(705 days)
VIDAS® FT4 is an automated quantitative enzyme immunoassay for use on the instruments of the VIDAS® family, for the determination of free thyroxine (FT4) in human serum or plasma (lithium heparin), using the ELFA technique (Enzyme Linked Fluorescent Assay). Measurement of Free Thyroxin is intended for use as an aid in the diagnosis and treatment monitoring of thyroid disorders.
VIDAS® FT4 is an automated quantitative enzyme immunoassay for use on the instruments of the VIDAS® family, for the determination of free thyroxine (FT4) in human serum or plasma (lithium heparin), using the ELFA technique (Enzyme Linked Fluorescent Assay). Measurement of free thyroxine is intended for use as an aid in the diagnosis and treatment monitoring of thyroid disorders.
The assay principle combines a one-step enzyme immunoassay competition method with a final fluorescent detection (ELFA).
The Solid Phase Receptacle (SPR®) serves as the solid phase as well as the pipetting device for the assay. Reagents for the assay are ready-to-use and pre-dispensed in the sealed reagent strips. All of the assay steps are performed automatically by the instrument. The reaction medium is cvcled in and out of the SPR several times.
The sample is collected and transferred into the well containing an alkaline phosphataselabeled anti-T4 antibody (conjugate). The antiqen present in the sample and the T4 antigen coated on the interior of the SPR compete for the available sites on the specific anti-T4 antibody conjugated to alkaline phosphatase.
During the final detection step, the substrate (4-Methyl-umbellifery) phosphate) is cvcled in and out of the SPR. The conjugate enzyme catalyzes the hydrolysis of this substrate into a fluorescent product (4-Methyl-umbelliferone) the fluorescence of which is measured at 450 nm. The intensity of the fluorescence is inversely proportional to the concentration of free thyroxine present in the sample. At the end of the assay, results are automatically calculated by the instrument in relation to the calibration curve stored in memory, and then printed out.
The provided text describes the performance of the VIDAS® FT4 device, an automated quantitative enzyme immunoassay for free thyroxine. However, it does not explicitly state "acceptance criteria" as a separate, pre-defined set of thresholds. Instead, it presents various performance study results (e.g., precision, linearity, correlation, analytical sensitivity, specificity) which implicitly demonstrate that the device meets the necessary performance expectations for its intended use and for demonstrating substantial equivalence to its predicate device.
1. Table of Acceptance Criteria and Reported Device Performance
As explicit acceptance criteria are not tabulated in the document, I will infer the performance metrics considered crucial from the studies presented. For "Acceptance Criteria," I will describe the objective assessed in each study.
| Performance Metric (Implied Acceptance Criteria) | Reported Device Performance (VIDAS® FT4) |
|---|---|
| Analytical Specificity | |
| Interference with Bilirubin | No significant interference up to 22.5 mg/dL. |
| Interference with Lipids | No significant interference up to 750 mg/dL. |
| Interference with Hemoglobin | No significant interference up to 500 mg/dL. |
| Interference with HAMA | No significant interference up to 0.2 mg/dL. |
| Interference with Albumin | No significant interference up to 6300 mg/dL. |
| Interference with Drugs | No significant interference observed up to specified concentrations for various drugs (e.g., Acetylsalicylic Acid: 32.61 mg/dL, Amiodarone: 0.58 mg/dL, Carbamazepine: 1.5 mg/dL, etc.). |
| Cross-reactivity (Structurally related molecules) | No significant interference observed at specified concentrations for 3,5-diiodotyrosine (16.770 µg/dL, 0.00095% cross-reactivity), 3,5-diodothyronine (27.310 µg/dL, 0.00040% cross-reactivity), and L-triiodothyronine (0.678 µg/dL, 0.02655% cross-reactivity). |
| Analytical Sensitivity | |
| Limit of Blank (LoB) | 0.02 ng/dL |
| Limit of Detection (LoD) | 0.07 ng/dL |
| Limit of Quantitation (LoQ) | 0.13 ng/dL (defined as lowest analyte concentration reproducibly measured with a within-laboratory precision CV of ≤ 20%). |
| Measurement Range | 0.13 ng/dL to 6.61 ng/dL. |
| Linearity | Linear over the whole measurement range (0.13 ng/dL to 6.61 ng/dL) on both VIDAS® and miniVIDAS® instruments. |
| Matrix Comparison | High correlation coefficients (r > 0.99) and regression analyses (slopes close to 1, intercepts close to 0) indicating equivalence between different blood collection tube types (plastic tube with clot activator, plastic tube with separation gel, plastic tube with lithium heparin, plastic tube with lithium heparin and separation gel) and the reference silicone-coated glass tube. E.g., Plastic tube with clot activator: Y = 0.98X + 0.01, r = 0.999. |
| Precision | VIDAS® instruments: |
| Repeatability CVs ranged from 2.3% to 6.3%. | |
| Reproducibility CVs ranged from 5.1% to 13.4%. | |
| miniVIDAS® instruments: | |
| Repeatability CVs ranged from 2.0% to 11.2%. | |
| Reproducibility CVs ranged from 2.8% to 15.4%. | |
| Correlation | VIDAS®: Slope 1.03 (0.99-1.06 CI), Intercept -0.02 (-0.13-0.05 CI), Correlation coefficient (r) 0.988 (0.980-0.993 CI) when compared to a commercially available Free T4 EIA. |
| miniVIDAS®: Slope 1.04 (1.00-1.08 CI), Intercept 0.01 (-0.06-0.12 CI), Correlation coefficient (r) 0.987 (0.977-0.992 CI) when compared to a commercially available Free T4 EIA. | |
| Reference Range / Expected Values | Established reference interval: 0.77 - 1.51 ng/dL (2.5th and 97.5th percentiles). 90% CI for lower limit: 0.70 - 0.79 ng/dL. 90% CI for upper limit: 1.41 - 1.59 ng/dL. This was determined from a population of 544 healthy subjects. |
2. Sample Sizes Used for the Test Set and Data Provenance
Due to the nature of an in vitro diagnostic (IVD) device, the "test set" is not a singular set of patient cases for a diagnostic decision, but rather refers to various samples used across different analytical and clinical performance studies. The data provenance is generally not explicitly stated as "country of origin" for these types of analytical validation studies but implies laboratory testing within the manufacturer's R&D facilities or contracted labs, primarily related to the device itself.
- Analytical Specificity (Interferences): For common interferences (bilirubin, lipids, hemoglobin, HAMA, albumin), the study involved serum samples at FT4 analyte levels close to the lower and higher limits of the euthyroid range. The number of samples for each interference type is not specified beyond "samples." For drugs, the number of samples is not specified. For structurally related molecules, the study involved tested FT4 concentrations of approximately 1.2 ng/dL and 2.5 ng/dL, but the number of samples is not explicitly given. This data is likely generated prospectively in a laboratory setting.
- Analytical Sensitivity (LoB, LoD, LoQ):
- LoB: One blank sample, N=60 measures per lot on each instrument (2 lots on one VIDAS®, 1 lot on one miniVIDAS®).
- LoD: Low concentration samples (number not specified for VIDAS®, 4 samples for miniVIDAS®), N=150 measures per lot on VIDAS®, N=100 measures per lot on miniVIDAS®.
- LoQ: 9 low concentration samples, N=40 measures per sample and per lot on each instrument (2 lots on one VIDAS®, 1 lot on one miniVIDAS®).
- This data is prospectively generated in a laboratory setting.
- Linearity: The study was conducted on the VIDAS® and miniVIDAS® instruments. The number of samples or points tested is not explicitly stated. This data is prospectively generated in a laboratory setting.
- Matrix Comparison: 31 sample sets (each set from one donor during one draw, consisting of a reference tube type and four different blood collection tubes). Samples ranged from 0.13 ng/dL to 6.45 ng/dL. This data is prospectively generated.
- Precision: Panel members covering the measuring range were tested. 6 samples for VIDAS® instruments, and 5 samples for miniVIDAS® instruments. Total N=240 measures for each sample/instrument type. This data is prospectively generated in a laboratory setting.
- Correlation: 54 samples were included in the study for comparison to a commercially available Free T4 EIA. Range tested: VIDAS® (0.41 - 6.42 ng/dL), miniVIDAS® (0.52 - 6.35 ng/dL). This data is prospectively generated.
- Reference Range / Expected Values: 544 apparently healthy subjects. The population characteristics are described (45.5% males, 55.5% female, 83.8% Caucasian, 6.1% African-American, 9.6% Hispanic and 0.6% Asian). The country of origin is not specified but the demographic breakdown suggests a Western population. This is prospective data collection.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
For an IVD device like VIDAS® FT4, "ground truth" is typically established by:
- Using reference materials with assigned values.
- Comparing to a legally marketed predicate device or a well-established, validated method (e.g., mass spectrometry, if applicable, though not explicitly mentioned here as a primary reference method).
- For clinical studies like reference range determination, it relies on clinical assessment of health status (e.g., "apparently healthy subjects").
In this documentation:
- Metrological traceability: The VIDAS® FT4 assay is standardized against the Elecsys® FT4 assay (Roche Diagnostic), which serves as a clinical reference method (predicate device).
- Value assignment procedure for calibrator (S1) and control (C1): Reference Calibrators are assigned values via a method comparison between VIDAS® FT4 and Roche Elecsys FT4.
- Correlation study: The VIDAS® FT4 assay was compared to a commercially available Free T4 EIA (likely the predicate Elecsys® FT4 Assay or similar). This serves as the ground truth for that specific study.
- Reference Range / Expected Values: This ground truth is based on the clinical status of "apparently healthy subjects." There is no mention of "experts" in the sense of clinicians or radiologists establishing ground truth for individual cases. The health status of the subjects would be determined by standard medical screening procedures, presumably overseen by medical professionals (e.g., physicians, lab personnel) but not explicitly detailed as "experts."
Therefore, there isn't a stated number of experts or specific qualifications in the traditional sense of consensus reading for image or pathology-based diagnostics. The ground truth relies on established analytical methods and clinical definitions of health.
4. Adjudication Method for the Test Set
Not applicable in the context of this IVD device's analytical and clinical performance studies as described. Adjudication (e.g., 2+1, 3+1) is typically used for resolving discrepancies in expert interpretations in studies involving subjective assessments (like radiology or pathology image analysis). For quantitative assays, the "ground truth" is determined by reference methods or validated values, not by expert consensus on individual results.
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 in vitro diagnostic (IVD) device for quantitative measurement of free thyroxine (FT4). It is not an AI-assisted diagnostic imaging or pathology device that involves human readers interpreting cases.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was Done
Yes, the studies presented are all standalone performance evaluations of the VIDAS® FT4 assay system (instrument + reagents + algorithm), which is an automated system designed to provide quantitative results directly. The results are "automatically calculated by the instrument in relation to the calibration curve stored in memory, and then printed out." Human involvement is limited to operating the instrument, performing calibration, and reviewing the generated reports, not to interpreting raw data points or making subjective diagnostic decisions the device is intended to automate.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth used primarily consists of:
- Reference Method Comparison: For several studies, the predicate Elecsys® FT4 assay or another commercially available, validated Free T4 EIA served as the comparative "ground truth" or reference method for demonstrating substantial equivalence.
- Reference Materials: For analytical sensitivity (LoB, LoD, LoQ) and linearity, the ground truth is based on gravimetrically prepared or otherwise certified reference materials with known concentrations.
- Clinical Definition: For the reference range determination, the ground truth for the healthy population was based on subjects deemed "apparently healthy."
8. The sample size for the training set
This document describes the validation of an IVD assay, not a machine learning or AI algorithm in the context of "training data." The assay relies on a pre-defined chemical reaction and detection method, with instrument calibration. Therefore, there is no "training set" in the sense of data used to train a predictive model. The "calibration curve" is established using a set of calibrators with known concentrations, which is a standard procedure for quantitative assays and not an AI training process.
9. How the ground truth for the training set was established
As there is no "training set" for an AI algorithm in this context, this question is not applicable. For the calibration of the assay, the "ground truth" (assigned values for calibrators) is established through reference method comparison with the Elecsys® FT4 assay and potentially other established metrological traceability chains, as described under "Value assignment procedure for calibrator (S1) and control (C1)."
§ 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.