(230 days)
The DiaSorin LIAISON® Folate assay uses chemiluminescent immunoassay (CLIA) technology for the quantitative determination of Folic acid in human serum. Folic acid measurements are used in the diagnosis and treatment of anemias. Assay results should be used in conjunction with other clinical or laboratory data to assist the clinician in making individual patient management decisions.
The assay must be performed on the LIAISON® XL Analyzer.
The LIAISON® Folate assay is a competitive chemiluminescence immunoassay (CLIA) for quantitative determination of Folic acid in serum. During the first incubation, Folic acid is dissociated from its binding protein. After five (5) minutes, a high pH buffer is added to prevent re-association to the binding protein. After five (5) minutes, Folic acid binds to a Folate Binding Protein on the solid phase, which competes with a Folic acid linked to an isoluminol derivative. After a third incubation, the unbound material is removed with a wash cycle. Subsequently, the starter reagents are added to initiate a flash chemiluminescent reaction. The light signal is measured by a photomultiplier as relative light units (RLU) and is inversely proportional to the concentration of Folic acid present in calibrators, controls, or samples.
Here's an analysis of the acceptance criteria and study that proves the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" for each performance characteristic in a pass/fail format. Instead, it presents study results which implicitly demonstrate the device's acceptable performance. For clarity, I've inferred common acceptance standards for such in vitro diagnostic assays where explicit criteria aren't given and formatted the reported performance against these.
| Performance Characteristic | Acceptance Criteria (Inferred for IVDs) | Reported Device Performance |
|---|---|---|
| Method Comparison | Good agreement with a legally marketed predicate device (e.g., R-value > 0.9, acceptable bias at medical decision levels). | Passing & Bablok regression: LIAISON® Folate = (y = 0.96x - 0.61); R = 0.948. |
| Bias at 4.41 ng/mL medical decision level: -0.772 ng/mL (95% CI: -1.550 to -0.130 ng/mL). | ||
| Interpretation: The R-value of 0.948 indicates strong correlation with the predicate. The bias at a medical decision level is quantified. | ||
| Precision | Low within-run, run-to-run, day-to-day, and total variability (low %CV). | Combined Lots (Reproducibility): %CVs range from 4.3% to 7.0%. |
| Single Lot (Total Within-Lot): %CVs range from 4.6% to 7.6%. | ||
| Interpretation: All reported %CVs are within generally accepted limits for quantitative immunoassays, indicating good precision. | ||
| Linearity | The device should demonstrate linearity across its stated measuring range with a strong correlation (R-value close to 1). | Regression equation: Observed Folate = 1.011 (Expected) - 0.147; R = 0.999. |
| Interpretation: An R-value of 0.999 demonstrates excellent linearity across the tested range (up to 20 ng/mL). | ||
| Recovery | %Recovery typically within 90-110% (or similar range) of the expected value. | % Recovery: Values ranged from 97.6% to 110.4% across 7 diluted samples. |
| Interpretation: All recovery values fall within the generally accepted 90-110% range, indicating accurate recovery after dilution. | ||
| Analytical Specificity (Cross-Reactivity) | Minimal or no significant cross-reactivity with structurally similar compounds or metabolites. | Aminopterin: 0.488% |
| Phenytoin: 0.000% | ||
| Methotrexate: 0.781% | ||
| Folinic Acid: 1.730% | ||
| Interpretation: Low percentages of cross-reactivity indicate good specificity. | ||
| Analytical Specificity (Interfering Substances) | No significant interference from common endogenous or exogenous substances at tested concentrations. | No interference observed for all listed substances (Hemoglobin, Bilirubin, Triglycerides, Cholesterol, Albumin, IgG, HAMA, Rheumatoid Factor, various drugs) at the respective tested concentrations. |
| Interpretation: The device is robust against common interferents. | ||
| Limit of Blank (LoB) | Very low, representing the highest concentration likely to be observed in a blank sample. | ≤1.2 ng/mL |
| Interpretation: A low LoB indicates effective distinction from zero analyte. | ||
| Limit of Detection (LoD) | The lowest concentration that can be reliably detected. | 1.4 ng/mL |
| Interpretation: Satisfactory detection capability for the intended use. | ||
| Limit of Quantitation (LoQ) | The lowest concentration at which analyte can be accurately quantified with acceptable precision and accuracy. | 1.6 ng/mL |
| Interpretation: The assay can reliably quantify Folate at concentrations starting from 1.6 ng/mL. | ||
| Stability (Reagent Cartridge) | Maintains performance over the claimed storage period. | Open vial: 6 weeks at 2-8°C |
| Interpretation: The device maintains performance for the stated duration. | ||
| Stability (Calibration Curve) | Maintains accuracy over the claimed period. | Calibration curve: 21 days |
| Interpretation: Calibration is stable for 21 days, suitable for routine use. | ||
| Traceability | Traceable to an internationally recognized standard. | Traceable to the WHO IS 03/178 (pg/mL). |
| Interpretation: Ensures accuracy and comparability of results with other standardized methods. |
2. Sample Size Used for the Test Set and Data Provenance:
- Test Set (Method Comparison): 157 human serum samples, spanning the assay range.
- Test Set (Expected Values/Reference Range): 166 prospectively collected serum samples from apparently healthy U.S. adults (21-59 years old) of mixed ethnic backgrounds (30% Caucasian, 32% African American, 38% Hispanic).
- Data Provenance: The method comparison study and the expected value study used human serum samples. The expected values study explicitly mentions "United States" for its population, implying the data is from the US and prospectively collected. The nature of the other analytical performance studies (precision, linearity, recovery, etc.) generally involves contrived or spiked samples and do not typically draw from specific patient populations or geographical locations.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:
- General Context: For an in vitro diagnostic (IVD) device like the LIAISON® Folate assay, the "ground truth" for the test set is established by the predicate device (Abbott Laboratories, ARCHITECT Folate, K092740) for method comparison, or by the inherent concentration of the analyte in the samples for analytical performance characteristics (like precision, linearity, etc.).
- No human "experts" established ground truth for the test set in the way radiologists might agree on an image diagnosis. Instead, the predicate device (an established, cleared medical device) serves as the reference standard for comparative effectiveness.
4. Adjudication Method for the Test Set:
- This is not applicable to the analytical performance studies of an in vitro diagnostic assay. Adjudication methods (like 2+1, 3+1) are typically used in clinical studies, particularly for diagnostic imaging or pathology, where human interpretation of results is involved and consensus among experts is needed to define the "true" diagnosis or finding for a given sample/case. Here, the comparison is against an instrument's measurement (predicate device) or against known concentrations.
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:
- This question is not applicable to this type of device. The LIAISON® Folate assay is an automated in vitro diagnostic device, not an AI-assisted diagnostic tool that humans interpret. There are no "human readers" involved in interpreting the results from this specific device.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, this entire submission describes the standalone performance of the LIAISON® Folate assay. It is an automated chemiluminescent immunoassay (CLIA) system (LIAISON® XL Analyzer) that quantitatively determines Folic acid in human serum. Its performance characteristics (precision, linearity, accuracy, etc.) are evaluated intrinsically as a standalone device, without human intervention in the result determination process once the sample is loaded.
7. The Type of Ground Truth Used:
- Method Comparison: The "ground truth" was established by measurements from the predicate device, the Abbott Laboratories, ARCHITECT Folate (K092740).
- Other Analytical Performance (e.g., Precision, Linearity, Recovery, Specificity): The "ground truth" was established internally through various experimental designs:
- Precision: By repeated measurements of samples with known or target concentrations.
- Linearity: By testing serial dilutions from a high-concentration sample, where the "expected" concentration is mathematically derived from the initial concentration and dilution factor.
- Recovery: By comparing measured concentrations of diluted samples to their calculated expected concentrations.
- Analytical Specificity: By comparing results of samples spiked with potential interferents/cross-reactants to unspiked samples.
- Limits (LoB, LoD, LoQ): Through statistical analysis of repeated measurements of blank and low-level samples.
8. The Sample Size for the Training Set:
- For an IVD like the LIAISON® Folate assay, there isn't a "training set" in the context of machine learning. The technology is based on established biochemical principles (chemiluminescence immunoassay) and reagents, rather than an AI/ML algorithm that learns from data. Therefore, this question is not applicable.
9. How the Ground Truth for the Training Set Was Established:
- As mentioned above, there is no "training set" for this type of device. The design and validation are based on chemical and biological principles and rigorous experimental testing, not machine learning model training.
§ 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.