substrate.

The total IgA calibration is based on a set of six WHO-standardized IgA Calibrators derived from human serum. They are used to establish an initial calibration curve, which may be used for up to 28 days on additional assays and can be stored by the instrument. Each additional assay includes calibrator (curve) controls that have to recover in defined ranges to ensure that the stored calibration curve is still valid. The Fluorescence-Immunoassay test system includes test-, method-specific and general reagents that are packaged as separate units.

The provided text describes the regulatory submission for the EliA™ Cardiolipin IgA Immunoassay and associated control devices. However, it does not contain any information about acceptance criteria or specific study results that prove the device meets such criteria.

The document primarily focuses on:

• 510(k) Summary details: Manufacturer, contact, device names, common name, classification, and date.
• Intended Use Statements: Explicitly stating what the EliA Cardiolipin IgA device is designed to measure (IgA antibodies to cardiolipin) and its purpose (aiding in diagnosis of APS and thrombotic disorders related to SLE) on Phadia 100 and Phadia 250 instruments.
• Special Conditions for Use: Prescription use only.
• Special Instrument Requirements: Phadia 100/250 automated immunoassay analyzers.
• General Description and Test Principle: Explains the fluorescence-immunoassay system, antigen coating, and methodology.
• Device Comparison: States that the new device and predicate (Quanta Lite IgA ACA (HRP), K953366) are both non-competitive solid phase ELISAs used for similar diagnostic aids.
• Laboratory Equivalence: Mentions that comparability is supported by a comparison study, clinically defined sera, and samples from healthy subjects, concluding with a statement of substantial equivalence.
• FDA Correspondence: Official letter acknowledging receipt and approval of the 510(k) submission, confirming substantial equivalence and providing regulatory information.
• Indications for Use Forms: Repeated forms for the main device and its associated positive and negative controls, reiterating their intended uses.

Therefore, I cannot provide the requested table of acceptance criteria and device performance, nor details about sample sizes for test/training sets, expert qualifications, adjudication methods, MRMC studies, standalone performance, or ground truth establishment based on the provided text.

The document states that a "comparison study between new and predicate device" and "results obtained for clinically defined sera" were used to support laboratory equivalence, but it does not present the data, the specific acceptance criteria, or the methodology of these studies.

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The BioPlex®2200 Antiphospholipid Syndrome (APLS) IgM kit is a multiplex flow immunoassav intended for the semi-quantitative detection of IgM antibodies to Cardiolipin (CL) and Beta-2 Glycoprotein I (B2GPI) in human serum and plasma (lithium heparin, sodium heparin, and sodium citrate). In conjunction with clinical findings, the test system is used as an aid in the diagnosis of primary Antiphospholipid Syndrome (APS) and those secondary to systemic lupus erythematosus (SLE) or SLE-like disorders.

The BioPlex 2200 APLS IgM kit is intended for use with the Bio-Rad BioPlex 2200 System.

The BioPlex 2200 Antiphospholipid Syndrome (APLS) IgM Calibrator Set is intended for the calibration of the corresponding BioPlex 2200 APLS IgM Reagent Pack.

The BioPlex 2200 Antiphospholipid Syndrome (APLS) IgM Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 Instrument and the corresponding BioPlex 2200 APLS IgM Reagent Pack in the clinical laboratory. The performance of the BioPlex 2200 APLS IgM Control Set has not been established with any other Antiphospholipid assay.

BioPlex® 2200 APLS IgM kit includes the following components:

• o One (1) 10 mL vial of Bead Set containing two different populations of dyed beads coated with Cardiolipin (CL) and Beta-2-Glycoprotein I (B2GPI). an Internal Standard bead (ISB). a Serum Verification bead (SVB), and a Reagent Blank bead (RBB) in a MOPS (3-[N-Morpholino] propanesulfonic acid) buffer supplemented with glycerol and protein stabilizers (porcine), and ProClin 300 (

Here's a summary of the acceptance criteria and study information for the BioPlex® 2200 Antiphospholipid Syndrome (APLS) IgM kit, based on the provided text:

Acceptance Criteria and Device Performance

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QUANTA Flash aCL IgA: Fully automated chemiluminescent immunoassay for the semiquantitative measurement of anti-cardiolipin (aCL) In human citrated plasma and serum on the BIO-FLASH® instrument, as an aid in the diagnosis of thrombotic disorders related to primary and secondary antiphospholipid syndrome (APS), when used in conjunction with other laboratory and clinical findings.

The QUANTA Flash aCL IgA Controls are intended for quality control purposes of the QUANTA Flash aCL IgA assay performed on the BIO-FLASH® instrument.

Fully automated chemiluminescent immunoassay for the semi-quantitative measurement of anti-B2 glycoprotein-1 ((S2GP1) IgA antibodies in human citrated plasma and serum on the BIO-FLASH® instrument, as an aid in the diagnosis of thrombotic disorders related to primary and secondary antiphospholipid syndrome, when used in conjunction with other laboratory and clinical findings.

The QUANTA Flash $2GP1 IgA Controls are intended for the quality control purposes of the QUANTA Flash B2GP1 IgA assay performed on the BIO-FLASH® instrument.

Not Found

I am sorry, but the provided text does not contain information about acceptance criteria or specific studies proving device performance. The document is a 510(k) premarket notification letter from the FDA, confirming substantial equivalence for QUANTA Flash™ B2GP1 IgA and QUANTA Flash™ aCL IgA devices and their controls. It outlines regulatory information and indications for use but does not detail performance metrics, study designs, sample sizes, or ground truth establishment.

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Enzyme linked immunoassay (ELISA) for the qualitative or semi-quantitative detection of Cardiolipin IgA antibodies in human serum to aid in the diagnosis of antiphospholipid syndrome (APS) and APS associated with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings.
Enzyme linked immunoassay (ELISA) for the qualitative or semi-quantitative detection of Cardiolipin IgG antibodies in human serum to aid in the diagnosis of antiphospholipid syndrome (APS) and APS associated with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings.
Enzyme linked immunoassay (ELISA) for the qualitative or semi-quantitative detection of Cardiolipin IgM antibodies in human serum to aid in the diagnosis of antiphospholipid syndrome (APS) and APS associated with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings.
Enzyme linked immunoassay (ELISA) for the qualitative : detection of Cardiolipin IgA, IgG and IgM antibodies in human serum to aid in the diagnosis of anti-phospholipid syndrome (APS) and APS associated with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings.

Not Found

The document provided is a 510(k) clearance letter from the FDA for several ImmuLisa Enhanced™ Cardiolipin Antibody (ACA) ELISA tests, indicating they are substantially equivalent to legally marketed predicate devices. It does not contain details about acceptance criteria or specific study results related to the performance of these devices.

The typical content of a 510(k) clearance is an affirmation of substantial equivalence, not a detailed report of clinical study outcomes or device performance against pre-defined acceptance criteria. Therefore, most of the information requested in your prompt cannot be extracted from this document.

Here's what can be inferred or stated based on the document:

• Acceptance Criteria and Reported Device Performance: Not provided in the document. The FDA determined substantial equivalence, but the specific performance of the device or the criteria it met are not detailed here.
• Sample size used for the test set and the data provenance: Not provided.
• Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable or provided, as this document is a regulatory clearance, not a study report.
• Adjudication method for the test set: Not applicable or provided.
• If a multi-reader multi-case (MRMC) comparative effectiveness study was done: Not applicable or provided, as these are in vitro diagnostic (IVD) tests, not typically subject to MRMC studies in the same way as imaging algorithms.
• If a standalone (i.e., algorithm only without human-in-the-loop performance) was done: Not applicable. These are lab-based ELISA tests, not AI algorithms.
• The type of ground truth used: Not specified, as the document doesn't detail the studies. For IVDs, ground truth is typically established by reference methods, clinical diagnosis, or patient outcomes.
• The sample size for the training set: Not applicable or provided, as these are lab-based ELISA tests, not AI algorithms requiring a training set in the machine learning sense.
• How the ground truth for the training set was established: Not applicable or provided.

In summary, this document is a regulatory approval notice and does not contain the detailed scientific study information requested. To find such information, one would typically need to review the 510(k) submission itself (which is often extensive and not publicly available in its entirety) or peer-reviewed publications related to the device.

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The BioPlex® 2200 APLS IgG and IgA kits are multiplex flow immunoassays intended for the semi-quantitative detection of IgG and IgA antibodies to Cardiolipin (CL) and Beta-2 Glycoprotein I (ß2GPI) in human serum and plasma (lithium heparin, sodium heparin, and sodium citrate). In conjunction with other clinical findings, the test systems are used as an aid in the diagnosis of primary Antiphospholipid Syndrome (APS) and those secondary to systemic lupus erythematosus (SLE) or SLE-like disorders.
The BioPlex 2200 APLS IgG and IgA kits are intended for use with the Bio-Rad BioPlex 2200 System

The BioPlex® 2200 APLS IgG and IgA IgG kit uses multiplex flow immunoassay, a methodology that greatly resembles traditional EIA, but permits simultaneous detection and identification of many antibodies in a single tube. "APLS" is an acronym for Anti-Phospholipid Syndrome.
Two (2) different populations of dyed beads are coated with the antigens associated with Cardiolipin (CL) and Beta-2-Glycoprpotein I (ß2GPI), respectively. The BioPlex 2200 System combines an aliquot of patient sample, sample diluent, and bead reagent into a reaction vessel. The mixture is incubated at 37°C. After a wash cycle, anti-human IgG or IgA antibody, conjugated to phycoerythrin (PE) is added to the dyed beads and this mixture is incubated at 37℃. The excess conjugate is removed in another wash cycle, and the beads are re-suspended in wash buffer. The bead mixture then passes through the detector. The identity of the dyed beads is determined by the fluorescence of the dyes, and the amount of analyte captured is determined by the fluorescence of the attached PE. Raw data is calculated in relative fluorescence intensity (RFI).
Three additional dyed beads, an Internal Standard Bead (ISB), a Serum Verification Bead (SVB) and a Reagent Blank Bead (RBB) are present in each reaction mixture to normalize detector response, to verify the addition of serum to the reaction vessel and the absence of significant non-specific binding in serum or plasma. Refer to the BioPlex 2200 System Operation Manual for more information.
The instrument is calibrated using a set of seven (7) distinct calibrator vials for APLS IgG kit and a set of three (3) distinct calibrator vials for the APLS IgA kit, all supplied separately by Bio-Rad Laboratories. For each aCL IgG and aß2GPI IgG, four (4) vials representing four (4) different antibody concentrations are used for semi-quantitative calibration. For each aCL IgA and aß2GPI IgA assay, two (2) vials representing two (2) different antibody concentrations are used for semi-quantitative calibration. The cut-off value and assignment of the calibrators are determined by performing concordance testing and Receiver Operator Characteristic (ROC) analysis, using clinical diagnosis as the standard. The results for aCL IgG and aCL IgA are expressed in GPL-U/mL and APL-U/mL units, respectively. The results for aß2GPI IgG and aß2GPI IgA are each expressed in U/mL units.
The APLS IgG and APLS IgA Control Sets are intended for use as an assayed quality control to monitor the overall performance of the BioPlex® 2200 instrument and BioPlex 2200 APLS IgG and IgA reagent packs in the clinical laboratory.
Each of the APLS IgG and APLS IgA Control Sets includes a negative control and a positive control for each aCL IgG or IgA and aß2GPI IgG or IgA in a human serum matrix made from defibrinated plasma, containing antibodies present for analytes within the APLS IgG or IgA kit. The positive controls are manufactured to give positive results. with values above the cutoff for each specific bead. The negative control is manufactured to give negative results, with values below the cutoff for each specific bead. The negative control must have a negative result, and the positive control must have a positive result.

Here's an analysis of the provided text regarding the BioPlex® 2200 Anti-Phospholipid Syndrome (APLS) IgG and IgA kits, structured according to your requested points:

Acceptance Criteria and Study for BioPlex® 2200 APLS IgG and IgA Kits

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally established by the performance metrics shown to be acceptable for the predicate devices and the clinical utility of the test. The document emphasizes achieving clinical accuracy through concordance testing and Receiver Operator Characteristic (ROC) analysis to establish cutoffs, which then dictate sensitivity and specificity. The specific numerical acceptance criteria (e.g., minimum sensitivity/specificity percentages) are not explicitly stated as "acceptance criteria" but are demonstrated by the comparative performance results deemed sufficient for substantial equivalence.

Based on the "Clinical Sensitivity and Specificity" section, the reported device performance is as follows:

2. Sample Size for Test Set and Data Provenance

• Sample Size for Clinical Performance (Comparative Testing & Sensitivity/Specificity):

  • Total Specimens: 804 specimens
    • 300 apparently healthy blood donors
    • 302 patients previously diagnosed with primary or secondary APS
    • 202 patients with other rheumatic or non-APS diseases
  • For the Clinical Sensitivity and Specificity section (which excluded 17 samples due to instrument errors): 487 samples for IgG assays (286 Diagnosed APS + 201 Non-APS Control) and 504 samples for IgA assays (302 Diagnosed APS + 202 Non-APS Control).

• Sample Size for Analytical Performance (Precision/Reproducibility): 8 human samples (4 panels of serum/plasma containing aCL IgG & IgA, aß2GPI IgG & IgA) tested in quadruplicate over five days (20 replicates per panel member).

• **Sample Size for Linearity: ** 3 APLS-positive patient samples for each analyte tested.

• Sample Size for Limit of Detection (LoD): Low negative and blank samples in 50 replicates.

• Sample Size for Interfering Substances: Samples prepared by blending negative human serum with positive samples and interferent/blank. Specific count not given but refers to multiple concentrations tested.

• Sample Size for Cross-Reactivity: Varies by disease state, ranging from 3 (CREST) to 34 (Systemic Lupus Erythematosus) samples per disease state.

• **Sample Size for Expected Values/Reference Range: ** 300 samples from apparently healthy donors (132 males, 168 females).

• Data Provenance:

  • "Patient specimens were purchased from commercial suppliers or rheumatology clinic labs and were frozen serum."
  • A clinical trial site performed the reproducibility study.
  • Healthy donor samples were used for prevalence and reference range.
  • The document implies the data is from retrospective samples (patients previously diagnosed with APS, purchased samples, etc.). The country of origin is not explicitly stated.

3. Number of Experts and Qualifications for Ground Truth

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

• For the clinical sensitivity and specificity study, the ground truth for APS patients is based on a "diagnosed APS" status. For controls, it's either "non-APS disease control patients" or "apparently healthy blood donors." The method by which these diagnoses were confirmed or by how many experts is not detailed.
• For the assay cut-off determination, it mentions "using clinical diagnosis as the standard" and later "103 samples from patients diagnosed as primary and secondary APS and 208 from normal healthy and 123 from non-APS cardiac donors."
• There's no mention of a panel of experts reviewing the cases used for ground truth.

4. Adjudication Method for the Test Set

The document does not describe any specific adjudication method (such as 2+1, 3+1, or other consensus methods) for establishing the ground truth of the test set. The clinical diagnosis appears to be a pre-existing classification of the samples.

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

This device is an in vitro diagnostic (IVD) assay, not an AI-assisted diagnostic tool for human readers. Therefore, an MRMC comparative effectiveness study involving human readers with and without AI assistance is not applicable and was not performed. The comparative effectiveness study performed was against predicate IVD devices.

6. Standalone (Algorithm Only) Performance

Yes, a standalone performance study was done. The entire study described for the BioPlex® 2200 APLS IgG and IgA kits (analytical performance, comparative performance, clinical sensitivity and specificity, linearity, precision, LoD, etc.) represents the standalone performance of the algorithm/device system. There is no "human-in-the-loop" component described for the device's function or evaluation. The system automatically measures specific antibodies and reports semi-quantitative results.

7. Type of Ground Truth Used

The primary type of ground truth used is clinical diagnosis (e.g., "patients diagnosed with primary or secondary APS," "normal healthy donors," "non-APS disease control patients").

8. Sample Size for the Training Set

The document does not explicitly describe a separate "training set" in the context of machine learning or AI algorithm development because the device is a multiplex flow immunoassay providing semi-quantitative results, not a machine learning model that is "trained."

However, the "Calibrator assignment" section describes a process that functionally serves a role akin to parameter tuning or establishing operational reference points:

• "Calibrator assignment is established for matched lots of BioPlex 2200 APLS IgG or IgA kit and calibrators using a master set of calibrators as reference and replicate analyses on multiple BioPlex 2200 instruments."
• The "cut-off value and assignment of the calibrators are determined by performing concordance testing and Receiver Operator Characteristic (ROC) analysis, using clinical diagnosis as the standard." This ROC analysis would involve a dataset to determine optimal cutoffs, which could be considered part of an initial "training" or optimization phase. The size of this specific dataset is partially revealed: "one clinical cohort has 103 samples from patients diagnosed as primary and secondary APS and 208 from normal healthy and 123 from non-APS cardiac donors." (Total 434 samples for cutoff determination.)

9. How Ground Truth for the Training Set Was Established

As noted above, there isn't a traditional "training set" for an AI model. For the calibrator assignment and cutoff determination, the ground truth was established by clinical diagnosis. The cut-off value was established by "optimizing for clinical accuracy" using ROC analysis against existing clinical diagnoses of APS (primary and secondary) and control groups (normal healthy, non-APS cardiac donors).

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The ZEUS ELISA Cardiolipin IgG/IgM/IgA Test System is intended for the in vitro, qualitative measurement of IgG, IgM and/or IgA antibodies directed to cardiolipin in human serum to aid in the diagnosis of primary antiphospholipid syndrome (PAPS) and secondary antiphospholipid syndrome (SAPS) in conjunction with other laboratory and clinical findings.

Not Found

I am sorry, but the provided text does not contain the detailed information required to answer your request about the acceptance criteria and the study proving the device meets those criteria. The document is an FDA 510(k) clearance letter for the "ZEUS ELISA Cardiolipin IgG/IgM/IgA Test System," describing its intended use and regulatory classification. It does not include specific study details such as:

• A table of acceptance criteria and reported device performance.
• Sample sizes or data provenance for test sets.
• Number or qualifications of experts for ground truth establishment.
• Adjudication methods.
• Details on Multi-Reader Multi-Case (MRMC) studies or effect sizes.
• Standalone algorithm performance.
• Type of ground truth used.
• Sample size for the training set.
• How ground truth for the training set was established.

This information would typically be found in a more detailed submission document, such as the 510(k) summary or a clinical study report, which is not provided here.

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1. EliA Cardiolipin IgG is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to cardiolipin in human serum and plasma (Li-heparin, EDTA, citrate) to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to secondary antiphospholipid syndrome in conjunction with other laboratory and clinical findings. EliA Cardiolipin IgG uses the the EliA IgG method on the instruments Phadia 100 and Phadia 250.

2. EliA Cardiolipin IgM is intended for the in vitro semi-quantitative measurement of IgM antibodies directed to cardiolipin in human serum and plasma (Li-heparin, EDTA, citrate) to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to secondary antiphospholipid syndrome in conjunction with other laboratory and clinical findings. EliA Cardiolipin IgM uses the the EliA IgM method on the instruments Phadia 100 and Phadia 250.

3. EliA B2-Glycoprotein I IgG is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to B2-Glycoprotein I in human serum and plasma (Li-heparin, EDTA, citrate) to aid in the diagnosis of antiphospholipid syndrome (APS) a as well as thrombotic disorders related to secondary antiphospholipid syndrome in conjunction with other laboratory and clinical findings. EliA B2-Glycoprotein I IgG uses the the EliA IgG method on the instruments Phadia 100 and Phadia 250.

4. EliA B2-Glycoprotein I IgM is intended for the in vitto semi-quantitative measurement of IgM antibodies directed to ß2-Glycoprotein I in human serum and plasma (Li-heparin, EDTA, citrate) to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to secondary antiphospholipid syndrome in conjunction with other laboratory and clinical findings. EliA B2-Glycoprotein I IgM uses the the EliA IgM method on the instruments Phadia 100 and Phadia 250.

5. EliA APS Positive Control 100 is intended for laboratory use in monitoring the performance of in vitro measurement of antibodies to cardiolipin and B2-Glycoprotein I with Phadia 100 using the EliA IgG or IgM method.

6. EliA APS Positive Control 250 is intended for laboratory use in monitoring the performance of in vitro measurement of antibodies to cardiolipin and ß2-Glycoprotein I with Phadia 250 using the EliA IgG or IgM method.

The new devices belong to a fully integrated and automated system for immunodiagnostic testing. It comprises a Fluorescence-Immunoassay test system using EliA single wells as the solid phase and is intended to be performed on the instruments Phadia 100 and Phadia 250. The conjugate for the EliA IgG method is mouse anti-human IgG beta-galactosidase, which uses 4-Methylumbellifery I-BD-Galactoside as substrate. The conjugate for the EliA IgM method is mouse anti-human IgM beta-galactosidase, which uses 4-Methylumbelliferyl-ßD-Galactoside as substrate. The total IgG and IgM calibration is based on a set of six WHO-standardized IgG and IgM Calibrators, respectively, derived from human serum. They are used to establish an initial calibration curve, which may be used for up to 28 days on additional assays and can be stored by the instrument. Each additional assay includes calibrator (curve) controls that have to recover in defined ranges to ensure that the stored calibration curve is still valid. The Fluorescence-Immunoassay test. system includes test-, method-specific and general reagents that are packaged as separate units.

The provided text is a 510(k) summary for in-vitro diagnostic devices (EliA Immunoassays) and a separate 510(k) notification for a medical device (PANPAC HSG Catheter Set).

The request asks for information regarding acceptance criteria and a study proving a device meets these criteria. However, for the EliA Immunoassays, the document focuses on establishing substantial equivalence to predicate devices rather than defining specific acceptance criteria for performance and then proving the device meets them through a detailed study.

Therefore, the following information can be extracted for the EliA Immunoassays, but it's important to note the nature of the submission (510(k) for IVDs) means the "acceptance criteria" discussed are largely related to analytical performance demonstrating equivalence to predicates, not clinical efficacy or diagnostic accuracy against a definitive gold standard in the same way a new AI-powered diagnostic might be evaluated.

Here's an attempt to answer the questions based on the provided text for the EliA Immunoassays:

1. Table of acceptance criteria and the reported device performance

The document does not explicitly present a table of predetermined acceptance criteria with corresponding reported device performance values in the format usually seen for novel device approvals. Instead, it makes a general statement about laboratory equivalence based on comparison studies. The emphasis is on "substantial equivalence" to predicate devices.

The reported device performance, in this context, is that all available data support that the new devices are substantially equivalent to the predicate devices.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

The document states: "The comparability of predicate device and new device is supported by a data set including:

• results obtained within a comparison study between new and predicate device
• results obtained for clinically defined sera
• results obtained for samples from apparently healthy subjects (normal population)."

However, specific sample sizes for these comparison studies are not provided in this summary.
Data provenance (country of origin, retrospective/prospective) is also not specified.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This type of information is not applicable or provided for this 510(k) submission. For in-vitro diagnostic devices like these immunoassays, ground truth for "clinically defined sera" would typically come from a clinical diagnosis of antiphospholipid syndrome (APS) or related thrombotic disorders, which involves a constellation of clinical findings and laboratory tests, not solely expert interpretation of an image or single test. The document does not detail how the clinical status of the "clinically defined sera" was established or by whom.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

This is not applicable or provided for this type of in-vitro diagnostic test. Adjudication methods are typically relevant for studies involving human interpretation of data, such as images, where multiple readers might offer differing opinions.

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 is not applicable or provided. The device is an immunoassay for semi-quantitative measurement of antibodies, not an AI-powered diagnostic interpreted by human readers. Therefore, an MRMC study and
the concept of human readers improving with AI assistance are irrelevant in this context.

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

Yes, the device operates in a standalone manner as an "in vitro semi-quantitative measurement" system. The instruments (Phadia 100 and Phadia 250) are "fully automated immunoassay analyzers, which include software for evaluation of test results." The results are generated directly by the instrument.

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

The "ground truth" implicitly used for the studies mentioned ("clinically defined sera" and "samples from apparently healthy subjects") would be a combination of clinical diagnosis for patients with APS or thrombotic disorders, and the absence of disease for healthy subjects. The document does not specify the exact diagnostic criteria or the methods used to determine these clinical statuses.

8. The sample size for the training set

The document does not specify a training set sample size. For a traditional immunoassay device like this, the concept of a "training set" in the context of machine learning (AI) is not directly applicable. The device's performance is established through analytical validation and comparison with predicate devices, rather than an AI model training process.

9. How the ground truth for the training set was established

As there is no mention of an AI training set, this question is not applicable. For the development and validation of the immunoassays, the "ground truth" for calibrators would be established through a set of six WHO-standardized IgG and IgM Calibrators, derived from human serum, as mentioned in the "General Description of the New Devices." These calibrators define the assay's measurement scale.

Summary Limitations:

The provided 510(k) summary is for traditional in-vitro diagnostic immunoassays, not an AI-powered device. Therefore, many of the questions asked, particularly those related to expert adjudication, MRMC studies, and AI-specific training/test sets, are not applicable to the content of this document. The document focuses on demonstrating substantial equivalence to existing predicate devices based on analytical performance and comparability studies, rather than a de novo clinical validation against specific diagnostic accuracy criteria.

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HemosIL AcuStar Anti-Cardiolipin IgG: Fully automated chemiluminescent immunoassay for the . semi-quantitative measurement of anti-cardiolipin (aCL) IgG antibodies in human citrate plasma and serum on the ACL™ AcuStar as an aid in the diagnosis of thrombotic disorders related to primary and secondary Antiphospholipid Syndrome (APS) when used in conjunction with other laboratory and clinical findings.
. HemosIL AcuStar Anti-Cardiolipin IgM: Fully automated chemiluminescent immunoassay for the semi-quantitative measurement of anti-cardiolipin (aCL) IgM antibodies in human citrated plasma and serum on the ACL™ AcuStar, as an aid in the diagnosis of thrombotic disorders related to primary and secondary Antiphospholipid Syndrome (APS) when used in conjunction with other laboratory and clinical findings.
HemosIL AcuStar Anti-Cardiolipin IgG Controls: For the quality control of the Anti-Cardiolipin . IgG assay performed on the ACL AcuStar.
HemosIL AcuStar Anti-Cardiolipin IgM Controls: For the quality control of the Anti-Cardiolipin . IgM assay performed on the ACL AcuStar.

HemosIL AcuStar Anti-Cardiolipin IgG is a chemiluminescent two-step immunoassay consisting of magnetic particles coated with cardiolipin and human purified B2GPI which capture, if present, the aCL antiphospholipid antibodies from the sample. After incubation, magnetic separation and a wash step, a tracer consisting of an isoluminol-labeled anti-human IgG antibody is added and may bind with the captured aCL IgG on the particles. After a second incubation, magnetic separation, and wash step, reagents that trigger the luminescent reaction are added, and the emitted light is measured as relative light units (RLUs) by the ACL AcuStar optical system. The RLUs are directly proportional to the aCL IgG concentration in the sample.
The ACL AcuStar aCL IgG assay utilizes a 4 Parameter Logistic Curve (4PLC) fit data reduction method to generate a Master Curve. The Master Curve is predefined and lot dependent and it is stored in the instrument through the cartidge barcode. With the measurement of calibrators, the predefined Master Curve is transformed to a new, instrument specific 4PLC Working Curve. The concentration values of the calibrators are included in the calibrator tube barcodes.

Hemos L AcuStar Anti-Cardiolipin IgM is a chemiluminescent two-step immunoassay consisting of magnetic particles coated with cardiolipin and human purified B2GPI which capture, if present, the aCL antiphospholipid antibodies from the sample. After incubation, magnetic separation, and a wash step, a tracer consisting of an isoluminol-labeled anti-human IgM antibody is added and may bind with the captured aCL IgM on the particles. After a second incubation, magnetic separation, and wash step, reagents that trigger the luminescent reaction are added, and the emitted light is measured as relative light units (RLUs) by the ACL AcuStar optical system. The RLUs are directly proportional to the aCL IgM concentration in the sample.
The ACL AcuStar aCL IgM assay utilizes a 4 Parameter Logistic Curve (4PLC) fit data reduction method to generate a Master Curve. The Master Curve is predefined and lot dependent and it is stored in the instrument through the cartridge barcode. With the measurement of calibrators, the predefined Master Curve is transformed to a new, instrument specific 4PLC Working Curve. The concentration values of the calibrators are included in the calibrator tube barcodes.

Hemos L AcuStar Anti-Cardiolipin IgG Controls: The Low and High Anti-Cardiolipin IgG Controls are prepared by means of a dedicated process and contain different concentrations of human aCL IgG antibodies.
Low Anti-Cardiolipin IgG Control: Control intended for the assessment of precision and accuracy of the assay at the normal or around cut-off aCL IgG levels.
High Anti-Cardiolipin IgG Control: Control intended for the assessment of precision and accuracy of the assay at the abnormal aCL IgG levels.
Hemos L AcuStar Anti-Cardiolipin IgM Controls: The Low and High Anti-Cardiolipin IgM ● Controls are prepared by means of a dedicated process and contain different concentrations of human aCL IgM antibodies.
Low Anti-Cardiolipin IgM Control: Control intended for the assessment of precision and accuracy of the assay at the normal or around cut-off aCL IgM levels.
High Anti-Cardiolipin IgM Control: Control intended for the assessment of precision and accuracy of the assay at the abnormal aCL IgM levels.

The provided text describes the performance data for the HemosIL AcuStar Anti-Cardiolipin IgG and IgM assays and their respective controls, which are automated chemiluminescent immunoassays used to aid in the diagnosis of thrombotic disorders related to Antiphospholipid Syndrome (APS).

Here's an analysis of the acceptance criteria and study information, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" for the clinical performance in a quantifiable manner (e.g., a required minimum sensitivity or specificity). However, it presents performance data for precision, clinical sensitivity, specificity, and agreement with a predicate device. For the purpose of this response, I will list the reported performance metrics.

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

• Sample Size for Clinical Outcome Study: 321 frozen citrated plasma samples.
• Sample Size for Method Comparison Study:
  • HemosIL AcuStar Anti-Cardiolipin IgG: 136 samples (those within the compared methods' test ranges from the clinical performance study).
  • HemosIL AcuStar Anti-Cardiolipin IgM: 267 samples (those within the compared methods' test ranges from the clinical performance study).
• Data Provenance: The text does not explicitly state the country of origin. The samples were "frozen citrated plasmas" from "6 different groups," including patients diagnosed with primary APS (PAPS), secondary APS (SAPS), systemic lupus erythematosus (SLE) with and without APS, cardiovascular disorders, and apparently healthy people. This indicates a retrospective collection of samples.

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 about the number of experts or their qualifications used to establish the ground truth for the test set. It mentions "individuals diagnosed as primary APS (SAPS), secondary APS (SAPS), systemic lupus erythematosus (SLE) but not APS and SLE-like by standard objective tests." This implies that the diagnosis (ground truth) was established through existing clinical assessments and standard objective tests, but not necessarily through a de novo expert consensus review for the purpose of this study.

4. Adjudication Method for the Test Set

The document does not describe any adjudication method (e.g., 2+1, 3+1) for establishing the ground truth or resolving discrepancies for the test set. The diagnoses were seemingly pre-existing.

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 to this device. The HemosIL AcuStar Anti-Cardiolipin assays are laboratory diagnostic tests (immunoassays) performed on an automated instrument (ACL™ AcuStar) to measure specific antibodies in patient samples. They are not AI-assisted imaging or clinical decision support tools that involve human "readers" or directly improve human "readers" with AI assistance. The results are quantitative measurements.

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

Yes, the performance data presented (precision, clinical sensitivity/specificity, method comparison) reflects the standalone performance of the HemosIL AcuStar assays. These are automated chemiluminescent immunoassays, meaning the algorithm (the assay's chemical reactions and instrument's measurement/calculation) provides a result without direct human intervention in the measurement or interpretation, beyond loading samples and controls and routine instrument operation. The results are then interpreted clinically by healthcare professionals.

7. The Type of Ground Truth Used

The ground truth used for the clinical outcome studies was based on the clinical diagnosis of the patient groups. Specifically, patients were categorized into groups such as Primary APS (PAPS), Secondary APS (SAPS), Systemic Lupus Erythematosus (SLE), SLE-like, cardiovascular disorders, and apparently healthy people. The "cut-off of 20 U/mL" was applied to the assay results to determine positive/negative status relative to these clinical diagnoses.

8. The Sample Size for the Training Set

The document does not explicitly mention a separate "training set" for the development of any algorithm or model. The description of the device (Section "Device Description") indicates that the instrument uses a "4 Parameter Logistic Curve (4PLC) fit data reduction method to generate a Master Curve," which is "predefined and lot dependent" and stored via a barcode. This suggests that the master curve might be established during manufacturing/development using a set of reference materials, but no specific "training set" of patient samples for algorithm refinement is mentioned in the context of the regulatory submission.

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

As no explicit "training set" is described for an AI/machine learning algorithm based on patient data, this question is not applicable in the context of this document. The "Master Curve" mentioned for calibration is established using calibrators with known concentrations, not a patient-derived training set with clinical ground truth.

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The TheraTest EL-aCL™screen and TheraTest EL-aCL™ IgM, InG, IgA are intended for use in clinical laboratories as an in vitro diagnostic test for the detection and measurement of autoantibodies in human serum directed against the phospholipid cardiolipin.

Not Found

I am sorry, but the provided text describes a 510(k) premarket notification for an in vitro diagnostic test (TheraTest EL-aCL™ screen and TheraTest EL-aCL™ IgM, IgG, IgA). This document is a regulatory approval letter from the FDA.

This type of device is a laboratory assay, not an AI/ML powered device, and therefore the concepts of "acceptance criteria" and "study that proves the device meets the acceptance criteria" as they apply to AI-powered medical devices (like those involving image analysis, decision support systems, etc.) are not directly relevant in the way you've framed the request with terms like "test set," "ground truth," "MRMC study," and "training set."

The document does not contain the information needed to fill out your request, as it does not describe an AI/ML algorithm or its development and validation.

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