(171 days)
Immunoassay for the in vitro quantitative determination of testosterone in human serum and plasma. The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassay analyzers.
Measurements of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males and, in females hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries, and androgenital syndromes.
The Elecsys Testosterone II immunoassay is based on a competitive test principle with streptavidin-coated microparticles and electrochemiluminescence detection. Results are determined using a calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve provided with the reagent bar code. The Elecsys Testosterone II reagent kit consists of a Reagent Pack (R1, R2, and M[Streptavidin-coated microparticles]).
The Elecsys® Testosterone II Immunoassay is a device for the in vitro quantitative determination of testosterone in human serum and plasma using electrochemiluminescence immunoassay (ECLIA). The study provided focuses on establishing substantial equivalence to a predicate device (Elecsys® Testosterone Assay, K964889) through method comparison tests and performance characteristic comparisons.
Here's an analysis of the provided information:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" in a numerical format that must be met (e.g., "slope must be between 0.9 and 1.1"). Instead, it demonstrates performance through regression analysis and comparisons to the predicate device and reference methods. The implicit acceptance is that the Elecsys® Testosterone II Assay performs comparably to the predicate device and accurately against reference standards.
The table below summarizes the key performance characteristics and method comparison results for the Elecsys® Testosterone II Assay as described:
| Feature | Elecsys® Testosterone II Assay Performance |
|---|---|
| Measuring Range | 2.5 – 1500 ng/dL (0.087 – 52.0 nmol/L) |
| Precision (Intermediate Precision, Total) | 18.5% CV @ 4.5 ng/dL, 8.4% CV @ 9.5 ng/dL, 3.2% CV @ 69.1 ng/dL, 2.8% CV @ 216 ng/dL, 2.8% CV @ 867 ng/dL, 3.4% CV @ 1300 ng/dL, 2.4% CV @ 1450 ng/dL |
| Precision (Repeatability, Within-Run) | 10.2% CV @ 4.5 ng/dL, 4.7% CV @ 9.5 ng/dL, 2.1% CV @ 69.1 ng/dL, 1.9% CV @ 216 ng/dL, 2.6% CV @ 867 ng/dL, 1.2% CV @ 1300 ng/dL, 1.5% CV @ 1450 ng/dL |
| LoQ (Functional Sensitivity) | 12.0 ng/dL |
| LoB (Limit of Blank) | 1.2 ng/dL |
| LoD (Limit of Detection) | 2.5 ng/dL |
| Method Comparison 1 (vs. validated ID/LC-MS/MS, itself validated vs ID-GC/MS) | n = 52 serum samples (8 - 1383 ng/dL) |
| Deming Regression: Slope = 1.024, y-int = -0.060, Correlation Coefficient (r) = 0.996 | |
| Method Comparison 2 (vs. ID-GC/MS reference method) | n = 55 serum samples (7.6 - 1383 ng/dL) |
| Deming Regression: Slope = 1.032, y-int = -0.055, Correlation Coefficient (r) = 0.999 | |
| Method Comparison 3 (vs. validated ID/LC-MS/MS for female samples) | n = 142 female serum samples (3 - 517 ng/dL) |
| Deming Regression: Slope = 0.928, y-int = 0.047, Correlation Coefficient (r) = 0.959 | |
| Method Comparison 4 (vs. Predicate Device, Elecsys® Testosterone Assay) | Male samples: n = 239 (6.3 - 1400 ng/dL) |
| Deming Regression: Slope = 0.971, y-int = 0.085, Correlation Coefficient (r) = 0.985 | |
| Female samples: n = 148 (2.5 - 926 ng/dL) | |
| Deming Regression: Slope = 0.984, y-int = -7.34, Correlation Coefficient (r) = 0.972 | |
| Male and Female Samples Combined: n = 387 (2.5 - 1400 ng/dL) | |
| Deming Regression: Slope = 0.989, y-int = -2.87, Correlation Coefficient (r) = 0.992 |
Acceptance Criteria (Implied):
While not explicitly stated as numerical acceptance criteria, the strong correlation coefficients (close to 1.0) and slopes (close to 1.0) and small y-intercepts in the regression analyses, coupled with low CVs for precision, indicate the device is performing comparably to both reference methods and the predicate device across its measuring range. This demonstrates that the new device is substantially equivalent to the legally marketed predicate.
2. Sample Sizes and Data Provenance
The studies are quantitative performance analyses of an in vitro diagnostic device, not human reader studies for image-based AI. Therefore, the "test set" concept here refers to the clinical samples used for method comparison.
- Test Set (Method Comparison):
- Study 1: 52 serum samples
- Study 2: 55 serum samples
- Study 3: 142 female serum samples
- Study 4: 239 male and 148 female serum samples (total 387)
- Data Provenance: Not explicitly stated, but the submission is from Roche Diagnostics, based in Indianapolis, IN, indicating a US-based submission. The nature of in vitro diagnostic device studies typically involves clinical samples, likely collected from various clinical sites. The document does not specify if the data is retrospective or prospective, but based on the type of study (method comparison), it would involve testing collected samples.
3. Number of Experts and Qualifications for Ground Truth
This is not applicable as the device is an immunoassay for quantitative determination of testosterone. The "ground truth" is established by highly accurate reference methods (ID-GC/MS and validated ID/LC-MS/MS), not by human experts interpreting data or images.
4. Adjudication Method
Not applicable. Adjudication methods (e.g., 2+1) are typically used for establishing ground truth in clinical evaluations involving subjective expert interpretation (like radiology reads). For quantitative assays, ground truth is based on objective measurements from reference methods.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This is an immunoassay device, not an AI or imaging device that would involve human readers.
6. Standalone (Algorithm Only) Performance
Yes, the studies evaluate the standalone performance of the Elecsys® Testosterone II Immunoassay. The assay directly measures testosterone levels, and its performance is assessed by comparing its results against established reference methods and the predicate device. There is no "human-in-the-loop" once a sample is loaded into the analyzer for the measurement itself.
7. Type of Ground Truth Used
The ground truth for the test set (method comparison studies) was established using:
- ID-GC/MS (Isotope Dilution Gas-Chromatography/Mass Spectrometry): This is considered a gold standard reference method for testosterone measurement, providing highly accurate and precise quantitative values.
- Validated ID/LC-MS/MS (Isotope dilution/liquid chromatographic-tandem mass spectrometry): This method was validated against the ID-GC/MS reference method and used as a highly accurate comparison method.
8. Sample Size for the Training Set
The document does not specify a "training set" in the context of machine learning. For an immunoassay, the concept of a training set typically refers to samples used during the development and optimization of the assay's reagents and calibration parameters. This information is usually proprietary to the manufacturer and not detailed in a 510(k) summary, which focuses on validation studies proving performance for regulatory submission.
9. How the Ground Truth for the Training Set Was Established
As there's no explicitly defined "training set" in the provided document, the method for establishing its ground truth is not detailed. However, for an immunoassay, the development process would involve extensive use of characterized calibrators and controls, often traceable to international reference standards, to establish the assay's curve and ensure accurate measurement across its range. These calibrators would be assigned values using highly accurate reference methods (like ID-GC/MS) similar to those used for the test set ground truth.
§ 862.1680 Testosterone test system.
(a)
Identification. A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males and, in females hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes.(b)
Classification. Class I.