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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 (

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).

*   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.

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The IDS SHBG assay is an in vitro diagnostic device intended for the quantitative determination of SHBG in human serum or plasma on the IDS System. Results are to be used as an aid in the diagnosis of androgen disorders

The IDS SHBG assay is an in vitro diagnostic device intended for the quantitative determination of sex hormone binding globulin (SHBG) in human serum and plasma on the IDS-iSYS Multi-Discipline Automated System. Results are to be used in conjunction with other clinical and laboratory data to assist the clinician in the diagnosis of androgen disorders.

The assay is based on chemiluminescence technology. 5 uL of patient sample or calibrators are incubated with biotinylated monoclonal anti-SHBG antibody, an acridinium labelled monoclonal anti-SHBG conjugate and streptavidin labelled magnetic particles. The magnetic particles are captured using a magnet and a wash step performed to remove any unbound analyte. Trigger reagents are added; the resulting light emitted by the acridinium label is directly proportional to the concentration of analyte in the original sample.

The IDS SHBG assay is an in vitro diagnostic device consisting of ready to use reagents provided in individual compartments within the reagent cartridge.

The reagent cartridge contains:

• Magnetic particles magnetic particles coated with streptavidin in a phosphate buffer containing preservatives
• -Biotin antibody - monoclonal anti-SHBG labelled with biotin in a buffer containing proteins and preservatives
• Conjugate monoclonal anti-SHBG labelled with an acridinium ester derivative in a buffer containing proteins and preservatives The calibrators consist of:
• Calibrators A and B are included in the assay kit. The calibrators consist of a human serum matrix with defined concentrations of SHBG and preservatives. Together with a lot specific master calibration curve, the calibrators will be used to perform adjustment of the master calibration curve.

The provided document is a 510(k) summary for the IDS SHBG assay, an in vitro diagnostic device for the quantitative determination of Sex Hormone Binding Globulin (SHBG). The document details the device's performance characteristics and compares it to a predicate device to demonstrate substantial equivalence.

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

Key Takeaway: This document describes the validation of an in vitro diagnostic (IVD) assay, not an AI/ML-based diagnostic device that typically involves human readers or image analysis. Therefore, many of the requested categories (e.g., number of experts, adjudication method, MRMC studies, human reader improvement with AI, standalone AI performance) are not applicable to this type of device and study. The ground truth in this context is established by reference methods or validated reference materials, typical for IVD assays.

1. Table of Acceptance Criteria and Reported Device Performance

The document describes several analytical performance characteristics that serve as "acceptance criteria" for the IDS SHBG assay. These are primarily related to the accuracy, precision, limits of detection, and specificity of the assay.

• Triglycerides: up to 3000 mg/dL
• Haemoglobin: up to 500 mg/dL
• Bilirubin (conjugated/unconjugated): up to 40 mg/dL
• Total Protein: up to 12 g/dL
• Biotin: up to 6000 ng/mL (and 1500 ng/mL)
• Rheumatoid Factor: up to 7000 IU/mL
• HAMA: up to 3000 ng/mL
• Cholesterol: up to 456 mg/dL
• Various common drugs (e.g., Acetaminophen, Ibuprofen, Ascorbic acid, Creatinine, Dopamine, Tetracycline, Tolbutamide, Tolazamide, Uric Acid). |
  | Analytical Specificity (Cross-Reactivity) | No significant cross-reactivity with structurally similar compounds or other biological substances up to tested concentrations. | Low/No significant cross-reactivity observed (50y:** 14.85 – 65.21 nmol/L (n=180)
  Premenopausal Females: 20.30 – 140.18 nmol/L (n=206)
  Postmenopausal Females: 11.30 – 127.31 nmol/L (n=120)
  (Based on 671 apparently healthy adults from the United States). |

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

• Precision/Reproducibility: 14 serum-based samples at different SHBG concentration levels covering the assay range. Tested across 21 days for one kit lot. (Table 11 shows individual sample IDs, CTLs, CALBs, IQCs)
• Linearity/Assay Reportable Range:
  • Linearity: A high human serum sample and a low human serum sample, plus 14 evenly spaced dilutions created by mixing high and low samples.
  • Automated Post-dilution Accuracy: 9 native samples with known SHBG concentrations obtained from the predicate device.
• Traceability of Calibrator:
  • Value assignment of Internal Reference Standards (IRs): At least 24 runs using three iSYS instruments, 2 kit lots, 3 replicates for each run. Serial dilutions of WHO 2nd international standard 08/266 used.
  • Value assignment of kit calibrators: At least 20 runs (14 runs using previous IR lot, 6 runs using international standard) using one iSYS instrument, 2 replicates for each run.
  • Value assignment verification: Internal quality controls at 3 SHBG levels tested in five replicates in one run and on each of three different iSYS instruments.
  • Correlation study (2-point calibration vs. IS 08/266 curve): 189 samples (139 serum, 50 K2 EDTA plasmas). Tested in two replicates using three lots (MB1, MB2, MB3) on one iSYS instrument.
• Detection Limit (LoB, LoD, LoQ):
  • LoB: LoB sample run in 12 replicates for each of 5 runs over 3 days, by one operator, on one different instrument for each of 3 manufacture batches (MB1, MB2B, MB3) = total 60 replicates per lot.
  • LoD: 7 LoD samples measured in duplicate. For each of 3 kit lots, 5 assays over 3 days by one operator on a different instrument = total 70 replicates per lot.
  • LoQ: Panel of 9 samples measured in singlicate two times per day. For each of 3 kit lots, 10 assays over 5 days by one operator on a different instrument = total 90 replicates per lot.
• Analytical Specificity (Interference): Two serum samples (low and high SHBG conc.) spiked with potential interferents. Control samples were also run. Number of replicates for each specific test not detailed but implied to be sufficient for statistical comparison.
• Analytical Specificity (Cross-Reactivity): Low and high SHBG samples spiked with various cross-reactants. Number of replicates for each specific test not detailed.
• Method Comparison: 136 samples, selected to represent a wide range of SHBG concentrations (2.54 - 172.12 nmol/L).
• Matrix Comparison: 69 samples (68 native, 1 diluted) covering a range of 0.51 to 238.45 nmol/L.
• Expected Values/Reference Range: 671 serum samples from apparently healthy adults (21-77 years old). Data Provenance: From the United States. Retrospective/Prospective: Not explicitly stated, but typically such studies for establishing reference ranges are retrospective collections of banked samples or a prospective study designed to collect samples from a healthy population.

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

Not Applicable (N/A).

This is an in vitro diagnostic (IVD) assay quantifying a biomarker (SHBG). "Ground truth" for an IVD assay is established through:

• Reference Methods: Such as the WHO 2nd international standard 08/266 for SHBG, against which the calibrators are standardized.
• Known Concentrations: Use of accurately prepared standards, spiked samples, or samples extensively characterized by reference methods.
• Clinical Data: For expected values, SHBG concentrations are measured in samples from defined healthy populations.

Therefore, the concept of "experts establishing ground truth" in the way it applies to image interpretation or AI-assisted diagnostics (e.g., radiologists labeling images) is not relevant here. The ground truth is analytical and based on metrological traceability to international standards.

4. Adjudication Method for the Test Set

N/A.

Adjudication methods (like 2+1, 3+1) are relevant for subjective interpretations (e.g., radiology reads) where discrepancies between readers need to be resolved to establish a definitive ground truth. For a quantitative IVD assay like IDS SHBG, the "reading" is a numerical output from the instrument based on chemical reactions. Accuracy is determined by comparison to reference materials or established methods, not by human adjudication of interpretations.

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

N/A.

This is an IVD assay, not an AI/ML diagnostic for human interpretation. No MRMC study or human reader improvement with AI assistance is applicable.

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

N/A.

This is not an AI/ML algorithm. The "device" is a fully automated immunoassay system (IDS-iSYS Multi-Discipline Automated System) that performs the biochemical analysis and reports a quantitative result without human "interpretation" of a signal beyond reading the numerical output. Its performance is evaluated as a standalone analytical system.

7. The Type of Ground Truth Used

The ground truth for the analytical performance studies (precision, linearity, detection limits, specificity, method comparison) is based on:

• International Reference Standards: Specifically, the WHO 2nd international standard for SHBG (IS 08/266) for traceability and calibration. This is the primary reference.
• Known Concentrations/Spiked Samples: Samples with defined, known concentrations of SHBG or interferents, prepared in a laboratory setting.
• Comparison to a Legally Marketed Predicate Device: The Siemens ADVIA Centaur SHBG assay (K151986) was used as a comparative method to assess agreement and accuracy (e.g., for method comparison and automated dilution accuracy).
• Healthy Population Data: For expected values/reference ranges, a large cohort of apparently healthy individuals were tested to establish population-specific normal ranges.

8. The Sample Size for the Training Set

N/A (for AI/ML 'training set' in the traditional sense).

For an IVD assay, the equivalent of a "training set" would be the samples and calibrators used during the assay's development and optimization phases to set parameters, establish reagent formulations, and fine-tune the system. This information is typically proprietary development data and is not explicitly detailed as a 'training set' in 510(k) summaries, which focus on the final validation/test data.

The closest analogous "training" or "calibration" process mentioned is the traceability and value assignment of calibrators:

• Value assignment of secondary standards (IRs) involves at least 24 runs (using 3 instruments, 2 kit lots, 3 replicates) comparing to the WHO international standard.
• Value assignment of IDS SHBG kit calibrators A and B involves at least 20 runs (1 instrument, 2 replicates) using the secondary standards and IS-08/266.
  These processes are used to establish the calibration curve for the assay.

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

N/A (for AI/ML 'training set').

As explained in point 8, the concept of a "training set" for an IVD assay is different from that for AI/ML. The "ground truth" for establishing the calibration and parameters of the assay is based on:

• Metrological traceability to the WHO 2nd international standard for SHBG (IS 08/266). This involved serial dilutions of the international standard in SHBG-depleted human serum to create reference points.
• Use of internal reference calibrators (IRs) that were themselves value-assigned against the WHO standard.

The goal is that the assay's measurements accurately reflect the true concentration of SHBG as defined by an international reference.

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The IDS-iSYS Intact PTH+ assay is an in vitro diagnostic device intended for the quantitative determination of intact PTH in human serum or plasma on the IDS-iSYS Multi-Discipline Automated System. Results are to be used in the differential diagnosis of hypercalcemia and hypocalcemia resulting from disorders of calcium metabolism.

The IDS-iSYS Intact PTH" assay is based on chemiluminescence technology. 100 uL of patient sample is incubated with a biotinylated polyclonal anti-PTH (39-84) antibody and an acridinium labelled PTH (13-34) antibody. Streptavidin labelled magnetic particles are added prior to a second incubation step. The magnetic particles are captured using a magnet and a wash step performed to remove any unbound analyte. Trigger reagents are added; the resulting light emitted by the acridinium label is directly proportional to the concentration of Intact PTH in the original sample.

IDS-iSYS Intact PTH reagent kit consists of one (1) Immunoassay Cartridge, two (2) vials each of 2 concentration Calibrator levels and a mini-CD containing the Instructions For Use (IFU), CRY files and Certificate of Analysis.

IDS-iSYS Intact PTHN Cartridge, sufficient for 100 tests, consists of reagents provided in individual compartment within a plastic container called the Cartridge. The IDS-iSYS Intact PTHN Cartridge contains the following ready to use reagents:

• · Magnetic particles coated with streptavidin in a phosphate buffer containing sodium azide as preservative (1% (w/w%).
• · Calibrator B: Two vials of lyophilized porcine serum matrix buffer containing high level PTH and sodium azide as preservative >1% (w/w%).

The submission is due to a new source of antibody for the assay.

This document describes the performance characteristics of the IDS-iSYS Intact PTHN assay, an in vitro diagnostic device for quantitative determination of intact PTH.

Here's an analysis of the acceptance criteria and study information provided:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as distinct numerical targets but are implicitly defined by the reported performance and the comparison to the predicate device. The information below summarizes the performance characteristics provided, which in a regulatory context, demonstrate the device meets its intended use and is substantially equivalent to the predicate.

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The IDS iSYS 25 VilD assay is intended for the quantitative determination of total 25-hydroxyvitamin D (125(OH)D) in hyman serum or plasma on the IDS iSYS Multi-Discipline Automated System. Results are to be used in conjunction with other clinical and laboratory data to assist the clinician in the assessment of vitamin D sufficiency in an adult population.

The IDS-iSYS 25 VitD Control Set is used for quality control of the IDS-iSYS 25 VitD assay on the IDS-iSYS Multi-Discipline Automated System.

The IDS-iSYS 25 VitDs reagent kit consists of one (1) Immunoassay Cartridge, one (1) vial each of 2 concentration Calibrator levels and a mini-CD containing the Instructions For Use (IFU), CRY files and Certificate of Analysis.

IDS-iSYS 25 VitDS Cartridge, sufficient for 100 tests, consists of reagents provided in individual compartment within a plastic container called the Cartridge. IDS-iSYS 25 VitDS Cartridge contains the following ready to use reagents:

• Magnetic particles coated with streptavidin in a phosphate . buffer containing sodium azide.
• . Sodium hydroxide solution.
• . 25(OH)D labelled with an acridinium ester derivative, in buffer containing bovine serum albumin with sodium azide.
• . Anti-25(OH)D sheep polyclonal antibody labelled with an biotin, in buffer containing bovine, sheep and mouse proteins and sodium azide.
• . Assay buffer containing proprietary displacing compounds, methanol and sodium azide.

The IDS-iSYS 25 VitD® Calibrators are included in the reagent kit. The ready to use calibrators contains human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide as preservative (

The provided document describes the IDS-iSYS 25VitD8 assay, a device for the quantitative determination of total 25-hydroxyvitamin D [25(OH)D] in human serum or plasma. Below is an analysis of its acceptance criteria and the studies performed.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal "acceptance criteria" for all performance characteristics in a single, consolidated table. However, it presents performance data for various analytical characteristics, and in some cases, implicitly defines acceptable ranges or desired outcomes for these studies. For instance, in the specificity study, an acceptance criterion of "

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The IDS-iSYS Aldosterone assay (IS-3300) is a device intended for use in clinical laboratories for the quantitative determination of Aldosterone in human EDTA plasma on the IDS-iSYS Multi-Discipline Automated System. Aldosterone measurements are used in the diagnosis and treatment of primary aldosteronism (a disorder caused by excessive secretion of Aldosterone by the adrenal gland), hypertension caused by primary aldosteronism, selective hyperaldosteronism, edematous states and other conditions of electrolyte balance.

The IDS-iSYS Aldosterone Control Set (IS-3330) is intended for use as assaved quality control samples to monitor the accuracy of the IDS-iSYS Aldosterone assay on the IDS-iSYS Multi-Discipline Automated System.

The IDS-iSYS Aldosterone Calibration Verifiers (IS-3335) are intended for medical purposes for use in the quantitative verification of calibration of the IDS-iSYS Aldosterone assay on the IDS-iSYS Multi-Discipline Automated System.

The IDS-iSYS Aldosterone assay is based on chemiluminescence technology. A biotinylated monoclonal anti-Aldosterone antibody is incubated with the sample, after an incubation step an Aldosterone acridinium conjugate is added and after a further incubation step streptavidin coated magnetic particles are added. Following a third incubation step the particles are "captured" using a magnet. After a washing step and addition of trigger reagents, the light emitted by the acridinium label is inversely proportional to the concentration of Aldosterone in the original sample.

Here's an analysis of the provided text to extract the requested information about acceptance criteria and the supporting study:

The provided document is a 510(k) Summary for the IDS-iSYS Aldosterone assay, control set, and calibration verifiers. It focuses on demonstrating substantial equivalence to a predicate device, as required for FDA clearance. The document details performance characteristics but does not explicitly state acceptance criteria in a pass/fail format typical of formal acceptance criteria documents. Instead, it reports performance values found during validation studies.

Here's the breakdown of the information you requested, based on what's available in the document:

1. Table of Acceptance Criteria and Reported Device Performance

As mentioned, explicit "acceptance criteria" are not listed in a single table. However, the performance characteristics are reported, and implicitly, these values are considered acceptable for demonstrating substantial equivalence. The table below compiles the reported performance data from the document.

Note: The document does not provide a column for "Acceptance Criteria" as a separate, pre-defined target. The "Reported Device Performance" is the outcome of the studies aiming to demonstrate acceptable performance.

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

• Precision/Reproducibility:

  • Sample Size: Six EDTA plasma samples (9 "samples" were run over 20 days, generating 80 replicates per sample concentration).
  • Data Provenance: Not explicitly stated, but clinical laboratory setting is implied. The phrase "two sites using three analyzers" could suggest multi-center testing, potentially from different locations/countries, but this is not specified. The studies were performed for the manufacturer for regulatory submission.

• Linearity/Assay Reportable Range:

  • Sample Size: One high plasma sample diluted with a low sample to create 11 dilution samples. Run in quadruplicate.
  • Data Provenance: Not specified, likely internal laboratory data for the manufacturer.

• Detection Limit (LoB, LoD, LoQ):

  • Sample Size:
    • LoB (Lot 1): One zero-aldosterone plasma sample, 10 replicates for 5 days (total 50 replicates).
    • LoD/LoQ (Lot 1): 7 samples, 2 replicates per sample, once per day for 8 days.
    • LoB (Lot 2): One zero-aldosterone plasma sample, 6 replicates for 5 days (total 30 replicates).
    • LoD (Lot 2): 8 samples, 2 replicates per sample, once per day for 5 days.
    • LoQ (Lot 2): 7 samples, 2 replicates per sample, once per day for 5 days.
  • Data Provenance: Not specified, likely internal laboratory data for the manufacturer. Two different sites and two different analyzers were used.

• Analytical Specificity (Interference and Cross-Reactivity):

  • Sample Size:
    • Interference: Two base plasma samples ("Low" and "High" Aldosterone concentrations), spiked with various potential interferents. For each interferent, 26 replicates for blank and spiked samples were compared.
    • Cross-reactivity: Stock solutions of various compounds diluted serially to create 7-point standard curves for each substance.
  • Data Provenance: Not specified, likely internal laboratory data for the manufacturer.

• Method Comparison:

  • Sample Size: 161 samples (including 12 altered samples).
  • Data Provenance: Not specified, implied to be clinical or patient samples. Whether these were retrospective or prospective, or their country of origin, is not mentioned.

• Reference Range Study (Expected Values):

  • Sample Size: 228 Caucasian adult samples.
  • Data Provenance: Collected in the US, prospective (samples collected under specific conditions: 7-10 am after overnight fasting, upright/supine positions).

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

This type of information is generally NOT applicable to in vitro diagnostic (IVD) devices like the Aldosterone assay described. For IVD assays, "ground truth" is typically established by:

• Reference methods/predicate devices (e.g., Diasorin Liaison Aldosterone assay for method comparison).
• Gravimetric preparation of standards and calibrators for traceability.
• Defined sample characteristics (e.g., "zero aldosterone plasma," "high plasma sample").

There were no human experts assessing images or making diagnoses that would require adjudication.

4. Adjudication Method for the Test Set

Not applicable, as this is an IVD assay, not a device requiring human interpretation of results in a diagnostic context that would call for adjudication of different interpretations.

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

Not applicable. This is an IVD assay for quantitative determination of a biomarker; there are no "human readers" interpreting results in the way an MRMC study would be designed for an imaging AI device.

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

Yes, the studies conducted (Precision, Linearity, LoD/LoQ, Analytical Specificity, Method Comparison) represent the standalone performance of the IDS-iSYS Aldosterone assay system. The device quantifies aldosterone in plasma samples directly, without human interpretation of results being a variable in its core analytical performance.

7. The Type of Ground Truth Used

The ground truth used for various studies includes:

• Reference materials: Aldosterone (≥95% HPLC; A9477Sigma-Aldrich) dissolved in Dioxane, with concentration calculated by UV quantitation using molar extinction coefficient (for calibrators and traceability).
• Predicate device results: The Diasorin Liaison Aldosterone assay (K130321) for method comparison.
• Spiked samples: For linearity, interference, and cross-reactivity studies, known concentrations of analyte or interferents were added to base samples to create "true" concentrations.
• Patient samples: For method comparison and reference range studies, patient samples were used. Their "truth" for method comparison was established by the predicate device. For reference ranges, the "truth" was the measured value distributed among a healthy population.

8. The Sample Size for the Training Set

The document describes performance studies (validation) but does not explicitly mention a "training set" in the context of machine learning. For an IVD assay, the development process involves reagent optimization, calibration curve fitting, etc., which conceptually use data, but this is not typically termed a "training set" like in AI/ML.

However, the "Master curve" and "two-point calibration" system is mentioned. The "logistic parameters of the Master calibration curve" are generated using "data of 20 runs Internal Reference Calibrators" (p.9). This could be considered analogous to a training process for establishing the core measurement algorithm, but it's not a training set for an AI inference model.

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

If we consider the generation of the "Master calibration curve" as a "training" process:

• Ground Truth: The "Internal Reference Calibrators" referenced (p.9) would serve as the ground truth. These calibrators are traceable to gravimetrically prepared Aldosterone standards using high-purity Aldosterone and UV quantitation (p.9).
• Establishment Method: The "new kit calibrator sets are run as 'unknowns' in duplicate in at least 20 assays on one analyser" (p.9). "The data of 20 runs Internal Reference Calibrators are used to generate the logistic parameters of the Master calibration curve by using Prism software package" (p.9).

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EUROIMMUN's 25-OH Vitamin D ELISA is intended for the quantitative determination of 25-OH Vitamin D and other hydroxylated vitamin D metabolites in human serum and plasma (EDTA, Li-heparin). Results are to be used in conjunction with other clinical and laboratory data to assist the clinician in the assessment of vitamin D sufficiency in adult populations.

EUROIMMUN 25-OH Vitamin D ELISA consists of a microwell ELISA plate coated with (sheep) monoclonal anti-25-OH vitamin D antibodies, 6 calibrators, 2 controls, Biotin, sample buffer, conjugate. wash buffer concentrate. enzyme TMB chromogen/substrate solution and stop solution.

This ELISA test kit is designed for the in vitro determination of 25-OH vitamin D in human serum or plasma samples. In the first analysis step, the calibrators and patient samples are diluted with biotin-labelled 25-OH vitamin D and added to microplate wells coated with (sheep) monoclonal anti-25-OH vitamin D antibodies. During the incubation an unknown amount of 25-OH vitamin D in the patient sample and a known amount of biotinlabelled 25-OH vitamin D compete for the antibody binding sites in the microplate wells plate. Unbound 25-OH vitamin D is removed by washing. For the detection of bound biotin-labelled 25-OH vitamin D, a second incubation is performed using peroxidase-labelled streptavidin. In a third incubation using the peroxidase substrate tetramethylbenzidine (TMB) the bound peroxidase promotes a colour reaction. The colour intensity is inversely proportional to the 25-OH vitamin D concentration in the sample. Results for the samples can be calculated directly using a standard curve.

Antibodies: sheep monoclonal antibodies which identify specifically 25-OH vitamin D3 and 25-OH vitamin D2.

Here's a summary of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

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

• Reproducibility:
  • Intra- and Inter-Assay: Minimum of 8 natural serum samples (2 spiked) for CV determination; 40 determinations for intra-assay CVs; 40 determinations performed in 10 different runs on 5 different days (with 4 replicates per run) for inter-assay CVs.
  • Lot-to-Lot: Minimum of 8 natural serum samples (2 spiked); 32 determinations performed in 8 different runs on 4 different lots (with 2 runs per lot and 4 replicates per run).
  • Data Provenance: "natural serum samples collected freshly in-house from obvious healthy blood donors".
• LoD: 200 determinations from 5 samples in the low range (2-10 ng/ml), measured in 5 independent runs with 8 replicates per run.
• Linearity/Assay Reportable Range: Sets of 11 sample preparations (natural negative sample + high positive samples), tested in double determinations.
• Cross-Reactivity: 25-OH Vitamin D free sample aliquoted and spiked with 7 potential cross-reacting Vitamin D metabolites.
• Interference: Sera at different 25-OH Vitamin D concentrations spiked with 6 potential interfering substances.
• Method Comparison w/Predicate Device:
  • Sample Size: 240 samples in total.
  • Data Provenance:
    • 141 prospective samples for 25-OH-Vitamin D testing from a clinical laboratory.
    • 28 samples from 25-OH-Vitamin D quality assessment programs (harvested from blood donated by venesection undergoing therapeutic for patients with hemochromatosis or polycythemia).
    • 5 samples from a 25-OH-Vitamin D quality control panel (untreated routine patient material).
    • 30 samples from normal blood donors.
    • 36 samples (15%) were spiked with 25-OH Vitamin D3 stock solution to ensure concentration distribution.
    • All patients gave informed consent. Samples are natural and not treated.
• Matrix Comparison: 38 sample pairs of serum and corresponding plasma (EDTA, Li-heparin) from donors. 3 sample pairs were spiked.
• Expected Values/Reference Range: 206 samples from healthy subjects (70 men, 136 women; average age 64 years; age range: 22–99 years) from a US commercial source (normal US blood donors from the US Midwest region, drawn early Oct 2010).

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

The document does not explicitly state the number of experts or their qualifications for establishing ground truth for the test set in terms of clinical interpretation. However, the performance studies (e.g., reproducibility, linearity) rely on in-house personnel and laboratory procedures, with calibrator and control value assignments confirmed by "2 different technicians" and "a different person for final release." Method comparison was against an "FDA-cleared reference assay," implying the predicate device serves as a reference for comparison.

4. Adjudication Method for the Test Set

No specific adjudication method (e.g., 2+1, 3+1) is mentioned or implied for the evaluation of the test set results for clinical interpretation. The performance studies describe analytical methods and statistical comparisons.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) assay, not an imaging device typically evaluated with MRMC studies. The "Method Comparison" section compares the device's analytical results against a predicate device, not human readers with and without AI assistance.

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

Yes, the studies described are for the standalone performance of the EUROIMMUN 25-OH Vitamin D ELISA assay, which is an algorithm-only (test kit) device. Its performance characteristics like linearity, reproducibility, limits of detection, and interference are evaluated intrinsically, and its results are then compared to a predicate device. There is no human-in-the-loop component for the device's operation, only human involvement in performing the laboratory tests (technicians) and interpreting the output for clinical use.

7. The Type of Ground Truth Used

The ground truth used varies based on the type of study:

• Reproducibility, LoB, LoD, Functional Sensitivity, Linearity, Cross-Reactivity, Interference: The ground truth is effectively the known concentrations of the analytes in the prepared samples (e.g., spiked samples, calibrators, controls, or precisely characterized samples). These are established through gravimetric methods, UV spectrophotometric analysis, and comparison with NIST and DEQAS standards, as well as predicate device measurements and HPLC.
• Method Comparison w/Predicate Device: The ground truth for comparison is the results obtained from the FDA-cleared predicate device, which is considered the reference method for this type of comparison.
• Matrix Comparison: The ground truth is the serum sample concentrations when comparing to plasma.
• Expected Values/Reference Range: The ground truth for establishing population reference intervals is the 25-OH Vitamin D levels measured in healthy subjects using the new device itself.

8. The Sample Size for the Training Set

The document does not describe a "training set" in the context of machine learning, as this is an in-vitro diagnostic ELISA kit. The term "training set" is not applicable here. The assay is based on chemical reactions and optical density measurements, not a learned algorithm in the typical sense.

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

As noted in #8, there isn't a "training set" in the machine learning context. The calibration and standardization of the assay (which could be considered analogous to "establishing ground truth" for the assay's internal function) involves:

• Gravimetric calibration using UV-Vis verified stock standards.
• Comparison with NIST standards and DEQAS quality assessment data.
• In-house quality control sera.
• Initial values for quality control sera assigned using the predicate device in conjunction with liquid chromatography (HPLC).
• Final calibrator values verified and assigned by adjusting initial values to meet specified ranges when tested against predicate assays.

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