(28 days)
The MAGLUMI 2000 FT4 assay is for in vitro diagnostic use in the quantitative determination of free thyroxine (FT4) in human serum. The measurement of FT4 is used in the diagnosis of thyroid disorders.
MAGLUMI 2000 FT4 kit consists of the following reagents: Magnetic Microbeads- coated with T4 antigen, BSA, NaN3(
Here's an analysis of the acceptance criteria and study findings for the MAGLUMI 2000 FT4 device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Precision | CV% within acceptable ranges for clinical chemistry devices at various concentrations (implied by CLSI EP5-A2). For example, Total CV for Control 1: ≤ 10% (often a general guideline for low-concentration analytes). Total CV for other controls/samples: ≤ 8-10% depending on concentration. Specific pre-defined limits are not explicitly stated, but the study aims to demonstrate acceptable precision. | Control 1 (1.006 ng/dL): Total CV 9.34% |
| Control 2 (1.9952 ng/dL): Total CV 7.81% | ||
| Control 3 (3.9978 ng/dL): Total CV 5.04% | ||
| Calibrator low (0.3333 ng/dL): Total CV 9.99% | ||
| Calibrator high (7.1929 ng/dL): Total CV 3.20% | ||
| Serum Pools/Patient Pools: Total CVs ranged from 3.76% to 9.96% | ||
| Linearity | The assay should demonstrate linearity across its claimed measuring range (0.19 to 10.0 ng/dL) with a strong correlation (R² close to 1) and a slope close to 1, and y-intercept close to 0 (implied by CLSI EP6-A). | Linear between 0.19 and 10.0 ng/dL. Observed = 0.9898 (Expected) + 0.01364, R² = 0.9991. |
| Stability (Reagents) | Reagents, calibrators, and controls should be stable for a specified shelf life at recommended storage conditions (e.g., 2-8°C for 12 months for accelerated stability, confirmed by real-time studies). | Accelerated stability at 37°C showed controls, calibrators, and reagents are stable for 12 months at 2-8°C. Real-time stability is on-going. |
| Detection Limit (Limit of Blank - LOB) | 95th percentile value from analyte-free samples (implied by CLSI EP17-A guidelines). A low LOB is desired. | 0.087 ng/dL (highest of 3 lots). |
| Detection Limit (Limit of Detection - LOD) | Lowest analyte concentration that can be detected (implied by CLSI EP17-A guidelines). A low LOD is desired. | 0.143 ng/dL (highest of 3 lots). |
| Detection Limit (Limit of Quantitation - LOQ) | Lowest analyte concentration that can be reproducibly measured with an intermediate precision CV of ≤ 20% (as per CLSI EP17-A guidelines). | 0.190 ng/dL (highest of 3 lots). |
| Interference (Cross-Reactivity) | % Cross-reactivity for relevant compounds should be very low (e.g., 0.95 or >0.98), a slope close to 1, and a y-intercept close to 0 (implied by CLSI EP9-A2). | Y = 1.0451X - 0.05375, R² = 0.9919, for MAGLUMI FT4 (y) vs. ADVIA CENTAUR FT4 (x). |
Note on Acceptance Criteria: The document often refers to CLSI guidelines (e.g., EP5-A2, EP6-A, EP17-A, EP9-A2) for performance characteristic studies. While explicit numerical acceptance criteria are not always stated directly in the text, compliance with these guidelines implicitly means that the performance falls within industry-accepted ranges and statistical thresholds. For precision, for instance, a total CV of less than 10% (or even lower for higher concentrations) is generally considered acceptable in clinical chemistry. For linearity and method comparison, an R² value close to 1, a slope near 1, and a y-intercept near 0 are standard indicators of good performance.
2. Sample Size Used for the Test Set and Data Provenance
- Precision Study:
- Sample Size: 240 measurements per control/calibrator/pool (N=240, from 80 samples analyzed per level on each of 3 instruments).
- Data Provenance: Not explicitly stated, but implied to be patient serum pools and native patient samples from clinical settings, likely domestic to the manufacturer's testing location or within industry standard practices for clinical evaluation. The study was conducted on "three controls, two calibrators, four spiked patient serum pools and four native patient sample pools."
- Linearity Study:
- Sample Size: 11 levels with FT4 concentrations from 0.19 to 10.0 ng/dL, each measured in quadruplicate on 3 lots of reagent.
- Data Provenance: Samples prepared by spiking T4 USP Standard into T4-free human serum samples.
- Detection Limit Study (LOB, LOD, LOQ):
- LOB: 80 measurements of T4 free human serum samples.
- LOD: Four levels of low samples, measured in 80 replicates over 5 days per sample.
- LOQ: Six low serum samples, in six replicates per run, one run per day, over 5 days.
- Data Provenance: T4 free human serum samples and low serum samples.
- Interference Study:
- Sample Size: Variable, involves preparing solutions, and for common drugs/interfering substances, three serum samples (low, medium, high FT4) per substance. For HAMA/RF/Protein, specific FT4 human serum samples.
- Data Provenance: Spiked solutions, human serum pools, FT4 human serum samples.
- Method Comparison Study:
- Sample Size: 224 human serum samples.
- Data Provenance: Human serum samples. Provenance (e.g., country of origin, retrospective/prospective) is not explicitly stated.
- Expected Values/Reference Range Study:
- Sample Size: 157 serum samples.
- Data Provenance: Normal, apparently healthy adult individuals (22 years and older). Provenance (e.g., country of origin, retrospective/prospective) is not explicitly stated.
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 device like the MAGLUMI 2000 FT4, the "ground truth" for analytical performance tests (precision, linearity, detection limits, interference) is typically established by the reference methods, spiked concentrations, or consensus values derived from the testing procedures themselves, rather than human expert opinion. For method comparison, the "ground truth" is typically the result from the established predicate device.
4. Adjudication Method for the Test Set
The concept of an "adjudication method" (like 2+1 or 3+1 for clinical diagnoses based on expert review) is not applicable to the analytical performance studies described for this in vitro diagnostic device. The studies rely on quantitative measurements and statistical analysis rather than subjective expert interpretation of results for ground truth.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study was not done. This type of study is primarily relevant for medical imaging devices or other diagnostic tools where human readers interpret results, and the AI system acts as an aid to improve human performance. For an automated in vitro diagnostic assay like MAGLUMI 2000 FT4, the performance is evaluated through direct analytical comparisons.
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 MAGLUMI 2000 FT4 device. These are analytical performance studies (precision, linearity, detection limits, interference, method comparison) that evaluate the device's ability to accurately and precisely measure FT4 concentrations in human serum, independent of human interpretation or intervention in the measurement process itself. The "algorithm" here refers to the immunoassay's chemistries and the instrument's measurement principles.
7. The Type of Ground Truth Used
- Precision: Reference materials (controls, calibrators) with established target values, and pooled human serum samples where the mean serves as a statistical "ground truth" for variability assessment.
- Linearity: Gravimetrically or volumetrically prepared "expected" concentrations of T4 in serum.
- Stability: Initial measurements at time 0, with subsequent measurements compared to these baselines.
- Detection Limits (LOB, LOD, LOQ): Analyte-free samples and low-concentration samples measured extensively to statistically determine minimum detectable/quantifiable levels.
- Interference (Cross-Reactivity): Known amounts of potential interferents/cross-reactants.
- Method Comparison: Results from the predicate device (Siemens ADVIA Centaur FT4) are used as the reference "ground truth" for comparison.
- Expected Values/Reference Range: Statistical distribution of measurements from a reference population (157 apparently healthy adults) to establish a normal range.
8. The Sample Size for the Training Set
This information is not provided. The document describes performance characteristic studies (test set), but does not detail the development or "training" specific to an AI algorithm for this device. For in vitro diagnostics, "training set" would typically refer to samples used during the assay development and optimization phase to establish parameters like calibration curves, reagent formulations, or instrument settings. The document focuses on validation studies.
9. How the Ground Truth for the Training Set Was Established
This information is not provided as a "training set" isn't explicitly defined in the context of this submission. If referring to the development/optimization phase of a typical immunoassay, ground truth would be established through:
- Reference materials: Highly purified FT4 standards.
- Known concentrations: Samples prepared with precise, known concentrations of FT4.
- Comparative data: Initial comparisons against existing reference methods or well-characterized assays during the research and development phase.
- Clinical samples: Use of a large number of clinical samples to optimize the assay's dynamic range and specificity.
§ 862.1695 Free thyroxine test system.
(a)
Identification. A free thyroxine test system is a device intended to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may therefore determine the clinical metabolic status of thyroxine. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases.(b)
Classification. Class II.