(135 days)
The ABS, Inc. TpP™ EIA is an enzyme linked immunoassay for the quantitative determination of soluble fibrin polymers in human plasma. It is indicated as an aid in assessing the risk of intravascular thrombosis and monitoring the efficacy of anticoagulant (heparin) therapy.
The TpP™ EIA employs a murine monoclonal antibody (MAb), specific for soluble fibrin polymer, as a capture antibody immobilized on a microtiter plate (MTP). This MAb recognizes a conformational epitope present only on the TpP™ entities but which is absent from fibrinogen and degradation products of fibrin and fibrinogen. During the first incubation phase TpP™ in human plasma specimens bind to the capture antibody. Afterwards the plate is rinsed, and a conjugate, another murine monoclonal antibody, labeled with horseradish peroxidase (HRP) is added to the well. This peroxidase conjugated MAb binds to a separate site on the TpP™ molecule during a second incubation period. Excess enzyme conjugated MAb is washed out and a subsequent application and incubation with tetramethylbenzidine (TMB) substrate follows. The reaction after TMB incubation is terminated with dilute sulfuric acid. The level of the TpP™ present in the specimen sample is determined colorimetrically from the enzymatic activity of detection MAb conjugate. The intensity of the color is proportional to the concentration of TpP™. Calibrator standard is provided with the kit.
Here's a breakdown of the acceptance criteria and study information for the ABS, Inc. TpP™ EIA, extracted and organized as requested:
Acceptance Criteria and Device Performance
| Acceptance Criteria Category | Specific Criteria/Metric | Reported Device Performance |
|---|---|---|
| Linear Reportable Range | Not explicitly stated as an acceptance criterion, but a performance metric. | 0 to 40 µg/mL |
| Minimum Detectable Level | Not explicitly stated as an acceptance criterion, but a performance metric. | 0.177 µg/mL |
| Interference | No significant interference from common substances (Hemoglobin, Bilirubin, Triglycerides, Urokinase). | No significant interference observed with tested substances at specified concentrations. |
| Precision | Not explicitly stated as acceptance criteria, but performance metrics. | Sample A (23.64 µg/mL): |
- Within-Run CV: 1.50%
- Total Precision CV: 10.15%
Sample B (7.91 µg/mL): - Within-Run CV: 3.70%
- Total Precision CV: 10.80% |
| Normal Range/Cutoff | Establishment of an effective cutoff value for risk assessment. | Best estimate cutoff: 6.65 µg/mL (determined by percentile evaluation) |
| Correlation with F1.2 | Positive correlation with F1.2 following surgery. | Positive correlation of 0.58 (p=0.008) observed immediately following surgery. TpP™ levels remained elevated longer than F1.2. |
| Monitoring Anticoagulant Efficacy | Ability to distinguish patients with inadequate anticoagulant therapy. | In 4 out of 25 PTCA patients with thrombotic complications, TpP™ values never returned to normal after heparinization. |
| Substantial Equivalence | Substantially equivalent to Organon Teknika Corporation's immunochemical assay Thrombonostika F1.26 (K9911434). | Data and information demonstrate substantial equivalence to Thrombonostika F1.26. |
Study Details
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Sample sizes used for the test set and the data provenance:
- Normal Range Determination:
- Total Subjects: 140
- Site #1: 115 healthy volunteers (Country of origin not specified, but the submission is from an American company, suggesting US)
- Site #2: 8 healthy volunteers and 17 outpatients (Country of origin not specified, but the submission is from an American company, suggesting US)
- Provenance: Retrospective/Cross-sectional for establishing normal range.
- Clinical Study (Aortic Aneurysm):
- Total Patients: 90
- Location: Johns Hopkins Medical School, Baltimore, MD (USA)
- Provenance: Prospective (patients recruited "who were undergoing procedures to repair aortic aneurysm").
- Clinical Study (PTCA):
- Total Patients: 25
- Location: Philadelphia Heart Institute (USA)
- Provenance: Prospective (patients "administered systemic heparin").
- Interference Testing: Not specified as a patient population, but involved normal plasma samples, likely from the US.
- Precision Testing: Two samples (A & B) tested with replicates across multiple runs, likely laboratory-prepared or pooled human plasma from the US.
- Normal Range Determination:
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not specify the number or qualifications of experts used to establish the ground truth for the test sets.
- For the normal range, the "best estimate of an effective cutoff value was determined to be 6.65 µg/mL by employing a percentile evaluation," implying a statistical method rather than individual expert consensus on specific cases.
- For the clinical studies, ground truth for patient outcomes (e.g., thrombotic complications, post-surgical recovery, hypercoagulable state) would have been established by attending physicians/medical staff based on clinical presentation and other diagnostic tests, but no specific "experts" for ground truth adjudication are mentioned in the context of this device's evaluation.
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Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- No adjudication method (e.g., 2+1, 3+1) is mentioned or described for establishing ground truth for any of the test sets. Clinical outcomes likely served as the de facto "ground truth" for the efficacy studies.
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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:
- No MRMC comparative effectiveness study was conducted or mentioned. This device is an in-vitro diagnostic (IVD) assay, not an AI-assisted diagnostic imaging or interpretation tool that would involve human "readers."
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this is an IVD assay, which by nature operates in a standalone mode, providing a quantitative result without direct "human-in-the-loop" interpretation for each specific test result beyond the clinical application of the measured value (e.g., a physician interpreting the 6.65 µg/mL cutoff). The performance metrics (linearity, precision, interference, correlation) represent the standalone performance of the assay.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- Normal Range: Statistical percentile evaluation of healthy individuals.
- Aortic Aneurysm Study: Clinical outcomes (post-surgical changes, correlation with F1.2 levels, which is a recognized marker for fibrin formation).
- PTCA Study: Clinical outcomes (occurrence of "serious thrombotic complications" and assessment of anticoagulant therapy efficacy based on these complications).
- Interference, Linearity, Precision: Laboratory-derived ground truth based on spiking known concentrations/substances and standard reference methods.
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The sample size for the training set:
- Training Set (for Normal Range/Cutoff): 140 subjects (115 healthy volunteers, 8 healthy volunteers, 17 outpatients) were used for determining the effective cutoff value of 6.65 µg/mL. This can be considered the dataset used to "train" or establish the normal operating parameters and cutoff for the assay.
- For the correlation and efficacy studies, these were essentially "validation" sets for the established operational characteristics.
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How the ground truth for the training set was established:
- For the normal range/cutoff determination, the ground truth was established by:
- Identifying subjects as "healthy volunteers" or "outpatients" (implying a clinical assessment of their health status).
- Performing the TpP™ EIA on their plasma samples.
- Employing a "percentile evaluation" method to determine the statistical distribution of TpP™ levels in these populations and derive the "best estimate of an effective cutoff value" (6.65 µg/mL). This is a statistical, rather than case-by-case, ground truth establishment.
- For the normal range/cutoff determination, the ground truth was established by:
§ 864.7320 Fibrinogen/fibrin degradation products assay.
(a)
Identification. A fibrinogen/fibrin degradation products assay is a device used to detect and measure fibrinogen degradation products and fibrin degradation products (protein fragments produced by the enzymatic action of plasmin on fibrinogen and fibrin) as an aid in detecting the presence and degree of intravascular coagulation and fibrinolysis (the dissolution of the fibrin in a blood clot) and in monitoring therapy for disseminated intravascular coagulation (nonlocalized clotting in the blood vessels).(b)
Classification. Class II (performance standards).