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This in vitro diagnostic method intended to quantitatively measure the concentration of cardiac Troponin 1 (Tn1) in human serum and plasma (lithium heparin) using the Bayer Immuno 1 system. When used in conjunction with other clinical data, such as presenting symptoms and diagnostic procedures, measurements of cardiac Tnl aids in the diagnosis of acute myocardial infarction (AMI) and in the risk stratification of patients with non-ST segment-elevation, acute coronary syndromes with respect to relative risk of mortality, myocardial infarction, or increased probability of ischemic events requiring urgent revalcularization procedures.

This diagnostic method is not intended for use on any other system.

The proposed Bayer Immuno 1™ Troponin I assay is an enzyme label sandwich assay using a monoclonal and polyclonal antibody. A Troponin I specific monoclonal antibody is labeled with fluorescein and a Troponin I specific goat affinity purified antibody is labeled with alkaline phosphatase (ALP). The solid phase consists of a suspension of magnetizable particles coated with antibody to fluorescein (mIMP reagent). Sample or calibrator, R1 reagent containing fluoresceinantibody conjugate, R2 reagent containing ALP-antibody conjugate and mIMP reagent are mixed and incubated at 37° C. In the presence of Troponin I a (fluorescein-conjugate: Troponin I:ALPconjugate) complex is formed and captured by the anti-fluorescein antibodies on the magnetic particles. The particles are washed and para-nitrophenyl phosphate solution is added. The ALP in the antibody conjugate reacts with the substrate to form para-nitrophenoxide and phosphate. Increasing absorbance due to the formation of para-nitrophenoxide is monitored at 405 nm and 450 nm. The dose response curve is directly proportional to the concentration of Troponin I in the sample. A linear point to point fit is used to construct the dose response curve. The Bayer Immuno 1 Troponin I assay has a range of 0 to 200 ng/mL and liguid calibrators are provided with values of 0,5,10,20,60, and 200 ng/mL Troponin I.

The provided document is a 510(k) summary for the Bayer Immuno 1™ System Troponin I Method, submitted to the FDA in 1999. It describes the device and its intended use, particularly focusing on an additional indication for risk stratification.

Based on the information provided in the document, here's a breakdown of the acceptance criteria and the study details:

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

The document does not explicitly state "acceptance criteria" or present a study comparing the device performance against specific targets for analytical or clinical performance (e.g., sensitivity, specificity, accuracy). Instead, it states that the proposed device is "substantially equivalent in technical performance and intended use to the FDA cleared device" (Bayer Immuno 1™ Troponin I Assay cleared under Document Control No. K973616). The changes are "limited to modifications in the indications for use."

Therefore, the "acceptance criteria" in this context would likely be that the updated device maintains the performance characteristics of the predicate device and that the new indication for use is supported without compromising safety or effectiveness. The document highlights the new indication for use: "...in the risk stratification of patients with non-ST segment elevation acute coronary syndromes with respect to relative risk of mortality, myocardial infarction or increased probability of ischemic events requiring urgent revascularization procedures."

Therefore, the "reported device performance" is essentially that it performs equivalently to the predicate device for its original indications and its added indication for risk stratification is supported. However, no specific performance metrics (like sensitivity, specificity, or agreement rates) related to this new indication are present in this summary.

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 does not provide any details on the sample size used for a test set, the country of origin of the data, or whether it was retrospective or prospective. The summary focuses on the device description and regulatory aspects rather than detailed clinical study results.

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 document does not provide any information about experts used to establish ground truth or their qualifications. Given that this is an in vitro diagnostic device for measuring Troponin I, the "ground truth" would typically refer to validated clinical outcomes (e.g., confirmed myocardial infarction, mortality) rather than expert consensus on image interpretation.

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

The document does not mention any adjudication method for a test set.

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 document describes an immunoassay method for measuring Troponin I, not an AI-assisted diagnostic tool or imaging system that would involve "human readers" or an MRMC study. Therefore, no MRMC comparative effectiveness study was done in the context of improving human reader performance with AI assistance.

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

This is an immunoassay device that provides a quantitative measurement. The device itself is "standalone" in that it performs the measurement without human-in-the-loop performance influencing the test result. However, the interpretation of the Troponin I concentration and its use in diagnosis and risk stratification requires clinical input (e.g., "When used in conjunction with other clinical data, such as presenting symptoms and diagnostic procedures..."). The summary does not present any data on the standalone performance in terms of diagnostic accuracy or risk stratification without clinical context.

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

The document does not explicitly state the type of ground truth used for any studies that might have supported the new indication. For the risk stratification indication, it is highly probable that the ground truth would have been based on outcomes data such as mortality, confirmed myocardial infarction, or the need for revascularization procedures. However, this is inferred, not stated. For the underlying quantitative measurement, the ground truth would be the true concentration of Troponin I in the sample.

8. The sample size for the training set

The document does not provide any information about the sample size for a training set. This is a traditional immunoassay device, not a machine learning or AI-based system that typically uses training sets in the same manner.

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

As described above, this is an immunoassay device, so the concept of a "training set" for ground truth establishment in the context of machine learning is not applicable here.

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This in vitro diagnostic procedure is a solid- phase enzyme immunoassay intended for the quantitative determination of Troponin I in human serum and plasma on the Bayer Immuno 1 system. When used in combination with other clinical data such as presenting symptoms and diagnostic procedures, measurement of Troponin I aids in the diagnosis of acute myocardial infarction.

The Baver Immuno 1 Troponin I™ assay is an enzyme label sandwich assay using a monoclonal and a polvclonal antibody. A Troponin I specific monoclonal antibody is labeled with fluorescein and a Troponin I specific goat affinity purified antibody is labeled with alkaline phosphatase (ALP). The solid phase consists of a suspension of magnetizable particles coated with antibody to fluorescein (mIMP reagent). Sample or cailbrator, R1 reagent containing fluorescein - antibody conjugate. R2 reagent containing ALP-antibody conjugate and mIMP reagent are mixed and incubated at 37°C. In the presence of Troponin I a (fluorescein-conjugate: Troponin I:ALPconjugate) complex is formed and captured by the anti fluorescein antibodies on the magnetic particles. The particles are washed and para-nitrophenvl phosphate solution is added. The ALP in the antibody conjugate reacts with the substrate to form para-nitrophenoxide and phosphate. Increasing absorbance due to the formation of para-nitrophenoxide is monitored at 405 nm and 450 nm. The dose response curve is directly proportional to the concentration of Troponin I in the sample. A linear point fit is used to construct the dose response curve. The Baver Immuno 1 Troponin ITM assay has a range of 0 to 200 ng/ml and liquid calibrators are provided with values of 0, 5, 10, 20, 60 and 200 ng/ml Troponin I. Bayer Immuno 1 Troponin I TEST point controls are provided with values of 3, 7, 50 ng/mL Troponin I.

Here's a breakdown of the acceptance criteria and study information for the Bayer Immuno 1™ System Troponin I method, based on the provided text:

Acceptance Criteria and Device Performance

The submission relies on demonstrating substantial equivalence to a predicate device, the Dade Stratus® Troponin I kit. Therefore, the "acceptance criteria" are implicitly defined by the performance characteristics of the predicate device and the new device's ability to demonstrate comparable performance. The key performance indicators evaluated are imprecision (precision), linearity (recovery), correlation with the predicate device, and minimum detectable concentration (detection limit).

Study Details

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

   • Imprecision: Human serum samples were analyzed. The number of samples is not explicitly stated, but the analysis involved duplicate measurements on two instruments over 18 days. This suggests a total of 18 days * X samples/day (where X is at least 1) * 2 duplicates * 2 instruments = at least 72 measurements (if only one sample type was used per run).
   • Linearity: Human AMI patient pools. The number of pools or individual samples is not specified.
   • Correlation: 279 patient samples.
   • Expected Values:
     • Healthy Red Cross blood donors: 197 specimens.
     • Angina patients: 64 specimens.
     • AMI patients: 41 specimens.
   • Data Provenance: Not explicitly stated, but likely retrospective as it involves analyzing "patient samples" and "specimens." The mention of "clinical trial sites" for the correlation study suggests multi-site data collection, but specific countries are not mentioned.

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

   • For expected values in different patient populations (healthy, angina, AMI), the "clinical diagnosis of angina" and "clinical diagnosis of AMI" serve as the ground truth. The number and qualifications of clinicians making these diagnoses are not specified.
   • For the correlation study, the "Dade Stratus® Troponin I method" is used as a reference for the Troponin I values in the patient samples, rather than an expert panel.

3. Adjudication method for the test set:

   • No adjudication method (e.g., 2+1, 3+1) is mentioned, as the study primarily relies on quantitative measurements and comparison to a predicate device or predefined clinical diagnoses.

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 MRMC study was done. This submission is for an in-vitro diagnostic (IVD) assay which provides a quantitative measurement, not an AI-assisted diagnostic imaging or interpretation device that would involve human "readers."

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

   • This is an in-vitro diagnostic assay, which by nature operates as a standalone system to measure analyte concentration. The performance characteristics described are "algorithm only" in the sense that they represent the performance of the assay itself in generating a quantitative result. There is no human "in-the-loop" once the sample is processed by the Immuno 1 system.

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

   • For correlation: The predicate device's measurements (Dade Stratus® Troponin I method) served as the comparative "ground truth" for the new device's measurements.
   • For expected values: Clinical diagnoses (e.g., "clinical diagnosis of angina," "clinical diagnosis of AMI") were used to categorize patients for expected value determination.
   • For linearity and imprecision: Ground truth is established by the known concentrations in engineered samples (calibrators, controls, diluted pools) or by statistical analysis of repeat measurements.

7. The sample size for the training set:

   • This submission describes performance characteristics and validation studies. No specific "training set" for an algorithm is mentioned, as the device is a chemical immunoassay, not a machine learning model.

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

   • As there is no distinct "training set" for an algorithm in this context, this question is not applicable. The assay itself involved development and optimization, but standard laboratory practices and known concentrations in controls and calibrators would have guided this, rather than a formal "ground truth for a training set" as understood in AI/ML contexts.

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