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The Nichols Advantage™ Chemiluminescence Erythropoietin Immunoassay is intended for use with the Nichols Advantage™ Specialty System for the quantitative determination of erythropoietin concentrations in human serum as an adjunct in the diagnosis of anemia and polycythemia.

Device Description

The Nichols Advantage™ EPO assay is a two-site chemiluminescence assay. Total assay duration is 30 minutes at 37°C.

14 Incubation: 20 minutes at 37℃. Sample or control (200uL), biotinylated polyclonal antibody (40uL), acridinium labeled mouse monoclonal antibody (10uL) are pipetted into a reaction well on the cuvette strip. Each antibody binds to a separate and distinct antigenic site on EPO to form a sandwich complex.

204 Incubation: 10 minutes at 37°C. Streptavidin coated magnetic particles (20uL) are added to the reaction mixture. After the 10 minute incubation, the sandwich complex is bound to the solid phase via the high affinity interaction of blotin and streptavidin. The reaction mixture is aspirated from the reaction well after the streptavidin magnetic particles are magnetically capfured onto the surface of the reaction well wall.

Acridinum esters emit light upon treatment with hydrogen peroxide and an alkaline solution. The Trigger 1 solution contains hydrogen peroxide in dilute acid and Trigger 2 solution contains sodium hydroxide. The system automatically injects Trigger 1 and 2 into the reaction well which oxidizes the acridinium ester. The oxidized product is in an excited state. The subsequent return to ground state results in the emission of light which is quantified in 2 seconds, and is expressed in relative light units (RLU) by the integrated system luminometer.

The amount of bound labeled antibody in RLU's is directly proportional to the concentration of EPO in the sample. Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent bar codes.

AI/ML Overview

The provided text describes the Nichols Advantage® Chemiluminescence Erythropoietin Immunoassay. Here's a breakdown of the requested information based on the document:

Acceptance Criteria and Device Performance

The document does not explicitly state formal "acceptance criteria" with pass/fail thresholds. Instead, it compares the performance characteristics of the new device (Nichols Advantage™ EPO) with those of a legally marketed predicate device (Nichols Chemiluminescence EPO kit). The underlying assumption is that if the new device demonstrates comparable performance to the predicate, it meets the requirements for substantial equivalence.

Table of Performance Characteristics (Comparison to Predicate Device):

Feature	Acceptance Criteria (Implied by Predicate Performance)	Reported Device Performance (Nichols Advantage™ EPO)
Precision (Within-Run)	%CV comparable to predicate device	Mean (mU/mL): 12.5, %CV: 10.4
		Mean (mU/mL): 92, %CV: 3.3
		Mean (mU/mL): 168, %CV: 2.6
		Mean (mU/mL): 502, %CV: 4.5
Precision (Total)	%CV comparable to predicate device	Mean (mU/mL): 12.5, %CV: 13.6
		Mean (mU/mL): 92, %CV: 5.5
		Mean (mU/mL): 168, %CV: 3.8
		Mean (mU/mL): 502, %CV: 5.6
Recovery	Value comparable to predicate device (93-120%)	87-111%
Parallelism	Value comparable to predicate device (84-108%)	91-116%
High Dose Hook	Value comparable to predicate device (50,000 mU/mL)	7,500 mU/mL
Specificity & Cross-Reactivity (Human Transferrin)	<0.001%	<0.001%
Specificity & Cross-Reactivity (Human α-2-Macroglobulin)	<0.001%	<0.001%
Specificity & Cross-Reactivity (Human α-1-Acid Glycoprotein)	<0.001%	<0.001%
Specificity & Cross-Reactivity (Human α-1-Antitryspin)	<0.001%	<0.001%
Interference (Hemoglobin)	no interference up to 25 mg/dL	no interference up to 500 mg/dL
Interference (Triglycerides)	no interference up to 1000 mg/dL	no interference up to 3000 mg/dL
Interference (Unconjugated Bilirubin)	no interference up to 100 mg/dL	no interference up to 20 mg/dL
Interference (Albumin)	no interference up to 5000 mg/dL	no interference
Interference (Gamma Globulin)	no interference up to 5000 mg/dL	no interference
Method Comparison (Correlation)	R value comparable to predicate, indicating linearity	R = 0.960
Method Comparison (Range of Results)	Comparable range	14.7 to 590 mU/mL

Study Details:

Sample sizes used for the test set and the data provenance:
- Precision (Test Set):
  - Within-Run: 66 replicates for each of 4 concentration levels.
  - Total Precision: 66 replicates for each of 4 concentration levels.
- Method Comparison (Test Set): n=88 samples.
- Data Provenance: Not explicitly stated (e.g., country of origin). The study seems to be conducted by the manufacturer, Nichols Institute Diagnostics. It is a prospective study given the device is new and being compared to an existing one.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is an in vitro diagnostic (IVD) assay for quantitative determination of erythropoietin. The "ground truth" for such assays is typically established by reference methods or gravimetric/volumetric standards, not human expert consensus. The document does not describe expert involvement for ground truth establishment.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable. This is an IVD assay, not an imaging or clinical decision support device requiring adjudication of expert interpretations.
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:
- Not applicable. This is an IVD assay and does not involve human readers for interpretation in the context of an MRMC study.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this is essentially a standalone performance evaluation of the immunoassay. The device performs the measurement and provides a quantitative result without human interpretative input beyond operating the system and performing quality control.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For an immunoassay, the "ground truth" for performance evaluations is typically established against calibrated reference materials or a validated reference method.
  - The document states that both assays "are standardized to the same WHO Standard (1st IS 87/684) for recombinant DNA derived erythropoietin." This indicates that the ground truth for measuring erythropoietin levels is tied to this internationally recognized standard.
  - Precision and linearity are assessed against known concentrations (derived from standards).
  - Recovery measures the ability to detect known amounts of added analyte.
  - Method comparison uses patient samples, but the "ground truth" for comparison is the measurement obtained from the predicate device (which itself is standardized).
The sample size for the training set:
- This is an immunoassay, not a machine learning model that requires a distinct "training set" in the conventional sense. The calibration curve is established using known concentrations of recombinant EPO standards according to an instrument-specific process described (2-point calibration and master curve via reagent bar codes). No separate training set size is provided.
How the ground truth for the training set was established:
- As noted above, this device does not have a "training set" in the AI/ML context. The calibration ("training") of the assay itself is done using recombinant EPO as standards and standardized to the WHO Standard (1st IS 87/684). This ensures that the instrument's measurement of EPO concentrations is accurate and traceable to an accepted reference.

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