(83 days)
The new TAS PT ONE test card, is intended to be used with the TAS Analyzer to determine the prothrombin time in citrated whole blood or plasma.
The TAS Prothrombin Time, ISI 1 (PT ONE) test card provides a one stage method which measures the clotting time of a sample after combining it with activator. This test consists of a single card that contains calcium chloride to initiate clotting in citrated blood samples, tissue thromboplastin as an activator, buffer, and stabilizers. Samples are tested by drawing venous or arterial blood into a sodium citrate tube and briefly mixing by gentle inversion. This allows the operator to control the start of the clotting reaction which requires recalcification. Because the sample is citrated, additional tests such as an aPTT can be performed with the same sample. The test card has a magnetic stripe on the back which encodes lot specific information such as number, expiration date, and calibration factors specific to that lot. A room temperature test card is removed from the pouch and the card is passed through the instrument's stripe reader to program the instrument to run a PT ONE. The instrument then requests patient and sample information and instructs the operator to insert a PT ONE test card. The card is quickly warmed and the operator is prompted to add a drop of sample to the card well. The sample is drawn into the card and rehydrates the PT ONE reagent which recalcifies the sample and begins the clotting reaction. As the reaction proceeds and clotting begins, the movement of the particles decreases, and the instrument signals the clotting time. Low levels of extrinsic clotting factors will cause prolongation of clotting time.
The provided document describes the TAS PT ONE Test Card, a medical device for determining prothrombin time.
Here's an analysis of the acceptance criteria and the study proving the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
| Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Precision | CV (%) should be low and comparable to the predicate device | Within-day CV: 1.8 to 4.5% across various sample types and control levels for PT ONE test cards. |
| Between-lot precision: No significant difference. | ||
| Between-operator precision: No significant difference. | ||
| Sensitivity to Coagulation Factors | Should respond to changes in factor activity (Factor II, V, VII, X) | Factor II: 20% |
| Factor V: 35% | ||
| Factor VII: 50% | ||
| Factor X: 45% | ||
| (Note: The new device shows increased sensitivity or similar sensitivity to the predicate device for these factors.) | ||
| Interference (Fibrinogen, Hematocrit, Heparin, Lipid, Temperature, Sample Fill) | Should not be significantly affected by common interferences within specified ranges | Fibrinogen: No significant effect from >15 mg/dL to 1200 mg/dL (2-second variation). |
| Hematocrit: No effect (0-55%). | ||
| Heparin: Slight effect above 0.75 U/ml. | ||
| Lipid: No effect up to 14 mg/ml. | ||
| Sample Temperature: No effect. | ||
| Acidified Citrate: Cannot be used. | ||
| Underfill/Overfill: Greatly underfilled tubes produced results outside normal range; overfilling had no substantial effect. | ||
| Correlation with Predicate Device | High correlation between results from the new device and the predicate device | Correlations of greater than 0.92 for each of several card lots tested. |
| ISI (International Sensitivity Index) | Should have a specific ISI value, ideally close to 1.0 for better standardization | Average ISI for blood and plasma of 1.0. |
| Stability | Should maintain performance over a reasonable shelf life | Room Temperature: Stable for two weeks. |
| Refrigerator Temperature: Stable for at least 39 weeks (studies ongoing). |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: 338 blood and plasma samples.
- Unique Patients/Donors: 101 people (normal donors or patients undergoing warfarin therapy).
- Data Provenance: Prospective, clinical testing was done at "one large hospital" (location not specified, but typically conducted in the country where regulatory approval is sought, implied to be the US).
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number of experts or their qualifications for establishing the ground truth during the clinical study. The "ground truth" reference here seems to be the results obtained from the predicate device (TAS PT test card), against which the new TAS PT ONE test card was compared. The assumption is that the results from the legally marketed predicate device are considered the established accurate reference for prothrombin time determination.
4. Adjudication Method for the Test Set
Not applicable. The study compares the performance of the new device against a predicate device. There is no mention of an independent adjudication process for discrepancies in results, as the predicate device's output serves as the reference point for comparison.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This device is an automated in vitro coagulation study system. There are no "readers" in the traditional sense accessing and interpreting images or data alongside AI. The device provides a quantitative result (clotting time), and its performance relates to agreement with a reference method, not reader improvement.
6. Standalone (Algorithm Only) Performance Study
Yes, this was a standalone performance study. The TAS PT ONE test card, used with the TAS Analyzer, functions as a standalone system to determine prothrombin time. Its performance was evaluated independently against the predicate device's results. There is no human-in-the-loop component for the interpretation of the clotting time by the device itself; the device provides the final clotting time result.
7. Type of Ground Truth Used
The "ground truth" for the clinical performance assessment was the results obtained from the predicate device (TAS PT test card) when used with the TAS Analyzer. This is a form of comparative effectiveness against an established, legally marketed device.
8. Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or algorithm development. The "preclinical testing" involved "in-house studies" at CDI, which would have been used for initial development and optimization. However, the specific size of this developmental data is not provided.
9. How the Ground Truth for the Training Set Was Established
As with point 8, the concept of a "training set" and its "ground truth" in an AI/ML context isn't directly applicable or described in this traditional medical device submission for an in vitro diagnostic. The "preclinical testing" establishing performance characteristics (precision, sensitivity, interference) would have used reference materials and established laboratory methods to determine expected values or behaviors, which would serve as the internal "ground truth" for development and calibration.
§ 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).