(55 days)
Immunoassay for the in vitro quantitative determination of thyroxine-binding capacity in human serum and plasma.
The Elecsys® test principle is based on competition principle. Total duration of assay: 18 minutes (37° C).
• 1st incubation (9 minutes): Sample (15 $\mu$ L), exogenous T4, and biotinylated T4-polyhapten (75 $\mu$ L).
•2nd incubation (9 minutes): After addition of a specific anti-T4 antibody labeled with a ruthenium complex (75 $\mu$ L), the polyhapten and the antibody derivative react to form a complex, the concentration of which is inversely proportional to the concentration of the excess, exogenous T4. This immunological complex is bound to the added streptavidin-coated microparticles (35 $\mu$ L) via the interaction of biotin and streptavidin.
·The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier (0.4 second read frame).
·Results are determined via a calibration curve which is instrumentspecifically generated by 2-point calibration and a master curve provided via the reagent bar code.
The provided text describes the Elecsys® T-Uptake Assay and its comparison to a predicate device, the Enzymun-Test® TBK (T4 Uptake). The studies performed are primarily focused on demonstrating substantial equivalence to the predicate device, rather than establishing acceptance criteria for novel performance.
Here's an analysis of the requested information based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" in the traditional sense of pre-defined thresholds for performance success. Instead, it presents a comparison to a predicate device, aiming to show "substantial equivalence." The performance characteristics shown are relative to the predicate and aim to demonstrate comparable or improved performance.
Implicit "Acceptance Criteria" (based on predicate device comparison) and Reported Performance:
| Feature | Implicit Acceptance Criteria (based on predicate) | Elecsys® T-Uptake Reported Performance |
|---|---|---|
| Precision | Comparable to Enzymun-Test® TBK within-run and total %CV at various control levels (Low, Mid, High) | Within-Run %CV: 2.15 (Control 1), 3.29 (Control 2), 2.39 (Control 3) |
| Total %CV: 3.25 (Control 1), 3.68 (Control 2), 2.66 (Control 3) | ||
| Lower Detection Limit | 0.2 TBI | 0.2 TBI |
| Linearity | 0.2 TBI to the value of the highest standard | 0.2 TBI to the value of the highest standard |
| Method Comparison | Reasonable correlation and agreement with Enzymun-Test® TBK (e.g., r-value close to 1, slope close to 1, intercept close to 0) | Least Squares: y = 0.99x - 0.03, r = 0.908, SEE = 0.04, N=319 |
| Passing/Bablok: y = 1.07x - 0.12, r = 0.908, SEE = 0.04, N=319 | ||
| Interfering Substances | Show no interference at specified concentrations (or comparable to predicate) | Bilirubin: No interference at 25 mg/dL |
| Hemoglobin: No interference at 1 g/dL | ||
| Lipemia: No interference at 1500 mg/dL | ||
| Biotin: No interference at 30 ng/mL | ||
| Specificity (% Cross-reactivity) | Comparable cross-reactivity profiles to the predicate device | L-T4: 100%, D-T4: 100%, L-T3: 1.5%, D-T3: 1.4%, 3-iodo-L-tyrosine: 0.002%, 3,5-diiodo-L-tyrosine: 0.01%, Tetraiodo-thyroacetic acid: 38.5% |
2. Sample Size Used for the Test Set and Data Provenance
- Precision:
- Elecsys® T-Uptake: N=60 for each of the three control levels.
- Enzymun-Test® TBK (Predicate): N=118 (Low), N=120 (Mid), N=119 (High).
- Method Comparison:
- Elecsys® T-Uptake vs. Enzymun-Test® TBK: N=319.
- Data Provenance: The document does not specify the country of origin of the data or whether it was retrospective or prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
N/A. This is a quantitative diagnostic assay for Thyroxine-Binding Capacity. The "ground truth" for such assays is typically established by the reference method or comparison to an established, validated predicate device (as done here). There are no experts establishing ground truth in the sense of image interpretation or clinical diagnosis.
4. Adjudication Method for the Test Set
N/A. As this is not an expert-driven diagnostic interpretation, no adjudication method like 2+1 or 3+1 is applicable.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No. This is an in vitro diagnostic device, not an imaging device that would typically involve human readers interpreting cases. Therefore, an MRMC study is not applicable.
6. If a Standalone Study Was Done
Yes, the performance characteristics of the Elecsys® T-Uptake Assay (e.g., precision, lower detection limit, linearity, interfering substances, specificity) were evaluated as a standalone product. However, the primary context for evaluating its performance is always in comparison to the predicate device to establish substantial equivalence.
7. The Type of Ground Truth Used
The ground truth for evaluating the Elecsys® T-Uptake Assay's performance is:
- Analytical Performance: Established through laboratory testing using known controls, standards, and samples for precision, linearity, detection limits, and interference.
- Comparative Performance: Established by comparing its results to a legally marketed predicate device (Enzymun-Test® TBK), which serves as the "reference standard" for demonstrating substantial equivalence.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning, as this is a chemical assay. The assay's calibration uses a 2-point calibration and a master curve provided via a reagent bar code. The development of the assay itself would have involved extensive R&D and optimization, but the specific sample sizes for such development or "training" (in a non-ML sense) are not provided.
9. How the Ground Truth for the Training Set Was Established
N/A. As this is an in vitro diagnostic assay based on a competition principle and electrochemiluminescence, there isn't a "training set" in the machine learning sense. The assay's accuracy and performance are established through rigorous analytical validation against known concentration standards and comparison to established methods, rather than learning from a labeled dataset.
§ 862.1715 Triiodothyronine uptake test system.
(a)
Identification. A triiodothyronine uptake test system is a device intended to measure the total amount of binding sites available for binding thyroid hormone on the thyroxine-binding proteins, thyroid-binding globulin, thyroxine-binding prealbumin, and albumin of serum and plasma. The device provides an indirect measurement of thyrkoxine levels in serum and plasma. Measurements of triiodothyronine uptake are used in the diagnosis and treatment of thyroid disorders.(b)
Classification. Class II. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.