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The IDS-iSYS Free Testosterone assay is an in vitro diagnostic device intended for the quantitative determination of free testosterone in human serum or the IDS system. Measurement of free testosterone is used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, impotence in male and in females; hirsutism (excessive hair) and virilization) due to tumors, polycystic ovaries and androgenital syndromes.

The IDS-iSYS Free Testosterone assay consists of a reagent cartridge. The reagent cartridge contains multiple reagents:

• MP3: Magnetic particles coated with Streptavidin in a phosphate Pluronic buffer with sodium azide (NaN3) as preservative (< 0.1%). 1 bottle, 2.5 mL.
• CONJ: Testosterone labelled with an acridinium ester derivative, in phosphate buffer containing bovine protein with ProClin 300 as preservative (< 0.0015%). 1 bottle, 3.5 mL
• Ab-BIOT: Monoclonal anti-Testosterone labelled with Biotin in MES buffer with ProClin 300 as preservative (<0.0015%). 1 bottle, 7.5 mL
• Cal A: Human serum matrix containing human free testosterone with sodium azide and ProClin 300 as preservatives (<0.1% and 0.0024% respectively). 1.0 mL per bottle
• Cal B: Human serum matrix containing human free testosterone with sodium azide and ProClin 300 as preservatives (<0.1% and 0.0024% respectively). 1.0 mL per bottle

The provided document describes the analytical performance of the IDS-iSYS Free Testosterone assay but does not detail a device performance study with acceptance criteria in the typical format of a clinical trial for an AI/ML medical device. Instead, it focuses on the analytical characteristics of the in vitro diagnostic device, comparing it to a predicate device and demonstrating its performance through various laboratory tests.

Here's an attempt to structure the information based on your request, with the understanding that not all requested points are directly applicable to this type of IVD submission:

1. Table of Acceptance Criteria and Reported Device Performance

For an in vitro diagnostic device like the IDS-iSYS Free Testosterone, "acceptance criteria" and "reported device performance" are typically defined by analytical performance characteristics, such as sensitivity, precision, linearity, and interference. The document presents these values but does not explicitly state pre-defined acceptance criteria for each measurement that would be found in a clinical study protocol. However, we can infer performance targets based on the data presented and common medical device standards (e.g., CLSI guidelines).

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

The "test set" in this context refers to the samples used for analytical validation studies.

• Analytical Limits (LoB, LoD, LoQ): 60 replicates of 4 blank samples and 6 low-concentration samples for LoB/LoD; 105 replicates of 7 low-concentration samples for LoQ.
• Repeatability: 10 serum samples, 80 replicates per sample.
• Reproducibility (System/Operator): 9 serum samples, 75 replicates per sample.
• Reproducibility (Lot-to-Lot): 9 serum samples, 75 replicates per sample.
• Linearity: The number of unique samples is not specified, but the study evaluated the measurement procedure's linearity from 0.12 pg/mL to 68.12 pg/mL.
• Cross-Reactivity: 2 samples (1.0 and 15 pg/mL free testosterone) spiked with various cross-reactants.
• Interference: 2 samples (1.0 and 45.0 pg/mL free testosterone) spiked with various interfering agents.
• Method Comparison: 241 samples. The document does not specify the country of origin or if these were retrospective or prospective samples, but they are patient samples covering a wide range of concentrations.
• Matrix Comparison: 40 samples for each matrix (SST, K2 EDTA, Li Heparin, Na Heparin) compared against serum.
• Expected Values:
  • Females: 130 (21-39 yrs), 57 (40-59 yrs), 67 (>=60 yrs)
  • Males: 129 (21-39 yrs), 138 (40-59 yrs), 42 (>=60 yrs)
    The provenance of these subjects is not stated, but they are described as "apparently healthy adults and children."

3. Number of Experts Used to Establish Ground Truth and Qualifications

This information is not applicable to this document. The "ground truth" for an IVD device like this is typically established by reference methods or gravimetric preparation of calibrators/controls, not by human expert opinion as would be the case for image-based AI/ML diagnostics. The values are quantitative measurements of a biochemical marker.

4. Adjudication Method for the Test Set

This information is not applicable. Adjudication methods (e.g., 2+1, 3+1) are common in studies where human readers interpret data (like medical images) and their agreement, or lack thereof, needs to be resolved. For an IVD, the "ground truth" is a measured concentration, and the accuracy is assessed against reference standards or established methods.

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

This information is not applicable. An MRMC study assesses how human readers' performance changes with and without AI assistance. This device is an in vitro diagnostic assay, directly measuring a biomarker without human interpretation in the workflow described.

6. Standalone (Algorithm Only) Performance

The performance data presented throughout the document (LoB, LoD, LoQ, precision, linearity, cross-reactivity, interference, method comparison, matrix comparison) is the standalone performance of the IDS-iSYS Free Testosterone assay. This device is a fully automated assay system, and its performance is evaluated independent of human interpretive steps.

7. Type of Ground Truth Used

The ground truth for the analytical studies is generally based on:

• Known concentrations: For LoB, LoD, LoQ, linearity, cross-reactivity, and interference, samples are prepared with known or target concentrations of free testosterone and potential interfering substances.
• Comparative methods: For method comparison, a "commercially available quantitative free testosterone ELISA" serves as the comparative method against which the IDS-iSYS Free Testosterone is measured.
• Reference Intervals: For expected values, "95% reference interval for apparently healthy adults and children" was calculated using a non-parametric method, likely referring to the distribution of measurements in that population.

8. Sample Size for the Training Set

This information is not provided and is typically not applicable in the same way it would be for an AI/ML device. For an IVD assay, "training" involves the development and optimization of the assay reagents, protocols, and calibration, rather than training a machine learning model on a distinct dataset. The "training set" for an IVD refers to the samples used to develop and refine the assay's performance characteristics and establish its calibration curve, which is distinct from the analytical validation samples.

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

This information is not explicitly provided in the document. For an IVD, the "ground truth" for developing a training set (i.e., for calibration) typically involves:

• Gravimetric preparation: Precisely weighing and dissolving a known amount of the analyte (free testosterone) in a suitable matrix to create primary calibrators with accurate, traceable concentrations.
• Reference methods: Using highly accurate and validated reference methods (e.g., LC-MS/MS, though not specified here) to assign values to calibrators or control materials.
• Standardization: Following established industry and regulatory standards (e.g., CLSI guidelines) for calibrator preparation and value assignment to ensure accuracy and traceability.

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IDS ACTH II assay is an automated in vitro diagnostic device intended for the quantitative, determination of ACTH in human K2 and K3 EDTA plasma on the IDS system. Results are to be used in conjunction with other clinical and laboratory data as an aid in the assessment of pituitary and adrenal gland function and the differential diagnosis of hyper- and hypo-cortisolism.

The IDS ACTH II assay consists of a reagent cartridge. The reagent cartridge contains multiple reagents:

• MP: Magnetic particles coated with mouse monoclonal anti-ACTH antibody and buffer containing phosphate with blocking proteins and ProClin 300 as preservative.
• R1: Mouse monoclonal anti-ACTH antibody labelled with an acridinium ester derivative, in buffer containing phosphate with BSA and ProClin 300 as preservative.
• R2: Buffer containing phosphate with blocking proteins and ProClin 300 as preservative.

The provided text describes the performance characteristics of the IDS ACTH II assay, which is an automated in vitro diagnostic device for the quantitative determination of ACTH in human K2 and K3 EDTA plasma. The study aims to demonstrate that the device meets the acceptance criteria for various analytical performance parameters.

Here's a breakdown of the requested information:

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

The document does not explicitly state "acceptance criteria" as a separate column for each test. Instead, it describes the methodology used to determine each performance characteristic and then presents the results. Based on the context and the nature of these studies, the reported values often serve as the demonstrated "performance" which, by the conclusion of the 510(k) summary, are deemed sufficient to support substantial equivalence. For analytical characteristics like Linearity, Interference, and Cross-Reactivity, the document does specify thresholds for acceptable performance.

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

• Analytical Limits (LoB, LoD, LoQ):
  • LoB and LoD: 60 replicates of 4 blank samples and 6 low concentration samples per reagent lot.
  • LoQ: 90 replicates of 6 low concentration samples per reagent lot.
• Precision (Repeatability): 5 plasma samples, 80 replicates each (duplicate, twice a day for 20 days).
• Precision (Reproducibility – between sites/systems): 5 plasma samples, 75 replicates each (5 replicates, once a day for 5 days on 3 systems).
• Precision (Reproducibility – between lots): 5 plasma samples, 75 replicates each (5 replicates, once a day for 5 days on 1 system using 3 reagent lots).
• Linearity: The sample size isn't explicitly stated as a single number but involved testing across the analytical measuring interval of 4 to 1000 pg/mL.
• Analytical Specificity (Interference): 2 samples containing 15 and 200 pg/mL ACTH for most interfering agents; 2 samples containing 30 and 500 pg/mL ACTH for Total Cholesterol.
• Analytical Specificity (Cross-Reactivity): 2 samples containing 20 and 400 pg/mL ACTH spiked with various cross-reactants.
• Method Comparison: 170 patient samples for comparison against the predicate device.
• Matrix Comparison: 55 matched samples for K2 vs K3 EDTA comparison.
• Expected Values (Reference Interval): 140 apparently healthy adults.

Data Provenance: The document does not specify the country of origin of the data or whether the samples were retrospective or prospective, except that the submitter is based in the United Kingdom.

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 is an in vitro diagnostic device (an assay), not an imaging or diagnostic AI system that requires expert interpretation for ground truth. The "ground truth" for the performance characteristic studies (like LoQ, precision, linearity, interference, cross-reactivity, and method comparison) is established by the analytical measurement itself, often compared against a reference method or known spiked concentrations. For method comparison, another commercially available, quantitative automated assay serves as the comparative reference. For the reference interval study, the "ground truth" is derived from the measured ACTH concentrations in a defined population of apparently healthy adults using the IDS ACTH II assay itself, following CLSI guidelines for establishing reference intervals.

Therefore, the concept of "experts establishing ground truth" in the way it applies to imaging studies (e.g., radiologists) is not relevant here.

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

Adjudication methods like 2+1 or 3+1 are typically used in clinical trials or diagnostic studies where there's human interpretation involved and potential for disagreement. This document describes analytical performance studies of an IVD assay, where the results are quantitative measurements. The methods followed standard CLSI guidelines (e.g., EP17-A, EP05-A3, EP06, EP07-A3, EP-9A2, C28-A3) for laboratory testing, which do not generally involve an adjudication process in the same way clinical judgment studies would.

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, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic assay, not an AI-assisted diagnostic tool that involves human readers.

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

This is an automated in vitro diagnostic assay, meaning it operates in a standalone manner (algorithm only, without human-in-the-loop performance for result generation or interpretation, beyond standard laboratory procedures). The performance data presented are for the device's inherent analytical capabilities.

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

• Analytical Limits, Precision, Linearity, Interference, Cross-Reactivity: Ground truth is established through controlled laboratory experiments using known concentrations (e.g., spiked samples, blank samples, reference materials) and rigorous statistical analysis as per CLSI guidelines.
• Method Comparison: The "ground truth" for method comparison is the measurement obtained from a predicate, commercially available quantitative automated assay using patient samples, against which the candidate device's measurements are compared.
• Reference Intervals: The "ground truth" for expected values is the statistical distribution of ACTH concentrations measured by the IDS ACTH II assay itself in a predefined population of apparently healthy adults (n=140).

8. The sample size for the training set

The concept of a "training set" is typically associated with machine learning or AI models. This document describes the validation of an IVD assay. The assay itself does not involve a machine learning model that requires a distinct training set. The various sample sizes mentioned in point 2 are for different performance characteristic evaluation tests.

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

As there is no "training set" in the context of an AI/ML model for this IVD assay, this question is not applicable. The assay's analytical characteristics are established through chemical and immunochemical principles and validated through the performance studies described.

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