(9 days)
The Nichols Advantage® Bio-Intact PTH (1-84) immunometric assay is intended for use with the Nichols Advantage® Specialty System to measure the levels of parathyroid hormone in serum and EDTA 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. Assay results should be used in conjunction with other clinical data to assist the clinician in making individual patient management decisions.
The Nichols Advantage® Chemiluminescence Bio-Intact PTH (1-84) Immunoassay is a two-site immuno-chemiluminometric IVD device with sufficient reagents for 100 tests, that are performed entirely on the Nichols Advantage® Specialty System (K961142; cleared February 18, 1997). Two goat polyclonal antibodies directed at epitopes on intact human PTH are used. One antibody ("capture reagent") is chemically labeled with biotin, while the second antibody ("detection reagent") is chemically labeled with acridinium ester for subsequent quantitative measurements. A sample of patient serum (preferred) or plasma is added to an assay cuvette, followed by addition of the two goat anti-PTH antibodies and the streptaviding outed magnetic particles. The reaction mixture is allowed to incubate for 30 minutes at 37°C. Because of the high affinity interaction between biotin-labeled antibody and streptavidin, the sandwich complex is captured onto the streptavidin-coated magnetic particles. The captured complex bound to the magnetic particle passes to the Nichols Specialty System for a wash to remove unbound components and/or patient substances. The washed captured complex bound to the magnetic particles within the cuvette wells are analyzed Nichols Specialty System's luminometer via the automatic injection of reagents that initiate the acridinium-based chemiluminescence quantitative reaction. The light is measured by the Nichols Specially System's luminometer and expressed as Relative Light Units (RLU). The amount of PTH bound-labeled antibody is directly proportional to the concentration of intact PTH in the serum or plasma sample.
The Nichols Advantage® Chemiluminescence Bio-Intact PTH (1-84) Immunoassay is intended for use with the Nichols Advantage® Specialty System to measure parathyroid hormone levels in serum and EDTA plasma. This is used for the differential diagnosis of hypercalcemia and hypocalcemia resulting from disorders of calcium metabolism. The device performance was compared to a previously FDA-cleared predicate device, the Nichols Intact PTH Immunoassay.
Here is a breakdown of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Implied by Predicate Equivalence) | Reported Device Performance (Nichols Advantage® Bio-Intact PTH (1-84) Immunoassay) |
|---|---|---|
| Precision | ||
| Within-Run Precision | Not greater than that of the predicate device. | Not greater than 4% (at doses > 5 pg PTH/mL) |
| Total Precision | Not greater than that of the predicate device. | Not greater than 8.5% (at doses > 5 pg PTH/mL) |
| Limit of Detection | Comparable to the predicate device. | At or below 1.5 pg/mL |
| Recovery | Acceptable range, comparable to predicate. | 93% to 103% |
| Parallelism | Acceptable range, comparable to predicate. | 92% to 111% |
| High Dose Hook Effect | No significant hook effect. | No High Dose Hook Effect observed up to 100,000 pg PTH/mL |
| Interference (PTH fragments) | Minimal interference. | PTH fragment 7-84 did not interfere at 3000 pg/mL; PTH fragments 39-68, 53-84, 44-68, 39-84 gave minimal interference. |
| Correlation with Predicate | High correlation (e.g., Pearson's r > 0.95). | Pearson's correlation coefficient (r) = 0.97 (95% CI: 0.96 to 0.98) |
| Regression with Predicate | Slope and intercept close to 1 and 0, respectively, or within an acceptable range for clinical equivalence. | Passing Bablok regression: y = 0.66x - 0.6 (95% CI slope: 0.64-0.68; intercept: -1.1 to -0.2) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 305 patient serum samples.
- Data Provenance: The document does not specify the country of origin. It can be inferred that the samples were collected retrospectively as they were "patient serum samples" assayed by both methods without modifications, suggesting existing samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- This information is not provided in the document. The "ground truth" for the test set was essentially the results from the predicate device.
4. Adjudication Method for the Test Set
- Not applicable in this context. The comparison was directly between the values generated by the new device and the predicate device, not against an adjudicated "ground truth" from human experts.
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
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This submission is for an in vitro diagnostic immunoassay, not an AI-powered image analysis or diagnostic assist device that would typically involve human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Yes, this was a standalone performance study. The Nichols Advantage® Chemiluminescence Bio-Intact PTH (1-84) Immunoassay operates automatically on the Nichols Advantage® Specialty System, and its performance was assessed directly against the predicate device. There is no "human-in-the-loop" component to the analytical performance of the assay itself, beyond routine laboratory procedures.
7. The Type of Ground Truth Used
- The "ground truth" for evaluating the new device's performance was the results obtained from an FDA-cleared predicate device, the Nichols Intact PTH Immunoassay. This is a common approach for establishing substantial equivalence for new IVD devices.
8. The Sample Size for the Training Set
- This information is not provided. The term "training set" is typically associated with machine learning or AI algorithms. For this immunoassay, performance characteristics (precision, LOD, recovery etc.) are established through internal validation studies, not a distinct "training set" in the AI sense.
9. How the Ground Truth for the Training Set Was Established
- Not applicable, as there is no mention of a "training set" in the context of an AI/ML algorithm. The calibration of the immunoassay system would be established using calibrators with known PTH concentrations, which are themselves traceable to a primary reference standard (though this specific traceability is not detailed in the provided text).
§ 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.