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The intended use of Chiron Diagnostics ACS:180 Ferritin Assay is for the quantitative determination of Ferritin in serum or plasma using the Chiron Diagnostics ACS:180® Automated Chemiluminescence Systems. It is to be used to aid in the diagnosis of iron deficiency anemia and iron overload.

The Chiron Diagnostics ACS:180 Ferritin assay is a two-site sandwich immunoassay using direct, chemiluminometric technology, which uses constant amounts of two anti-ferritin antibodies. The first antibody, in the Reagent, is a polyclonal goat anti-ferritin antibody labeled with acridinium ester. The second antibody, in the Solid Phase, is a monoclonal mouse anti-ferritin antibody, which is covalently coupled to paramagnetic particles. The ACS:180 system automatically performs the following steps:

• dispenses 25 uL of sample into a cuvette .
• . dispenses 100 µL of Lite Reagent and 450 µL of Solid Phase and incubates for 7.5 minutes at 37°C
• . separates, aspirates, and washes the cuvettes with reagent water4
• . dispenses 300 uL each of Reagent 1 and Reagent 2 to initiate the chemiluminescent reaction
• . reports results according to the selected option, as described in the system operating instructions or in the online help system

A direct relationship exists between the amount of ferritin present in the patient sample and the amount of relative light units (RLUs) detected by the system.

Here's an analysis of the provided text regarding the acceptance criteria and supporting study for the Chiron Diagnostics ACS:180 Ferritin assay:

The document is a 510(k) summary for a medical device submitted to the FDA, which focuses on demonstrating substantial equivalence to a predicate device rather than setting new, explicit acceptance criteria in the same way a clinical trial might. However, performance characteristics are presented that implicitly serve as acceptance criteria for regulatory clearance based on equivalence.

1. Table of Acceptance Criteria and Reported Device Performance

• Mean 13.1 ng/mL: Within-run %CV = 2.76, Total %CV = 4.98
• Mean 54.8 ng/mL: Within-run %CV = 2.64, Total %CV = 6.07
• Mean 162.7 ng/mL: Within-run %CV = 2.73, Total %CV = 4.68
• Mean 359.5 ng/mL: Within-run %CV = 3.62, Total %CV = 5.08 |
  | Expected Results in Healthy and Diseased Populations: Values should align with known physiological ranges. | Expected Results:
• Normal Males (N=142): Geo. Mean = 94 ng/mL, 95th Percentile = 22-322 ng/mL
• Normal Females (N=134): Geo. Mean = 46 ng/mL, 95th Percentile = 10-291 ng/mL
• Iron Deficiency (N=60): Geo. Mean = 11.6 ng/mL, Total Observed Range = 0.68-34.5 ng/mL
• Other Anemias (N=7): Geo. Mean = 610.8 ng/mL, Total Observed Range = 13.0-1390.8 ng/mL
• Iron Overload (N=44): Geo. Mean = 1899.6 ng/mL, Total Observed Range = 334.6-8573.0 ng/mL
• Renal Dialysis (N=31): Geo. Mean = 312.3 ng/mL, Total Observed Range = 31.3-1321.2 ng/mL
• Chronic Liver Disease (N=34): Geo. Mean = 1967.1 ng/mL, Total Observed Range = 7.9-12826.0 ng/mL |

2. Sample Size for the Test Set and Data Provenance

• Method Comparison: 276 samples in the range of 3.1 to 1621 ng/mL were used for comparison against an alternate chemiluminescent method.
• Precision: 4 samples were assayed, each 3 times in 8 assays.
• Expected Results (Reference Ranges):
  • Normal Males: 142 subjects
  • Normal Females: 134 subjects
  • Iron Deficiency: 60 patients
  • Other Anemias: 7 patients
  • Iron Overload: 44 patients
  • Renal Dialysis: 31 patients
  • Chronic Liver Disease: 34 patients

Data Provenance: The document does not explicitly state the country of origin or whether the studies were retrospective or prospective. Given the nature of a 510(k) submission for an in-vitro diagnostic, these studies are typically conducted by the manufacturer as prospective analytical and clinical performance evaluations, but specific details are not provided.

3. Number of Experts and Qualifications for Ground Truth

Not applicable. This device is an in-vitro diagnostic assay for quantitative measurement. Its "ground truth" is established through analytical validation against reference methods, known concentrations, and correlation with clinical diagnoses rather than expert interpretation of images or clinical cases. The reference ranges for healthy and sick populations are derived from the observed values in those cohorts, where the diagnosis of the condition itself would have been made by medical professionals, but this isn't "expert adjudication" of device output.

4. Adjudication Method for the Test Set

Not applicable. As noted above, this is a quantitative immunoassay, not a diagnostic imaging or interpretive device that requires expert adjudication of its output.

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

Not applicable. This is an IVD for quantitative measurement of a biomarker, not a diagnostic imaging aid for human interpretation. Therefore, an MRMC study comparing human readers with and without AI assistance is not relevant to this device.

6. Standalone (Algorithm Only) Performance

Yes, the studies presented are standalone performance studies of the assay device. The "Method Comparison" and "Precision" sections directly evaluate the analytical performance of the ACS:180 Ferritin assay without human-in-the-loop interpretation of its quantitative results. The "Expected Results" section provides reference ranges and observed values in different patient populations, demonstrating the device's ability to produce diagnostically relevant results on its own.

7. Type of Ground Truth Used

• Analytical Performance (Sensitivity, Reportable Range, Precision): Ground truth is established through known concentrations of ferritin controls, international reference standards (if applicable, though not specified here), and replicate measurements using the device itself.
• Method Comparison: The "ground truth" for method comparison is the results obtained from an "alternate chemiluminescent method," suggesting an established, comparable method already in use.
• Expected Results: The ground truth for the clinical categories (e.g., "Normal Males," "Iron Deficiency," "Iron Overload") is based on clinical diagnosis of the subjects/patients included in those cohorts. The document states, "The following values for patients with several diagnosed conditions were determined," implying the patients were already diagnosed with these conditions through standard clinical practice before their samples were tested.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or AI development. For an immunoassay like this, the development process involves reagent formulation and optimization, calibration, and internal validation studies. The reported performance characteristics likely represent the outcome of extensive internal development and validation, but specific "training set" sizes are not applicable as there isn't an algorithm being trained in the typical AI sense.

9. How Ground Truth for the Training Set was Established

Not applicable for this type of device. As explained in point 8, the concept of a "training set" and associated ground truth establishment (in the AI/ML context) is not relevant for the development and validation of a traditional immunoassay device. The assay development would involve ensuring accurate measurement through chemical and immunological principles, using calibrated materials, and verifying performance through analytical and clinical validation studies as detailed in the document.

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For the quantitative determination of folate in serum or EDTA plasma and red blood cells using the Folate BA (Biotin Avidin) assay on the Chiron Diagnostics ACS: 180® Automated Chemiluminescence Systems.

The Chiron Diagnostics ACS:180 Folate assay is a competitive immunoassay using direct chemiluminescent technology. Folate in the patient sample competes with acridinium esterlabeled folate in the Lite Reagent for a limited amount of biotin-labeled folate binding protein. Biotin-labeled folate binding protein binds to avidin which is covalently coupled to paramagnetic particles in the Solid Phase. In the ACS:180 Folate assay the sample is pretreated to release the folate from endogenous binding proteins in the sample. The system performs the following steps for calibrators, quality control samples, and patient samples: dispenses 150 uL of sample into a cuvette, dispenses 50 µL of DTT, dispenses 100 µL of folate binding protein and 200 µL of Solid Phase and incubates for 5.0 minutes at 37°C, dispenses 100 µL of Lite Reagent and incubates for 2.5 minutes at 37°C, separates, aspirates, and washes the cuvettes with reagent water, dispenses 300 uL each of Reagent 1 and Reagent 2 to initiate the chemiluminescent reaction, reports results according to the selected option, as described in the system operating instructions or in the online help system. An inverse relationship exists between the amount of folate present in the patient sample and the amount of relative light units (RLUs) detected by the system.

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

Device Name: Chiron Diagnostics ACS: 180 Folate Assay
Intended Use: For the quantitative determination of folate in serum or EDTA plasma and red blood cells using the Folate BA (Biotin Avidin) assay on the Chiron Diagnostics ACS:180® Automated Chemiluminescence Systems.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" with pass/fail thresholds. Instead, it presents "Performance Characteristics" which indicate the expected performance of a well-functioning assay. I will interpret these performance characteristics as the de-facto acceptance criteria for the device, given they are presented as a summary of safety and effectiveness.

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

• Sensitivity/Analytical Sensitivity: 20 replicate determinations of the folate zero standard in 7 assays with 3 lots of reagents. (Total of 20 x 7 x 3 = 420 measurements, but focused on the zero standard.) The country of origin for this data is not specified, nor is whether it was retrospective or prospective, but it implies a controlled laboratory study.
• Method Comparison (Serum): 258 serum samples.
• Method Comparison (RBC): 189 red blood cell samples.
• Expected Results/Reference Range (Serum): 263 serum samples, described as "apparently healthy males and females".
• Expected Results/Reference Range (RBC): 109 red blood cell samples, described as "apparently healthy males and females".
• Precision: Four samples were assayed six times with three lots of reagents in 23 runs on four systems (n = 138 for each sample). (Total of 4 samples * 6 replicates * 23 runs = 552 sample measurements; or, 4 samples * 138 measurements per sample = 552 total measurements).

Data Provenance: The document states that "The data was obtained on apparently healthy males and females from the United States" for the Expected Results (reference ranges). For other sections (e.g., method comparison, precision, sensitivity), the country of origin and design (retrospective/prospective) are not explicitly stated but are implied to be from a controlled laboratory setting (likely prospective) given the nature of the tests.

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

The document does not mention the use of experts to establish ground truth for the test set in the traditional sense of consensus or adjudication for diagnostic imaging studies.

However, for the deficient categories in the "Expected Results" table, the diagnosis was established based on "bone and/or peripheral blood smear pathology and other criteria including: megaloblastic anemia, folate deficient diet, malabsorption, alcoholism, Tropical Sprue, abnormal blood parameters including mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and hematocrit (HCT)." While this indicates a clinical diagnosis process, it doesn't specify if a panel of experts was used or their qualifications for this specific study. It implies standard diagnostic practices were followed.

4. Adjudication Method for the Test Set

No explicit adjudication method (e.g., 2+1, 3+1) is mentioned for any of the studies described. The ground truth for deficient samples appears to rely on a set of clinical and pathological criteria rather than expert consensus on individual cases specifically for the study.

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

No. This document describes the performance characteristics of an in vitro diagnostic (IVD) assay (a lab test), not an AI-assisted diagnostic imaging device. Therefore, a multi-reader, multi-case (MRMC) comparative effectiveness study with human readers improving with AI vs without AI assistance is not applicable and was not performed.

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

Yes, this is a standalone performance study. The document details the analytical performance of the ACS:180 Folate assay system (an automated chemiluminescence system) itself, independent of human interpretation of its results. The reported metrics (sensitivity, reportable range, method comparison, precision, expected ranges) are all inherent to the device's function.

7. The Type of Ground Truth Used

• Analytical Sensitivity, Reportable Range, Precision: Ground truth is established by the known concentrations of calibrated standards and controls used in the assay.
• Method Comparison: Ground truth is functionally established by an "alternate chemiluminescent method" (the predicate or another established assay), rather than an absolute gold standard. The aim is to show agreement with an existing method.
• Expected Results (Normal/Deficient Ranges):
  • Normal: Derived from samples obtained from "apparently healthy males and females". The assumption is that these individuals represent a "normal" folate status.
  • Deficient: Diagnosed by "bone and/or peripheral blood smear pathology and other criteria including: megaloblastic anemia, folate deficient diet, malabsorption, alcoholism, Tropical Sprue, abnormal blood parameters including mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and hematocrit (HCT)." This is clinical diagnostic ground truth.

8. The Sample Size for the Training Set

The document does not describe a "training set" as it would for a machine learning algorithm. This is a conventional IVD assay, not an AI/ML-based device in the modern sense. The "training" in this context would refer to internal development and optimization by the manufacturer, for which sample sizes are not typically reported in such summaries.

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

As stated above, the concept of a "training set" and its associated ground truth establishment is not relevant in the context of this traditional IVD assay and its regulatory submission. The device's performance is characterized against known analytical standards and clinical classifications, not by 'learning' from a labeled dataset.

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For the quantitative determination of free triiodothyronine (FT3) in serum using the Chiron Diagnostics ACS:180® Automated Chemiluminescence Systems.

Measurements obtained by this test are used in the diagnosis and treatment of thyroid diseases.

Trilodothyronine (3,5,3'-L-triiodothyronine, T3) is a hormone synthesized and secreted from the thyroid gland, and formed by peripheral deiodination of thyroxine (T4). T3 and T4 are secreted into the circulation in response to thyroid stimulating hormone (TSH) and play an important role in requlating metabolism

In the circulation, 99.7% of T3 is reversibly bound to transport proteins, primarily thyroxinebinding globulin (TBG) and to a lesser extent albumin and prealbumin. The remaining T3 does not bind to transport proteins, but is free in the circulation. This unbound fraction of the total T3 concentration is free triiodothyronine (free T3, FT3). Unbound T3 is metabolically active.

Free T3 levels correlate with T3 secretion and metabolism. In hypothyroidism and hyperthyroidism, free T3 levels parallel changes in total T3 levels. However, measuring free T3 is useful when altered levels of total T3 occur due to changes in T3 binding proteins, especially TBG. TBG levels remain relatively constant in healthy individuals, but certain conditions such as normal pregnancy and steroid therapy can alter these levels. In these conditions, free T3 levels are unchanged, while total T3 levels parallel the changes in TBG.

The Chiron Diagnostics ACS:180 FT3 assay is a competitive immunoassay using direct, chemiluminescent technology. FT3 in the sample competes with a T3 analog, which is covalently coupled to paramagnetic particles in the Solid Phase, for a limited amount of a combination of acridinium ester-labeled monoclonal mouse anti-T3 antibodies in the Lite Reagent.

The system automatically performs the following steps:

• dispenses 50 µL of sample into a cuvette ●
• dispenses 100 µL of Lite Reagent and incubates for 5.0 minutes at 37 C ●
• dispenses 450 µL of Solid Phase and incubates for 2.5 minutes at 37 C .
• separates, aspirates, and washes the cuvettes with reagent water ●
• dispenses 300 µL each of Reagent 1 and Reagent 2 to initiate the chemiluminescent . reaction
• . reports the results according to the selected option, as described in the system operating instructions or in the online help system

An inverse relationship exists between the amount of FT3 present in the patient sample and the amount of relative light units (RLUs) detected by the system.

The provided text describes the Chiron Diagnostics ACS:180 FT3 assay, a device for quantifying free triiodothyronine (FT3) in serum. The information is extracted from a 510(k) Summary for regulatory submission.

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

Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined "acceptance criteria" in the form of thresholds for performance metrics. Instead, it presents the results of performance studies. The table below summarizes the reported performance characteristics.

Study Details

2. Sample size used for the test set and the data provenance:

• Expected Results/Reference Range Study:

  • Sample Size: 594 apparently healthy adult individuals for the primary range determination, and an additional 185 apparently healthy individuals for a confirmatory study.
  • Data Provenance: Not specified (e.g., country of origin). The studies appear to be prospective for establishing the reference range, as they studied "apparently healthy adult individuals."

• Method Comparison Study:

  • Sample Size: 359 samples.
  • Data Provenance: Not specified (e.g., country of origin, retrospective or prospective).

• Precision Study:

  • Sample Size: 3 samples (each assayed 6 times in each of 12 runs, on 4 systems). This describes a robust internal validation, rather than a "test set" of patient samples in the same way as the method comparison.
  • Data Provenance: Not specified.

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

This information is not provided in the document. For an in vitro diagnostic device measuring a quantitative analyte like FT3, "ground truth" is typically established by reference methods or validated laboratory measurements rather than expert consensus on images or clinical assessments. The studies appear to compare the device's measurements against themselves (precision) or against an "alternate method" (method comparison), where the "alternate method" would serve as the reference for comparison, not necessarily a human expert consensus.

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

This concept of "adjudication" is generally applicable to qualitative assessments (e.g., image interpretation) where there might be disagreement among human readers. For a quantitative immunoassay, adjudication as described (e.g., 2+1 consensus) is not applicable and therefore not mentioned. The method comparison study directly compared numerical results.

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 device is an automated immunoassay, not an AI-assisted diagnostic imaging system that would involve human readers interpreting cases. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and none was performed or described.

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

The device described is inherently a standalone automated system. The performance characteristics (sensitivity, reportable range, precision, method comparison) are all measurements of the algorithm's and system's performance without human intervention in the result generation or calculation process. Therefore, the presented studies are standalone performance assessments of the device.

7. The type of ground truth used:

• For Expected Results/Reference Range: The "ground truth" was derived from the measured FT3 values in a large cohort of "apparently healthy adult individuals," establishing a statistical range for a healthy population.
• For Analytical Sensitivity/Reportable Range: The ground truth for these metrics is inherent to the assay's ability to detect and quantify the analyte against zero standards or known concentrations.
• For Method Comparison: The "ground truth" was established by an "alternate method." The specific nature or gold standard status of this alternate method is not detailed, but it serves as the reference for comparison.
• For Precision: The ground truth is the inherent variability of the assay itself, measured through repeated assessments of the same samples.

8. The sample size for the training set:

The document does not specify a "training set" sample size. This is typical for a traditional immunoassay, which does not employ machine learning algorithms that require a distinct training phase with labeled data in the same way AI algorithms do. The assay is based on chemical reactions and optical detection, with internal calibration curves determining its performance characteristics.

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

As there is no mention of a "training set" in the context of machine learning, this question is not applicable to the described device. The assay's operational parameters and calibration are established through laboratory R&D and validation processes, not through a 'training set' for an algorithm.

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The Chiron Diagnostics ACS:Centaur BR assay is an in vitro diagnostic test for the quantitative serial determination of cancer antigen CA 27.29 in human serum using the Chiron Diagnostics ACS:Centaur" Automated Chemiluminescence System. The test is intended for use as an aid in monitoring patients previously treated for Stage Il or Stage III breast cancer. Serial testing for CA 27,25 in the serum of patients who are clinically free of disease should be used in conjunction with other clinical methods used for the early detection of cancer recurrence. The test is also intended for use as an aid in the management of breast cancer patients with metastatic disease by monitoring the progression or regression of disease in response to treatment.

The Chiron Diagnostics ACS:Centaur BR assay is a fully automated, competitive immunoassay using direct, chemiluminescent technology. The Lite Reagent is composed of a monoclonal mouse antibody specific for CA 27.29, labeled with acridinium ester. The antibody used in the assay, MAb B27,29, binds to a peptide epitope in the tandem repeat region of the MUC-1 gene product. The Solid Phase is composed of purified CA 27.29, which is covalently coupled to paramagnetic particles. After onboard pretreatment, the sample is incubated with both Lite Reagent and Solid Phase simultaneously for 7.5 minutes.

Here's an analysis of the provided text, focusing on acceptance criteria and the study proving device performance:

1. Table of Acceptance Criteria and Reported Device Performance

Note on Implied Acceptance Criteria: The document primarily provides performance data without explicitly stating pre-defined acceptance criteria. However, when evaluating substantial equivalence, the performance of the new device is compared to a legally marketed predicate device. Therefore, the "acceptance criteria" are implicitly that the new device's performance should be comparable to or better than the predicate's, and meet general expectations for a diagnostic assay. A correlation coefficient of 0.99 is generally considered excellent for method comparisons.

2. Sample Size and Data Provenance for the Test Set

• Sample Size for Test Set: 225 samples were used for the accuracy study comparing the ACS:Centaur BR to the predicate device.
• Data Provenance: Not explicitly stated. The document doesn't mention the country of origin of the data or whether it was retrospective or prospective.

3. Number of Experts and Qualifications for Ground Truth

• This information is not provided in the given text. The study described is a method comparison (accuracy) study against a predicate device, not a study where a ground truth needed to be established by experts for classification or diagnosis.

4. Adjudication Method for the Test Set

• None. Adjudication is typically used when multiple observers assess a case and their interpretations need to be reconciled to establish a single ground truth. In this method comparison study, the "ground truth" for the new device's accuracy is its agreement with the predicate device's measurements. There are no human readers or diagnostic interpretations described that would require adjudication.

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

• No, an MRMC study was not done. The study described is an analytical performance study comparing a new immunoassay to a predicate immunoassay. It does not involve human readers interpreting results or assessing the impact of AI assistance.

6. Standalone (Algorithm Only) Performance Study

• Yes, this is an analogous standalone performance study. The ACS:Centaur BR Immunoassay is an in-vitro diagnostic device that provides a quantitative measurement. The "algorithm" here is the entire immunoassay system (reagents, analyzer, and analytical process). The "standalone" performance is measured by its analytical sensitivity, measuring range, and accuracy when compared to a reference method (the predicate device). It's operating without human intervention for the measurement itself, only for collecting and interpreting the results.

7. Type of Ground Truth Used

• The "ground truth" for the accuracy study was the measurements obtained from the predicate device, the ACS:180 BR Immunoassay. This is a form of reference method comparison, where a new method's results are compared against an already established and validated method.

8. Sample Size for the Training Set

• The document does not explicitly mention a "training set" in the context of machine learning or algorithm development. For an immunoassay, the "training" equivalent would be the development and optimization of the assay itself through various experiments. The reported data relates to the final, validated product's performance.

9. How Ground Truth for the Training Set Was Established

• As a training set is not explicitly mentioned in the context of this immunoassay's validation, this information is not applicable/provided. The development of an immunoassay involves optimizing reagents and reaction conditions, which is an iterative process, but not typically referred to as "establishing ground truth for a training set" in the same way it would be for a machine learning model.

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The Chiron Diagnostics ACS:Centaur CEA Immunoassay is for the quantitative determination of carcinoembryonic antigen in serum to aid in the management of cancer patients in whom changing concentrations of CEA are observed using the Chiron Diagnostics ACS:Centaur Automated Chemiluminescence Systems.

The Chiron Diagnostics ACS:Centaur CEA immunoassay is a two-site immunoassay using direct chemiluminometric technology, which uses constant amounts of two antibodies. The first antibody, in the Lite Reagent, is a purified polyclonal rabbit anti-CEA antibody labeled with acridinium ester. The second antibody, in the Solid Phase, is a monoclonal mouse anti-CEA antibody covalently coupled to paramagnetic particles. A direct relationship exists between the amount of CEA present in the patient sample and the amount of relative light units (RLU's) detected by the system.

Here's a breakdown of the acceptance criteria and study information for the ACS:Centaur CEA Immunoassay, based on the provided text:

Acceptance Criteria and Device Performance

Study Details

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

   • Sample Size: 284 samples.
   • Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). However, the context of a new device being compared to a legally marketed predicate suggests these were clinical samples.

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

   • This information is not provided in the given document. The "ground truth" for accuracy in this context is the measurement by the predicate device (ACS:180 CEA), not expert interpretation.

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

   • This is not applicable as the evaluation is a direct comparison of quantitative measurements from two immunoassay devices, not expert adjudication of clinical findings.

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:

   • No, this was not a MRMC study. This device is an in-vitro diagnostic (IVD) immunoassay, not an AI-powered image analysis or clinical decision support tool designed to assist human readers. Therefore, the concept of human reader improvement with/without AI assistance is not relevant.

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

   • Yes, this was a standalone performance evaluation of the ACS:Centaur CEA immunoassay device itself. It measures CEA concentration directly from serum samples without human interpretation of raw data in the same way an AI algorithm would operate. Its performance is compared to another device (the predicate), not human performance.

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

   • The "ground truth" for accuracy in this study was the quantitative measurement obtained from the predicate device, the ACS:180 CEA Immunoassay. The study sought to demonstrate substantial equivalence to an already legally marketed device.

7. The sample size for the training set:

   • This information is not provided in the document. For an immunoassay device, the "training set" might refer to data used during the development and calibration of the assay, but specific details about this are not included in the 510(k) summary.

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

   • This information is not provided in the document. Similar to the training set size, the specifics of how internal calibration standards or reference materials were established during the assay development are beyond the scope of this 510(k) summary.

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The Chiron Diagnostics ACS:Centaur PSA2 Immunoassay is for the quantitative determination of prostate specific antigen in serum to aid in the management of cancer patients in whom changing concentrations of PSA are observed using the Chiron Diagnostics ACS:Centaur Automated Chemiluminescence Systems.

Prostate-specific antigen (PSA) is a single-chain glycoprotein normally found in the cytoplasm of the epithelial cells lining the acini and ducts of the prostate gland. PSA is a neutral serine protease of 240 amino acids involved in the lysis of seminal coagulum.

PSA is detected in the serum of males with normal, benign hypertrophic, and malignant prostate tissue. PSA is not detected in the serum of males without prostate tissue (because of radical prostatectomy or cystoprostatectomy) or in the serum of most females. The fact that PSA is unique to prostate tissue makes it a suitable marker for monitoring men with cancer of the prostate. PSA is also useful for determining possible recurrence after therapy when used in conjunction with other diagnostic indices.

The Chiron Diaqnostics ACS:Centaur PSA2 immunoassay is a two-site immunoassay using direct chemiluminometric technology, which uses constant amounts of two antibodies. The first antibody, in the Lite Reagent, is a purified polyclonal sheep anti-PSA antibody labeled with acridinium ester. The second antibody, in the Solid Phase, is a monoclonal mouse anti-PSA antibody covalently coupled to paramagnetic particles. A direct relationship exists between the amount of PSA present in the patient sample and the amount of relative light units (RLU's) detected by the system.

Acceptance Criteria and Device Performance for Chiron Diagnostics ACS:Centaur PSA2 Immunoassay (K981839)

1. Table of Acceptance Criteria and Reported Device Performance

Note: The document does not explicitly state numerical acceptance criteria in a dedicated section. The "Performance Data" section details the device's capabilities, and the high correlation with the predicate device (r = 0.99) strongly implies that this level of agreement was the acceptance criteria for accuracy to demonstrate substantial equivalence. The minimum detectable concentration demonstrates the lower limit of reliable measurement, implying an acceptance of this level of analytical sensitivity.

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

• Sample Size: 287 samples were used for the accuracy study comparing the ACS:Centaur PSA2 with the ACS:180 PSA2.
• Data Provenance: The document does not specify the country of origin of the data. It is a retrospective analysis comparing the performance of the new device against the predicate device using existing samples.

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

This device is an immunoassay for quantitative determination of PSA levels. The "ground truth" in this context is the quantitative measurement of PSA itself. Therefore, human experts are not directly involved in establishing the ground truth for individual samples in the same way they would be for image interpretation.

The ground truth for the comparison was established by the predicate device, the ACS:180 PSA2 Immunoassay. The performance of this predicate device would have been validated previously, likely involving method comparison studies with established reference methods or clinical samples.

4. Adjudication Method for the Test Set

The concept of an adjudication method (e.g., 2+1, 3+1) is not applicable here as the test set involves quantitative measurements from an immunoassay, not subjective interpretations requiring expert consensus. The comparison is a direct numerical correlation between the new device and the predicate device.

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

No MRMC comparative effectiveness study was conducted or is applicable for this type of device. This device is an automated immunoassay, meaning there are no human "readers" in the diagnostic process to compare or improve.

6. Standalone Performance Study

Yes, a standalone performance study was conducted. The "Performance Data" section describes the sensitivity and accuracy of the ACS:Centaur PSA2 Immunoassay as a standalone device, as it measures PSA concentration independently and then compares its output to the predicate device. The correlation study directly assesses the performance of the algorithm (the immunoassay technology) without human intervention in the measurement process.

7. Type of Ground Truth Used

The ground truth used for the comparison was measurements from a legally marketed predicate device (ACS:180 PSA2 Immunoassay). This is a form of comparative ground truth, where the performance of the new device is validated against an existing, accepted method. While not pathology or outcomes data directly, the predicate device's measurements are considered the established "truth" for this comparison of analytical performance. The clinical utility of PSA measurements (which pathology and outcomes data would inform) is assumed to be established by the predicate device's history and the broader medical literature.

8. Sample Size for the Training Set

The document does not specify a training set or its sample size. Immunoassays are generally developed and optimized through extensive experimentation and reagent optimization, rather than a "training set" in the machine learning sense. The performance data presented are for the validated, final device.

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

As no explicit training set is mentioned in the context of the immunoassay, the concept of establishing ground truth for it as per AI/ML terminology is not applicable. The development of the immunoassay involves chemical and biological engineering principles, with validation steps along the way, not a "ground truth" derived from expert consensus on a training dataset. The established "truth" for such systems typically comes from meticulously prepared reference materials, calibrators, and robust analytical methods.

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The intended use of ACS:Centaur AFP Immunoassay is for the quantitative determination of alpha-fetoprotein (AFP) in the following:

• human serum and in amniotic fluid from specimens obtained at 15 to 20 weeks gestation, * as an aid in detecting open neural defects (NTD) when used in conjunction with ultrasonography and amniography testing,
• human serum, as an aid in managing non-seminomatous testicular cancer when used in * conjunction with physical examination, histology/pathology, and other clinical evaluation procedures, using the Chiron Diagnostics ACS:Centaur Automated Chemiluminescence System.

The Chiron Diagnostics ACS:Centaur AFP immunoassay is a two-site immunoassay using direct chemiluminometric technology, which uses constant amounts of two antibodies. The first antibody, in the Lite Reagent, is a purified polyclonal rabbit anti-AFP antibody labeled with acridinium ester. The second antibody, in the Solid Phase, is a monoclonal mouse anti-AFP antibody covalently coupled to paramagnetic particles. A direct relationship exists between the amount of AFP present in the patient sample and the amount of relative light units (RLU's) detected by the system.

Here's an analysis of the provided text regarding the acceptance criteria and the study proving the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

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

• Sample Size: 498 serum samples
• Data Provenance: Not specified (e.g., country of origin, retrospective or prospective).

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

The provided summary does not explicitly state the number of experts or their qualifications used to establish ground truth for the test set. The accuracy is reported as a correlation with a predicate device (ACS:180 AFP). This suggests that the "ground truth" for the test set was the results obtained from the predicate device, rather than a separate expert-driven ground truth establishment process.

4. Adjudication Method for the Test Set

No adjudication method is mentioned. The comparison is directly between the new device's readings and the predicate device's readings.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance

This information is not applicable. The device described (ACS:Centaur AFP Immunoassay) is a standalone diagnostic assay, not an AI-assisted interpretation tool for human readers. Therefore, no MRMC study or AI assistance effect size is relevant here.

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

Yes, a standalone performance assessment was done. The reported performance metrics (sensitivity, accuracy, correlation coefficient) are for the device (immunoassay system) operating independently to measure AFP concentration. There is no human-in-the-loop component described for these performance evaluations.

7. The Type of Ground Truth Used

The ground truth for the accuracy assessment was the results obtained from the predicate device, ACS:180 AFP Immunoassay. The study is essentially a comparison of the new device's measurements against an established, legally marketed device's measurements, assuming the predicate device provides a reliable measure of AFP.

8. The Sample Size for the Training Set

The document does not specify a training set or its sample size. This type of immunoassay development typically involves initial analytical validation and calibration, but the provided summary focuses on the performance comparison with the predicate device, which is more akin to a clinical validation set.

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

Since no explicit training set is detailed, the method for establishing its ground truth is not provided. For an immunoassay, the "training" aspect would generally involve calibrating the system using known concentrations of AFP and optimizing reagents/protocols. The ground truth for this would be the known, prepared concentrations of AFP standards. However, the document doesn't detail this process.

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For the quantitative determination of cardiac troponin I in serum or heparinized plasma and as an aid in the diagnosis of acute myocardial infarction using the Chiron Diagnostics ACS: 180® Automated Chemiluminescence Systems.

Not Found

The provided documents are an FDA 510(k) clearance letter for the Chiron Diagnostics ACS:180® Troponin I Assay. While they confirm the device's substantial equivalence and provide its intended use, they do not contain detailed information about acceptance criteria, specific study designs, or performance metrics beyond the general statement of substantial equivalence.

Therefore, I cannot fully answer your request based solely on the provided text. The FDA clearance letter typically refers to information submitted by the manufacturer in their 510(k) application, which would contain such details.

However, based on the context of a 510(k) submission for an in-vitro diagnostic (IVD) device like a Troponin I assay, I can infer the types of information that would likely be present in the full submission, and frame a partial answer accordingly:

Based on the provided FDA 510(k) clearance letter (K980528) for the Chiron Diagnostics ACS:180® Troponin I Assay, the following information can be inferred or is directly stated, but detailed specifics on acceptance criteria and study data are not present in these documents.

The letter confirms the device is substantially equivalent to legally marketed predicate devices and is intended for "quantitative determination of cardiac troponin I in serum or heparinized plasma and as an aid in the diagnosis of acute myocardial infarction using the Chiron Diagnostics ACS: 180® Automated Chemiluminescence Systems."

To fully address your request, one would need to review the complete 510(k) submission (e.g., the Special Controls Guidance Document for Cardiac Troponin devices, or the specific studies performed by Chiron Diagnostics).

Here's an outline of what would typically be found in a 510(k) submission for such a device, and why the provided documents don't offer the detailed answers:

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

• Information in provided document: Not present.
• Inferred: For an IVD like this, acceptance criteria would typically include:
  • Analytical Sensitivity: Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LoQ).
  • Analytical Specificity: Interference studies (hemoglobin, triglycerides, bilirubin, common medications), cross-reactivity with other cardiac or skeletal muscle proteins.
  • Precision/Reproducibility: Within-run (intra-assay) and between-run (inter-assay) precision (CV%) at various concentrations, often near the medical decision points.
  • Linearity/Reportable Range: Demonstration that the assay accurately measures concentrations across its claimed range.
  • Accuracy/Method Comparison: Comparison against a legally marketed predicate device or a reference method using patient samples, typically assessed by correlation (regression analysis) and bias (e.g., Bland-Altman plots). This would be key for demonstrating "substantial equivalence."
  • Clinical Performance (aid in diagnosis of AMI): This would involve sensitivity and specificity for diagnosing AMI, usually against a clinical endpoint (e.g., WHO criteria for AMI, or consensus diagnosis by clinicians). This would involve establishing cutoff values.

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

• Information in provided document: Not present.
• Inferred: The 510(k) submission would detail:
  • Sample Size: Typically hundreds to thousands of patient samples for method comparison and clinical performance studies. Smaller numbers for analytical performance (e.g., precision, linearity).
  • Provenance: This would state whether samples were from specific hospitals, regions, or collected to meet specific demographic criteria. They would likely be retrospective, but could include prospective elements for clinical studies. The country of origin would be 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)

• Information in provided document: Not present.
• Inferred: For the "aid in the diagnosis of acute myocardial infarction" claim:
  • Ground Truth for AMI: Typically established by a panel of independent cardiologists or emergency physicians, sometimes alongside a review of patient charts, ECGs, cardiac imaging, and serial cardiac marker results, based on established clinical guidelines (e.g., ESC/ACC/AHA/WHF Universal Definition of Myocardial Infarction). These experts would need to be board-certified with relevant clinical experience. The number would vary, but typically 2-3 independent clinicians would review each case.

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

• Information in provided document: Not present.
• Inferred: If multiple experts were used to establish clinical ground truth for AMI, an adjudication method would be employed. Common methods include:
  • Consensus: All experts must agree.
  • Majority Rule: E.g., 2 out of 3 agree.
  • Adjudicator: If there's disagreement among initial reviewers, a senior expert (the "plus 1") reviews the case and makes the final determination.

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

• Information in provided document: Not present.
• Inferred: This device is an in-vitro diagnostic assay (blood test), not an imaging AI diagnostic device for "human readers." Therefore, an MRMC study comparing human reader performance with and without AI assistance is not applicable to this type of device. The "AI" is the automated instrument (ACS:180) that performs the assay, not a cognitive aid for a human interpreter of an image.

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

• Information in provided document: Yes, implicitly.
• Answer: The performance metrics for an IVD assay (like sensitivity, specificity, accuracy, precision, etc.) are inherently "standalone" in the sense that they reflect the analytical and clinical performance of the assay system itself, irrespective of human interpretation in real-time. The result is quantitative (a number), and its diagnostic utility is then interpreted by a clinician.

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

• Information in provided document: Not present explicitly in the clearance letter.
• Inferred:
  • Analytical Performance: Ground truth for concentration would be established by reference methods, gravimetric dilutions, or certified reference materials.
  • Clinical Performance (for AMI diagnosis): The 'ground truth' for the diagnosis of Acute Myocardial Infarction would be established by a combination of:
    • Clinical judgment/Expert Consensus: As described in point 3, based on comprehensive patient data (symptoms, ECG changes, imaging, and potentially serial cardiac marker trends from a predicate device or reference method).
    • Outcomes Data: Patient follow-up to confirm definitive diagnosis or rule out AMI.

8. The sample size for the training set

• Information in provided document: Not present.
• Inferred: While "training set" is more common for machine learning, for an IVD assay, method development involves extensive testing and optimization. The sample size for validation studies (which are analogous to "test sets" for performance evaluation) is distinct from the samples used during initial research, development, and optimization. The 510(k) would focus on the validation study sample sizes.

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

• Information in provided document: Not present.
• Inferred: For the development/optimization phase of an IVD, ground truth for calibrators and controls would be established by meticulous analytical chemistry techniques and comparison to established reference standards. For clinical performance optimization, similar methods to those in point 7 would be used, but in an iterative process to refine assay parameters and cutoffs.

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The Chiron Diagnostics ACS:180 Tobramycin Assay is for the quantitative determination of tobramycin in serum or plasma using the Chiron ACS:180 Automated Chemiluminescence Systems. Monitoring the patient's serum or plasma tobramycin levels is important both to ensure that the drug is present in therapeutic concentrations and to avoid toxicity.

The Chiron Diagnostics ACS:180 Tobramycin assay is a competitive immunoassay using direct, chemilumenescent technology. Tobramycin in the patient sample competes with acradinium ester-labeled tobramycin in the Lite Reagent for a limited amount of monoclonal mouse anti-tobramycin antibody, which is covalently coupled to the paramagnetic particles in the Solid Phase. An inverse relationship exists between the amount of tobramycin present in the patient sample and the amount of relative light units (RLUs) detected by the ACS:180® system.

Here's a summary of the acceptance criteria and study details for the Chiron Diagnostics ACS:180 Tobramycin Assay, based on the provided text:

Acceptance Criteria and Device Performance

Study Details

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

   • Sample Size: 293 samples.
   • Data Provenance: Not specified (e.g., country of origin, retrospective or prospective).

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

   • Not applicable/Not provided. The "ground truth" for the accuracy study was an "alternate fluorescence polarization (FPIA) method," which is a laboratory method, not expert-based.

3. Adjudication method for the test set:

   • Not applicable. The comparison was against a laboratory method.

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:

   • No. This device is an automated immunoassay for drug level measurement, not an AI-assisted diagnostic imaging or interpretation tool involving human readers.

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

   • Yes. The performance described for the ACS:180 Tobramycin assay is its standalone, automated performance.

6. The type of ground truth used:

   • Alternative Method Comparison: The accuracy of the ACS:180 Tobramycin assay was assessed by comparing its results against an "alternate fluorescence polarization (FPIA) method." This constitutes a comparative method study, where the FPIA method serves as the reference or "ground truth."

7. The sample size for the training set:

   • Not provided. The document describes performance data, but does not detail the development or training of the assay (which, in this context, refers to the development of the immunoassay reagents and calibration, not an AI model).

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

   • Not provided. As this is not an AI/machine learning model in the conventional sense, the concept of a "training set" and its "ground truth establishment" as typically applied to AI does not directly apply in the same way. The development of an immunoassay involves optimizing reagent concentrations, antibody specificity, and calibration using known standards, but these details are not in the provided summary.

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The Chiron Diagnostics ACS:180 Myoglobin Assay is used for the quantitative determination of Myoglobin in serum or plasma and as an aid in the diagnosis of acute myocardial infarction using the Chiron Diagnostics ACS Automated Chemiluminescence Systems.

Myoglobin is a oxygen-binding, heme protein, found in cardiac and skeletal muscle. Myoglobin is noted for its rapid release into the circulation following tissue injury. Elevated levels of myoglobin can be found in conditions of muscle damage, such as acute and chronic skeletal muscle disease, renal failure, myocarditis, open-heart surgery, and after heavy exercise. Myoglobin releases into the circulation as early as 2 to 4 hours after cell damage, peaks at between 9 and 12 hours, and returns to normal within 24 to 36 hours. In the absence of skeletal muscle trauma, myoglobin has been used as an early indicator of myocardial infarction, and therefore as a rule out indicator. Myoglobin has a negative predictive value of 99%, which improves the rule out capabilities of the emergency department and helps reduce the number of patients inappropriately admitted to the Coronary Care Units with symptoms atypical of acute myocardial infarction. When used in combination with other cardiac markers such as CK-MB or cTnl, the ACS myoglobin assay is a valuable diagnostic tool to be used in the early evaluation of the potential acute myocardial infarction patient. The Chiron Diagnostics ACS:180 Myoglobin assay is a two-site sandwich immunoassay using direct chemiluminometric technology, which uses constant amounts of two antibodies. The first antibody, in the Lite Reagent, is a polyclonal goat anti-myoglobin antibody labeled with acridinium ester. The second antibody, in the Solid Phase, is a monoclonal mouse anti-myoglobin antibody covalently coupled to paramagnetic particles.

Here's a breakdown of the acceptance criteria and study information for the KCN4325 device, based on the provided document:

Acceptance Criteria and Device Performance

Note: The document does not explicitly state "acceptance criteria" with predefined thresholds. Instead, it presents the results of performance studies that are implicitly accepted as demonstrating the device's suitability for its intended use, especially given the FDA's 510(k) clearance. The "Acceptance Standard" column is derived from the fact that the reported performance was deemed sufficient for regulatory approval.

Study Information

1. Sample Size Used for the Test Set and Data Provenance:

   • Reference Range: 703 serum and plasma samples from "apparently healthy individuals."
   • Method Comparison: 123 samples in the range of 27 to 957 ng/mL (μg/L).
   • Precision: 8 samples.
   • Data Provenance: Not specified (e.g., country of origin). The studies appear to be prospective as they were conducted to establish performance characteristics for the device's submission.

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

   • This information is not provided in the document. For an immunoassay like this, the "ground truth" for method comparison would typically be the results from the predicate or established method itself, which would have its own validation. For reference ranges, the "truth" is the biological measurement in a healthy population.

3. Adjudication Method for the Test Set:

   • Not applicable or not specified. This type of adjudication is more common in image-based diagnostic systems or clinical trials requiring expert consensus on complex findings. For a quantitative assay, the comparison is against another assay or a statistically derived range.

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:

   • No. This is an automated immunoassay for Myoglobin detection, not an AI-assisted diagnostic tool that involves human readers interpreting images or complex data. Therefore, an MRMC study with human readers assisting AI is irrelevant.

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

   • The studies described (Reference Range, Analytical Sensitivity, Reportable Range, Method Comparison, Precision) are all standalone performance evaluations of the ACS:180 Myoglobin assay as an algorithm/device only. The "ACS Automated Chemiluminescence Systems" implies an automated, standalone operation without direct human intervention in the result generation after sample loading.

6. The type of ground truth used:

   • Reference Range: Biological measurements from a "healthy individual" population.
   • Analytical Sensitivity/Reportable Range: Defined by the assay's ability to statistically differentiate from a zero standard and measure within a calibrated range.
   • Method Comparison: Results from an "alternate myoglobin EIA method" (a predicate or established laboratory method).
   • Precision: Intrinsic variability of the assay itself, calculated from replicate measurements.

7. The sample size for the training set:

   • Not specified. This document describes the performance studies for a diagnostic device prior to marketing. These assays are typically developed and calibrated by the manufacturer based on internal R&D, not a "training set" in the machine learning sense. The reported studies are more akin to validation or test sets.

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

   • Not applicable/Not specified. As mentioned above, a "training set" in the machine learning context is not directly referred to or implied for this type of immunoassay. The development and establishment of the assay's calibration curve and parameters (which could be considered analogous to a 'training phase' in a broad sense) would be based on the scientific principles of immunoassay and extensive in-house research and development using various known concentration samples and standards.

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