(157 days)
This kit is intended for the quantitative determination of human thyroid stimulating hormone (hTSH) in blood specimens dried on filter paper as an aid in screening newborns for congenital (neonatal) hypothyroidism using the GSP instrument.
The GSPTM Instrument is a fully automated, high throughput batch analyzer for time resolved analysis of samples in microtitration plates. It is in intended for in vitro quantitative / qualitative determination of analytes in body fluids.
The GSP instrument (genetic screening processor) is a fully automated, high throughput batch analyzer for timeresolved and prompt fluorescence analysis of samples in microtitration plates. It is intended for in vitro quantitative and qualitative determination of analytes in body fluids. The GSP instrument and GSP chemistries are for professional use only.
The GSPTM Neonatal hTSH assay is a solid phase, twosite fluoroimmunometric assay based on the direct sandwich technique in which two monoclonal antibodies (derived from mice) are directed against two separate antigenic determinants on the hTSH molecule. Calibrators, controls and test specimens containing hTSH are reacted simultaneously with immobilized monoclonal antibodies directed against a specific antigenic site on the ß hTSH subunit and europium-labeled monoclonal antibodies (directed against a different antigenic site located partly on the B subunit and partly on the a subunit) in assay buffer. The assay buffer elutes hTSH from the dried blood spots on the filter paper disks. The complete assay requires only one incubation step.
DELFIA Inducer dissociates europium ions from the labeled antibody into solution where they form highly fluorescent chelates with components of DELFIA Inducer. The fluorescence in each well is then measured. The fluorescence of each sample is proportional to the concentration of hTSH in the sample.
Here's a summary of the acceptance criteria and study information for the GSP Neonatal hTSH kit, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Precision (TSH) | "Total variation (% CV)" should be acceptably low for assay use. | Using full calibration curve on each plate: |
- Sample 1 (10.5 µU/mL): 10.1% CV
- Sample 2 (23.2 µU/mL): 8.9% CV
- Sample 3 (102 µU/mL): 8.5% CV
- Sample 4 (241 µU/mL): 8.7% CV
Using one calibration curve valid for 24h:
- Sample 1 (10.6 µU/mL): 9.9% CV
- Sample 2 (23.4 µU/mL): 8.3% CV
- Sample 3 (102 µU/mL): 7.7% CV
- Sample 4 (241 µU/mL): 7.9% CV |
| Linearity (TSH) | Should be linear across the intended reportable range. | Linear from 0.66 uU/mL to 375 uU/mL blood. |
| Limit of Blank (LoB) | Acceptably low to distinguish from blank. | 0.96 uU/mL blood. |
| Limit of Detection (LoD)| Acceptably low for clinical application. | 1.31 uU/mL blood. |
| Limit of Quantitation (LoQ)| Lowest concentration with total CV 95-97%) with predicate device. | Site 1: 98.4% (95% CI: 97.9%-99.0%)
Site 2: 98.4% (95% CI: 97.8%-98.9%) |
| Method Comparison (Positive Agreement) | Good agreement (>70%) for positive samples with predicate device. | Site 1: 75.9% (95% CI: 66.1%-85.7%)
Site 2: 75.3% (95% CI: 66.0%-84.6%) |
| Method Comparison (Negative Agreement) | Good agreement (>98-99%) for negative samples with predicate device. | Site 1: 99.4% (95% CI: 99.0%-99.8%)
Site 2: 99.5% (95% CI: 99.1%-99.8%) |
| Internal Method Comparison (Deming Regression) | Slope near 1, intercept near 0, demonstrating good correlation. | Slope: 0.97 (95% CI: 0.94, 1.01)
Intercept: -0.21 (95% CI: -0.37, -0.16) |
Note: The document provides specific performance results but often implies the acceptance criteria through the presentation of these results in the context of predicate device comparison and clinical guidelines (e.g., AAP recommendations for TSH cut-offs).
2. Sample Sizes Used for the Test Set and Data Provenance
-
Precision Study:
- Sample Size: 4 spiked dry whole blood spot samples, run over 23 days in 27 runs, each consisting of 2 plates with 4 replicates per sample. (Specific total number of individual measurements for precision across all samples is not explicitly stated but is substantial: 4 samples * 27 runs * 2 plates * 4 replicates = 864 individual measurements.)
- Data Provenance: The document does not specify the country of origin for these spiked samples. It is implied to be laboratory-generated per NCCLS (CLSI) guidelines. Retrospective or prospective is not specified, but typically, these are prospective internal lab studies.
-
Detection Limit Study:
- LoB Sample Size: 216 blank samples.
- LoD Sample Size: 432 determinations (72 blank and 216 low-level samples included).
- Data Provenance: Not specified, but implied to be prospective internal lab studies following CLSI guidelines.
-
Analytical Specificity (Cross-reactivity) Study:
- Sample Size: Not explicitly stated how many individual samples were used for each interferent, but presented for two different hTSH concentrations for each cross-reactant (hFSH, hLH, hCG).
- Data Provenance: Not specified, likely prospective internal lab studies.
-
Comparison Studies (Site 1 & Site 2):
- Site 1 Test Set Sample Size: 2053 samples (total). 20 diagnosed positive samples.
- Site 2 Test Set Sample Size: 2104 samples (total). 26 known positive samples.
- Data Provenance: Not explicitly stated, but these are likely clinical samples from the sites where the studies were performed. The terms "routine screening and spiked blood spot samples" are used in the Internal Method Comparison, suggesting a mix, but for Site 1 and Site 2 comparisons, they appear to be real-world samples. Retrospective or prospective is not specified, but comparison studies like this often use retrospective collections or samples run in a prospective manner against a standard.
-
Internal Method Comparison:
- Sample Size: N=162 samples.
- Data Provenance: "routine screening and spiked blood spot samples". Not specified by country.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- No information is provided regarding the number or qualifications of experts used to establish ground truth for the test set.
- For the comparison studies, "diagnosed positive samples" and "known positive samples" are mentioned, suggesting a clinical diagnosis as the implicit ground truth, but the method of diagnosis is not detailed, nor are the experts involved.
4. Adjudication Method for the Test Set
- No adjudication method is described. The comparison studies simply compare the GSP device's classification with that of the predicate device. For "diagnosed positive samples," the diagnosis itself serves as a form of ground truth, but how conflicting diagnoses (if any) were resolved is not stated.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
- No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) test, not an image-reading or human-interpretation device. The studies described focus on the analytical performance of the instrument and kit, and its agreement with a predicate IVD device. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was Done
- Yes, the studies presented are all standalone (algorithm only) performance. The GSP Instrument and GSP Neonatal hTSH kit are automated systems for quantitative determination of hTSH. The results are generated directly by the instrument and its associated software/algorithm, without human interpretation as part of the primary measurement. Human users operate the instrument, but their "reading" of the result is simply recording the quantitative value provided by the system.
7. The Type of Ground Truth Used
- For the Precision, Linearity, Detection Limit, and Analytical Specificity studies:
- The ground truth is reference values based on known dilutions or spiked concentrations in samples, following recognized laboratory standards (e.g., CLSI documents).
- For the Comparison Studies (Site 1 & Site 2) and Internal Method Comparison:
- The ground truth is primarily based on the results obtained from the predicate device (AutoDELFIA Neonatal hTSH kit), which is an already legally marketed and established method for hTSH screening.
- Additionally, for a subset of samples, "diagnosed positive samples" or "known positive samples" are mentioned, implying clinical diagnosis of congenital hypothyroidism (likely based on follow-up and confirmatory tests) served as a form of clinical ground truth for these specific cases.
8. The Sample Size for the Training Set
- No information is provided about a specific "training set" for the GSP Neonatal hTSH kit or instrument. This is typical for traditional IVD assays, which are developed and validated using analytical methods and comparison to established predicate devices, rather than machine learning algorithms that require distinct training and test sets in the same way. The development and optimization of the assay would involve various experiments, but these are not typically referred to as a "training set" in this context.
9. How the Ground Truth for the Training Set Was Established
- As a specific "training set" is not mentioned in the context of an AI/ML algorithm development, this question is not applicable based on the provided document. The development of such an IVD kit involves extensive analytical characterization and optimization, but not in the framework of machine learning training data.
§ 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.