(99 days)
The CoaguChek Pro PTN test cartridge is for the quantitative determination of the prothrombin time of freshly drawn whole blood, using the CoaguChek Pro System. It is intended for health care professional use only.
The prothrombin time test is used to measure coagulation by activating the extrinsic pathway. The PTN test is sensitive to deficiencies of factors II, V, VII, and X. The prothrombin time is an in vitro determination of the time required for a clot to form via the extrinsic pathway. The prothrombin time is useful in monitoring the prolonged coagulation response of patients undergoing coumarin therapy. Many diseases and drugs can prolong or prevent coagulation by altering the balance of clotting factors involved in coagulation.
The PTN test is initiated by inserting a CoaguChek Pro PTN test cartridge into the instrument. The instrument reads a code on the test cartridge to determine test identity and lot number. The test cartridge contains a sample application well, a reagent chamber, and a reaction path. After the instrument heats the test cartridge, a drop of fresh, whole blood is placed on the test cartridge sample application well. Blood is drawn into the reagent chamber by capillary action, where it mixes with the reagent to initiate coagulation. The blood sample moves along the reaction path until a clot forms. The laser optical system detects the clot by monitoring blood flow; endpoint is reached when the blood stops moving. The time from sample application to clot detection is the prothrombin time. The displayed result is equivalent to laboratory plasma prothrombin time results. Because each newly-manufactured lot is calibrated to an internal reference lot, any lot-to-lot variability between reagents is corrected electronically using information coded on the lot-specific code key.
The provided text describes the CoaguChek Pro PTN Test and Controls, intended for the quantitative determination of prothrombin time in whole blood.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. A table of acceptance criteria and the reported device performance
The document provides a comparison of performance characteristics between the CoaguChek Pro PTN Test (the new device) and its predicate device, the CoaguChek PT Test. While it does not explicitly state "acceptance criteria," the predicate device's performance often serves as a benchmark for substantial equivalence.
| Claim | CoaguChek PT Test (Predicate - Benchmark) | CoaguChek Pro PTN Test (Reported Performance - New Device) |
|---|---|---|
| Mean Normal | 12 seconds | |
| 1.0 INR | 12 seconds | |
| 1.0 INR | ||
| Verified Assay Range | 9.6 - 34.4 seconds | |
| 0.64 - 8.2 INR | 10.7 - 37.8 seconds | |
| 0.8 - 9.9 INR | ||
| Factor Sensitivity | Factors II, V, VII, and X | Factors II, V, VII, and X |
| Verified Hematocrit Range | 32% - 52% | 23% - 53% |
| Precision with Controls (Between-Day CV) | Level 1: 12.6 sec (3.7%) | |
| Level 2: 23.2 sec (4.1%) | Level 1: 11.6 sec (5.2%) or 0.9 INR (10.8%) | |
| Level 2: 21.6 sec (5.5%) or 3.2 INR (11.6%) | ||
| Precision with Blood (CV) | Capillary: 17.2 sec (2.2%) CV | |
| Venous: 17.6 sec (1.9%) CV | Capillary: 17.7 sec (3.8%) CV or 2.31 INR (8.4%) CV | |
| Venous: 18.6 sec (3.3%) CV or 2.57 INR (8.2%) CV | ||
| Accuracy (Correlation with reference method) | Venous Whole Blood (vs. MLA700): | |
| N=81 | ||
| Y=0.859X + 1.3 | ||
| R=0.985 | Venous Whole Blood (vs. MLA900C): | |
| N=561 | ||
| Y=0.974X + 0.12 | ||
| R=0.922 |
Analysis of Performance vs. Benchmark:
- Mean Normal, Verified Assay Range, Factor Sensitivity: The new device (CoaguChek Pro PTN) shows equivalent or improved ranges and sensitivity compared to the predicate device.
- Verified Hematocrit Range: The new device demonstrates a wider verified hematocrit range (23% - 53%) compared to the predicate (32% - 52%), indicating an improvement in applicable patient populations.
- Precision:
- With Controls: The CVs for the new device controls are slightly higher than the predicate in some cases (e.g., Level 1 between-day CV is 5.2% vs 3.7%). However, the use of INR for the new device also provides additional precision information. Without explicit acceptance criteria, it's hard to definitively say if these slight differences are within acceptable limits, but they are presented for comparison.
- With Blood: Similar to controls, the CVs for the new device with blood samples are slightly higher in some instances.
- Accuracy:
- The new device was compared against a different reference instrument (MLA900C for the new device vs. MLA700 for the predicate).
- The sample size for the new device's accuracy study is substantially larger (N=561) compared to the predicate (N=81).
- The R-value (0.922) for the new device's accuracy is lower than the predicate (0.985), indicating a slightly weaker linear correlation with its reference method, but still indicating a strong correlation. The slope (0.974) and intercept (0.12) are closer to the ideal 1.0 and 0, respectively, than the predicate's (0.859 and 1.3).
2. Sample size used for the test set and the data provenance
- Accuracy Test Set (Venous Whole Blood):
- Sample Size: N = 561
- Data Provenance: Not explicitly stated (e.g., country of origin). The study involved "Venous Whole Blood," implying human samples, likely collected prospectively for the study given the comparison to a reference laboratory method. There is no information to indicate it was retrospective.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not applicable. The ground truth for this medical device (prothrombin time measurement) is established by a reference laboratory method (MLA900C), not by human expert consensus or interpretation.
4. Adjudication method for the test set
Not applicable. The study compares the device's output to a quantitative measurement from a reference laboratory instrument. There is no human adjudication process described.
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 device is a quantitative diagnostic test for prothrombin time, not an imaging or interpretative AI system involving human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the device (CoaguChek Pro PTN Test) operates as a standalone automated system. The performance characteristics presented are for the device itself, without human intervention in the measurement process other than sample application. The comparison is between the device's quantitative output and a reference laboratory instrument's output.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth for the test set (accuracy study) was established using a reference laboratory method/instrument, specifically the MLA900C for venous whole blood samples.
8. The sample size for the training set
The document does not mention a "training set" in the context of machine learning or AI. This device appears to be a traditional diagnostic instrument relying on biochemical and mechanical principles, not a machine learning model. Therefore, direct training set information is not provided.
9. How the ground truth for the training set was established
As there is no mention of a machine learning "training set," this question is not applicable. The device's internal calibration is mentioned: "Because each newly-manufactured lot is calibrated to an internal reference lot, any lot-to-lot variability between reagents is corrected electronically using information coded on the lot-specific code key." This suggests a manufacturing calibration and quality control process rather than a typical machine learning ground truth establishment for a training set.
§ 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).