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510(k) Data Aggregation
(262 days)
The ADVIA Centaur Anti-Thyroid Peroxidase II (aTPOII) assay is for in vitro diagnostic use in the quantitative measurement of autoantibodies against thyroid peroxidase in human serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur XP system.
Anti-thyroid peroxidase (aTPO) measurements are used, in conjunction with a clinical assessment, as an aid in the diagnosis of autoimmune thyroiditis and/or Graves' disease.
The ADVIA Centaur Anti-Thyroid Peroxidase II (aTPOII) consists of:
- aTPOII ReadyPack® primary reagent pack (Lite Reagent, Solid Phase)
- aTPOII CAL
Devices sold separately and included in the ADVIA Centaur® Anti-Thyroid Peroxidase II (aTPOII) are: - ADVIA Centaur aTPOII MCM (MCM 1, MCM 2–4)
- ADVIA Centaur aTPOII QC
- ADVIA Centaur aTPOII DIL ReadyPack ancillary reagent pack
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(267 days)
The Atellica IM Thyroglobulin (Tg) assay is for in vitro diagnostic use in the quantitative measurement of thyroglobulin in human serum and plasma (EDTA and lithium heparin) using the Atellica IM Analyzer.
Thyroglobulin measurements are used as an aid in monitoring differentiated thyroid cancer patients who have undergone thyroidectomy with or without radioiodine ablation.
The Atellica IM Thyroglobulin (Tg) assay includes:
- Tg ReadyPack primary reagent pack:
- Lite Reagent: mouse monoclonal anti-human Tg antibody labeled with acridinium ester (~1.13 μg/mL); bovine serum albumin (BSA); mouse IgG; buffer; stabilizers; preservatives (7.5 mL/reagent pack).
- Solid Phase: streptavidin-coated paramagnetic microparticles preformed with biotinylated mouse monoclonal antihuman Tg antibody (~267 μg/mL); BSA; mouse IgG; buffer; stabilizers; preservatives (15.0 mL/reagent pack).
- Ancillary Well Reagent: BSA; bovine gamma globulin; buffer; preservatives (6.0 mL/reagent pack).
- Tg CAL: After reconstitution, human thyroglobulin; BSA; buffer; stabilizers; preservatives (2.0 mL/vial).
The following devices are sold separately:
- Atellica IM Tg MCM:
- MCM 1: After reconstitution, bovine serum albumin (BSA); buffer; stabilizers; preservatives (1.0 mL/vial).
- MCM 2–5: After reconstitution, various levels of human thyroglobulin; BSA; buffer; stabilizers; preservatives (1.0 mL/vial).
Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided FDA 510(k) summary for the Atellica IM Thyroglobulin (Tg) assay:
Device: Atellica IM Thyroglobulin (Tg) Assay
Purpose: Quantitative measurement of thyroglobulin in human serum and plasma as an aid in monitoring differentiated thyroid cancer patients who have undergone thyroidectomy with or without radioiodine ablation.
1. Table of Acceptance Criteria and Reported Device Performance
The provided document describes various performance characteristics, which serve as acceptance criteria for the device. The reported performance is directly from the summary.
| Acceptance Criteria Category | Specific Acceptance Criteria (implicit from study design) | Reported Device Performance |
|---|---|---|
| Detection Capability | LoB, LoD, LoQ determined per CLSI EP17-A2 | LoB: 0.039 ng/mL (0.059 pmol/L) LoD: 0.044 ng/mL (0.067 pmol/L) LoQ: 0.050 ng/mL (0.076 pmol/L) |
| Precision | Precision determined per CLSI EP05-A3 (within-laboratory and repeatability) | Repeatability (CV%): 1.2% - 6.4% across various concentrations Within-Laboratory Precision (CV%): 2.3% - 9.0% across various concentrations |
| Reproducibility | Reproducibility determined per CLSI EP05-A3 (across sites, runs, days) | Reproducibility (CV%): 1.9% - 5.8% across various concentrations |
| Linearity | Linearity determined per CLSI EP06-ed2 within stated assay range | Linear for 0.050–150 ng/mL (0.076–227 pmol/L) |
| Specimen Equivalence | Performance equivalence across serum, EDTA plasma, lithium heparin plasma | Performance confirmed equivalent across serum, EDTA plasma, lithium heparin plasma, and associated gel barrier tubes. |
| Interferences (HIL) | Bias < 10% for Hemoglobin, Bilirubin, Lipemia at specified concentrations | No bias > 10% observed for tested HIL substances. |
| Interferences (Other Substances) | Bias < 10% for various common substances/medications/biomarkers at specified concentrations | No bias > 10% observed for tested other substances. |
| Cross-Reactivity | Cross-reactivity < 1.0% for specified substances (T3, T4, TSH, Galectin-3, T2) | Cross-reactivity < 1.0% for tested substances. |
| Reagent Stability | Defined on-board and reconstituted calibrator stability | 28 days on-board; Calibrators stable 45 days (2-8°C) / 60 days (≤ -20°C, thaw once). |
| Sample Stability | Defined stability for various sample types and storage conditions | Stable 3-4 days (2-8°C), 4 days (RT), 12-24 months (frozen); ≤ 4 freeze-thaw cycles. |
| High Dose Hook Effect | No hook effect within a specified concentration range | No hook effect up to 80,000 ng/mL (121,200 pmol/L). |
| Expected Values | Reference intervals established per CLSI EP28-A3c | Healthy Adults: 2.44–74.9 ng/mL Post-thyroidectomy adults: < 1.27 ng/mL |
| Clinical Performance | Sensitivity and specificity calculated by comparing assay results to structural disease (SD) at a defined cut-off (0.2 ng/mL). Confidences intervals for these parameters. | Sensitivity: 98.2% (95% CI: 94.6%, 100.0%) Specificity: 53.4% (95% CI: 47.8%, 58.0%) PPV: 10.0% (95% CI: 8.7%, 11.2%) NPV: 99.8% (95% CI: 99.5%, 100.0%) |
2. Sample Size Used for the Test Set and Data Provenance
- Clinical Performance Test Set Sample Size: 291 serum samples collected from 189 subjects.
- Data Provenance:
- The document states "A prospective, multi-center study was conducted." This indicates prospective data collection across multiple sites.
- The country of origin is not explicitly stated in the provided text.
- All samples were from subjects diagnosed with differentiated thyroid cancer, 6 or more weeks following thyroidectomy or radioiodine ablation.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
- The document does not specify the number of experts or their qualifications for establishing the ground truth (structural disease). It simply states: "SD [Structural Disease] was established and classified as either positive or negative by cross-sectional or functional imaging results."
- This suggests that the ground truth was derived from standard clinical imaging reports rather than a consensus of independent expert readers specifically for this study.
4. Adjudication Method for the Test Set
- The document does not describe an adjudication method for the test set's ground truth (structural disease). It implies that the imaging results themselves provided the classification. This means there was no adjudication process as typically seen with multiple human readers reviewing images.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
- No, an MRMC comparative effectiveness study was not done.
- This study is for an in vitro diagnostic (IVD) assay (a lab test), not an AI-assisted imaging or diagnostic tool where human readers work with or without AI. The performance metrics presented are for the analytical and clinical performance of the assay itself, comparing its results to a ground truth (structural disease status), not to human reader performance or improvement with AI.
6. If a Standalone Performance Study Was Done
- Yes, this is effectively a standalone (algorithm only) performance study.
- The Atellica IM Tg assay is an automated in vitro diagnostic device. Its performance characteristics (sensitivity, specificity, precision, linearity, etc.) are evaluated intrinsically, independent of human interpretation of the assay result values. The output is a quantitative measurement of thyroglobulin.
7. The Type of Ground Truth Used
- Ground truth for clinical performance: Structural disease (SD) status obtained from "cross-sectional or functional imaging results."
- Ground truth for analytical performance (LoB, LoD, LoQ, Precision, etc.): Established through laboratory protocols and reference materials (e.g., CLSI guidelines, certified reference materials like BCR CRM 457, spiked samples, control materials).
8. The Sample Size for the Training Set
- The document does not specify a separate training set or its sample size for the Atellica IM Tg assay.
- For IVD assays like this, the "training" is typically inherent in the assay's development and optimization process (e.g., reagent formulation, calibration curve development), which uses various known samples and standards, rather than a distinct, labeled "training dataset" as would be seen for a machine learning algorithm. The performance characteristics studies presented are akin to a "verification/validation set."
9. How the Ground Truth for the Training Set Was Established
- As a traditional IVD assay, there isn't a "training set" in the sense of a machine learning model.
- Ground truth for assay development and calibration: This would have been established using reference materials (like BCR CRM 457), characterized control samples, and potentially a large panel of clinically characterized patient samples used during the assay's development and optimization phases. These activities are part of the broader product development lifecycle rather than a distinct "training set" with ground truth generated by experts in the context of a clinical study for submission. Standardization is explicitly noted as traceable to BCR CRM 457, which serves as a primary standard for establishing the quantitative accuracy of the assay.
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(35 days)
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(192 days)
The ADVIA Centaur® TSH3-Ultra II (TSH3ULII) assay is for in vitro diagnostic use in the quantitative determination of thyroid-stimulating hormone (TSH, thyrotropin) in human serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur® XP system. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.
This assay is a third-generation assay that employs anti-FITC monoclonal antibody covalently bound to paramagnetic particles, an FITC-labeled anti-TSH capture mouse monoclonal antibody, and a tracer consisting of a proprietary acridinium ester and an anti-TSH mouse monoclonal antibody conjugated to bovine serum albumin (BSA) for chemiluminescent detection.
The provided text describes the ADVIA Centaur® TSH3-Ultra II (TSH3ULII) assay, a device for in vitro diagnostic quantitative determination of thyroid-stimulating hormone (TSH). The document covers the device's indications for use, comparison with a predicate device, and performance characteristics data.
Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Design Goal) | Reported Device Performance |
|---|---|---|
| Detection Capability | N/A (LoB, LoD, LoQ are reported values, not acceptance criteria for determination) | - Limit of Blank (LoB): 0.005 µIU/mL (mIU/L) - Limit of Detection (LoD): 0.008 µIU/mL (mIU/L) - Limit of Quantitation (LoQ): 0.010 µIU/mL (mIU/L) (Lower than predicate device's LoQ of 0.008 µIU/mL, but within acceptable range for the new device as specified in assay range) |
| Precision | - Repeatability (Within-Run): - ≤ 12% CV for 0.020–0.299 µIU/mL (mIU/L) - ≤ 6% CV for ≥ 0.300–90.000 µIU/mL (mIU/L) - ≤ 7% CV for > 90.000 µIU/mL (mIU/L) - Within-Laboratory (Total Precision): - ≤ 16% CV for 0.020–0.299 µIU/mL (mIU/L) - ≤ 8% CV for ≥ 0.300–90.000 µIU/mL (mIU/L) - ≤ 10% CV for > 90.000 µIU/mL (mIU/L) | Reported values (all calculated Repeatability CV and Within-Laboratory CV values are within the specified limits): - Serum A (0.088 µIU/mL): Repeatability CV 2.5%, Within-Lab CV 3.6% - Serum B (0.196 µIU/mL): Repeatability CV 1.8%, Within-Lab CV 3.1% - Serum C (0.507 µIU/mL): Repeatability CV 1.7%, Within-Lab CV 2.6% - Serum D (4.752 µIU/mL): Repeatability CV 2.3%, Within-Lab CV 2.7% - Serum E (46.749 µIU/mL): Repeatability CV 2.4%, Within-Lab CV 4.0% - Serum F (97.929 µIU/mL): Repeatability CV 2.2%, Within-Lab CV 3.5% Similar acceptable results for Plasma and Controls. |
| Reproducibility | - Reproducibility (Total): - ≤ 18.5% CV for 0.020-0.299 µIU/mL (mIU/L) - ≤ 10.5% CV for ≥ 0.300-90.000 µIU/mL (mIU/L) - ≤ 12.5% CV for > 90.000 µIU/mL (mIU/L) | Reported values (all calculated Reproducibility CV values are within the specified limits): - Serum A (0.090 µIU/mL): Reproducibility CV 3.11% - Serum B (0.178 µIU/mL): Reproducibility CV 4.87% - Serum C (0.474 µIU/mL): Reproducibility CV 2.21% - Serum D (4.684 µIU/mL): Reproducibility CV 2.47% - Serum E (56.562 µIU/mL): Reproducibility CV 2.33% - Serum F (99.522 µIU/mL): Reproducibility CV 4.12% Similar acceptable results for Plasma and Controls. |
| Assay Comparison | - Correlation coefficient (r) ≥ 0.95 - Slope of 1.0 ± 0.1 | - Correlation coefficient (r): 0.999 - Regression Equation (Slope): 0.97 (within 1.0 ± 0.1) |
| Specimen Equivalency | - Correlation coefficient (r) ≥ 0.95 - Slope of 0.95-1.05 | - Plasma, EDTA vs. Serum: r = 0.999, Slope = 0.99 (within 0.95-1.05) - Plasma, lithium heparin vs. Serum: r = 0.990, Slope = 1.01 (within 0.95-1.05) |
| Interferences (HIL) | Bias due to hemoglobin, bilirubin (conjugated/unconjugated), and Intralipid does not exceed 10% | Hemoglobin (500mg/dL), Bilirubin (40mg/dL), Intralipid (1000mg/dL) do not exceed 10% bias at TSH concentrations of ~0.900 µIU/mL and ~8.000 µIU/mL. |
| Interferences (Other Substances) | Bias due to various common substances does not exceed 10% | Various substances (e.g., Acetaminophen, Aspirin, Biotin, Heparin, Ibuprofen, Levothyroxine) at specified concentrations do not exceed 10% bias at TSH concentrations of ~0.900 µIU/mL and ~8.000 µIU/mL. |
| Cross-Reactivity | Cross-reactivity of hCG, FSH, and LH does not exceed 5% | hCG (200000 mIU/mL), FSH (1500 mIU/mL), LH (600 mIU/mL) at specified concentrations do not exceed 5% cross-reactivity at TSH concentrations of ~0.400, 5.00, 17.00, and 90.00 µIU/mL. |
| Linearity | Device is linear throughout its measuring interval (0.010–150.000 µIU/mL) | "The assay is linear for the measuring interval of 0.010–150.000 µIU/mL (mIU/L)." |
| High-Dose Hook Effect | Results for TSH concentrations above the measuring interval and up to 3000 µIU/mL should report > 150 µIU/mL (not a paradoxical decrease) | "Patient samples with TSH concentrations above the measuring interval and as high as 3000 µIU/mL will report > 150 µIU/mL (mIU/L)." (This confirms the absence of a significant high-dose hook effect within this specified range, meaning the device displays the result as above the measurable range.) |
The study that proves the device meets the acceptance criteria is detailed across the "Performance Characteristics Data" section (Section 8) of the 510(k) Summary.
2. Sample Size Used for the Test Set and Data Provenance
- Detection Capability (LoQ): Not specified (CLSI Document EP17-A2 was followed).
- Precision: 80 measurements (replicates of 2, 2 runs/day, 20-day protocol) for each of the 6 serum samples, 5 plasma samples, and 5 control samples. Total N for Precision study is 80 x (6+5+5) = 1280 measurements.
- Reproducibility: 225 measurements (replicates of 5, 1 run/day, 5-day protocol) for each of the 6 serum samples, 5 plasma samples, and 5 control samples. Total N for Reproducibility study is 225 x (6+5+5) = 3600 measurements.
- Assay Comparison: 973 samples.
- Specimen Equivalency:
- Plasma, EDTA vs. Serum: 52 samples.
- Plasma, lithium heparin vs. Serum: 57 samples.
- Interferences (HIL and Other Substances): Samples at two TSH concentrations (~0.900 µIU/mL and ~8.000 µIU/mL) were tested for each interfering substance. The exact number of individual samples tested is not given, but multiple samples would be required for the two TSH levels per substance.
- Cross-Reactivity: Samples at four TSH concentrations (~0.400, 5.00, 17.00, and 90.00 µIU/mL) were spiked with hCG, FSH, or LH. The exact number of individual samples is not given.
- Linearity: Not explicitly stated, but performed in accordance with CLSI Document EP06-ed2, which involves testing multiple diluted samples.
- High-Dose Hook Effect: Samples with TSH concentrations up to 3000 µIU/mL were evaluated. The number of samples tested is not explicitly stated.
Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given it's an in vitro diagnostic device, the samples would generally be human biological specimens, likely collected from a clinical laboratory setting. The use of CLSI documents (Clinical and Laboratory Standards Institute) suggests standard laboratory practices.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This information is not provided in the document. For an in vitro diagnostic assay like TSH, "ground truth" is typically established by:
- The reference method against which the new assay is compared (for accuracy/assay comparison). In this case, "ADVIA Centaur TSH3-UL assay" is used as the comparative assay (the predicate device).
- Traceability to an international standard (WHO 3rd International Reference Preparation for human TSH (IRP 81/565)), which implies that the TSH values are calibrated against a universally accepted standard, rather than expert consensus on individual patient cases.
4. Adjudication Method for the Test Set
This refers to the process of resolving discrepancies in expert opinions, which is not applicable here as it is an analytical performance study for an IVD, not an interpretative AI device requiring human expert label agreement.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically performed for AI-assisted diagnostic imaging devices where human readers interpret medical images with and without AI assistance. This document pertains to an in vitro diagnostic assay, which involves automated quantitative measurement of a biomarker.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, implicitly. The entire performance characterization (Detection Capability, Precision, Reproducibility, Assay Comparison, Specimen Equivalency, Interferences, Cross-Reactivity, Linearity, High-Dose Hook Effect) is describing the standalone performance of the TSH3-Ultra II assay as an automated laboratory test. There is no mention of "human-in-the-loop" for this device's intended diagnostic function.
7. Type of Ground Truth Used
The ground truth for the performance studies is established by:
- Reference materials/standards: For accuracy, the assay is traceable to the World Health Organization (WHO) 3rd International Reference Preparation for human TSH (IRP 81/565).
- Comparative method: For assay comparison, the predicate device (ADVIA Centaur TSH3-UL assay) results serve as the comparative standard.
- Defined concentrations: For precision, linearity, interferences, and cross-reactivity, samples with known or spiked concentrations of TSH or interfering substances are used.
8. Sample Size for the Training Set
The document does not report a training set sample size. This is because the ADVIA Centaur TSH3-Ultra II is a chemical immunoassay, not a machine learning or AI-based device that would typically involve a "training set" in the computational sense. The "development" process for such an assay involves reagent formulation, assay optimization, and calibration curve development, which are distinct from training an AI model.
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, this question is not applicable. The assay's analytical characteristics are established through various studies (precision, accuracy, linearity, etc.) using calibrated materials and established reference methods, as detailed in the performance characteristics.
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(601 days)
The ADVIA Centaur® NT-proBNPII (PBNPII) assay is for in vitro diagnostic use in the quantitative determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) in human serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur® XP system.
In the Emergency Department (ED) and Outpatient (OP) populations, measurements of NT-proBNP are used as an aid in the diagnosis of heart failure (HF) in patients with clinical suspicion of new onset or worsening HF.
The ADVIA Centaur® NT-proBNPII (PBNPII) assay kit includes the Primary Reagent ReadyPack and the Calibrator. The Primary Reagent ReadyPack contains Lite Reagent, Solid Phase Reagent, and Ancillary Well Reagent. The Calibrator includes Low and High Calibrators which are lyophilized.
The provided document discusses the ADVIA Centaur® NT-proBNPII (PBNPII) assay, an in vitro diagnostic device for measuring N-terminal pro-brain natriuretic peptide (NT-proBNP) to aid in the diagnosis of heart failure in Emergency Department (ED) and Outpatient (OP) populations. The submission aims to demonstrate substantial equivalence to the predicate device, the Roche Elecsys proBNP II assay (K072437).
Here's an analysis of the acceptance criteria and the studies that support them:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" as a single, consolidated table with pass/fail values for all performance characteristics. Instead, it presents various performance studies with their results. Based on the "Comparison of Technological Characteristics with the Predicate Device" and the "Performance Characteristics" sections, we can infer some criteria and compare the device's performance.
| Performance Characteristic | Acceptance Criteria (Implied/Predicate) | Reported Device Performance (ADVIA Centaur PBNPII) |
|---|---|---|
| Intended Use | Aid in diagnosis of suspected congestive heart failure. | Aid in diagnosis of HF in ED and OP populations with clinical suspicion of new onset or worsening HF. |
| Measurement | Quantitative | Quantitative |
| Technology | Chemiluminescence immunoassay | Chemiluminescence immunoassay (1-step sandwich) |
| Sample Type | Plasma and Serum | Human serum, plasma (EDTA and lithium heparin) |
| Assay Range | 5-35,000 pg/mL (Predicate) | 35-35,000 pg/mL |
| Hook Effect | No hook effect up to 300,000 pg/mL (Predicate) | No hook effect up to 300,000 pg/mL (will report >35,000 pg/mL) |
| Precision (Total CV) | For Serum: e.g., <4.6% @ 44 pg/mL, <1.8% @ 2,410 pg/mL (Predicate) | For Serum: 6.7% @ 116 pg/mL, 4.0% @ 271 pg/mL, 2.3% @ 380 pg/mL, 2.1% @ 806 pg/mL, 2.0% @ 1,597 pg/mL, 2.8% @ 25,073 pg/mL. QCs also within acceptable limits (presumably). |
| Reproducibility | Not explicitly stated, typically within acceptable CV limits across sites. | Total CVs ranging from 3.0% to 5.0% for serum samples (141-10428 pg/mL) and 3.3% to 4.5% for controls. |
| Linearity | N/A (implied to be demonstrated across assay range) | Linear for 35-35,000 pg/mL |
| Limit of Blank (LoB) | LoB < LoD (Predicate) | 13 pg/mL |
| Limit of Detection (LoD) | 5.00 pg/mL (Predicate) | 20 pg/mL |
| Limit of Quantitation (LoQ) | 50.0 pg/mL (Predicate) | 35 pg/mL |
| Interference (HIL & Other) | Bias not to exceed 10% (Implied) | Bias due to hemoglobin, bilirubin, lipemia <10%; various other substances also do not interfere (bias <10%). |
| Cross-Reactivity | Not Detectable / <1.0% for most (Implied, similar to predicate) | Most cross-reactants <1.0% or not detectable. ProBNP (glycosylated) 1.0%-19.0%, ProBNP (non-glycosylated) 13.0%-30.0%. |
| Specimen Equivalency | Regression equation close to y=x+0, r close to 1 (Implied) | Plasma (EDTA, Lithium heparin), SST, RST vs. Serum: Regression equations y=1.00x +/- small constant, r ~0.999-1.000. |
| Clinical Performance (ED Pop.) | Likelihood Ratios (LR+, LR-) and Post-test Risk (Implied to be clinically useful for diagnosis) | Age-dependent rule-in/out cutoffs provided with LR+ and LR- (0.06-0.09 for Negative LR-, suggesting good rule-out). |
| Clinical Performance (OP Pop.) | Sensitivity, Specificity, PPV, NPV (Implied to be clinically useful for diagnosis) | Overall: Sensitivity 86.0%, Specificity 64.3%, PPV 34.4%, NPV 95.5% (at 125 pg/mL cutoff). Detailed breakdown by age/sex also provided. |
Note: The "Acceptable Criteria" values for precision were primarily taken directly from comments in the tables (indicated by "<" followed by a number), which appear to be the applicant's internal criteria rather than directly from the predicate. The predicate's precision data is shown for comparison purposes in the "Comparison of Technological Characteristics."
2. Sample Size Used for the Test Set and Data Provenance
- Precision and Reproducibility:
- Precision: Assayed in duplicate in 2 runs per day for 20 days. Number of samples not explicitly stated but implied to be multiple levels of serum and QCs (6 serum, 3 QC samples listed).
- Reproducibility: N=90 samples assayed in duplicate in 2 runs per day for 5 days at 3 sites.
- Linearity: Not specified.
- Detection Limit (LoB, LoD, LoQ): Not specified.
- Interference (HIL & Other Substances): Not specified.
- Cross-Reactivity: Not specified.
- Specimen Equivalency: N=50 samples for each tube type comparison to serum.
- Expected Values (Reference Study Group): 723 apparently healthy subjects (362 females, 361 males).
- Clinical Performance (ED Population): 3128 subjects with signs and symptoms of acute HF who presented to the ED. 1148 adjudicated as acute HF, 1980 as without HF.
- Clinical Performance (OP Population): 1033 OP subjects with signs and symptoms of new onset HF. 185 adjudicated as new onset HF, 848 as without HF.
Data Provenance: The document does not explicitly state the country of origin for the clinical study data or if it was retrospective or prospective. However, the term "prospectively enrolled" is used for both the ED and OP clinical performance studies, indicating these were prospective studies.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
- Clinical Performance (ED Population): An "independent central adjudication panel of expert clinicians (Cardiologists)" determined the diagnosis and severity of HF. The exact number of experts is not stated, nor are their specific qualifications (e.g., number of years of experience).
- Clinical Performance (OP Population): An "independent central adjudication panel of expert clinicians (Cardiologists)" determined the diagnosis of new onset HF. Similar to the ED population, the exact number and specific qualifications are not detailed.
4. Adjudication Method (for the test set)
The adjudication method used by the "independent central adjudication panel of expert clinicians (Cardiologists)" is not explicitly described (e.g., 2+1, 3+1, none). It only states they "determined" the diagnosis.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was done. This device is an in vitro diagnostic assay (laboratory test), not an imaging or interpretive device that typically involves human readers in the same way an MRMC study would apply. Therefore, there is no effect size reported for human readers improving with or without AI assistance.
6. Standalone Performance Study
Yes, a standalone (algorithm only) performance study was performed for the assay. The entire "Performance Characteristics" section (9.1 through 9.12) describes the analytical and clinical performance of the ADVIA Centaur PBNPII assay in isolation, without human interpretation of the assay results in the context of the study design. The clinical utility is assessed by how accurately the assay's quantitative results correlate with the adjudicated clinical diagnosis.
7. Type of Ground Truth Used
- Clinical Performance (ED and OP Populations): Clinical diagnosis adjudicated by an "independent central adjudication panel of expert clinicians (Cardiologists)." This falls under expert consensus clinical diagnosis.
- Analytical Performance (Precision, Linearity, Detection Limits, Interference, Cross-Reactivity, Specimen Equivalency): These are quantitative measurements against established reference methods, standards, or known concentrations, serving as the ground truth for analytical validity.
8. Sample Size for the Training Set
The document describes an in vitro diagnostic assay for measuring biomarkers. These types of assays typically do not have a "training set" in the same sense as machine learning algorithms, which require labeled data for model development. Instead, they involve method development and validation experiments. The document describes studies for:
- Establishing expected values (reference study group, N=723).
- Establishing disease study groups for statistical analysis of correlation (ED population N=1148, OP population N=185).
- Various analytical validation studies such as precision, linearity, and detection limits.
Therefore, the concept of a "training set" for the assay, in the context of algorithm development, is not directly applicable or discussed. The studies mentioned above contribute to the overall validation and characterization of the assay's performance.
9. How the Ground Truth for the Training Set Was Established
As mentioned above, the concept of a "training set" for an assay like this is not directly applicable. If we consider the data used to characterize the assay's performance as analogous to "training data" (i.e., the data used to define the assay's characteristics and clinical cut-offs), then:
- Clinical Cut-offs: The clinical cut-offs for the ED and OP populations were established based on the measured NT-proBNP values in patient populations (ED and OP disease study groups) where the diagnosis of heart failure was determined by an "independent central adjudication panel of expert clinicians (Cardiologists)." This expert consensus clinical diagnosis serves as the ground truth for establishing the clinical utility of the various cut-off values.
- Reference Intervals: The reference interval was established using 723 apparently healthy subjects. The "healthy" status would have been determined through standard medical screening and criteria, serving as the ground truth for defining the normal range.
- Analytical Studies: Ground truth for analytical studies (e.g., linearity, detection limit) is established through reference materials, spiked samples with known concentrations, and comparison to established methods or gold standard instrumentation.
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(418 days)
The Emit® II Plus Buprenorphine Assay is a homogeneous enzyme immunoassay with a 5 ng/mL cutoff. The assay is intended for use in laboratories for the qualitative and/or semiquantitative analyses of buprenorphine in human urine. Emit® II Plus assays are designed for use with a number of chemistry analyzers.
The semiquantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/Mass Spectrometry (LC/MS) or permitting laboratories to establish quality control procedures.
The Emit® II Plus Burrenorphine Assay provides only a preliminary analytical test result. A more specific alternative chemical method(s) must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/ MS) or LC/MS are the preferred confirmatory methods. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.
For Professional Use.
Caution: Federal (USA) law restricts this device to sale by or on the order of a licensed healthcare professional.
For in vitro diagnostic use.
The Emit® II Plus Buprenorphine Assay is a homogeneous enzyme immunoassay technique used for the analysis of specific compounds in human urine. The assay is based on competition between drug in the specimen and drug labeled with the recombinant glucose-6-phosphate dehydrogenase (rG6PDH) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, so the drug concentration in the specimen can be measured in terms of enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH in the presence of glucose-6phosphate (G6P), resulting in an absorbance change that is measured spectrophotometrically. Endogenous serum G6PDH does not interfere because the coenzyme NAD functions only with the bacterial (Leuconostoc mesenteroides) enzyme employed in the assay.
The Emit® II Plus Buprenorphine Assay reagents are provided liquid, ready to use and may be used directly from the refrigerator. The product is sold in three (3) kit sizes: 28 mL, 115 mL, and 1000 mL. Reagents 1 and 2 are provided as a matched set. They should not be interchanged with components of kits with different lot numbers.
Antibody/Substrate Reagent 1: Mouse monoclonal antibodies to buprenorphine (0.53 µg/mL)*.NAD (6.9 mM), G6P (10.9 mM), bovine serum albumin, preservatives, and stabilizers. *The antibody titer and enzyme conjugate activity may vary from lot to lot.
Enzyme Reagent 2: Norbuprenorphine labeled with bacterial rG6PDH (0.50 µg/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers, where the antibody titer and enzyme conjugate activity may vary from lot to lot.
The marketing submission for the Siemens Healthineers Emit® II Plus Buprenorphine Assay (K221605) demonstrates that the device meets its acceptance criteria through various performance studies. Below is a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as strict numerical thresholds in the provided document, but rather demonstrated through the qualitative agreement and recovery percentages, as well as precision and specificity profiles. Based on the "Method Comparison" results, the implicit acceptance criterion for qualitative agreement against LC/MS/MS is a high percentage, and for recovery, it's generally close to 100%. For specificity, it's low or negligible cross-reactivity with other substances (ideally less than the cutoff concentration when tested at high concentrations). For precision, it's low coefficient of variation (CV).
| Metric / Acceptance Criteria | Reported Device Performance (Emit® II Plus Buprenphine Assay on DxC 500 AU) |
|---|---|
| Method Comparison (Qualitative Agreement with LC/MS/MS) | 92.5% Agreement |
| Recovery vs Nominal Value | Ranges from 95% to 104% (average ~98.5%) |
| Recovery vs LC/MS/MS | Ranges from 86% to 100% (average ~93.8%) |
| Precision (Repeatability %CV) | 1.1% to 6.6% (for relevant concentration ranges) |
| Precision (Within-Lab Precision %CV) | 2.8% to 6.6% (for relevant concentration ranges) |
| Total Reproducibility Precision %CV | 3.0% to 5.3% |
| Specificity (Cross-reactivity with Buprenorphine Metabolites) | Buprenorphine: 98%, Norbuprenorphine: 106%, Glucuronides: 0.10% |
| Specificity (Cross-reactivity with Structurally Related Compounds) | <0.1% for all tested compounds at 100,000 ng/mL |
| Specificity (Cross-reactivity with Structurally Un-Related Compounds) | All tested compounds at high concentrations (µg/mL) showed 'Neg' response for the -40% Control and 'Pos' for the +40% Control, indicating no interference impacting the cutoff. |
| Interference (Endogenous and Exogenous Substances) | All tested substances showed 'Neg' response for the -40% Control and 'Pos' for the +40% Control, indicating no interference impacting the cutoff. |
| Interference (pH and Specific Gravity) | All tested pH and specific gravity levels showed 'Neg' response for the -40% Control and 'Pos' for the +40% Control, indicating no interference impacting the cutoff. |
2. Sample Size Used for the Test Set and Data Provenance
- Method Comparison: 120 native urine individual patient samples. The samples were collected from external suppliers, received frozen, and thawed before testing. 21% were within -50% of the cutoff and 19% within +50% of the cutoff. The provenance is not explicitly stated in terms of country of origin but implies human urine samples from external suppliers. The study design is retrospective, using previously collected samples.
- Recovery: 9 urine samples prepared by spiking buprenorphine into negative urine pools.
- Precision (Repeatability and Within-Lab): 11 urine samples prepared by spiking buprenorphine into negative urine pools.
- Precision (Reproducibility): 3 urine samples (Negative Control, Cutoff Calibrator, Positive Control from Emit II Plus Specialty Drug Control line).
- Limit of Detection: 4 blank samples and 4 low-level samples (buprenorphine spiked into drug-free urine). A minimum of 60 replicate measurements per sample set.
- Specificity and Cross-reactivity: The number of unique compounds tested is substantial (listed in Tables 9, 10, and 11), with samples assayed in five replicates for each compound.
- Interference: Various endogenous and exogenous substances, as well as pH and specific gravity variations, were tested at specified concentrations. Samples were assayed in five replicates.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- For the Method Comparison study, the ground truth was established by LC/MS/MS (Liquid Chromatography/Mass Spectrometry/Mass Spectrometry). This is a highly specific and sensitive analytical method considered the gold standard for drug confirmation testing. No human experts are explicitly described as establishing the ground truth; it's based on the instrumental analytical results.
- For Recovery, the ground truth (nominal value) for spiked samples was determined gravimetrically based on stock concentration and confirmed by LC/MS/MS.
- For Precision, Limit of Detection, Specificity, and Interference, the ground truth is based on the known concentrations of spiked substances or the known characteristics of the samples (e.g., drug-free urine, specific pH levels). Instrumental analysis is used to determine the device's measurement against these known values.
4. Adjudication Method for the Test Set
- For the qualitative analysis in the Method Comparison, the results from the Emit® II Plus Buprenorphine Assay on DxC 500 AU were compared directly against the results from LC/MS/MS. A 2x2 box plot was used to assess qualitative agreement. There is no mention of a human adjudication method (e.g., 2+1 or 3+1), as the comparison is between two analytical methods.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC comparative effectiveness study was done. This device is an in vitro diagnostic assay, not an AI-assisted interpretation device that would involve human readers.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
- Yes, the entire performance evaluation presented is a standalone study of the analytical performance of the Emit® II Plus Buprenorphine Assay on the DxC 500 AU Clinical Chemistry Analyzer. There is no human-in-the-loop component for interpreting the assay's results; the device produces qualitative or semi-quantitative analytical results directly.
7. Type of Ground Truth Used
- Analytical Ground Truth:
- LC/MS/MS (Liquid Chromatography/Mass Spectrometry/Mass Spectrometry) for method comparison and as a reference for recovery studies.
- Known concentrations of spiked urine samples (gravimetrically determined nominal values) for recovery, precision, limit of detection, specificity, and interference studies. This involves preparing samples with precisely known amounts of the analyte or interfering substances.
- Drug-free urine pools for negative controls and spiking experiments.
8. Sample Size for the Training Set
- The document describes performance evaluation studies for a device, not a machine learning algorithm that requires a "training set." Therefore, there is no mention of a training set or its sample size in the context of this device's regulatory submission.
9. How the Ground Truth for the Training Set Was Established
- As this is not a machine learning-based device, there is no training set and thus no ground truth established for a training set. The studies focus on demonstrating the analytical performance of the immunoassay against recognized analytical standards and spiked samples with known concentrations.
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(207 days)
The Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) assay is an in vitro diagnostic test for the quantitative measurement of procalcitonin in human serum and plasma (lithium heparin, K2EDTA, and K3EDTA) using the Dimension® EXL™ integrated chemistry system with LOCI® Module.
The Dimension EXL LOCI® BRAHMS PCT assay is intended for use in conjunction with other laboratory findings and clinical assessments, as an aid in:
· The risk assessment of critically ill patients on their first day of Intensive Care Unit (ICU) admission for progression to severe sepsis and septic shock.
• Assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission using percentage change in PCT levels over time.
· Decision making on antibiotic therapy for patients with suspected or confirmed lower respiratory tract infections (LRTI) - defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) - in an inpatient setting or an emergency department.
· Decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis.
The Dimension EXL LOCI BRAHMS PCT assay is a homogeneous sandwich chemiluminescent immunoassay based on LOCI technology. The LOCI reagents include two synthetic bead reagents and one biotinylated anti-procalcitonin (anti-PCT) monoclonal antibody. The first bead reagent (Sensibeads) is coated with streptavidin and contains photosensitizer dye. The second bead reagent (Chemibeads) is coated with two anti-PCT monoclonal antibodies and contains chemiluminescent dye. Sample is incubated with biotinylated antibody and Chemibeads to form bead-PCT-biotinylated antibody sandwiches. Sensibeads are added and bind to the biotin to form bead-pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from Sensibeads which diffuses into the Chemibeads, triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is a direct function of the procalcitonin (PCT) concentration in the sample.
The provided document describes the performance characteristics of the Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) assay and its equivalence to a predicate device.
Here's a breakdown of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance |
|---|---|---|
| Precision | Within-lab %CV: ≤ 10.0% for QC1, QC2, QC3, Serum 2, 3, 4, 5; ≤ 15.0% for Plasma, Serum 1. | Lot FB1218: QC1 (4.3%), QC2 (2.2%), QC3 (2.5%), Plasma (4.0%), Serum 1 (4.0%), Serum 2 (2.7%), Serum 3 (2.0%), Serum 4 (1.5%), Serum 5 (2.7%). All Pass. Lot FC1218: QC1 (3.3%), QC2 (4.2%), QC3 (2.6%), Plasma (4.0%), Serum 1 (3.0%), Serum 2 (2.7%), Serum 3 (2.7%), Serum 4 (2.1%), Serum 5 (2.3%). All Pass. |
| Total %CV: ≤ 10.0% for QC1, QC2, QC3, Serum 2, 3, 4, 5; ≤ 15.0% for Plasma, Serum 1. | Lot FB1218: QC1 (7.1%), QC2 (3.5%), QC3 (3.2%), Plasma (6.0%), Serum 1 (5.0%), Serum 2 (4.1%), Serum 3 (2.7%), Serum 4 (3.0%), Serum 5 (5.5%). All Pass. Lot FC1218: QC1 (6.2%), QC2 (4.5%), QC3 (3.2%), Plasma (6.0%), Serum 1 (6.0%), Serum 2 (3.6%), Serum 3 (3.2%), Serum 4 (3.1%), Serum 5 (5.8%). All Pass. | |
| Reproducibility | Total Reproducibility (CV%) for various PCT levels. (No explicit criteria mentioned in the document, but results are provided indicating good reproducibility). | MDP1 (0.10 ng/mL): 7.0%, MDP2 (0.25 ng/mL): 4.4%, MDP3 (0.48 ng/mL): 3.8%, MDP4 (1.95 ng/mL): 3.8%, MDP5 (8.94 ng/mL): 4.2%, MDP6 (41.01 ng/mL): 9.3%. |
| Detection Capability | LoB < LoD, LoD ≤ 0.04 ng/mL, LoQ ≤ 0.05 ng/mL (using within-lab %CV of 20%). | LoB: 0.03 ng/mL, LoD: 0.04 ng/mL, LoQ: 0.05 ng/mL. All claims met. |
| Linearity | Regression statistics (deviation from linearity for non-linear pools) at all levels tested demonstrated a ≤20% deviation (≤ 0.04 ng/mL for the lowest sample) from the predicted linear fit. | The study demonstrated a linear range of 0.03 to 55.05 ng/mL, which supports a measuring interval of 0.05 to 50.00 ng/mL. Results met the acceptance criteria. |
| Dilution Recovery | Recoveries for all specimens ranged from 88 to 108%. | Ten native serum specimens diluted 1:20 with saline. Recoveries ranged from 88% to 108% (mean 98%). Pass. Manual dilution supports an extended measuring interval from 50.00 ng/mL to 1000.00 ng/mL. |
| Interference (HIL) | ≤10% interference from hemoglobin, bilirubin, and lipemia. | Bilirubin (Conjugated/Unconjugated, 40 mg/dL): 0% or 1% bias. Hemoglobin (1000 mg/dL): -5% or -7% bias. Lipemia (2000 mg/dL): 0% or 3% bias. All met ≤10% criteria. |
| Non-Interfering Substances | Bias due to substances ≤10% at PCT analyte concentrations of 0.25 and 2.00 ng/mL. | Most substances tested (Acetaminophen, Acetylsalicylic acid, Amoxicillin, Azithromycin, Caffeine, Cefotaxime, Celecoxib, Cetirizine HCl, Cholesterol, Dextran 40, Dextromethorphan, Dobutamine, Dopamine, Doxycycline, EDTA, Epinephrine, Ethanol, Fentanyl, Fluorescein, Furosemide, HAMA (various concentrations, except high levels), Heparin, Human Immunoglobulin (IgG), Human serum albumin, Human serum gamma globulin, Ibuprofen, Imipenem, Levofloxacin, Loratadine, Nicotine, Noradrenaline, Oxymetazoline HCl, Phenylephrine, Prednisolone, Rheumatoid Factor, Salmeterol, Tiotropium, Triglycerides, Vancomycin) showed ≤10% bias. |
| Interfering Substances | Biotin >10% interference at >1200 ng/mL. HAMA >10% interference at 32.5 mg/mL (HAMA 1) and 65.0 mg/mL (HAMA 1 and 2), Total Protein >10% interference at 15.0 g/dL. | Biotin: >10% interference at 1500 ng/mL (-19% bias at 1.88 ng/mL PCT) and 3510 ng/mL (-26% to -29% bias). HAMA 1: -10% to -12% bias at 65.0 mg/mL and -11% to -12% bias at 32.5 mg/mL. HAMA 2: -14% to -13% bias at 65.0 mg/mL and -11% bias at 32.5 mg/mL (at 2.19 ng/mL PCT). Total Protein: -18% bias at 15.0 g/dL. These led to specific labeling cautions. |
| Cross-Reactivity | No explicit criterion provided, only results of testing. | No significant cross-reactivity observed with Calcitonin (Human, Eel, Salmon), Katacalcin (Human), α-CGRP, and β-CGRP. For example, Human Calcitonin at 8 ng/mL showed 0.00% to -0.50% cross-reactivity. |
| Hook Effect | No hook effect for PCT concentrations up to 2000.00 ng/mL. | For patient specimens with PCT concentrations between 50.00 ng/mL and 2000.00 ng/mL the assay will report results as "Above Assay Range" (> 50.00 ng/mL). |
| Sample Carryover | No sample carryover from high to low samples. | Calculated to be 0.00 ng/mL. No sample carryover observed. |
| Method Comparison | Strong correlation (r), passing Deming/Passing-Bablok regression, high percentage agreement at clinical cutoffs with predicate device. | Measuring Interval (0.05-50.00 ng/mL): Lot FB1218: r = 0.958, Slopes 1.07, Intercepts -0.01. Lot FC1218: r = 0.963, Slopes 1.04, Intercepts 0.00 to -0.01. Positive % agreement: 96.1-97.8%, Negative % agreement: 89.1-97.5%, Overall % agreement: 95.9-97.5% across various cut-offs (0.10, 0.25, 0.50, 2.00 ng/mL). Extended Measuring Interval (0.05-1000.00 ng/mL): Lot FB1218: r = 0.988, Slopes 1.08, Intercepts -0.01. Lot FC1218: r = 0.991, Slopes 1.05, Intercepts 0.00 to -0.01. Positive % agreement: 96.5-98.0%, Negative % agreement: 89.1-97.5%, Overall % agreement: 96.1-97.6% across various cut-offs. These results demonstrate substantial equivalence to the predicate device. |
| Matrix Comparison | No significant difference based on Passing-Bablok regression analysis between serum and plasma samples. | All specimen types (Serum (SST), Serum (RST), Lithium Heparin plasma, Sodium Heparin plasma, K2EDTA plasma, and K3EDTA plasma) showed high correlation coefficients (0.996-0.998) and regression equations close to y=x (slopes around 0.98-1.00, intercepts around 0.00-0.01 ng/mL) when compared to Serum (SST), indicating no significant difference. |
| Reference Interval Verification | Reference interval claim of <0.10 ng/mL verified. | The reference interval claim in the Instructions For Use is <0.10 ng/mL [<0.10 µg/L] verified using 33 apparently healthy individuals. |
| Reagent Stability | Real-time shelf life (12 months), Calibration interval (7 days), Unopened onboard stability (30 days), Opened onboard stability (3 days). | Shelf life: Two lots demonstrated 12 months of stability (ongoing). Calibration interval: Results support 7 days. Unopened onboard stability: Results support 30 days. Opened onboard stability: Results support 3 days. |
| Sample Stability | Storage and handling recommendations in IFU are supported (room temp 8h, refrig 24h, frozen -70C/90d -20C/90d, 6 freeze-thaw cycles, onboard 1h). | Studies supported all specified conditions for serum and plasma tube types (SST, RST, Li Hep, Na Hep, K2EDTA, K3EDTA) at various PCT levels, showing accurate results. |
2. Sample sizes for the test set and data provenance:
- Precision Studies: 80 replicates for each sample (QC and serum/plasma pools) for each lot (total 2 lots tested).
- Reproducibility Study: 225 replicates per sample ID (5 replicates/day x 5 days x 3 instruments x 3 reagent lots).
- Detection Capability: No specific sample size mentioned, CLSI EP17-A2 was referenced.
- Linearity: 16 samples.
- Dilution Recovery: 10 native serum specimens.
- Interference and Cross-Reactivity: Human serum pools, specifically "approximately 0.25 ng/mL and 2.00 ng/mL PCT". The exact number of individual samples is not explicitly stated.
- Hook Effect: Testing for PCT concentrations up to 2000.00 ng/mL. Number of samples not explicitly stated.
- Sample Carryover: 11 separate runs, each testing a pattern of high and low samples (21 tests per run).
- Method Comparison: 595 native human serum samples within the concentration range of 0.05-1000.00 ng/mL.
- Matrix Comparison: 76 matched sets (Serum, Lithium Heparin plasma, Sodium Heparin plasma, K2EDTA plasma, and K3EDTA plasma - except RST with 75 matched sets).
- Reference Interval Verification: Serum and plasma specimens from 33 apparently healthy individuals.
Data Provenance: The studies used human serum and plasma samples, as indicated by terms like "native human serum samples" and "patient-sourced internal standards." The document does not specify the country of origin, but it mentions Siemens Healthcare Diagnostics, Inc. in Newark, Delaware, USA, as the applicant. The nature of the studies (e.g., method comparison, stability) suggests these are retrospective analyses of collected samples or controlled laboratory experiments. It does not explicitly state prospective or retrospective data collection for all studies, but method comparison using "native human serum samples" implies existing clinical samples from a test set.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This device is an in vitro diagnostic (IVD) test for quantitative measurement of procalcitonin (PCT). The "ground truth" here is not established by human readers/experts in the same way as, for example, a diagnostic imaging AI. Instead, the ground truth for this type of device is based on:
- Reference Method/Predicate Device: For method comparison, the predicate device (B·R·A·H·M·S PCT sensitive KRYPTOR) serves as the reference for comparison.
- Analytical Standards: For studies like linearity, detection capability, and precision, the "ground truth" or true value of PCT is established using known concentrations in control materials, calibrators, or by spiking samples with recombinant PCT. These are typically prepared and validated by qualified laboratory professionals following established analytical chemistry principles and CLSI guidelines.
- Defined Clinical Cut-offs: While the device aids in decision-making, the clinical cut-offs (e.g., 0.10 ng/mL, 0.25 ng/mL) are established within medical guidelines and clinical practice, not by individual experts for the purpose of validating this specific device's performance.
Therefore, the concept of "number of experts and their qualifications for establishing ground truth" as it applies to image interpretation AI is not directly applicable here. The "experts" would be the scientists and laboratorians who designed and executed the analytical validation studies according to CLSI guidelines and robust quality control practices.
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 studies involving human readers interpreting diagnostic images or clinical cases where disagreement needs to be resolved by a tie-breaker. This is an in vitro diagnostic assay with quantitative results. Therefore, adjudication in that sense is not applicable or done. The performance is assessed against quantitative metrics, reference methods, or predicate devices.
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:
An MRMC comparative effectiveness study is not applicable for this device. This is a standalone in vitro diagnostic assay that provides a quantitative measurement of a biomarker (PCT) in clinical specimens. It does not involve human readers interpreting cases with or without AI assistance, nor does it involve improving human reader performance.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, the studies presented are all standalone performance studies for the Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) assay. The device measures PCT levels directly from patient samples, and its performance characteristics (precision, linearity, detection capability, interference, method comparison, etc.) are evaluated intrinsically without direct human interpretation influencing the measurement outcome. The role of the human is in operating the instrument, collecting samples, and interpreting the numerical results in a clinical context.
7. The type of ground truth used (expert concensus, pathology, outcomes data, etc):
The ground truth used for this quantitative in vitro diagnostic device is primarily based on:
- Assigned Values of Calibrators and Control Materials: For accuracy, precision, and linearity studies, known concentrations of PCT in calibrators and quality control materials serve as the ground truth. These values are established through rigorous analytical methods and traceability chains.
- Reference Method/Predicate Device Results: In the method comparison study, the results from the legally marketed predicate device (B·R·A·H·M·S PCT sensitive KRYPTOR) are used as the reference against which the candidate device's performance is compared to establish substantial equivalence.
- Spiking with Recombinant Procalcitonin: For studies like dilution recovery, interference, and cross-reactivity, samples are often "spiked" with known concentrations of highly purified recombinant procalcitonin (or interfering substances) to create samples with a known "true" concentration of the analyte for testing the assay's behavior.
8. The sample size for the training set:
This document describes the validation of an in vitro diagnostic assay, not a machine learning or AI algorithm in the context of typical "training" and "test" sets. Therefore, there isn't a "training set" in the sense of data used to train a predictive model. The development of such assays involves extensive R&D and analytical optimization, but a specific "training set sample size" as asked in the context of AI is not applicable.
9. How the ground truth for the training set was established:
As mentioned above, there is no "training set" in the AI/ML context. The development and optimization of an IVD assay like this involve:
- Immunoassay Design: Selection of specific antibodies (monoclonal anti-PCT antibodies) that bind to the analyte.
- Reagent Formulation: Optimizing concentrations of reagents (sensibeads, chemibeads, biotinylated antibody, assay buffer) and reaction conditions to achieve desired sensitivity, specificity, and dynamic range.
- Analytical Verification Studies: These studies (like those described in the document, e.g., precision, linearity, detection capability) are used iteratively during development to ensure the assay performs as intended. The "ground truth" during this phase would be known concentrations of purified analyte, reference materials, and comparison to established methods or predicate devices.
The "ground truth" is thus established through fundamental analytical chemistry principles, quantitative measurements, and comparison to internationally recognized standards or well-characterized reference materials and methods.
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(588 days)
For in vitro diagnostic use in the quantitative determination of digoxin in serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur® XP systems.
Measurements obtained by this device are used in the diagnosis and treatment of digoxin overdose and in monitoring levels of digoxin to ensure appropriate therapy.
The ADVIA Centaur Digoxin assay reagents come in the following configurations:
5 ReadyPack primary reagent packs containing ADVIA Centaur DIG Lite Reagent and Solid Phase, ADVIA Centaur DIG Master Curve card (250 Tests)
1 ReadyPack primary reagent pack containing ADVIA Centaur DIG Lite Reagent and Solid Phase, ADVIA Centaur DIG Master Curve card (50 Tests)
The ReadyPack consists of the following:
ADVIA Centaur DIG ReadyPack® primary reagent pack; Lite Reagent: 2.5 ml/reagent pack monoclonal mouse anti-digoxin antibody (~26.4 ng/mL) labeled with acridinium ester in protein buffered saline with sodium azide (0.11%) and preservatives.
ADVIA Centaur DIG ReadyPack primary reagent pack; Solid Phase Reagent: 12.5 mL/reagent pack digitoxin (~2 ng/mL) covalently coupled to paramagnetic particles in protein buffered saline with sodium azide (0.11%) and preservatives.
The provided document pertains to the 510(k) summary for the ADVIA Centaur Digoxin assay, specifically regarding the addition of plasma sample types (EDTA and lithium heparin) to its indications for use. It's a submission for an in vitro diagnostic (IVD) device, not an AI/ML-based medical device that relies on complex image analysis or similar algorithms. Therefore, many of the requested details about acceptance criteria, test sets, expert ground truth, MRMC studies, standalone performance, and training sets are not applicable to this type of device and its regulatory submission.
The "acceptance criteria" for this device are demonstrated through analytical performance studies, specifically specimen equivalency and interference studies, to confirm that adding plasma as a sample type does not negatively impact the assay's performance compared to the previously cleared serum sample type.
Here’s an attempt to structure the available information relevant to your request, while highlighting the parts that are not applicable to this specific device (as it's an IVD test, not an AI/ML diagnostic system):
Device: ADVIA Centaur® Digoxin assay
Purpose of Study: To demonstrate substantial equivalence for the addition of plasma (EDTA and lithium heparin) as a valid sample type for the ADVIA Centaur® Digoxin assay.
1. Table of Acceptance Criteria and Reported Device Performance
For an IVD assay like the ADVIA Centaur Digoxin assay, "acceptance criteria" are typically defined by precision, accuracy (often assessed through method comparison/equivalent methods), interference, linearity, and analytical sensitivity. The provided document focuses on demonstrating specimen equivalency and interference for the new sample types.
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Specimen Equivalency | Regression statistics indicating strong agreement with serum (e.g., slope near 1.0, intercept near 0, high correlation coefficient). | Dipotassium EDTA plasma vs. Serum:Regression Equation: y = 1.02x - 0.02 ng/mLCorrelation Coefficient (r): 0.996Lithium heparin plasma vs. Serum:Regression Equation: y = 1.06x - 0.03 ng/mLCorrelation Coefficient (r): 0.990 |
| Interference | Clinically insignificant bias (e.g., less than a certain percentage) when interfering substances are present at relevant concentrations. | Canrenone: 2.7% (at 1.11 ng/mL Digoxin), -0.5% (at 2.12 ng/mL Digoxin)Dipotassium EDTA: -0.4% (at 0.91 ng/mL Digoxin), -1.1% (at 3.12 ng/mL Digoxin)Heparin: 8.9% (at 0.61 ng/mL Digoxin), -1.7% (at 3.66 ng/mL Digoxin)Potassium Canrenoate: 2.8%, -1.0%Spironolactone: 1.0%, 2.5% |
Note: The document implies that the observed regression statistics and low bias values are acceptable for demonstrating substantial equivalence.
2. Sample Sizes Used for the Test Set and Data Provenance
- Dipotassium EDTA plasma: 51 samples
- Lithium heparin plasma: 50 samples
- Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. Typically, such analytical validation studies for IVDs are prospective and conducted in a controlled lab environment.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
N/A. This is an IVD assay measuring a chemical concentration. "Ground truth" is established by the analytical method itself and comparison to a reference method or validated primary sample type (serum in this case). It does not involve expert interpretation of images or clinical data in the way an AI diagnostic would require. The "experts" are the analytical chemists and lab professionals performing and validating the assay.
4. Adjudication Method for the Test Set
N/A. Adjudication methods (like 2+1, 3+1) are common in clinical trials or studies where human interpretation or consensus is required to establish ground truth from ambiguous or complex data (e.g., radiology images). For an IVD assay, the comparison is against an established analytical method (serum) or reference standard; there's no need for adjudication of readings.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
N/A. MRMC studies are used to assess the effectiveness of diagnostic tools, particularly imaging, by comparing the performance of multiple human readers across multiple cases, often with and without AI assistance. This is not applicable to a quantitative biochemical assay.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was Done
The entire test (ADVIA Centaur Digoxin assay) is a standalone system for measuring digoxin concentration. Its performance is measured directly (e.g., accuracy, precision). There is no "human-in-the-loop" performance in the sense of clinical decision support from an AI. The device directly produces a numerical result.
7. The Type of Ground Truth Used
The "ground truth" for specimen equivalency was the measurement of digoxin in serum samples using the predicate ADVIA Centaur Digoxin assay (which was already cleared). The new plasma results were compared against these serum results. For interference, the ground truth is the known concentration of digoxin in the spiked samples.
8. The Sample Size for the Training Set
N/A. This is an IVD assay, not an AI/ML model that requires training data. The assay's reagents and methodology are developed through R&D, not trained on a dataset.
9. How the Ground Truth for the Training Set was Established
N/A. (See point 8).
Conclusion from the Document:
The study concludes that the modified ADVIA Centaur® Digoxin assay, with the addition of plasma sample types, is substantially equivalent in principle and performance to the Predicate Device (ADVIA Centaur® Digoxin assay cleared under 510(k) K931213). This equivalence is based on the analytical performance data, specifically the specimen equivalency and interference studies.
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(532 days)
For in vitro diagnostic use in the quantitative determination of human chorionic gonadotropin (hCG) in serum or plasma (EDTA or lithium heparin) using the ADVIA Centaur® XP system.
Human chorionic gonadotropin measurements are intended for use as an aid in the early detection of pregnancy.
The ADVIA Centaur® Total hCG assay reagents come in the following configurations:
5 ReadyPack primary reagent packs containing ADVIA Centaur Total hCG Lite Reagent and Solid Phase ADVIA Centaur and ADVIA Centaur CP Total hCG Master Curve card (250 Tests)
1 ReadyPack primary reagent pack containing ADVIA Centaur Total hCG Lite Reagent and Solid Phase ADVIA Centaur and ADVIA Centaur CP Total hCG Master Curve card (50 Tests)
The ReadyPack consists of the following:
ADVIA Centaur ThCG ReadyPack® primary reagent pack; Lite Reagent: 5.0 mL/reagent pack polyclonal goat anti-hCG antibody (~0.1 µg/mL) labeled with acridinium ester in buffered saline with sodium azide (0.1%) and preservatives
ADVIA Centaur ThCG ReadyPack primary reagent pack; Solid Phase Reagent: 22.5 mL/reagent pack monoclonal mouse anti-hCG antibody (~0.02 mg/mL) covalently coupled to paramagnetic particles in buffered saline with sodium azide (0.1%) and preservatives
ADVIA Centaur ThCG ReadyPack ancillary reagent pack; ThCG Diluent: 25.0 mL/reagent pack buffered heat-treated equine serum with EDTA, sodium azide (< 0.1%), and preservatives
ADVIA Centaur ThCG Diluent: 50.0 mL/vial buffered heat-treated equine serum with EDTA, sodium azide (< 0.1%), and preservatives
This document describes the validation of the ADVIA Centaur® Total hCG assay, primarily focusing on the addition of plasma (EDTA and lithium heparin) sample claims.
Here's an analysis of the acceptance criteria and the studies that demonstrate the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Detection Capability | LOQ (Limit of Quantification), LOD (Limit of Detection), LOB (Limit of Blank) within specified ranges. | LOQ: 4.0 mIU/mL (IU/L) LOD: 3.0 mIU/mL (IU/L) LOB: 2.0 mIU/mL (IU/L) |
| Precision | CV% within acceptable limits for various hCG concentrations (specified in CLSI EP05-A3). | Serum A (Mean 6.63 mIU/mL): Repeatability CV 4.4%, Between-Run CV 1.3%, Between-Day CV 3.6%, Within-Lab CV 5.8% Serum B (Mean 15.85 mIU/mL): Repeatability CV 3.3%, Between-Run CV 2.8%, Between-Day CV 2.0%, Within-Lab CV 4.8% Serum C (Mean 819.28 mIU/mL): Repeatability CV 2.5%, Between-Run CV 2.7%, Between-Day CV 1.5%, Within-Lab CV 4.0% Control 1 (Mean 7.43 mIU/mL): Repeatability CV 4.1%, Between-Run CV 2.0%, Between-Day CV 4.3%, Within-Lab CV 6.2% Control 2 (Mean 24.64 mIU/mL): Repeatability CV 2.5%, Between-Run CV 0.6%, Between-Day CV 2.3%, Within-Lab CV 3.5% Control 3 (Mean 164.66 mIU/mL): Repeatability CV 1.8%, Between-Run CV 0.5%, Between-Day CV 1.6%, Within-Lab CV 2.5% |
| Method Comparison (vs. Predicate) | High correlation (r value close to 1) and a slope and intercept indicating agreement (slope near 1, intercept near 0). | Equation: ADVIA Centaur Total hCG = 0.96 (Atellica IM ThCG assay) - 3.0 mIU/mL Correlation coefficient (r): 0.997 |
| Specimen Equivalence | Slope of 0.90–1.10 for alternate tube types versus serum, and high correlation coefficients. | Dipotassium EDTA plasma vs. Serum (N=53): Slope 0.99, Intercept 0.3, r 1.00 Lithium heparin plasma vs. Serum (N=51): Slope 1.01, Intercept -0.3, r 1.00 |
| Linearity | Results spanning the entire assay range meet acceptance criteria. | Results met acceptance criteria, supporting an analytical measuring range from 4.0 mIU/mL to 1000 mIU/mL. |
| Dilution Recovery | % Recovery within an acceptable range (typically 90-110% or similar). | Mean % Recovery: 1:2 dilution (91%), 1:4 dilution (98%), 1:8 dilution (95%), 1:16 dilution (101%). Individual recovery values varied, but overall means were within typical acceptable ranges. |
| Interferences | % Bias from interfering substances within acceptable limits (typically ±10% or similar). | Human Serum Albumin: -0.3% to -0.2% bias Acetaminophen: -0.5% to 2.7% biasAcetylsalicylic acid: 0.4% to 2.7% biasHeparin: -8.2% to 1.6% biasIbuprofen: -1.4% to 0.3% biasEDTA: 1.8% to 4.1% biasEthanol: -1.1% to 2.7% biasAtropine: -1.5% to 0.0% biasCaffeine: 1.1% to 6.1% biasGentisic acid: -1.1% to 4.3% bias (All seem to meet typical ±10% bias acceptance criterion). |
| HIL Interference | % Bias from Hemolysis, Icterus, and Lipemia within acceptable limits. | Bilirubin (Conjugated): -1.0% to 3.3% bias Bilirubin (Unconjugated): -0.8% to 1.7% bias Hemoglobin: -0.5% to 1.3% bias Intralipid: -3.3% to -3.7% bias (All seem to meet typical ±10% bias acceptance criterion). |
| Expected Values (Reference Range) | Established reference intervals for non-pregnant and postmenopausal females. | Non-Pregnant Females (Age: ≤40, N=130): 0.03 – 0.6 mIU/mL Postmenopausal Females (Age: ≥41, N=150): 0.02 – 2.9 mIU/mL |
| Cross-Reactivity | Minimal interference from related hormones (FSH, TSH, LH, hGH, PRL). | Data provided for various hCG concentrations with and without cross-reactants. For example, for FSH at 500mIU/mL, hCG values without cross-reactant ranged from 0.5-493.1 mIU/mL, and with cross-reactant ranged from 1.6-475.4 mIU/mL. Similar data for TSH, LH, hGH, and PRL. (Implied acceptance is that the cross-reactants do not significantly alter the hCG measurement, which the provided data appears to support given the relative magnitudes). |
| Sample Handling/Stability | Stability for specified conditions (refrigeration, room temp, on-board, freeze/thaw cycles). | Storage refrigerated (2-8°C) for up to 48 hours. Storage at room temperature (25°C) for up to 8 hours. Kept on-board (30°C) for up to 8 hours. Frozen and thawed up to 1 time. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Detection Capability: No specific sample size disclosed for LOB/LOD/LOQ determination in this summary.
- Precision: 320 total replicates for each of the 6 samples (3 serum, 3 control) over 20 days (e.g., 2 runs/day x 20 days x 2 replicates/run).
- Method Comparison: 117 samples (range 7.6 to 977.6 mIU/mL).
- Specimen Equivalence: 53 pairs for Dipotassium EDTA plasma vs. Serum; 51 pairs for Lithium heparin plasma vs. Serum.
- Linearity: Samples spanning the entire assay range. Specific number not provided.
- Dilution Recovery: Multiple samples tested across 4 dilution ratios (1:2, 1:4, 1:8, 1:16). Number of individual samples varies per dilution.
- Interferences (General, HIL): Not explicitly stated, but performed "used the paired-difference approach" at two analyte concentrations for each interferent.
- Expected Values (Reference Range): 130 non-pregnant females (≤40) and 150 postmenopausal females (≥41).
- Cross-Reactivity: Not explicitly stated, but multiple hCG values (low to high) tested against each cross-reactant.
Data Provenance: The document does not explicitly state the country of origin for the clinical samples. It is a submission by Siemens Healthcare Diagnostics, Inc. based in Tarrytown, New York, USA, suggesting the work was likely conducted or overseen in the USA, but the origin of patient samples is not specified. The studies are retrospective, as they involve characterizing the performance of the assay with collected samples, rather than following patients prospectively as part of the study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
For in vitro diagnostic assays like this, which measure an analyte (hCG), the "ground truth" is typically the concentration of the analyte itself, often established by a reference method or highly characterized reference materials for standardization, or by the clinical diagnosis. This is not a device where human experts (e.g., radiologists) interpret images or clinical data to establish a ground truth.
- Standardization: The ADVIA Centaur Total hCG assay is traceable to the World Health Organization (WHO) 5th IS 7/364 reference material. This material itself serves as the 'ground truth' for defining hCG concentration.
- Expected Values: The reference range study for Non-Pregnant and Postmenopausal Females established through a CLSI guideline, where the "ground truth" for non-pregnant status would be clinical assessment, and the hCG measurement would be the result to define the range.
Therefore, the concept of "number of experts used to establish ground truth" as it applies to image interpretation or clinical diagnosis is not directly applicable here. The ground truth is fundamentally analytical (traceability to reference standards) and clinical classification (e.g., non-pregnant status).
4. Adjudication Method for the Test Set
Not applicable for this type of in vitro diagnostic device study. Adjudication methods (like 2+1, 3+1) are typically used in clinical studies where individual expert opinions need to be reconciled for clinical endpoints or image interpretations. Here, the studies are analytical performance evaluations.
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 device is an in vitro diagnostic assay, not an AI-assisted diagnostic imaging device or a system involving human readers interpreting outputs.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies described are for the standalone analytical performance of the ADVIA Centaur® Total hCG assay. The device measures hCG quantitatively; its performance characteristics (precision, linearity, interference, etc.) are inherent to the assay and instrument system, independent of human interpretation of the measurement itself. The "without human-in-the-loop" concept applies.
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)
The ground truth depends on the specific performance characteristic:
- Analytical Ground Truth: For characteristics like method comparison, linearity, dilution recovery, interferences, and cross-reactivity, the ground truth is often defined by:
- Reference Methods: The predicate device (Atellica IM ThCG assay)
- Spiked Samples: Known concentrations of analyte or interfering substances added to samples.
- Traceability to International Standards: WHO 5th IS 7/364 reference material.
- Clinical Ground Truth: For the "Expected Values" study, the ground truth of "non-pregnant" or "postmenopausal" status would be established through clinical assessment of the individuals providing the samples.
8. The Sample Size for the Training Set
This document describes a 510(k) submission for an in vitro diagnostic (IVD) assay, not a machine learning or AI algorithm development. Therefore, the concept of a "training set" in the context of AI is not applicable. The assay's methods are based on established immunoassay principles, and the performance characteristics are determined through analytical validation studies.
9. How the Ground Truth for the Training Set Was Established
As explained in point 8, the concept of a training set for an AI/ML algorithm is not relevant for this traditional IVD assay validation. The assay is developed based on scientific and chemical principles, and its performance is validated against specific criteria using various types of samples.
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(515 days)
The ADVIA® Chemistry Enzymatic Hemoglobin A1c (A1c E) assay is an in vitro diagnostic assay for the quantitative determination of mmol/mol HbA1c (IFCC) and % HbA1c (DCCT/NGSP) in human anticoagulated venous whole blood and hemolysate for use on the ADVIA® Chemistry Systems. Measurement of Hemoglobin A1c is used as an aid in the diagnosis and monitoring of long-term blood glucose control in patients with diabetes mellitus, and as an aid in the identification of patients at risk for developing diabetes mellitus.
The ADVIA® Chemistry Enzymatic Hemoglobin A1c (A1c E) assay measures hemoglobin A1c in human anticoagulated whole blood and hemolysate. The assay consists of three reagents (R1, R2, and Pretreatment Solution), which are liquid and ready to use.
The assay offers both an automated and a manual application. The automated application (A1c_E) lyses the anticoagulated whole blood specimen on the system for the automated application (A1c E). Samples may also be lysed manually using the ADVIA® Chemistry A1c_E Pretreatment Solution to obtain hemolysate for the manual application (A1c_EM). The two applications yield the same results.
The provided document is a 510(k) Summary for a medical device called the ADVIA® Chemistry Enzymatic Hemoglobin A1c (A1c E) Assay. This document describes a submission seeking FDA clearance for a modification to an existing device, specifically to extend the low end of the analytical measuring range of total hemoglobin (tHb).
However, the document does not contain the detailed study results, acceptance criteria tables with performance data, information on sample sizes for test and training sets, expert qualifications, or adjudication methods that would be typically found in a comprehensive study report proving a device meets acceptance criteria.
The 510(k) Summary states that "Performance data were needed to evaluate the change" and "The verification study of linearity was done in accordance with the CLSI standard recognized by the FDA. This study along with other verification activities demonstrate equivalent performance to the predicate and effective risk mitigations. The studies met pre-determined acceptance criteria." and "Testing verified all acceptance criteria were met."
While these statements confirm that studies were conducted and met acceptance criteria, the specific details requested in your prompt (e.g., the actual table of acceptance criteria vs. performance, sample sizes, expert involvement, etc.) are not present in this summary document.
Therefore, I cannot provide the requested information from this document. To answer your prompt, I would need a more detailed study report or clinical trial summary that includes the actual performance data and study design specifics.
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