(29 days)
The Quantra® System is composed of the Quantra Hemostasis Analyzer, QPlus Cartridge, and Quantra Quality Controls Level 1 and 2. The Quantra System is intended for in vitro diagnostic use.
The Quantra Hemostasis Analyzer uses Sonic Estimation of Elasticity via Resonance (SEER) Sonorheometry, an ultrasound-based technology, to measure the shear modulus of whole blood during coagulation. The system is intended to be used by trained professionals at the point-of-care and in clinical laboratories to evaluate the viscoelastic properties of whole blood.
The QPlus Cartridge is a multi-channel cartridge that provides semi-quantitative indications of the coagulation state of a 3.2% citrated venous or arterial whole blood sample. The QPlus Cartridge includes tests to assess coagulation characteristics via the intrinsic pathway, via the extrinsic pathway, and includes tests with a heparin neutralizer. The QPlus Cartridge is indicated for use in cardiovascular or major orthopedic surgeries before, during, and following the procedure.
The QStat Cartridge is a multi-channel cartridge that provides semi-quantitative indications of the coagulation and clot lysis state of a 3.2% citrated venous whole blood sample. The QStat Cartridge includes tests to assess coagulation characteristics via the intrinsic pathway, via the extrinsic pathway, and includes a test with tranexamic acid to evaluate clot lysis characteristics. The QStat Cartridge is indicated for use in trauma and liver transplantation procedures.
The Quantra System is indicated for the evaluation of blood coagulation in perioperative patients age 18 years and older to assess possible hypocoagulable and hypercoagulable conditions. Results obtained with the Quantra System should not be the sole basis for patient diagnosis.
The Quantra® System is composed of the Quantra Hemostasis Analyzer, QPlus Cartridge, and Quantra Quality Controls Level 1 and 2. The Quantra Hemostasis Analyzer uses Sonic Estimation of Elasticity via Resonance (SEER) Sonorheometry, an ultrasound-based technology, to measure the shear modulus of whole blood during coagulation. The system is intended to be used by trained professionals at the point-of-care and in clinical laboratories to evaluate the viscoelastic properties of whole blood. The QPlus Cartridge is a multi-channel cartridge that provides semi-quantitative indications of the coagulation state of a 3.2% citrated venous or arterial whole blood sample. The QPlus Cartridge includes tests to assess coagulation characteristics via the intrinsic pathway, via the extrinsic pathway, and includes tests with a heparin neutralizer. The QStat Cartridge is a multi-channel cartridge that provides semi-quantitative indications of the coagulation and clot lysis state of a 3.2% citrated venous whole blood sample. The QStat Cartridge includes tests to assess coagulation characteristics via the intrinsic pathway, via the extrinsic pathway, and includes a test with tranexamic acid to evaluate clot lysis characteristics.
The provided text is a 510(k) summary for a software modification to the Quantra Hemostasis Analyzer. The primary change is extending the QPlus Cartridge maximum assay time for reporting clot stiffness results from 15 minutes to 25 minutes.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly present a formal "Acceptance Criteria" table with specific quantitative thresholds. Instead, the "J. CLINICAL AND NON-CLINICAL STUDIES" section describes the studies conducted and their outcomes, which implicitly serve as the demonstration that the device performs acceptably for the modified function.
| Study Type | Implicit/Explicit Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Interfering Substance Testing | No specific quantitative acceptance criteria mentioned, but the goal was to evaluate "Not Computable" results. | "As previously observed, rivaroxaban and dabigatran demonstrated a dose response effect of clot time parameter prolongation (starting at 100 ng/mL and at all levels tested, ≥ 25 ng/mL, respectively) and clot stiffness parameter reduction (starting at 200 and 100 ng/mL respectively)." This confirms the device's behavior in the presence of these anticoagulants within the extended time frame. |
| Precision Testing: Whole Blood Repeatability Study | Demonstration of acceptable precision (imprecision). | "Total imprecision, including variability between operators, cartridge lots, instruments, and test replicates ranged from 5.8% to 14.4% CV." This indicates that the repeatability of the device, even with the extended assay time, is within an acceptable range for a diagnostic test. |
| Clinical Performance Testing | Strong correlation with a predicate device (ROTEM delta) for comparative measurements (r > 0.8). | "Linear regression summary results for all comparisons showed r > 0.8 (0.82 to 0.94) for the correlation analysis, demonstrating a strong correlation of QPlus parameters to corresponding ROTEM delta parameters." This confirms the device's accuracy and consistency with an established method, even with the extended assay time. |
2. Sample Size Used for the Test Set and Data Provenance:
- Interfering Substance Testing: "similar protocols, acceptance criteria, and sample sizes were utilized" as a previous submission (DEN180017). The exact sample size for this specific study is not explicitly stated in the provided text.
- Precision Testing (Whole Blood Repeatability): The exact sample size is not explicitly stated. It mentions "contrived whole blood requiring an assay time within the extended maximum assay time."
- Clinical Performance Testing: "Clinical samples were collected from adult cardiac surgery patients undergoing treatment in the intensive care unit at a single medical center." The exact number of samples is not explicitly stated. The data provenance is prospective (samples collected for the study) and from a single medical center (country implied to be USA, given FDA submission).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- The document describes a comparative study against a predicate device (ROTEM delta) and evaluations of precision and interference. It does not rely on expert consensus for "ground truth" derived from image interpretation (as would be common for AI/ML in radiology).
- For the clinical performance testing, ground truth is established by the independent measurement from the ROTEM delta, a cleared predicate device.
4. Adjudication Method for the Test Set:
- Since the ground truth is established by comparison to an existing analytical instrument (ROTEM delta) and precision/interference testing, no expert adjudication method (like 2+1 or 3+1 for imaging) is described or relevant for this type of in vitro diagnostic device's performance evaluation.
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?
- No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) measurement system, not an AI-assisted diagnostic imaging interpretation tool. Therefore, the concept of "human readers improving with AI assistance" is not applicable here.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- The performance studies described (interference, precision, clinical correlation) evaluate the device's performance as a standalone system in generating the measurements (clot time, clot stiffness, etc.). The device itself is an automated system providing quantitative results. Human intervention is primarily in sample collection, loading, and interpreting the output, but the measurement itself is automated by the device's algorithm.
7. The Type of Ground Truth Used:
- Analytical/Instrumental Ground Truth:
- For Interfering Substance Testing: The ground truth is the known concentration of the interfering substance and the expected effect on coagulation parameters.
- For Precision Testing: The ground truth is the consistency/repeatability of the device's own measurements across repeated tests, aiming for low variability.
- For Clinical Performance Testing: The ground truth is derived from the measurements obtained by the ROTEM delta, which is a widely accepted and cleared predicate device for viscoelastic properties of blood. This is a comparative ground truth against an established method.
8. The Sample Size for the Training Set:
- This is a software modification (extended assay time) for an in vitro diagnostic device. The document does not mention any specific training set in the context of machine learning or AI models. The device's underlying technology (SEER Sonorheometry) is based on physical principles, not on learned patterns from a large training dataset in the way a deep learning algorithm would be. The "training" for this type of device would typically involve calibration and validation during development, but not an "AI training set" as commonly understood.
9. How the Ground Truth for the Training Set Was Established:
- As no AI/ML "training set" is described, this question is not applicable in the context of the provided document. The device's measurements are based on established scientific principles and comparison to a predicate device, rather than a machine learning model that requires a ground-truthed training set.
§ 864.5430 Coagulation system for the measurement of whole blood viscoelastic properties in perioperative patients.
(a)
Identification. A coagulation system for the measurement of whole blood viscoelastic properties in perioperative patients is an in vitro diagnostic device used to evaluate blood coagulation, fibrinolysis, or both, in perioperative patients, as an aid in the assessment of coagulopathies when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include detailed documentation of, and results from, the following:
(i) A study assessing precision using protocols determined to be acceptable by FDA, to cover the measurement range for each reported parameter (test output). Testing must include native specimens with coagulation profiles representative of the intended use population. In order to cover the measuring range, testing may include a limited number of contrived specimens, not to exceed 10 to 20 percent, or as otherwise deemed appropriate by FDA. The contrived specimens must be prepared to resemble clinical specimens. This testing must evaluate repeatability and reproducibility and provide assessments of within-run, within-day, between-run, between-day, between-reagent lot, between-instrument, between-site, and between-operator precision, as applicable to the system;
(ii) Studies that demonstrate the performance of each parameter (test output) throughout the claimed measurement range, to include linearity studies or dose-response studies, as applicable to the parameter (test output);
(iii) Potential interferent study that includes evaluation of hemolyzed and lipemic samples as potential interferents; exogenous and endogenous interferents associated with each patient population intended for use with the device, and which might be expected to affect assay performance, must be evaluated; and potential interferents that are specific for, or related to, the technology or methodology of the device. Evaluation of all potential interferents must be performed using a protocol determined to be acceptable to the FDA (
e.g., an FDA-recognized standard) and include both normal and abnormal specimens covering coagulation profiles representative of the intended use population;(iv) A study that evaluates specimen stability under the intended conditions for specimen collection, handling, and storage, using samples that cover the coagulation profiles representative of the intended use population, and using protocols determined to be acceptable by FDA;
(v) A multisite clinical study, determined to be acceptable by FDA, demonstrating performance, relative to clinically relevant and clinically validated laboratory test(s) for each parameter (test output). Further, the study must meet all of the following criteria:
(A) The study must be performed in the intended use population and include representation from all patient populations for whom the device is intended to be used. Potential endogenous and exogenous interferents for each target patient population must be evaluated or known prior to the study;
(B) The study must be conducted at a minimum of three external sites representative of the intended use setting by the intended operators;
(C) Test samples must be collected at time intervals relevant to the device's use in the intended use population;
(D) Clinical specimens, which cover coagulation profiles representative of the intended use population, must be evaluated at each of the three clinical sites in the study;
(E) Analysis of the concordance of clinical interpretation of patient coagulation status made from individual test parameter (test output) results as compared to clinical interpretation of coagulation status from a clinically relevant laboratory test or tests (
e.g., a comparative viscoelastic device or standard laboratory tests) must be conducted; and(F) Expected (reference) values for each parameter (test output) must be demonstrated by testing a statistically appropriate number of samples from apparently healthy normal individuals;
(vi) For a device with a user interface that has information that needs to be interpreted by the user in correctly using the device to achieve the intended test results or a device that does not provide a final output that is a comprehensive interpretation of all parameter (test output) results, a study evaluating the ability of device users to correctly interpret results;
(vii) For any device indicated to guide blood product use, a clinical outcome study determined to be acceptable by FDA that specifically validates the device's indicated use in guiding blood product use; and
(viii) For any device indicated to guide use of medication, a clinical outcome study determined to be acceptable by FDA that specifically validates the device's indicated use in guiding use of medication.
(2) The labeling required under § 809.10(b) of this chapter must include the following:
(i) A summary of results from the study required by paragraph (b)(1)(i) of this section, including repeatability, reproducibility, and assessments of within-run, within-day, between-run, between-day, between-reagent lot, between-instrument, between-site, and between-operator precision, as applicable to the system.
(ii) The claimed measurement range of each parameter (test output), as supported by demonstrated performance of the parameter (test output) throughout the claimed measurement range, including studies required by paragraphs (b)(1)(i) through (iii) and (v) of this section, and, if applicable, paragraphs (b)(1)(vii) and (viii) of this section.
(iii) Identification of known interferents, including all endogenous, exogenous, technology-specific, and patient population-specific interferents, specific to each parameter (test output). The information must include the concentration(s) or level(s) at which interference was found to occur and the concentration range or levels at which interference was not found to occur.
(iv) Information regarding the multisite clinical study required by paragraph (b)(1)(v) of this section, including:
(A) Each patient population evaluated;
(B) Each intended use setting and the operators;
(C) A summary of the results, including the concordance analysis to clinically relevant laboratory test(s); and
(D) Demonstrated expected (reference) values for each parameter (test output).
(3) The labeling required under § 809.10 of this chapter must include the following:
(i) A limiting statement that the result(s) from the device is(are) not intended to be used as the sole basis for a patient diagnosis.
(ii) Unless appropriate clinical outcome studies are done in accordance with paragraph (b)(1)(vii) of this section that specifically validate an indication for the device's use in guiding blood product use, a limiting statement that the device has not been evaluated to guide blood product use.
(iii) Unless appropriate clinical outcome studies are done in accordance with paragraph (b)(1)(viii) of this section that specifically validate an indication for the device's use in guiding use of medication, a limiting statement that the device has not been evaluated to guide use of medication.