(49 days)
For the in vitro quantitative determination of intact parathyroid hormone in human serum and plasma for the differential diagnosis of hypercalcemia and hypocalcemia.
The ELECSYS® Parathyroid Hormone Test System is based on a two step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection. Results are determined usin a calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve provided with the reagent bar code.
The provided text describes the 510(k) submission for the ELECSYS® Parathyroid Hormone Test System. It focuses on demonstrating substantial equivalence to a predicate device rather than explicitly defining and meeting acceptance criteria through a specific study with a separate "acceptance criteria" table. However, we can infer performance criteria and reported performance from the comparison tables.
Here's an analysis based on the provided document:
Evaluation of ELECSYS® Parathyroid Hormone Test System
The submission aims to demonstrate substantial equivalence to the Nichols RIA test for Parathyroid Hormone (K954418). The "acceptance criteria" are implicitly set by the performance characteristics of the predicate device, and the ELECSYS® system attempts to match or improve upon these.
1. Table of Inferred Acceptance Criteria and Reported Device Performance
Since explicit acceptance criteria are not stated, we infer them from the performance characteristics of the predicate device. The "Reported Device Performance" refers to the ELECSYS® Parathyroid Hormone Test System's performance.
| Feature | Inferred Acceptance Criteria (Based on Predicate Device) | Reported Device Performance (ELECSYS® PTH Test System) |
|---|---|---|
| Within-Run Precision (%CV) | 3.4% at 40 pg/mL, 1.8% at 266 pg/mL | 5.4% at 30.0 pg/mL, 4.0% at 62.2 pg/mL, 4.0% at 271 pg/mL, 5.8% at 44.3 pg/mL, 3.4% at 161 pg/mL, 3.9% at 702 pg/mL |
| Total Precision (%CV) | 6.6% at 38 pg/mL, 6.1% at 277 pg/mL | 5.9% at 30.0 pg/mL, 4.3% at 62.2 pg/mL, 4.3% at 271 pg/mL, 7.1% at 44.3 pg/mL, 5.0% at 161 pg/mL, 5.4% at 702 pg/mL |
| Analytical Sensitivity | 1 pg/mL | 1.20 pg/mL |
| Measuring Range | 1.0 pg/mL - highest calibrator | 1.20-5000 pg/mL (0.127-530 pmol/L) |
| Expected Values | 10-65 pg/mL | 15-65 pg/mL (1.6-6.9 pmol/L) |
| Limitations (Interference) | No high dose hook effect up to 100,000 pg/mL | No interference from bilirubin up to 65 mg/dL, hemoglobin up to 1.5 g/dL, intralipid up to 1500 mg/dL, biotin up to 50 ng/mL, rheumatoid factor up to 1500 U/mL, No high dose hook effect up to 17,000 U/mL |
| Open Vial Stability | Reconstituted - 6 weeks (2-8° C) | Open vial - 12 weeks (2-8° C) |
Note: The acceptance criteria are "inferred" as the document primarily presents a comparison for substantial equivalence rather than explicitly stated, pre-defined acceptance thresholds for a new device submission. The goal is to show performance that is comparable or better than the predicate.
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state the sample sizes used for the precision or sensitivity studies, nor does it specify the country of origin or whether the data was retrospective or prospective. It presents summary performance characteristics.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This information is not applicable and not provided in the document. This is an in vitro diagnostic device for quantitative determination of a biomarker, not a device requiring expert interpretation of images or clinical outcomes for ground truth establishment in the traditional sense. The "ground truth" for analytical performance (precision, sensitivity) is determined by established laboratory methods and statistical analysis.
4. Adjudication Method for the Test Set
Not applicable. As this is an in vitro diagnostic device, adjudication methods (like 2+1 reading) are typically not used for analytical performance evaluations.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No. An MRMC study is relevant for devices involving human interpretation of complex data (e.g., medical images). This document describes an in vitro diagnostic assay, not a device that would require an MRMC study.
6. If a Standalone (i.e. Algorithm Only Without Human-in-the-Loop Performance) Was Done
This device is a standalone assay. The performance characteristics described (precision, sensitivity, specificity, measuring range, stability) are inherent to the algorithm and chemical reagents of the ELECSYS® Parathyroid Hormone Test System itself, without a human-in-the-loop performance component beyond standard laboratory operation.
7. The Type of Ground Truth Used
For analytical performance characteristics (precision, sensitivity, measuring range, etc.), the "ground truth" is established through:
- Reference Methods/Materials: Traceable to a commercially available RIA PTH test (as stated for traceability). This implies the use of validated reference standards and methods to determine absolute values or concentrations.
- Statistical Analysis: Precision (within-run and total precision) is determined by running multiple samples and calculating the coefficient of variation (%CV), a statistical measure.
- Spiking/Dilution Studies: Analytical sensitivity and measuring range are typically established through studies using known concentrations of the analyte.
- Interference Studies: Known interfering substances are added to samples to assess their impact.
8. The Sample Size for the Training Set
This information is not provided. For an in vitro diagnostic assay, the "training set" might refer to samples used during assay development and optimization (e.g., calibrators, validation panels), but the document does not detail this. The "calibration curve" is generated on each instrument, using a 2-point calibration and a master curve provided with the reagent.
9. How the Ground Truth for the Training Set Was Established
The document states that results are determined using a "calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve provided with the reagent bar code." This implies that the ground truth for calibration is established by:
- Calibrators: Standard solutions with known, precisely determined concentrations of parathyroid hormone are used for the 2-point calibration. These calibrators would have their "ground truth" established through rigorous analytical methods, likely traceable to international or recognized reference standards (though specific details are not provided beyond traceability to a "commercially available RIA PTH test").
- Master Curve: A predefined curve based on extensive development and validation, which corrects for lot-to-lot and instrument variations. The ground truth for this master curve would be established through a comprehensive process of characterization using a large panel of samples with reference values.
§ 862.1545 Parathyroid hormone test system.
(a)
Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia (abnormally high levels of calcium in the blood) and hypocalcemia (abnormally low levels of calcium in the blood) resulting from disorders of calcium metabolism.(b)
Classification. Class II.