(111 days)
Immunoassay for the in vitro quantitative determination of progesterone in human serum and plasma.
Competition principle. Total duration of assay: 18 minutes (37 °C). · Ist incubation (9 min.): 50 uL sample - in the presence of a progesterone-derivative labeled with a ruthenium complex(65 uL)** are incubated with Danazol to release progesterone. After addition of biotinylated polyclonal ·2nd incubation (9 min.): progesterone-specific antibodies (50 uL) and streptavidin-coated microparticles (50 uL), progesterone from the sample competes with the labeled progesterone derivative for the antibody binding sites. At the same time the entire complex becomes bound to the solid phase via interaction of biotin and streptavidin. The proportion of labeled progesterone derivative bound to the solid phase is inversely proportional to the progesterone content of the sample. · The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier (0.4 second read frame). ·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 code. **Tris(2,2'-bipyridy))ruthenium(II) complex (Ru(bpy)2+3)
Here's an analysis of the provided text, focusing on acceptance criteria and the study data:
The document is a 510(k) Summary for the Boehringer Mannheim Elecsys® Progesterone Assay, comparing it to a predicate device, the Enzymun® Progesterone Assay. It focuses on demonstrating substantial equivalence.
1. Table of Acceptance Criteria and Reported Device Performance
It's important to note that the document doesn't explicitly state "acceptance criteria" in the format of pass/fail thresholds against which the new device is being judged. Instead, it presents performance characteristics of both the new device (Elecsys® Progesterone Assay) and the predicate device (Enzymun® Progesterone Assay) to demonstrate substantial equivalence. The implication is that if the Elecsys® performance is comparable to or better than the predicate, it meets the unstated "acceptance criteria" for equivalence.
Therefore, the table below presents the performance characteristics as reported for both devices. The "Acceptance Criteria" column is derived from the performance of the predicate device, assuming the new device must achieve comparable or better results.
| Feature / Performance Characteristic | Implied Acceptance Criteria (from Predicate Enzymun® Progesterone) | Reported Device Performance (Elecsys® Progesterone) |
|---|---|---|
| Within-Run %CV (Low Level) | 13.3% | 3.7% |
| Within-Run %CV (Mid Level) | 3.6% | 1.9% |
| Within-Run %CV (High Level) | 2.3% | 0.7% |
| Total %CV (Low Level) | 22.4% | 6.8% |
| Total %CV (Mid Level) | 5.9% | 3.1% |
| Total %CV (High Level) | 2.6% | 0.8% |
| Lower Detection Limit | 0.4 ng/mL | 0.05 ng/mL |
| Linearity Range | 0.4-30 ng/mL (deviation ± 10%) | 0.05-100 ng/mL (deviation ± 10%) |
| Method Comparison (vs. Enzymun Test® Progesterone) - r value | 0.997 (Least Squares) | 0.9914 (Least Squares) |
| Method Comparison (vs. Enzymun Test® Progesterone) - SEE (Least Squares) | 0.717 | 0.620 |
| Interfering Substances (Bilirubin tolerance) | No interference at 64.5 mg/dL | No interference at 25 mg/dL (lower reported tolerance) |
| Interfering Substances (Hemoglobin tolerance) | No interference at 1 g/dL | No interference at 0.6 g/dL (lower reported tolerance) |
| Interfering Substances (Lipemia tolerance) | No interference at 250 mg/dL | No interference at 400 mg/dL |
| Interfering Substances (Biotin tolerance) | No interference at 50 ng/mL | No interference at 30 ng/mL (lower reported tolerance) |
Observations from the table:
- The Elecsys® Progesterone Assay generally shows significantly better precision (lower %CV) at all levels compared to the predicate device.
- The Lower Detection Limit of the Elecsys® assay is much lower, indicating improved sensitivity.
- The Linearity Range of the Elecsys® assay is much wider, indicating a broader measurable range.
- The Method Comparison shows a strong correlation for both devices to the same predicate, with the Elecsys® having a slightly lower 'r' value but also a lower 'SEE' (Standard Error of Estimate) when compared to the Enzymun Test® Progesterone, suggesting good agreement.
- The Interfering Substances data shows some instances where the documented tolerance for the Elecsys® is lower than the predicate (Bilirubin, Hemoglobin, Biotin), while for Lipemia, it is higher. This might require specific clinical considerations.
2. Sample Sizes Used for the Test Set and Data Provenance
- Sample Size for Test Set:
- Precision (Within-Run & Total %CV): For each of the "Low", "Mid", and "High" levels, N=60 samples were used for both the Elecsys® and Enzymun® assays.
- Method Comparison:
- Elecsys® Progesterone: N=53 samples
- Enzymun® Progesterone: N=48 samples
- Data Provenance: The document does not explicitly state the country of origin. It is a 510(k) submission to the FDA, so it typically implies data relevant to US market requirements. The data type is retrospective, as sample collections and analyses would have occurred prior to the submission date.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- This document is for an in vitro diagnostic (IVD) assay. The concept of "ground truth" established by human experts (like radiologists for imaging) is not directly applicable here.
- For IVDs, the "ground truth" is typically established by reference methods or highly accurate laboratory measurements. In this case, the Elecsys® assay's standardization is mentioned to be against "Enzymun® Progesterone," and the predicate's standardization is stated as "ID-GC/MS" (Isotope Dilution Gas Chromatography/Mass Spectrometry), which is a highly accurate reference method for quantitative measurements.
4. Adjudication Method for the Test Set
- Adjudication methods (like 2+1, 3+1) are typically used for subjective assessments, such as reviewing medical images or clinical outcomes.
- For an IVD assay measuring an analyte quantitatively, adjudication is not performed in the same manner. The "adjudication" is inherent in the analytical process itself, with quality control, calibration, and comparison to established reference methods (like ID-GC/MS for the predicate). Data points that fall outside expected ranges might be flagged and re-tested, but there isn't an expert panel adjudicating results in the sense of clinical decision-making.
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 was not done. This document pertains to an in vitro diagnostic (IVD) quantitative assay, not an AI-assisted diagnostic tool that involves human "readers" interpreting results. Therefore, the concept of human reader improvement with/without AI assistance does not apply.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
- This is an in vitro diagnostic assay, essentially a "standalone algorithm" in its function. It provides a quantitative measurement of progesterone. The "performance" characteristics detailed (precision, linearity, detection limit, method comparison) are its standalone performance.
- However, it's not an "AI algorithm" in the modern sense. It's an automated immunoassay system that delivers a result based on chemical reactions and instrumental measurements. Human interaction is primarily for sample loading, running controls, and interpreting the quantitative result within a clinical context, not for interpreting the raw data to derive the result itself.
7. The Type of Ground Truth Used
- For the Elecsys® Progesterone Assay, the "ground truth" for its performance comparison appears to be the Enzymun-Test® Progesterone Assay (the predicate). The method comparison section ("Vs Enzymun-Test® Progesterone") explicitly states this.
- For the Enzymun® Progesterone Assay (the predicate), its standardization is indicated as ID-GC/MS (Isotope Dilution Gas Chromatography/Mass Spectrometry), which is widely considered a highly accurate and precise reference method for quantitative analytical measurements, serving as a robust "ground truth" in analytical chemistry.
8. The Sample Size for the Training Set
- The document does not explicitly mention a "training set" in the context of machine learning or AI. This is a traditional immunoassay.
- The "calibration curve" is generated by "2-point calibration and a master curve provided via the reagent bar code." This calibration process uses specific calibrator materials, not necessarily what would be termed a "training set" in an AI/ML context. The number of samples for generating a master curve is not specified but would be conducted by the manufacturer.
9. How the Ground Truth for the Training Set Was Established
- As a traditional immunoassay, there isn't a "training set" with ground truth in the AI/ML sense.
- The concept of "ground truth" for calibration materials would relate to their certified concentration values, which are typically established through highly accurate reference methods (e.g., gravimetry, titrimetry, or methods like ID-GC/MS) performed by qualified analytical chemists at the manufacturer.
§ 862.1620 Progesterone test system.
(a)
Identification. A progesterone test system is a device intended to measure progesterone (a female hormone) in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of disorders of the ovaries or placenta.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.