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The Procise CRP assay is a time-resolved fluorescence energy transfer immunoassay for the quantitative determination of C-Reactive Protein (CRP) levels in human serum. The test is carried out by means of the ProciseDx Analyzer.

Measurement of CRP aids in evaluation of injury to body tissues, inflammatory disorders. The instrument and assay are for use by trained professionals in the clinical laboratory. For in vitro diagnostic use only. Not for point of care use.

The Procise CRP assay is a homogeneous sandwich immunoassay assay that uses a fluorescence resonance energy transfer (FRET) signal to detect and quantify CRP. FRET is a process in which a donor molecule, in an excited state, transfers excitation energy to an acceptor fluorophore when the two are brought into close proximity. Upon excitation at a characteristic wavelength the energy absorbed by the donor is transferred to the acceptor, which in turn emits light energy. The level of light emitted from the acceptor fluorophore is directly proportional to the degree of donor/acceptor complex formation.

The Procise CRP assay format is designed as a competitive format. A monoclonal anti-CRP antibody and exogenous CRP antigen are labeled with donor and acceptor fluorophores, respectively. The monoclonal antibody specific for CRP is labelled with the donor fluorophores and the CRP antigen is labelled with the acceptor fluorophore. Similar to other competitive assay formats, as the concentration of CRP increases a proportional decrease in the signal is observed.

The Procise CRP Assay Kit, ProciseDx Instrument, and ProciseDx Calibration Cartridge (K201256) is a device for the quantitative determination of C-Reactive Protein (CRP) levels in human serum. It is intended to aid in the evaluation of injury to body tissues, infection, and inflammatory disorders.

Here's an analysis of the acceptance criteria and the study proving the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The FDA clearance document does not explicitly state "acceptance criteria" in a quantified table for all performance characteristics. Instead, it presents the results of individual studies and implicitly expects them to demonstrate substantial equivalence to the predicate device and meet typical analytical performance standards for in vitro diagnostic devices. Below is a summary of the performance characteristics obtained from the studies. For qualitative criteria like specificity, "No significant interference" serves as the reported performance, implying it met an internal acceptance threshold. For quantitative metrics like precision, the reported values are the performance.

Detailed Study Information:

2. Sample Sizes Used for the Test Set and Data Provenance:

• Precision (Within-Laboratory): 6 serum samples tested; 160 test results generated per sample (2 replicates x 2 runs x 20 days x 2 lots). Data provenance is not explicitly stated (e.g., country of origin, retrospective/prospective), but the study design suggests controlled laboratory experiments, likely prospective.
• Precision (Between-site): 5 serum samples (3 patients, 2 QCs) tested; 180 determinations per sample (3 replicates x 2 runs x 5 days x 2 instruments x 3 sites). Data provenance is not explicitly stated (e.g., country of origin), but the multi-site nature suggests controlled laboratory experiments, likely prospective.
• Linearity: 11 dilution levels of pooled human serum samples (range 3.6 to 161.0 mg/L CRP). Each dilution measured in 3 or 4 replicates. Data provenance not explicitly stated, likely laboratory-prepared samples.
• Analytical Specificity/Interference: 3 pooled human serum samples with varying CRP concentrations (12.3, 52.9, and 89.7 mg/L). Each sample spiked with interferents and measured in 3 replicates. Data provenance not explicitly stated, likely laboratory-prepared samples.
• Accuracy (Instrument): 11 dilution levels (1.0 to 41.2 mg/L CRP) of ERM® -DA474/IFCC serially diluted with CRP-depleted human serum. Each diluted sample tested in 3 replicates, original ERM® -DA474/IFCC tested in 6 replicates. Data provenance not explicitly stated, likely laboratory-prepared samples.
• Detection Limits (LoB, LoD, LoQ):
  • LoB: 4 analyte-depleted serum samples. Each tested in 5 replicates per run, 1 run per day for 3 days (total 60 measurements per reagent lot).
  • LoD: 5 low-level serum samples. Each tested in 4 replicates per run, 1 run per day for 3 days (total 60 measurements per reagent lot).
  • LoQ: 5 low measurand content serum samples. Each tested in 4 replicates per run, 1 run per day for 3 days (total 24 measurements).
    Data provenance for these serum samples is not explicitly stated, but they are likely from human sources (e.g., blood banks, clinical labs), and the testing is prospective.
• Method Comparison with Predicate Device: 81 serum samples spanning the assay measuring interval (5.3 - 134.0 mg/L). Data provenance is not explicitly stated, but these are patient samples, likely collected retrospectively or prospectively from a clinical setting.
• Expected Values/Reference Range: 170 samples (88 male, 82 female) from normal healthy subjects. Data provenance is not explicitly stated, but these are human subjects, likely collected prospectively.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:

The device is an in vitro diagnostic (IVD) assay for measuring a biomarker (CRP). For such devices, "ground truth" is typically established by reference methods, certified reference materials, or values obtained from a predicate device, rather than expert consensus on images or clinical cases.

• For Accuracy/Traceability: The ground truth for CRP concentration was established using ERM® -DA474/IFCC, which is a certified reference material. This does not involve human experts establishing ground truth in the traditional sense of medical image interpretation.
• For Method Comparison: The predicate device, Orion Diagnostica QuikRead go CRP (K142993), serves as the reference for comparison, effectively establishing the comparative "ground truth" for the new device's performance.

Therefore, the concept of "number of experts" and "qualifications of those experts" as it might apply to image-based AI studies is not directly applicable here.

4. Adjudication Method for the Test Set:

Adjudication methods (like 2+1, 3+1) are typically used in studies involving subjective assessment (e.g., by radiologists interpreting images) to resolve discrepancies among experts. Since this device measures a quantitative biomarker and uses reference methods or a predicate device for comparison, there is no human adjudication process involved in establishing the "ground truth" values for the test samples. The values are either inherent to the reference material or determined by the predicate method.

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. An MRMC comparative effectiveness study is not applicable as this is an in vitro diagnostic (IVD) device for quantitative measurement of a biomarker, not a device that involves human interpretation of images or other qualitative data, nor is it an AI-assisted diagnostic tool for human readers. Therefore, there is no "human readers improve with AI vs without AI assistance" to report.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

Yes, the studies presented are all standalone performance evaluations of the device (Procise CRP assay on the ProciseDx Analyzer). This is a laboratory-based automated assay that measures CRP concentration directly. Its performance is evaluated purely based on its analytical output against known standards or predicate methods, without human interpretation as part of the measurement process itself. While trained professionals are required to use the instrument, the performance characteristics reported (precision, linearity, accuracy, etc.) are solely attributable to the device's measurement capabilities.

7. The Type of Ground Truth Used:

The ground truth used for the studies includes:

• Certified Reference Materials: ERM® -DA474/IFCC for traceability and instrument accuracy.
• Predicate Device Measurements: Measurements from the Orion Diagnostica QuikRead go® CRP device for method comparison.
• Prepared Samples with Known Concentrations: For linearity, interference, and stability studies, samples were either serially diluted from known concentrations or pooled and spiked to achieve specific, known levels.
• Clinically Characterized Samples: For the reference range study, samples were from "normal healthy subjects" with specific exclusion criteria (e.g., obesity), but the CRP levels themselves were determined by the device, establishing a reference interval rather than confirming a specific pre-defined "ground truth" for each individual sample's CRP value.

8. The Sample Size for the Training Set:

The document does not specify a separate "training set" in the context of machine learning or AI. This device is an immunoassay, not an AI-driven prediction model. Therefore, the concept of a training set as understood in AI development is not directly applicable. The "training" of the assay is its inherent chemical and optical design, and its calibration is based on reference materials.

9. How the Ground Truth for the Training Set Was Established:

Again, the concept of a "training set" and associated ground truth establishment is not relevant for this type of immunoassay device. The device's operational parameters and calibration are established through laboratory experiments using certified reference materials and established analytical methods, not through a machine learning training process with a specific "training set" and corresponding ground truth labels.

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