(86 days)
Intended for use with the Nichols Advantage Specialty System for the quantitative determination of prostate specific antigen (PSA) in human serum and is to be used as an adjunct in the management of patients with prostate cancer.
The Nichols Advantage™ PSA is a two-site chemiluminescence assay. Total duration of assay is 30 minutes at 37ºC.
1st Incubation: 20 minutes at 37℃. Sample or control or calibrator (20uL), biotinylated monoclonal PSA specific antibody (80uL), and acridinium labeled rabbit specific antibody (50uL) react to form a sandwich complex.
2nd Incubation: 10 minutes at 37℃. Assay buffer (50uL) and streptavidin coated magnetic particles (25uL) are added to the reaction mixture. After the 10 minute incubation, the sandwich complex is bound to the solid phase via the interaction of biotin and streptavidin.
The reaction mixture is aspirated from the reaction well after the streptavidin magnetic particles are magnetically captured onto the surface of the reaction well wall. The magnetic particles are washed three times with system wash buffer.
Acridinium 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 dilute sodium hydroxide. The system automatically injects Trigger 1 and 2 into the reaction well which oxidize 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 PSA 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.
Here's a breakdown of the acceptance criteria and the study information for the Nichols Advantage™ Chemiluminescence Prostate Specific Antigen Assay, based on the provided text:
Acceptance Criteria and Reported Device Performance
| Feature | Acceptance Criteria (Implied by Predicate) | Nichols Advantage™ PSA Performance |
|---|---|---|
| Precision: | ||
| Intra-Assay | %CV similar to predicate (e.g., 4.3-4.8% for higher concentrations) | Pool 1 (0.6 ng/mL): 6.1% CV |
| Pool 2 (3.9 ng/mL): 2.3% CV | ||
| Pool 3 (23.6 ng/mL): 2.7% CV | ||
| Inter-Assay | %CV similar to predicate (e.g., 2.4-5.4% for higher concentrations) | Pool 4 (0.7 ng/mL): 9.8% CV |
| Pool 5 (4.2 ng/mL): 3.6% CV | ||
| Pool 6 (27.7 ng/mL): 9.1% CV | ||
| Sensitivity | 0.1 ng/mL | 0.1 ng/mL |
| High Dose Hook | No hook effect up to 5,000 ng/mL | No hook effect up to 5,000 ng/mL |
| Recovery | 92-95% | 93-106% |
| Parallelism | Not available for predicate (implies demonstrating acceptable parallelism for the new device will suffice) | 89-108% |
| Interfering Substances | No interference up to at least the levels of the predicate (e.g., hemoglobin 200 mg/dL, bilirubin 25 mg/dL, lipemia 2320 mg/dL, PAP 1,000 ng/mL) | Hemoglobin: 800 mg/dL |
| Bilirubin: 25 mg/dL | ||
| Lipemia (triglycerides): 2325 mg/dL | ||
| PAP: 1,000 ng/mL | ||
| Method Comparison (vs. Predicate) | Strong correlation (R-value) and close agreement in values (slope near 1, intercept near 0) | n=183 split samples |
| Range (Hybritech): 0.1 to 24.6 ng/mL | ||
| Range (Nichols): 0.1 to 22.3 ng/mL | ||
| y = 0.974x + 0.25 | ||
| 95% CI slope: 0.906 - 1.042 | ||
| 95% CI intercept: -0.34 to 0.84 | ||
| R = 0.885 |
(Note: The acceptance criteria are "implied" based on the comparison to the predicate device. For diagnostic assays, achieving comparable or better performance characteristics than a legally marketed predicate is the standard for substantial equivalence.)
Study Details:
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Sample Size used for the test set and the data provenance:
- Method Comparison Test Set: n=183 split samples.
- Data Provenance: Not explicitly stated (e.g., country of origin), but the samples were described as "human serum" for PSA determination. The study is retrospective in the sense that existing samples within a certain range were used for testing, but it's not specified if they were collected specifically for this study or were banked samples.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This information is not provided in the document. For in-vitro diagnostic (IVD) devices like this PSA assay, the "ground truth" for the test set in method comparison studies is typically the measurement obtained from the predicate device itself. The primary goal is to show agreement with the established predicate, rather than using external experts for "ground truth."
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- This concept is not applicable for this type of IVD method comparison study. Adjudication methods like 2+1 are typically used in imaging or clinical outcome studies where there's subjective interpretation or a need to resolve discrepancies between multiple human readers/assessments. Here, the comparison is directly between two quantitative analytical devices.
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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, an MRMC comparative effectiveness study was not done. This device is a quantitative in-vitro diagnostic immunoassay, not an AI-assisted diagnostic tool that aids human readers. Therefore, the concept of human readers improving with AI assistance is not relevant to this submission.
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If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, the performance characteristics presented (precision, sensitivity, recovery, parallelism, interference, and method comparison) represent the standalone performance of the device (instrument and reagents). The Nichols Advantage™ PSA assay is a fully automated system that delivers quantitative results directly, without human interpretation as part of the primary diagnostic output (though a clinician interprets the numerical result in the context of a patient's overall health).
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The "ground truth" for the method comparison study was the Hybritech Tandem®-R PSA, the predicate device. The study aims to demonstrate substantial equivalence by correlating the new device's results with those of the legally marketed predicate. For other performance metrics (like precision, sensitivity, recovery), the "ground truth" is established by standard laboratory practices and reference materials.
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The sample size for the training set:
- This information is not provided in the document. For a traditional immunoassay device like this, the term "training set" in the context of deep learning or AI algorithms is not directly applicable. However, the device would have undergone extensive validation and development, which involves numerous samples used to optimize reagents, instrument parameters, and calibration curves. These would be internal R&D samples, not explicitly termed a "training set" in this context. The document only covers the performance characteristics of the finalized product.
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How the ground truth for the training set was established:
- As mentioned above, the concept of a "training set" and establishing its "ground truth" in the AI sense is not directly applicable here. For the development and optimization of the assay, the "ground truth" would be established through careful analytical studies using:
- Reference materials/calibrators with known PSA concentrations.
- Clinical samples characterized by established methods (e.g., the predicate device) or clinical diagnosis.
- Spiking studies where known amounts of PSA are added to samples to assess recovery.
- These processes ensure the assay accurately measures PSA levels, which forms the basis for its intended use.
- As mentioned above, the concept of a "training set" and establishing its "ground truth" in the AI sense is not directly applicable here. For the development and optimization of the assay, the "ground truth" would be established through careful analytical studies using:
§ 866.6010 Tumor-associated antigen immunological test system.
(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.