(358 days)
The Xprecia Prime™ Coagulation System, which includes the INR Coagulation Analyzer (Meter) and PT/INR Test Strips, is for the determinational Normalized Ratio (INR) for the monitoring of oral anticoagulation therapy with Warfarin (a vitamin K antagonist) in fresh capillary whole blood from a fingerstick. The results are reported in INR as well as in seconds. It is intended to be used to monitor patients 18 years of age or older who are stable on vitamin K antagonist therapy for at least six weeks and is not intended for use in patients who are transitioning from heparin treatment to vitamin K antagonist therapy. The Xprecia Prime™ Coagulation System is an in-vitro diagnostic device intended for multi-patient use in professional healthcare settings including CLIA Waived and Point of care settings.
The Xprecia Prime™ Coagulation System has been specifically designed to monitor INR of patients undergoing anticoagulation therapy with warfarin (Vitamin K antagonist). It consists of the Xprecia Prime " Coagulation Analyzer, Xprecia Prime™ PT/INR Test Strips and Xprecia " Systems PT Controls.
The Xprecia Prime™ Coagulation System analyses a blood sample taken from the patient by fingerstick. The sample is transferred from the patient's finger to a test strip that has been inserted in the Xprecia Prime™ Coagulation Analyzer. The blood is mixed with a reagent contained within the strip and the analyzer detects when clotting has occurred. The result is then displayed on the analyzer's screen in either units known as the International Normalized Ratio (INR) or in calibrated seconds.
The provided text describes the acceptance criteria and the study that proves the device meets those criteria for the Xprecia Prime Coagulation System.
1. Table of Acceptance Criteria and the Reported Device Performance:
| Performance Characteristic | Acceptance Criteria (Implicit/Explicit) | Reported Device Performance |
|---|---|---|
| Precision/Reproducibility | ||
| Intermediate Precision (CV) | $\le$5% (for 3 LOC's across the range) | Level 1: 2.2% |
| Level 2: 1.0% | ||
| Level 3: 1.1% | ||
| Reproducibility (CV) | $\le$6% (for LQC material) | Level 1: 2.0% |
| Level 2: 1.3% | ||
| Capillary Repeatability (CV) | 95% of results falling within. | Normal range of 0.9 to 1.1 INR with more than 95% of all results falling within that range. |
2. Sample Size for the Test Set and Data Provenance:
- Precision/Reproducibility:
- Intermediate Precision: Single site, 20 days, two runs/day, two replicates (total N for LQC is not explicitly stated but implied by the study design).
- Reproducibility: 5-day study, multiple sites, untrained intended use operators (IUO), LQC material (total N for LQC not explicitly stated).
- Capillary Repeatability: Enrolled subjects, duplicate results (total N not given, but mentioned as "all sites").
- Assay Reportable Range: Established through method comparison studies.
- Interference Limits: Whole blood from normal subjects and patients on VKA therapy, spiked separately with interferents (N not explicitly stated).
- Hematocrit Range: 371 patients across four intended use sites. Data collected included capillary blood samples for Xprecia Prime System INR, citrated plasma samples for central laboratory INR (Sysmex® CS-2500), and measured EDTA venous whole blood hematocrit.
- Method Comparison with Predicate Device: 401 capillary samples. (Provenance: Not explicitly stated, but often multi-site clinical studies occur in the US for FDA submissions, however, the location specified for the predicate device comparison is not mentioned).
- Method Comparison with Reference Device: 397 samples. Performed at 4 clinical sites in the US.
- Expected Values/Reference Range: 120 patients who were not on oral anticoagulant therapy. (Provenance: Not explicitly stated, but likely from clinical sites involved in other studies).
Data Provenance: The studies for "Method Comparison with Reference Device" were performed at 4 clinical sites in the US. Most other studies imply fresh patient samples or LQC material, suggesting prospective data collection for the specific studies. The general provenance for all studies aside from the one specified as US is not explicitly stated in the provided text.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:
This device is an in-vitro diagnostic (IVD) device for measuring Prothrombin Time (PT) and International Normalized Ratio (INR), which are quantitative measurements. The ground truth for this type of device is typically established against a recognized reference method (e.g., laboratory analyzer) or a predicate device, rather than through expert consensus on qualitative interpretation.
For the method comparison studies:
- Reference Method: Sysmex® CS 2500 laboratory analyzer using Dade® Innovin® reagent. This is an automated laboratory instrument, so it doesn't involve "experts" establishing ground truth in the traditional sense of medical image interpretation. The "ground truth" is the result provided by the established laboratory method.
- Predicate Device: CoaguChek® XS System. Similarly, the predicate device's results serve as a comparative standard.
Therefore, the concept of "number of experts" and their "qualifications" for establishing ground truth for this specific IVD device is not directly applicable in the way it would be for, say, an AI-powered diagnostic imaging tool. The accuracy is assessed by comparing quantitative results to established analytical methods.
4. Adjudication Method for the Test Set:
Not applicable in the context of quantitative IVD assays compared to a reference method or predicate device. Adjudication methods like "2+1" or "3+1" are typically used in clinical studies where expert consensus is needed to establish a qualitative ground truth (e.g., presence or absence of a disease in imaging). For this device, the "ground truth" is the numerical reading from the reference or predicate device/method.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance:
Not applicable. This device is an in-vitro diagnostic (IVD) system, a standalone quantitative measurement device for INR. It does not involve human readers interpreting images or data with or without AI assistance. Therefore, an MRMC study is not relevant to its evaluation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
Yes, the studies evaluate the standalone performance of the Xprecia Prime™ Coagulation System (meter and test strips). The system provides a direct INR or PT in seconds result. The "algorithm" or measurement principle of the device is evaluated directly against reference methods or predicate devices. There is no human interpretation step in the device's output itself; a healthcare professional uses the device to obtain a numerical result.
7. The Type of Ground Truth Used:
The ground truth used for performance evaluation (specifically for method comparison and reportable range) was:
- Results from a reference laboratory analyzer: Siemens Sysmex® CS-2500 using Dade® Innovin® reagent.
- Results from a predicate device: CoaguChek® XS System.
- Expected values/reference range was established by testing samples from healthy individuals not on anticoagulant therapy.
8. The Sample Size for the Training Set:
The provided document describes performance studies, which generally fall under verification and validation (V&V) testing. For IVD devices, a "training set" is more relevant for machine learning algorithms. While the device contains software, the nature of the electrochemical measurement and factory calibration suggests a traditional development process. The document does not explicitly mention a "training set" in the context of developing a machine learning model. Instead, it refers to:
- Factory calibration: "Each lot of Xprecia Prime™ PT/INR Test Strips is factory calibrated to a reference lot of human recombinant thromboplastin traceable to the World Health Organization International Reference Preparation." This calibration process uses reference materials to ensure accuracy, which is somewhat analogous to training but not typically quantified as a "sample size for a training set" in the ML sense.
9. How the Ground Truth for the Training Set Was Established:
As mentioned above, a "training set" in the machine learning sense is not explicitly detailed. The fundamental "ground truth" for the device's measurement integrity and accuracy is established through:
- Traceability to WHO International Reference Preparation: For the PT/INR Test Strips, ensuring that the thromboplastin reagent is standardized against accepted international references.
- Analytical methods and reference materials: The device's electrochemical detection method is designed to measure thrombin activity, correlated with accepted PT/INR values from established reference methods and predicate devices.
§ 864.7750 Prothrombin time test.
(a)
Identification. A prothrombin time test is a device used as a general screening procedure for the detection of possible clotting factor deficiencies in the extrinsic coagulation pathway, which involves the reaction between coagulation factors III and VII, and to monitor patients receiving coumarin therapy (the administration of one of the coumarin anticoagulants in the treatment of venous thrombosis or pulmonary embolism).(b)
Classification. Class II (performance standards).