(71 days)
The Nichols Advantage® Chemiluminescence Ferritin Immunoassay is designed for use with the Nichols Advantage® Specialty System for the quantitative determination of ferritin in human serum or plasma. This assay is intended to aid in the diagnosis of iron deficiency anemia and iron overload.
The Nichols Advantage® Ferritin Assay is a two-site chcmiluminescence assay for use with the Nichols Advantage® Specialty System
Here's an analysis of the provided text, focusing on the acceptance criteria and the study details:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" as a separate section with pass/fail thresholds. Instead, it presents the device's performance characteristics and compares them to a predicate device. I've extracted the performance data for the Nichols Advantage® Ferritin device.
| Performance Characteristic | Nichols Advantage® Ferritin Reported Performance |
|---|---|
| Intra-Assay | |
| Mean 16 ng/mL | 4.6 %CV |
| Mean 48 ng/mL | 3.9 %CV |
| Mean 159 ng/mL | 4.4 %CV |
| Mean 437 ng/mL | 4.9 %CV |
| Inter-Assay | |
| Mean 19 ng/mL | 12.2 %CV |
| Mean 47 ng/mL | 7.2 %CV |
| Mean 153 ng/mL | 6.3 %CV |
| Mean 372 ng/mL | 5.9 %CV |
| Recovery | 94 - 104 % |
| Parallelism | 99 - 114 % |
| High Dose Hook Effect | Greater than 16,000 ng/mL |
| Specificity | 100% (Spleen Ferritin) |
| Cross-Reactivity | 100% (Liver Ferritin) |
| Method Comparison | |
| Range of Results | 2.3 ng/mL to 608 ng/mL |
| Linear Regression Equation | y = 0.94x - 4.7 ng/mL |
| Correlation Coefficient (r) | 0.98 |
Implicit Acceptance Criteria: The acceptance criteria for this type of submission (510(k)) are implicitly that the new device performs "substantially equivalently" to the predicate device. While specific thresholds are not listed, the comparable performance across these metrics is intended to demonstrate that the new device is as safe and effective as the predicate.
Study Proving Acceptance Criteria:
The document describes several studies conducted to characterize the performance of the Nichols Advantage® Chemiluminescence Ferritin Immunoassay.
2. Sample Size Used for the Test Set and Data Provenance
- Intra-Assay:
- For each of the four mean concentration levels, 20 samples (n=20) were used.
- Inter-Assay:
- For each of the four mean concentration levels, 20 samples (n=20) were used.
- Method Comparison:
- The document states "Range of Results: 2.3 ng/mL to 608 ng/mL" and provides a correlation coefficient. However, the exact number of samples used for this particular method comparison study is not explicitly stated.
- 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 Ground Truth for the Test Set and Qualifications of Those Experts
This type of immunoassay device does not typically rely on "expert consensus" or "radiologist interpretation" for establishing ground truth in the same way imaging devices do. The ground truth for performance characteristics like precision, recovery, and linearity is established through:
- Reference materials/standards: Precision studies (intra-assay, inter-assay) use samples with known or established concentrations.
- Known spikes/dilutions: Recovery and parallelism studies involve adding known amounts of analyte or diluting samples, where the expected values serve as the ground truth.
- Comparison to a well-established method: The method comparison study uses a predicate device (Chiron Diagnostics ACS:180® Ferritin +C Assay) as a reference, where the results from the predicate device serve as a comparator for the 'truth' measure.
Therefore, the concept of "experts establishing ground truth" in the diagnostic imaging sense is not applicable here.
4. Adjudication Method for the Test Set
Not applicable. The types of studies described (e.g., precision, recovery, method comparison) do not involve subjective interpretation or a need for adjudication methods like 2+1 or 3+1. The results are quantitative measurements.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Improvement with/without AI
Not applicable. This is an in-vitro diagnostic (IVD) device (a laboratory test) and not an AI-powered imaging or diagnostic interpretation system that involves human readers. Therefore, an MRMC study or the concept of human readers improving with/without AI assistance is not relevant.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies described reflect the standalone performance of the Nichols Advantage® Chemiluminescence Ferritin Immunoassay. It's a fully automated system (the Nichols Advantage® Specialty System) that quantifies ferritin levels, and the performance characteristics reported are those of the device itself, without human interpretation playing a direct role in the measurement process.
7. The Type of Ground Truth Used
The ground truths used for the various performance characteristics are:
- Precision (Intra-Assay, Inter-Assay): Established concentrations of control materials or pooled patient samples.
- Recovery & Parallelism: Expected values based on known additions (spikes) or dilutions of samples.
- High Dose Hook Effect: The presence or absence of a hook effect at extremely high concentrations is determined by observing the assay's response to spiked samples.
- Specificity and Cross-Reactivity: Known concentrations of ferritin from different sources (spleen, liver) or potential interfering substances are used to assess the assay's accuracy in identifying only the target analyte.
- Method Comparison: The results obtained from the established, legally marketed predicate device (Chiron Diagnostics ACS:180® Ferritin +C Assay) serve as the comparative ground truth.
8. The Sample Size for the Training Set
The document does not provide information about a "training set" or its sample size. For an IVD device like this, the development typically involves calibration, reagent optimization, and performance verification. There isn't an explicit "training set" in the machine learning sense. The performance characteristics described are typically part of a validation or verification study, not a distinct training phase.
9. How the Ground Truth for the Training Set Was Established
Since no training set is mentioned in the machine learning context, this question is not applicable based on the provided text. The calibration and optimization of such assays would generally involve using characterized reference materials and calibrators, for which concentrations are established through methods traceable to international standards or established physicochemical techniques.
§ 866.5340 Ferritin immunological test system.
(a)
Identification. A ferritin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the ferritin (an iron-storing protein) in serum and other body fluids. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia.(b)
Classification. Class II (performance standards).