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Immunoassay for the in vitro quantitative determination of testosterone in human serum and plasma.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the cobas e 601 immunoassay analyzer.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) due to tumors, polycystic ovaries, and adrenogenital syndromes.

The Elecsys Testosterone II immunoassay makes use of a competitive test principle using streptavidin-coated microparticles and electrochemiluminescence detection. Results are determined using a calibration curve that is generated specifically on each instrument by a 2point calibration and 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 device is an immunoassay for the in vitro quantitative determination of testosterone in human serum and plasma. The device is intended for use on the cobas e 601 immunoassay analyzer.

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for the Elecsys Testosterone II are based on various analytical performance characteristics. The table below summarizes some of the key performance criteria and the reported performance of the candidate device (Elecsys Testosterone II, K211685) in comparison to its predicate device (Elecsys Testosterone II, K093421).

2. Sample Size Used for the Test Set and Data Provenance

• Precision (5-Day): 5 aliquots of each control (PreciControl Universal Level 1 and Level 2) and human serum samples per run, 1 run per day for 5 days with 3 lots. (Implies multiple individual human serum samples but the exact number isn't specified, and the controls are commercial products).
• Precision (21-Day): 2 replicates of 2 controls and 5 samples, 2 runs per day over 21 days using 1 reagent lot. (Implies 5 individual human serum samples, plus two controls).
• Linearity: One human serum sample with high analyte content was serially diluted (25 steps).
• Endogenous Interferences: Not explicitly stated, but implies analysis of testosterone concentrations with and without spiked interfering substances.
• Biotin Interference: Not explicitly stated, but implies multiple testosterone samples spiked with biotin.
• Common Drug Interferences: Not explicitly stated, but implies multiple samples tested with common drugs.
• Special Drug Interferences: Samples (with testosterone concentrations near 0.5 ng/mL and near 5.0 ng/mL) were divided into aliquots and spiked with Testosterone Undecanoate. The number of samples is not explicitly stated.
• Analytical Specificity/Cross-Reactivity: One testosterone level (0.5 ng/mL) in human serum matrix was spiked with potential cross-reactants. The number of samples is not explicitly stated.
• Sample Matrix Comparison: At least 40 serum/plasma pairs (Native or spiked samples).
• Method Comparison to Predicate: 168 samples (Native single samples and spiked single samples).

Data Provenance: The studies used human serum and plasma samples, as well as control materials. The specific country of origin is not explicitly stated, but Roche Diagnostics has facilities in Indianapolis, IN (USA), Mannheim, Germany, and Penzberg, Germany, suggesting a potential international origin or a combination of origins for their sample collection. The studies described are analytical performance evaluations, which are typically prospective in design for device validation.

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

This device is an in vitro diagnostic (IVD) quantitative assay for testosterone. The "ground truth" for such assays typically refers to the reference method (e.g., ID-GC/MS) or the established value of control materials. It does not involve expert readers reviewing images or clinical data to establish a diagnostic truth. Therefore, the concept of "experts" in the context of interpretation of results is not directly applicable here. The establishment of ground truth for accuracy and calibration is based on:

• Traceability/Standardization: ID-GC/MS ("Isotope Dilution - Gas Chromatography/Mass Spectrometry"). This is a highly accurate and precise analytical method that serves as a reference.
• Calibrators: Testosterone II CalSet II (Calibrators 1 and 2) are used, which are themselves traceable to the ID-GC/MS method.

4. Adjudication Method for the Test Set

Not applicable. As described above, this is an IVD assay, not an imaging-based diagnostic where adjudication of expert readings would be necessary. The performance is assessed by comparing results to reference methods or known concentrations, or through statistical analyses of precision and linearity.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No MRMC comparative effectiveness study was mentioned. This type of study is typically relevant for interpretative diagnostic devices (e.g., radiology AI tools) where human readers interpret cases with and without AI assistance. The Elecsys Testosterone II is a laboratory assay that provides a quantitative numerical result, and therefore, does not involve human readers interpreting "cases" in the same way.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

The performance studies described (Precision, LoB, LoD, LoQ, Linearity, Interferences, Cross-Reactivity, Sample Matrix Comparison, Method Comparison) are all standalone performance evaluations of the assay system (reagents + instrument) without human-in-the-loop interpretation. The device's primary function is to quantitatively measure testosterone, and its performance is assessed directly against analytical standards and reference methods.

7. The Type of Ground Truth Used

• Reference Method: ID-GC/MS (Isotope Dilution - Gas Chromatography/Mass Spectrometry) serves as the primary reference method for traceability and standardization.
• Known Concentrations: Control materials (e.g., PreciControl Universal) and spiked samples with known concentrations of analytes and interferents are used.
• Predetermined Clinical Values: Samples for method comparison include those that span the measuring range, implying a range of clinically relevant testosterone levels.

8. The Sample Size for the Training Set

The document describes analytical performance studies for validation (test set), but does not explicitly mention a "training set" in the context of algorithm development. Immunoassays like the Elecsys Testosterone II are typically developed and optimized using a range of samples during the research and development phase to establish reagent formulations, reaction kinetics, and calibration curves. However, the exact sample sizes for this initial developmental "training" are not usually detailed in 510(k) summaries, which focus on the validation data.

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

Similar to point 8, the document does not detail the "training set" for algorithm development. For IVD assays, the "training" involves establishing the master curve and optimizing reagents to accurately measure testosterone across its dynamic range. This optimization would rely on:

• Characterized reference materials: Samples with known testosterone concentrations, often established by highly accurate reference methods like ID-GC/MS.
• Clinical samples: A broad range of human serum and plasma samples from various populations (males, females, different age groups, healthy, and those with relevant disorders) would be used to ensure the assay performs reliably across the intended use population.
• Spiked samples: Samples with known additions of testosterone or interfering substances to evaluate various aspects of assay performance.

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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:

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.

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