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.

AI/ML Overview

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.

Summary

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Image /page/0/Picture/0 description: The image shows a logo for Cardiovascular Diagnostics Inc. The logo features the letters "CD" in a stylized font, with a triangle above and below the letters. The text "CARDIOVASCULAR DIAGNOSTICS INC." is written above the logo. The image is in black and white.

RECEIVED

26 Dec 95 13 29

FDA/CDRH/ODE/DMC

Summary of Safety and Effectiveness Information VI.

K955843 MAR 18 1996

510(K) summary

Cynthia Pritchard, Ph.D. Submitted by: Director of Test Development

Cardiovascular Diagnostic, Inc. Address: 5301 Departure Drive Raleigh, NC 27604

Phone:

1-919-954-9871, ext. 248

1-919-954-9932 Fax:

Cynthia Pritchard, Ph.D. Contact: Director of Test Development

December 1, 1995 Date of Summary:

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VI. Summary of Safety and Effectiveness Information

Trade name: Thrombolytic Assessment System Prothrombin Time Test Card (TAS PT ONE Test Card)

Common Name: TAS PT ONE Test Card

Classification Name: systems for in vitro coaqulation studies, automated or semiautomated instruments and associated reagents and controls used to perform a series of coagulation studies and coagulation factor assays (Class II. 21 C.F.R. 864.5425)

Predicate Device: The proposed TAS PT ONE test card made with thromboplastin from human placenta is substantially equivalent to the marketed TAS PT test card made with rabbit brain thromboplastin (K882456).

Description of the Device: 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.

Intended Use: 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.

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Summary of Safety and Effectiveness Information

TAS PT ONE Test card

Comparison of old and new TAS PT test cards

Characteristic	Cleared PT	proposed PT ONE
Intended use	determination of prothrombin time	same
Card format	flat shallow reaction chambermounted on a thin plastic card	same
Sample type	citrated whole blood or plasma	same
Reagent	thromboplastin, plus PIOP a	same
Source	rabbit brain	humanplacenta
Reaction	formation of a fibrin clot	same
Analyzer	TAS	same
Signal monitored	photo-optical detection of PIOPmovement in a magnetic field	same
Signal interpretation	monitoring of clot formation bydecrease in PIOP movement	same
Results	clotting time	same
Interpretation of results	increase in clotting time indicateslow levels or inhibition of clotting factors	same
ISI	approx 1.6	approx 1.0
Quality control	self tests performed by analyzer atpower up and throughout operation, plusperiodic functional testing of each test cardwith quality control plasmas	same

a paramagnetic iron oxide particles

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Summary of Safety and Effectiveness Information TAS PT ONE Test card

Nonclinical Performance Data: Preclinical testing was done at CDI using TAS PT ONE test cards and the TAS analyzer to determine the performance characteristics of the system. In-house studies showed that the PT ONE test cards responded similarly to different clotting factors, coagulation inhibitors, and interference factors as the existing PT test cards. However, the new TAS PT ONE test cards were more sensitive to changes in factor activity and therefore exhibited longer clotting times in response to decreasing factor levels.

The proposed TAS PT ONE test cards are stable for two weeks at room temperature, and for at least 39 weeks at refrigerator temperatures. These studies are ongoing.

	Cleared PT		Proposed PT ONE
Sample type	Mean	CV (%)	Mean	CV (%)
citrated whole blood	11.5	5.6	9.8	2.4
citrated plasma	11.9	3.7	10.6	1.7
level I control plasma	11.5	3.3	12.9	1.7
level II control plasma	19.5	4.3	29.4	3.6
level III control plasma	29.9	4.8	56.5	6.8

Within day precision of TAS PT test cards with various sample types

During 20 days of testing of the proposed TAS PT ONE test cards, coefficients of variation ranged from 1.8 to 4.5, and means from 11.9 to 12.8 seconds. There was no significant difference in precision of results produced with the PT ONE by multiple operators, nor between lots of test cards.

Sensitivity of PT ONE results to coagulation factor deficiencies

Factor	Cleared PT	Proposed PT ONE
II	20	20
V	35	35
VII	45	50
X	45	45

Fibrinogen levels from >15 mg/dL to 1200 mg/dl have no significant effect on PT ONE test card results; total variation in clotting time over this range was two seconds . Acidified citrate cannot be used to obtain samples for this test. Hematocrit (0-55%) has no effect on results obtained. Heparin levels above 0.75 U/ml have a slight effect. Lipid, to at least 14 mg/ml, had no effect. There was no effect of sample temperature. These characteristics are similar for the existing and proposed TAS PTS test cards.

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Summary of Safety and Effectiveness Information TAS PT ONE Test card

Underfill of blood collection tubes had a greater effect on PT ONE results than did overfilling, but only tubes that were greatly underfilled produced samples that gave results outside the normal range for both test card types. Overfilling did not have a substantial effect on PT ONE results.

Clinical Performance Data: Clinical testing was done at one large hospital to establish substantial equivalence of the TAS PT ONE test cards to the TAS PT test card (the predicate device). Three hundred thirty eight blood and plasma samples drawn from 101 people (normal donors or patients undergoing warfarin therapy) were tested by the existing and proposed PT test cards on the TAS Analyzer. The correlation of test results from the PT ONE test cards and those from PT test cards had correlations of greater than 0.92 for each of several card lots tested.

The PT ONE test card was determined by CDI and by two independent testing labs to have an average ISI for blood and plasma of 1.0.

Conclusions: Sufficient information is included in this application to demonstrate that the TAS PT ONE test card, together with the TAS Analyzer, is as safe and effective as a legally marketed device (PT test cards) and that it does not raise different questions of safety and efficacy.

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Regulation Number and Section

§ 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).