(105 days)
The diaDexus PLAC™ test is an enzyme immunoassay for the quantitative determination of Lp-PLA2 (lipoprotein-associated phospholipase A2) in human plasma, to be used in conjunction with clinical evaluation and patient risk assessment as an aid in predicting risk for coronary heart disease, and ischemic stroke associated with atherosclerosis.
The diaDexus PLAC™ test kit contains Lp-PLA2 calibrators, monoclonal anti-Lp-PLA2 (4B4) antibody conjugated to horseradish peroxidase, monoclonal anti-Lp-PLA2 (2C10) antibodycoated microwell strips with a stripwell frame, various buffers and related reagents, and a package insert. Each stripwell can be used for performing only one set of tests (i.e. single use). One plate may accommodate up to 40 clinical samples when assayed in duplicate. The kit expiration date and storage conditions are indicated on the package.
The diaDexus PLAC™ test is based on the standard principle of a sandwich enzyme immunoassay using two specific monoclonal antibodies. A set of Lp-PLA2 calibrators is used to plot a standard curve of absorbance (y-axis) versus Lp-PLA2 concentration in ng/mL (x-axis) from which the Lp-PLA2 concentration in the test sample can be determined. The concentration of Lp-PLA2 in each sample and control is then interpolated from the standard curve using a point-to-point curve fit with appropriate calibration curve fitting software.
Here's a breakdown of the acceptance criteria and the study details for the diaDexus PLAC™ Test, based on the provided text:
Acceptance Criteria and Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Analytical Sensitivity (Detection Limit) | 1.3 ng/mL |
| Linearity/Assay Range | 90 – 897 ng/mL |
| Intra-assay Precision (n=80) | 4.3 %CV (throughout assay range) |
| Inter-assay Precision (n=20) | 6.3 %CV to 8.7 %CV (throughout assay range) |
| Interfering Substances | No appreciable interference from: |
- Hemoglobin (500 mg/dL)
- Triglycerides (3,000 mg/dL)
- Cholesterol (500 mg/dL)
- Bilirubin (20 mg/dL)
- Albumin (6.2 g/dL)
- Aspirin (50 mg/dL)
- Tylenol® (20 mg/dL)
- Vitamin C (50 mg/dL)
- Benadryl® (50 mg/dL)
- Orinase (100 mg/dL)
- Pravachol® (446 µg/dL) |
Study Information
2. Sample Size Used for the Test Set and Data Provenance:
- Test Set Sample Size: 956 banked EDTA-plasma samples.
- 194 cases (subsequently suffered an ischemic stroke)
- 762 controls (stroke-free at time of censor)
- Data Provenance:
- Country of Origin: United States.
- Type: Retrospective (banked samples from a large, multi-center, observational epidemiology study sponsored by the National Institutes of Health's National Heart, Lung, and Blood Institute - the ARIC study).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:
- The document states that "stroke... was defined by the ARIC investigators." It does not specify the number of experts or their specific qualifications beyond "qualified experts" generally overseeing the study.
4. Adjudication Method for the Test Set:
- The document does not specify a formal adjudication method (e.g., 2+1, 3+1). The ground truth for stroke events was "defined by the ARIC investigators," implying established diagnostic criteria within that study.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:
- No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not performed. This study focuses on the standalone performance of the diagnostic test (Lp-PLA2 levels) as a predictor.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
- Yes, a standalone performance study was done. The clinical study evaluated the association of Lp-PLA2 levels (measured by the test) with the risk of ischemic stroke, independently of human interpretation of the test results for individual patient diagnosis. The test itself is an enzyme immunoassay, providing a quantitative value.
7. The Type of Ground Truth Used:
- Outcomes Data: The ground truth was based on documented clinical outcomes: whether participants subsequently suffered an ischemic stroke as defined by the ARIC investigators.
8. The Sample Size for the Training Set:
- The document does not specify a separate training set size for the clinical study. The 956 samples appear to be the "test set" used to evaluate the association between Lp-PLA2 levels and stroke outcomes. For the analytical characterization, various sample sizes (e.g., n=80 for intra-assay precision, n=20 for inter-assay precision) were used for establishing performance characteristics like precision, linearity, and sensitivity, but these are for analytical validation rather than a "training set" in the machine learning sense.
9. How the Ground Truth for the Training Set Was Established:
- As a distinct "training set" is not explicitly mentioned for the clinical validation of the predictive capability in the context of the provided text, information on how its ground truth was established is not available. The "ground truth" for the main clinical study (which could be considered a "test set" for the prediction model) was established by the ARIC investigators' definition of ischemic stroke as an outcome.
§ 866.5600 Low-density lipoprotein immunological test system.
(a)
Identification. A low-density lipoprotein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein in serum may aid in the diagnosis of disorders of lipid (fat) metabolism and help to identify young persons at risk from cardiovascular diseases.(b)
Classification. Class II (performance standards).