(45 days)
IMMULITE 2000 Folic Acid is for in vitro diagnostic use with the IMMULITE 2000 Analyzer – for the quantitative measurement of folic acid in serum, heparinized plasma or ascorbic acid-treated whole blood, as an aid in clinical diagnosis and treatment of anemia.
IMMULITE® 2000 Folic Acid is a clinical device for use with the IMMULITE® 2000 Automated Immunoassay Analyzer. IMMULITE 2000 Folic Acid is a chemiluminescent immunoassay. The assay begins with a 2-cycle, on-board sample treatment of patient serum, plasma or ascorbic acid-treated whole blood. The sample, along with ligand-labeled folic acid, is first treated with dithiothreitol (DTT), in a reaction tube containing no bead, and then with sodium hydroxide/potassium cyanide (NaOH/KCN), in a second treatment cycle. The treated sample is transferred to a second reaction tube containing a murine anti-folate binding protein antibody-coated polystyrene bead and folate binding protein (FBP). During a 30-minute incubation, folic acid released from binding proteins in the patient sample competes with ligand-labeled folic acid for binding with FBP. The bead is washed and alkaline phosphatase labeled anti-ligand is added. During the final 30-minute incubation, the alkaline phosphatase anti-ligand binds to the ligand-labeled folate that was bound to the bead during the first incubation. The unbound enzyme conjugate is removed by centrifugal wash. Substrate is then added. The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, is then added and the test unit is incubated for a further 10 minutes. The chemiluminescent substrate undergoes hydrolysis in the presence of alkaline phosphatase to yield an unstable intermediate. Production of this intermediate results in a sustained emission of light. The bound complex - and thus also the photon output - is inversely proportional to the concentration of folic acid in the sample.
Here's an analysis of the provided text, focusing on acceptance criteria and the study that demonstrates the device meets them:
Acceptance Criteria and Device Performance
The provided document describes a 510(k) submission for the IMMULITE® 2000 Folic Acid device. The study performed is a method comparison against a legally marketed predicate device (DPC's IMMULITE® Folic Acid). In such a comparison, the acceptance criteria are generally established to demonstrate substantial equivalence, meaning the new device performs similarly enough to the predicate that it can be considered safe and effective for its intended use.
While explicit "acceptance criteria" are not listed as numerical thresholds in this summary, the reported device performance in the method comparison study provides the evidence for acceptance. The primary metric for showing equivalence in this context is the linear regression analysis and the correlation coefficient (r). A high correlation coefficient (close to 1) indicates that the two methods produce very similar results across the range of concentrations tested.
Here's a table summarizing the implicit acceptance criteria based on standard practice for method comparisons and the reported performance:
| Acceptance Criterion (Implicit for Method Comparison) | Reported Device Performance (IMMULITE® 2000 vs. IMMULITE® Predicate) |
|---|---|
| High correlation (r-value close to 1) indicating strong agreement between methods. | Serum: r = 0.996 |
| Hemolysates: r = 0.981 | |
| Slope of linear regression close to 1 indicating similar relative measurement between methods. | Serum: Slope = 0.96 |
| Hemolysates: Slope = 1.18 | |
| Y-intercept of linear regression close to 0 indicating similar absolute measurement between methods (minimal bias). | Serum: Y-intercept = -0.54 ng/mL |
| Hemolysates: Y-intercept = -29 ng/mL | |
| Similar mean values between the two methods over the tested concentration range. | Serum: |
| IMMULITE® 2000 Mean: 8.3 ng/mL | |
| IMMULITE® Predicate Mean: 9.2 ng/mL | |
| Hemolysates: | |
| IMMULITE® 2000 Mean: 128 ng/mL | |
| IMMULITE® Predicate Mean: 134 ng/mL | |
| Concentration range of samples tested adequately covers the clinically relevant range. | Serum: 1.8 to 20 ng/mL |
| Hemolysates: 46 to 260 ng/mL |
The "Conclusion" section explicitly states: "The data presented in this summary of safety and effectiveness is the data the Food and Drug Administration used in granting DPC substantial equivalence for IMMULITE® 2000 Folic Acid." This confirms that the reported performance met the FDA's implicit acceptance criteria for substantial equivalence.
Study Details
Here's a breakdown of the specific information requested about the study:
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A table of acceptance criteria and the reported device performance: (Provided above)
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Sample size used for the test set and the data provenance:
- Serum test set: 156 samples
- Hemolysates test set: 49 samples
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. However, given it's a regulatory submission for a clinical diagnostic device, it is typically expected that the data would be from a relevant clinical population and likely collected prospectively or from a well-characterized retrospective bank. The submission date (Oct 26, 1999) suggests it would be from that era's standard clinical testing.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is not applicable as the "ground truth" for this type of device (quantitative immunoassay) is not established by human experts in the same way as, for example, image interpretation. The ground truth is the measurement provided by the predicate device, which is presumed to be accurate and reliable.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable. Adjudication methods are typically used in studies involving subjective interpretation (e.g., radiology reads) where multiple experts might disagree. In this case, the reference method (predicate device) provides the "reference standard."
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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, an MRMC comparative effectiveness study was not done. This study is a technical method comparison between two automated immunoassay devices, not an assessment of human reader performance, with or without AI assistance.
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, this was a standalone study of the IMMULITE® 2000 Folic Acid analyzer. The device performs the quantitative measurement of folic acid in patient samples without direct human intervention in the measurement process itself, beyond sample loading and results interpretation. The study evaluates the algorithm's (device's) performance against a predicate device.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The "ground truth" or reference standard for this method comparison study was the measurements obtained from the legally marketed predicate device, DPC's IMMULITE® Folic Acid.
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The sample size for the training set:
- The document does not explicitly mention a "training set" in the context of machine learning or AI. For a traditional immunoassay device, the development process would involve internal validation and optimization, but not typically a "training set" as understood in current AI contexts. The sample sizes mentioned (156 serum, 49 hemolysates) are for the pivotal performance evaluation (test set) against the predicate.
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How the ground truth for the training set was established:
- Not applicable, as a "training set" in the AI sense is not described. The device's underlying principles are based on established immunoassay chemistry and detection, with the predicate device serving as the reference for performance validation.
§ 862.1295 Folic acid test system.
(a)
Identification. A folic acid test system is a device intended to measure the vitamin folic acid in plasma and serum. Folic acid measurements are used in the diagnosis and treatment of megaloblastic anemia, which is characterized by the presence of megaloblasts (an abnormal red blood cell series) in the bone marrow.(b)
Classification. Class II.