(122 days)
The LIAISON® 25 OH Vitamin D TOTAL Assay uses chemiluminescent immunoassay (CLIA) technology for the quantitative determination of 25-hydroxyvitamin D and other hydroxylated vitamin D metabolites in human serum to be used in the assessment of vitamin D sufficiency using the LIAISON® Analyzer family. Assay results should be used in conjunction with other clinical or laboratory data to assist the clinician in making individual patient management decisions in an adult population.
The LIAISON® 25 OH Vitamin D assay is a direct competitive chemiluminescence immunoassay (CLIA) for quantitative determination of total 25 OH vitamin D in serum. During the first incubation. 25 OH Vitamin D is dissociated from its binding protein and binds to the specific antibody on the solid phase. After 10 minutes the tracer, (vitamin D linked to an isoluminol derivative) is added. After a second10 minute 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 25 OH vitamin D present in calibrators, controls, or samples.
The provided document describes the DiaSorin LIAISON® 25 OH Vitamin D TOTAL Assay, a chemiluminescent immunoassay for the quantitative determination of 25-hydroxyvitamin D in human serum. This is an in vitro diagnostic (IVD) device, and the acceptance criteria and study detailed are for its analytical performance, not for clinical diagnostic accuracy in the way a device like an AI for image analysis would be evaluated. As such, concepts like "experts to establish ground truth," "adjudication methods," "MRMC comparative effectiveness," and "standalone AI performance" are not directly applicable to this IVD assay and its performance evaluation. Ground truth in this context refers to established reference methods or known concentrations.
Here's an analysis based on the provided text, adapted for an IVD device:
1. Table of Acceptance Criteria (Inferred) and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" as a table with predefined thresholds, but rather reports the performance characteristics observed in validation studies. The "acceptance criteria" are implied by what is considered acceptable performance for such an assay in the context of regulatory submission (e.g., meeting CLSI guidelines, demonstrating adequate precision, linearity, and minimal interference).
| Performance Metric | Inferred Acceptance Criteria (Typical for IVDD) | Reported Device Performance |
|---|---|---|
| Method Comparison (Correlation with Predicate) | High correlation coefficient (R > 0.9, ideally closer to 1), slope close to 1, intercept close to 0. | LIAISON® = 1.047 (RIA) + 2.41; R = 0.936 (against DiaSorin 25 OH Vitamin D RIA) |
| Reproducibility/Precision (Within-Run %CV) | Typically 0.99) | Observed = Expected 1.01x - 0.180; R = 0.995 |
| Functional Sensitivity | Defined by manufacturer based on clinical utility; typically where %CV exceeds 20%. | ≤4.0 ng/mL (defined as the concentration at which %CV exceeds 20%) |
| Interfering Substances (Change in Results) | Typically ≤10% change in results at specified concentrations. | Hemolyzed: ≤10% change up to 200 mg/dL hemoglobin |
| Lipemic: ≤10% change up to 589 mg/dL triglycerides | ||
| Icteric: ≤10% change up to 40 mg/dL conjugated bilirubin | ||
| Icteric: ≤10% change up to 40 mg/dL unconjugated bilirubin | ||
| Cholesterol: ≤10% change up to 301 mg/dL | ||
| Uric acid: ≤10% change up to 20 mg/dL | ||
| Total Protein: ≤10% change up to 12 g/dL |
2. Sample Sizes and Data Provenance for Test Set (Validation Studies)
- Method Comparison: 587 samples.
- Data Provenance: Samples were obtained from a clinical reference laboratory. The country of origin is not specified but given DiaSorin Inc.'s location in Minnesota, USA, and the FDA submission, it's likely primarily US data. It's retrospective (collected for testing).
- Reproducibility/Precision: A coded panel of 6 serum samples, plus 2 levels of kit controls. The exact number of replicates per sample/control at each site is not given, but it was a 20-day study.
- Data Provenance: Samples prepared by DiaSorin Inc. (likely US). The study was performed at DiaSorin Inc. and 2 external sites.
- Dilution Linearity: Two (2) serum pools.
- Data Provenance: Not explicitly stated, but likely laboratory-prepared serum pools.
- Functional Sensitivity: Samples prepared at nominal concentrations of 2.0 - 14.0 ng/mL.
- Data Provenance: Not explicitly stated, but likely laboratory-prepared samples.
- Interfering Substances: Specific substances at various concentrations.
- Data Provenance: Not explicitly stated, but likely laboratory-prepared samples or spiked samples.
3. Number of Experts and their Qualifications to Establish Ground Truth for the Test Set
This requirement is not applicable to this type of IVD device evaluation for analytical performance. The "ground truth" for analytical studies is established by:
- Using a well-established reference method (e.g., the predicate DiaSorin 25 OH Vitamin D RIA for method comparison).
- Using gravimetrically prepared or certified reference materials for precision, linearity, and functional sensitivity.
- Spiking experiments for interfering substances.
There are no human experts "adjudicating" diagnostic outputs in this context; it's a quantitative measurement device.
4. Adjudication Method for the Test Set
Not applicable. As described above, this is an analytical performance study, not a diagnostic accuracy study requiring adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No. This is an automated immunoassay, not an AI-assisted diagnostic imaging device that involves human reader interpretation. Therefore, MRMC studies and "human readers improve with AI vs without AI assistance" are not relevant.
6. If a Standalone (algorithm only without human-in-the-loop performance) was done
Yes, the entire performance evaluation presented is a standalone (algorithm only) performance assessment, as it describes the analytical characteristics of the LIAISON® 25 OH Vitamin D TOTAL Assay system itself, without human interpretation as part of the primary result generation process. The device provides a quantitative number.
7. The Type of Ground Truth Used
- Method Comparison: The DiaSorin 25 OH Vitamin D RIA (a previously cleared predicate device) served as the comparative "ground truth" or reference method.
- Reproducibility/Precision: The known concentrations of the prepared serum samples and controls served as the reference for evaluating precision.
- Dilution Linearity: The expected concentrations based on dilution of known pools served as the reference.
- Functional Sensitivity: The known nominal concentrations of prepared samples were used.
- Interfering Substances: The known concentrations of added interfering substances were used to test their impact on the assay results.
8. The Sample Size for the Training Set
This is not applicable in the typical sense for this device. The LIAISON® 25 OH Vitamin D TOTAL Assay is a chemiluminescent immunoassay, not a machine learning or AI algorithm that undergoes "training" on a dataset in the way an AI model would. Its "training" is in the form of R&D and optimization of the assay reagents and protocols to achieve desired analytical performance. There isn't a "training set" of patient data for an algorithm.
9. How the Ground Truth for the Training Set was Established
Not applicable for the same reasons as (8). The assay's performance is optimized through traditional wet-lab biochemistry and immunoassay development, not algorithm training data.
§ 862.1825 Vitamin D test system.
(a)
Identification. A vitamin D test system is a device intended for use in clinical laboratories for the quantitative determination of 25-hydroxyvitamin D (25-OH-D) and other hydroxylated metabolites of vitamin D in serum or plasma to be used in the assessment of vitamin D sufficiency.(b)
Classification. Class II (special controls). Vitamin D test systems must comply with the following special controls:(1) Labeling in conformance with 21 CFR 809.10 and
(2) Compliance with existing standards of the National Committee on Clinical Laboratory Standards.