(85 days)
The DiaSorin TSH-CTK-3 is an immunoradiometric assay for the quantitative determination of thyrotropin (TSH) in human serum. Measurements of TSH levels are used as an aid in the diagnosis of thyroid or pituitary disorders.
The TSH-CTK-3 is an immunoradiometric assay for the quantitative determination of thyrotropin (TSH) in human serum. Two monoclonal antibodies recognizing different binding sites on the antigen (intact hTSH and ß subunit of TSH) are used in excess. The monoclonal antibody to intact hTSH is labeled with Iodine-125 (tracer). The other monoclonal antibody to the ß subunit of TSH is immobilized on the inner surface of the tube (coated tube system). During the incubation both antibodies react with TSH molecules of the sample to form a sandwich-type complex bound to the tube (bound fraction B). Unbound tracer is removed with a wash step. After the washing step the radioactivity of the tubes is measured. The radioactivity measured is directly proportional to the TSH concentration of the respective sample. Using samples of known TSH concentration (standards) a radioactivity-concentration-profile (standard curve) is constructed by which TSH values of unknown samples can be determined by means of their respective radioactivity. TSH concentrations in terms of mU TSH/L are calibrated against WHO 2nd IRP 80/558.
The TSH-CTK-3 device is an immunoradiometric assay (IRMA) intended for the quantitative determination of Thyrotropin (TSH) in human serum. Measurements of TSH levels are used as an aid in the diagnosis of thyroid and pituitary disorders.
Here's an analysis of its acceptance criteria and the study proving its performance:
1. Table of Acceptance Criteria and Reported Device Performance
| Parameter | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Sensitivity (Analytical) | Not explicitly stated | 0.04 mU/L |
| Sensitivity (Functional) | Not explicitly stated | 0.09 mU/L |
| Total Precision (%CV) | Not explicitly stated | 2% - 13% |
| Recovery (mean) | Not explicitly stated | 98.7% +/- 1.4% |
| Linearity | Correlation coefficient (r) close to 1 | y = 0.93x + 0.52, r = 0.998 |
| Linearity of Dilution | Correlation coefficient (r) close to 1 | y = 1.02x + 0.19, r = 0.999 |
| Endogenous Substance Interference | No significant interference | No significant interference observed at Hemoglobin (500mg/dL), Cholesterol (1000mg/dL), Bilirubin (15mg/dL). Interference observed with Triglycerides (330mg/dL) |
| Sample Types | Serum only | Serum. (Note: Serum and Plasma show some differences, so intended use is for Serum only.) |
| Reference Range (Serum Only) | Established range | 0.25 - 3.51 mU/L |
| Method Comparison (vs. Predicate) | High correlation (r) | Correlation coefficient of 0.99 with Ventrex hTSH 125I IRMA kit |
Note: The document provided does not explicitly state numerical acceptance criteria for many parameters, but rather reports the performance results. The implication for parameters like linearity and method comparison is that a high correlation coefficient (close to 1) indicates acceptable performance. For sensitivity and precision, the reported values are presented as the device's performance characteristics.
2. Sample Size Used for the Test Set and Data Provenance
- Analytical Sensitivity: 40 replicates of the zero standard. Data provenance is not specified but appears to be from internal laboratory testing.
- Functional Sensitivity: 14 serum pools, assayed in 1 run per day for 5 days. Data provenance is not specified but appears to be from internal laboratory testing.
- Total Precision: Not specified for the number of samples, but determined according to NCCLS guidelines. Data provenance is not specified but appears to be from internal laboratory testing.
- Linearity/Linearity of Dilution: Not specified for the number of samples, but "samples" were diluted. Data provenance is not specified but appears to be from internal laboratory testing.
- Endogenous Substance Interference: Not specified for the number of samples, but tested with specific concentrations of hemoglobin, cholesterol, bilirubin, and triglycerides. Data provenance is not specified but appears to be from internal laboratory testing.
- Method Comparison: 95 individuals. Data provenance is not specified but implies a clinical sample set. The study type is retrospective, as existing samples from individuals were evaluated in both kits.
- Reference Range: 100 apparently healthy adults from Western Europe. This is prospective for establishing the reference range for the device.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This device is an in-vitro diagnostic (IVD) assay for measuring a specific biomarker (TSH). The "ground truth" for such assays is typically established through biochemical methods, reference materials, and comparison to established predicate devices, rather than expert interpretation of images or observations.
- Standards/Calibration: Calibrated against WHO 2nd IRP 80/558. This is a globally recognized reference standard for TSH.
- Method Comparison: Compared against the Ventrex hTSH 125I IRMA kit (predicate device). The predicate device itself has established performance based on previous regulatory approvals.
Therefore, the concept of "experts establishing ground truth" in the manner of radiologists or pathologists for, say, an imaging device, does not directly apply here. The accuracy of the measurements itself, validated against reference standards and predicate devices, constitutes the "ground truth establishment." No specific number or qualifications of "experts" are stated in this context.
4. Adjudication Method for the Test Set
Not applicable in the context of a biochemical assay where quantitative measurements are directly compared to reference standards or predicate device results. There is no subjective interpretation requiring adjudication.
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 relevant for diagnostic devices that involve human interpretation (e.g., imaging devices read by radiologists). This device is an automated biochemical assay.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
Yes, the performance data presented is for the standalone performance of the TSH-CTK-3 assay. It describes the analytical and functional characteristics of the device itself (e.g., sensitivity, precision, recovery, linearity, interference, method comparison) without human intervention in the measurement process after sample processing.
7. The Type of Ground Truth Used
- Reference Standard: WHO 2nd IRP 80/558 was used for calibrating TSH concentrations.
- Comparison to Predicate Device: The Ventrex hTSH 125I IRMA kit served as the comparative ground truth for method comparison.
- Biochemical Measurement: The inherent biochemical properties and accurate measurement of TSH concentration are the fundamental ground truth for this type of assay.
8. The Sample Size for the Training Set
This document does not specify a separate "training set" in the context of machine learning or AI algorithms. For traditional IVD assays like this IRMA, the development process involves using various samples (standards, controls, patient samples) during optimization and calibration. The "standards" (seven levels, human serum based) used to construct the radioactivity-concentration-profile serve as a form of calibration data, but the term "training set" with its specific implications for AI is not used or applicable here.
9. How the Ground Truth for the Training Set Was Established
As noted above, the concept of a "training set" in the AI sense is not applicable. For establishing the calibration curve (analogous to the "learning" phase for an assay), the device uses:
- Known TSH Concentrations (Standards): Seven levels of human serum-based standards with nominal concentrations ranging from 0.02-0.92 mU/L.
- Standardization: These standards are stated to be "Standardized against the World Health Organization (WHO) Reference Program 80/558." This means their TSH concentrations were accurately determined and traceable to an international reference material, establishing their "ground truth" for calibration purposes.
§ 862.1690 Thyroid stimulating hormone test system.
(a)
Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known as thyrotrophin and thyrotrophic hormone, in serum and plasma. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.(b)
Classification. Class II.