(454 days)
The ROTEM® delta Thromboelastometry System is designed for invitro diagnostic use by professionals in a laboratory environment. The ROTEM® system is intended to be used to provide a qualitative and quantitative indication of the coagulation state of a blood sample. For this purpose the ROTEM® system records the clot firmness changes in a sample of citrated whole blood as the sample clots, retracts and Ivses in real time. The analyzer output consists of a qualitative graphical representation (mirrored coagulation curve - clot firmness over time) and several defined numerical parameters describing the curve quantitatively.
The ROTEM® system provides specific blood modifiers (so-called reagents) intended to be used with the system, as additive to the blood sample.
The results of the ROTEM® analysis should not be the sole basis for a patient diagnosis, but should be evaluated together with the patient's medical history (anamnesis), the clinical picture and, if necessary, further coagulations tests.
The ROTEM® delta is a non-invasive diagnostic instrument designed to monitor and analyze the coagulation state of a blood sample in order to assist in the assessment of patient clinical hemostasis conditions. The indication for ROTEM® delta use is with adult patients where an evaluation of their blood coagulation properties is desired.
Coagulation evaluations with the ROTEM® delta are commonly used to assess clinical conditions in organ transplantation, cardiovascular surgery, cardiology procedures and trauma to assess post-operative hemorrhage and / or thrombosis.
ROTROL N is a quality control material for monitoring accuracy and precision of tests carried out on the ROTEM® delta Thromboelastometry System.
ROTROL P is a quality control material for monitoring accuracy and precision of tests carried out on the ROTEM® delta Thromboelastometry System.
The in-TEM® assay is a semi-quantitative in vitro diagnostic assay used on the ROTEM® delta Thromboelastometry System to monitor the coagulation process via the intrinsic pathway in citrated whole blood specimens. Clotting characteristics are described by the functional parameters Clotting Time (CT), Speed of Clot Formation (CFT and alpha angle), Clot Firmness (A20/MCF) and Clot Lysis (LOT, ML, LI(x)).
The hep-TEM® assay is a semi-quantitative in vitro diagnostic assay used on the ROTEM® delta Thromboelastometry System to monitor the coagulation process, via the intrinsic pathway in the presence of unfractionated heparin, in citrated whole blood specimens. The hep-TEM® reagent is used to inactivate heparin in patients receiving unfractionated heparin. Clotting characteristics are described by the functional parameters Clotting Time (CT), Speed of Clot Formation (CFT and alpha angle), Clot Firmness (A20/MCF) and Clot Lysis (LOT, ML, LI(x)).
The NATEM assay is a semi-quantitative in vitro diagnostic assay used on the ROTEM® delta Thromboelastometry System to monitor the coagulation process, contact-activated by the surface of the measurement cell, in citrated whole blood specimens. Clotting characteristics are described by the functional parameters Clotting Time (CT), Speed of Clot Formation (CFT and alpha angle), Clot Firmness (A20/MCF) and Clot Lysis (LOT, ML, LI(x)).
The star-TEM® Reagent is intended for use as a recalcification reagent in the NATEM and INTEM assays on the ROTEM® delta Thromboelastometry System.
The ROTEM® delta Thromboelastometry System consists of a fourcolumn instrument (with integrated computer module, computer controlled electronic pipette, software), system reagents (in-TEM® hep-TEM®, star-TEM®), quality controls (ROTROL N, ROTROL P) and measurement cells (Cup and Pin pro). The blood sample is filled into a cylindrical cup. A pin oscillates permanently while it is immersed in the blood holding cup. The motion of the pin is detected by an optical detection system. Data are processed and analyzed by a computer with special software. If no clotting takes place, the movement of the pin is not obstructed. When a clot forms and attaches itself to the pin and cup surfaces, the movement is obstructed. As the clot becomes firmer, the rotational movement of the pin is reduced. The rotational movement of the pin is converted into an amplitude with the following definitions applying to the thromboelastogram (TEM): An amplitude of 0 mm means unobstructed rotation, while an amplitude of 100mm can be regarded as infinite firmness and blocking of the pin by the clot. The TEM amplitude is a measure of the clot firmness.
The document is a 510(k) summary for the ROTEM® delta Thromboelastometry System, seeking substantial equivalence to the predicate device, the Thrombelastograph® Coagulation Analyzer (TEG®) - 5000 Series. The study primarily focuses on comparing the performance of ROTEM® delta with the predicate device across several coagulation parameters.
The acceptance criteria for the ROTEM® delta were based on precision and a method comparison with the predicate TEG® 5000.
1. Table of Acceptance Criteria and Reported Device Performance
| Parameter Type | Acceptance Criteria (Implicit from Study Description) | Reported ROTEM® Delta Performance |
|---|---|---|
| Precision | High precision expected in primary parameter; adequate precision in secondary parameters | Primary Parameter: Clot Firmness (MCF) - Shown to have high precision. |
| Secondary Parameters: Coagulation Kinetics (CT, CFT, Alpha Angle) - Shown to have adequate precision. | ||
| Method Comparison with TEG® | - Equality of clot firmness |
- Linear correlation for kinetic parameters (r > 0.8) | Clot Firmness (MCF vs. MA): Demonstrated equality.
Kinetic Parameters (CT vs. R, CFT vs. K, Alpha Angle vs. Angle): Showed a linear correlation (r > 0.8). It was noted that the slope of correlation was not equal to one and intercepts were not equal to zero, which was expected due to different activation reagents and distinct reference ranges between the two systems.
Heparin Sensitivity: ROTEM® showed different heparin sensitivities compared to TEG®. ROTEM® was more sensitive for higher heparin concentrations, allowing analysis in cases where TEG® was unable to demonstrate coagulation. |
| Reference Ranges | Reproducible and consistent across centers | Reference ranges for NATEM and INTEM were estimated using CSL1 protocols on three clinical US reference sample groups. These showed no significant center-to-center deviations and were in accordance with earlier studies on European reference groups. |
| Interfering Substances | Expected dose-response curves and interferences | Investigated for aprotinin, tranexamic acid, EACA. Dose-response curves investigated for heparin, dilution, and urokinase on the INTEM model, verifying diagnostic principles. |
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state the numerical sample size for the test set used in the method comparison study with the TEG® 5000. It mentions that "three clinical US reference sample groups" were used to estimate reference ranges for NATEM and INTEM. The provenance of this data is stated as US and the study appears to be prospective for the estimation of reference ranges. For the method comparison, it implies testing on various samples to establish correlations and differences in heparin sensitivity, but specific numbers are not provided.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of study does not rely on expert consensus or human interpretation to establish ground truth. It is a comparison of quantitative measurements from two medical devices. The "ground truth" implicitly refers to the accuracy and precision of the measurements themselves, and the correlation between the device and its predicate.
4. Adjudication Method for the Test Set
Not applicable. As a device comparison study involving quantitative measurements, there would be no adjudication method in the sense of expert review for image interpretation or diagnosis. The "adjudication" is based on statistical analysis of the measured parameters.
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
Not applicable. This study is for a Thromboelastometry System, which is an in-vitro diagnostic device for analyzing blood coagulation. It is not an AI-assisted diagnostic tool that involves human readers interpreting images or data. Therefore, an MRMC study or assessment of human reader improvement with/without AI assistance is not relevant.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
The ROTEM® delta is inherently a standalone device in the sense that the instrument's software processes the measurements and produces the quantitative results (e.g., CT, CFT, MCF, etc.) and graphical outputs. The performance described (precision, method comparison, sensitivity to interfering substances) represents the standalone performance of the device's measurement and processing capabilities. Clinicians then interpret these results, but the generation of the results themselves is automated.
7. The Type of Ground Truth Used
The ground truth for this device comparison is established by:
- Predicate Device Measurements: The TEG® 5000 served as the predicate, and its measurements were essentially the "truth" against which the ROTEM® delta's measurements were compared for substantial equivalence.
- Known Physiological Responses: The sensitivity to heparin, dilution, and lysis induced by urokinase are based on established physiological and pharmacological effects on coagulation, serving as an expected "truth" for how the device should respond.
- Reference Ranges: Established through established clinical laboratory protocols (CSL1) on healthy reference populations.
8. The Sample Size for the Training Set
Not applicable. This type of device (Thromboelastometry System) does not typically involve "training sets" in the machine learning sense. The device's algorithms are based on established biophysical principles of coagulation detection and signal processing, not on iterative machine learning from a large dataset. Calibration and control materials are used for device setup and quality control, but these are distinct from training sets for AI algorithms.
9. How the Ground Truth for the Training Set was Established
Not applicable. As stated above, a training set for machine learning is not used for this type of device.
§ 864.5425 Multipurpose system for in vitro coagulation studies.
(a)
Identification. A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.(b)
Classification. Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.