(12 days)
Immunoassay for the in vitro quantitative determination of troponin T in human serum and plasma. Elecsys Troponin T can be used as an aid in the differential diagnosis of acute coronary syndrome to identify necrosis, e.g., acute myocardial infarction. The test is further indicated for the risk stratification of patients presenting with acute coronary syndrome and for cardiac risk in patients with chronic renal failure. The test may also be useful for the selection of more intensive therapy and intervention in patients with elevated levels of cardiac Troponin T. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys family of immunoassay analyzers.
The Elecsys® Troponin T STAT assay is a two step sandwich immunoassay with streptavidin micro particles and electrochemiluminescence detection, for the measurement of human TnT in serum or plasma.
Here's an analysis of the acceptance criteria and the study details for the Elecsys® Troponin T STAT Assay, based on the provided document:
Acceptance Criteria and Device Performance for Elecsys® Troponin T STAT Assay
The document describes a modified device (4th Generation) and compares its performance to a predicate device (3rd Generation). The acceptance criteria are implicitly established by demonstrating comparable or improved performance to the predicate device, particularly for key analytical parameters.
1. Table of Acceptance Criteria (Implicitly based on Predicate Performance) and Reported Device Performance
| Characteristic | Acceptance Criteria (Predicate Device Performance) | Reported Device Performance (Modified Device) |
|---|---|---|
| Intended Use | Immunoassay for the in vitro quantitative determination of troponin T in human serum and plasma. Aid in differential diagnosis of acute coronary syndrome, risk stratification, and cardiac risk in chronic renal failure. Useful for selection of intensive therapy in patients with elevated cardiac Troponin T. For use on Roche Elecsys family of immunoassay analyzers. | Same |
| Indications for Use | Aid in differential diagnosis of acute coronary syndrome, risk stratification, and cardiac risk in chronic renal failure. Useful for selection of intensive therapy in patients with elevated cardiac Troponin T. | Same |
| Assay Principle | Electrochemiluminescent immunoassay | Same |
| Traceability/ Standardization | Standardized against the 2nd generation Troponin T test | Standardized against the 3rd generation Elecsys Troponin T test; traceable to the 2nd generation test |
| Calibration Frequency | Elecsys 2010: After 1 month (same reagent lot), after 7 days (same reagent kit on analyzer). Elecsys 1010: With every reagent kit, after 7 days (20-25 °C), after 3 days (25-32 °C). | Elecsys 2010: After 1 month (same reagent lot), after 7 days (same reagent kit on analyzer). Elecsys 1010: With every reagent kit, after 7 days (20-25 °C). (Note: Predicate had additional 3-day frequency for Elecsys 1010 at higher temp; modified device does not list this, implying it's either removed or covered by the 7-day at 20-25C) |
| Sample Type | Human serum, K3-EDTA and Na-citrate plasma. | Human serum, K2- and K3-EDTA, Li-heparin, and Na-citrate plasma. (Expanded to include K2-EDTA and Li-heparin plasma) |
| Reagent Stability | Unopened: Up to stated expiration date at 2-8 °C. After opening: 12 weeks at 2-8 °C, 8 weeks on Elecsys 2010, 8 weeks on Elecsys 1010 (20-25 °C; up to 20 hours opened in total). | Same |
| Calibrator | Elecsys Troponin T STAT CalSet | Same |
| Controls | Elecsys PreciControl Troponin T or Elecsys PreciControl Cardiac. | Elecsys PreciControl Troponin T. (Note: Predicate allowed "or Elecsys PreciControl Cardiac"; modified device specifies "PreciControl Troponin T") |
| Duration of Assay | 9 minutes | Same |
| Measuring Range | 0.010-25.00 ng/mL | Same |
| Precision | Within-run (human serum): 1.1% CV at 0.47 ng/mL, 1.1% CV at 2.63 ng/mL, 1.4% CV at 11.5 ng/mL. Within-run (PreciControl): 4.2% CV at 0.10 ng/mL, 3.0% CV at 5.07 ng/mL. Total (human serum): 5.8% CV at 0.47 ng/mL, 5.4% CV at 2.63 ng/mL, 5.7% CV at 11.5 ng/mL. Total (PreciControl): 9.3% CV at 0.10 ng/mL, 6.0% CV at 5.07 ng/mL. | Within-run (human serum): 4.5% CV at 0.047 ng/mL, 2.0% CV at 0.652 ng/mL, 2.9% CV at 6.08 ng/mL. Within-run (PreciControl): 2.2% CV at 0.137 ng/mL, 2.5% CV at 2.89 ng/mL. Total (human serum): 6.2% CV at 0.047 ng/mL, 4.6% CV at 0.652 ng/mL, 5.6% CV at 6.08 ng/mL. Total (PreciControl): 3.5% CV at 0.137 ng/mL, 4.7% CV at 2.89 ng/mL. |
| Concentration at 10% CV | 0.03 ng/mL | Same |
| Hook Effect | No hook effect up to 400 ng/mL | Same |
| Analytical Sensitivity | Lower detection limit: 0.01 ng/mL. Lowest concentration giving 10% CV: 0.03 ng/mL. | Same |
| Limitations – Interference | No interference from: icterus up to 27 mg/dL bilirubin, hemolysis up to 0.1 g/dL, Lipemia up to 1500 mg/dL Intralipid, Biotin up to 50 ng/mL, Rheumatoid factor up to 2000 U/mL. Falsely depressed results with higher hemoglobin. Plasma with heparin or oxalate/fluoride showed sample-dependent low TnT values vs. serum. Contains additives for monoclonal mouse antibodies, antibodies to streptavidin. Extremely high titers of antibodies to ruthenium can cause interference. Results assessed with patient's medical history. | Same limitations reported for icterus, hemolysis, lipemia, biotin, rheumatoid factor, falsely depressed results with higher hemoglobin, and additives for interference. Modified language for plasma interference: "Plasma samples collected using tubes containing oxalate/fluoride revealed sample-dependent low TnT values when compared to results obtained on serum samples." (Note: original also mentioned heparin, which is now an acceptable sample type). |
Summary of Acceptance: The modified device demonstrates comparable performance across most parameters and shows improvements in sample types accepted (K2-EDTA and Li-heparin plasma) and potentially tighter precision at some concentrations compared to its predicate. The calibration frequency has a slight difference for Elecsys 1010 at higher temperatures, and the specific controls used are now narrower. The modifications in precision values suggest that new studies were done to establish these figures, and they are presented as the device's performance. The "acceptance criteria" for these would have been to meet or demonstrate improved analytical performance metrics compared to the predicate, which appears to be the case (e.g., lower CVs at comparable or different concentration points).
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state a single dedicated "test set" sample size or its provenance in the way one would for a clinical validation or a standalone AI study. Instead, it describes analytical performance characteristics that would have been derived from various studies using different samples:
- Precision (Within-run and Total): The precision data is reported for "human serum" and "PreciControl" (a control material). It lists specific CVs at different concentration points. While the exact number of samples or runs to generate these CVs is not provided, this would typically involve multiple replicates of samples at different concentrations across multiple runs and days.
- Interference Studies: These require testing samples spiked with various interferents (icterus, hemolysis, lipemia, biotin, rheumatoid factor) and comparing them to unspiked samples.
- Sample Type Evaluation: Plasma samples (K3-EDTA, Na-citrate, K2-EDTA, Li-heparin) are compared to serum samples, implying a set of patient samples collected in different tube types.
- Data Provenance: The document does not specify the country of origin of the data or whether it was retrospective or prospective. Given it's an in-vitro diagnostic device submission, the analytical studies are typically conducted by the manufacturer, likely in a controlled laboratory setting.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This is an analytical device (immunoassay) for quantitative measurement of a biomarker. Therefore, traditional "ground truth" as established by expert consensus (e.g., radiologists interpreting images) or pathology is not applicable in the same way as for diagnostic imaging or pathology devices.
- Ground Truth (Analytical): For an immunoassay, the "ground truth" or reference values are established through highly controlled laboratory methods, calibrated against international standards if available, and verified through other reference methods or highly accurate assays. The device itself is designed to measure the concentration of Troponin T, and its accuracy is assessed against the expected concentration in reference materials or patient samples already characterized.
- Experts: The development and validation of such an assay would involve analytical chemists, biochemists, clinical chemists, and other scientific experts who design, perform, and interpret these analytical studies, rather than clinical experts establishing a "diagnosis" as ground truth.
4. Adjudication Method for the Test Set
Adjudication methods like 2+1 or 3+1 are typically used in clinical studies where human interpretation of data (e.g., images, clinical symptoms) is being evaluated and discrepancies resolved. This is not directly applicable to the analytical performance studies of an immunoassay device. The performance metrics (precision, sensitivity, specificity, interference) are determined by quantitative laboratory measurements and statistical analysis.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. MRMC studies are relevant for devices where human readers interpret output (e.g., medical images) and the AI's impact on their performance is being evaluated. This document is for an automated immunoassay where the device provides a quantitative result directly. The device's "effectiveness" is in its analytical accuracy and precision in measuring Troponin T.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, the studies presented indirectly represent a standalone performance evaluation. The Elecsys® Troponin T STAT Assay is an automated immunoassay designed to provide a quantitative measurement. The precision, measuring range, analytical sensitivity, hook effect, and interference studies describe the performance of the algorithm/device itself (the immunoassay system) independent of human interpretation of the primary data (other than loading samples and reading the final numerical result). This is inherently a "standalone" evaluation for such a device.
7. Type of Ground Truth Used
For this immunoassay, the "ground truth" is established through:
- Reference Materials/Standards: Calibrators and control materials with known or assigned Troponin T concentrations are used to calibrate the device and verify its accuracy. The document states its traceability to the 2nd and 3rd generation Troponin T tests.
- Spiked Samples: For interference studies, samples are "spiked" with known concentrations of interferents, and the ground truth is the expected Troponin T concentration in the absence of interference.
- Comparative Methods: Although not explicitly detailed in this summary, often new assays are compared to established reference methods or highly accurate laboratory methods to establish accuracy.
8. Sample Size for the Training Set
The document describes a 510(k) for a device modification, focusing on analytical performance rather than a machine learning algorithm that requires a "training set" in the computational sense. Therefore, there is no explicit mention of a "training set" as it would apply to AI/ML models.
The device is an immunoassay, meaning its "learning" or optimization during development would involve:
- Reagent Formulation and Optimization: Iterative testing and adjustment of antibodies, buffers, and detection systems.
- Calibration Curve Development: Generating data points to establish the relationship between signal and concentration.
These development activities would involve numerous experiments and a large number of samples, but not usually referred to as a "training set" in this context.
9. How the Ground Truth for the Training Set Was Established
As noted above, a "training set" in the computational sense is not directly applicable here. The "ground truth" during device development (analogous to training) would be established by:
- Careful preparation of standard solutions with known concentrations of Troponin T.
- Characterization of patient samples or quality control materials using established reference methods or highly accurate laboratory assays to determine their true Troponin T levels.
- These known concentrations are then used to develop and validate the device's ability to accurately measure Troponin T, forming the basis for its calibration and performance specifications.
§ 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system.
(a)
Identification. A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.(b)
Classification. Class II.