(422 days)
The INCSTAR 25-Hydroxyvitamin D 1251 RIA Kit is intended for the quantitative measurement of 25-hydroxyvitamin D and other hydroxylated vitamin D metabolites in human serum or plasma to be used in the assessment of vitamin D sufficiency.
This assay requires serum or plasma samples to be extracted with acetonitrile to free vitamin D and its metabolites which are almost completely associated with binding proteins as well as remove lipids which would interfere with the assay. Calibrators (kit standards) containing known concentrations of 25hydroxycholecalciferol (25-OH Vitamin D3) in a human serum matrix are likewise extracted. The primary antibody (goat anti-25-OH vitamin D) selected for use in the assay demonstrates high affinity and equal cross-reactivity to both 25(OH)D2 and 25(OH)Da but very low cross-reactivity to non-hydroxylated vitamin D2 or D3 and 1.25(OH)2 D. The primary antiserum used in the assay does recognize several other dihvdroxylated metabolites of vitamin D; however, these metabolites are found in relatively low concentrations in the circulation and are believed to be of minor biological importance. During the assay reaction, samples compete with an 1251 labeled analog of 25-OH D3 for binding sites on the primary antiserum. Phase separation is accomplished using a donkey anti-goat, polyethylene glycol precipitating reagent. The amount of radioactivity contained in the resulting precipitate is inversely proportional to the concentration of 25-OH-D present in the sample.
The provided text describes the INCSTAR 25-Hydroxyvitamin D 125I RIA Kit, a device intended for the quantitative measurement of 25-hydroxyvitamin D and other hydroxylated vitamin D metabolites in human serum or plasma.
Here's an analysis of the acceptance criteria and study information provided:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the comparison to established methods (HPLC and CPBA) and the achievement of strong correlation coefficients. While explicit numerical thresholds for acceptance are not stated as "acceptance criteria," the reported performance demonstrates "substantial equivalence" to these methods.
| Acceptance Criterion (Implied) | Reported Device Performance |
|---|---|
| Agreement with HPLC methods | Study 1 (n=72): INCSTAR = 0.954 (HPLC) + 1.327; correlation coefficient = 0.993 |
| Agreement with CPBA methods | Study 1 (n=72): INCSTAR = 0.998 (CPBA) - 0.639; correlation coefficient = 0.981 |
| Study 2 (n=106): INCSTAR = 1.229 (CPBA) - 5.092; correlation coefficient = 0.942 | |
| Range of 25-OH-D values handled | Study 1: 4.7 to 186 ng/mL |
| Study 2: 7.4 to 461 ng/mL | |
| Cross-reactivity | High affinity and equal cross-reactivity to 25(OH)D2 and 25(OH)D3; very low cross-reactivity to non-hydroxylated vitamin D2 or D3 and 1,25(OH)2 D. Recognizes several other dihydroxylated metabolites, but these are in low concentrations and considered of minor biological importance. |
2. Sample Size Used for the Test Set and Data Provenance
- Study 1:
- Test Set Sample Size: 72 serum samples (36 from each of two external sites).
- Data Provenance: Not explicitly stated, but "various patient groups" and "external sites" suggest real-world, likely retrospective, human data. The country of origin is not mentioned.
- Study 2:
- Test Set Sample Size: 106 serum samples.
- Data Provenance: Not explicitly stated, but "one external site" and "various patient groups" suggest real-world, likely retrospective, human data. The country of origin is not mentioned.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not provided in the given text. The "ground truth" for the test set is established by comparison to existing, accepted methods (HPLC and CPBA), which are themselves laboratory techniques rather than expert human interpretation.
4. Adjudication Method for the Test Set
This information is not applicable as the ground truth is established by quantitative laboratory methods (HPLC and CPBA), not by expert consensus requiring adjudication.
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
An MRMC comparative effectiveness study was not done. This device is a quantitative assay (RIA kit) for measuring a biomarker, not an AI-assisted diagnostic imaging tool that would involve human readers.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
This is a standalone device in the sense that its performance is measured independently against reference methods. It's a laboratory assay that produces a quantitative result; there isn't a "human-in-the-loop" component in its direct operation or interpretation that would typically apply to AI/imaging diagnostics. Its performance is the algorithm's (assay's) performance.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The ground truth used is measurement by established laboratory methods, specifically:
- High-Pressure Liquid Chromatography (HPLC)
- Competitive Protein Binding Assay (CPBA)
These are considered established and accepted methods for determining 25-OH-D levels.
8. The Sample Size for the Training Set
The text does not provide information about a separate "training set" in the context of machine learning. This is a traditional in vitro diagnostic (IVD) kit, not an AI/ML device that requires a distinct training phase in the same way. The development and validation of the kit itself would have involved extensive R&D, but the concept of a "training set" as defined for AI is not applicable here.
9. How the Ground Truth for the Training Set Was Established
As noted above, the concept of a "training set" in the AI/ML sense is not directly applicable to this type of device based on the provided text. The kit's internal components (e.g., antibody specificity, assay conditions) would have been developed and optimized against known standards and characterized samples, but this is part of the product development rather than a ground truth establishment for a training set in the AI context.
§ 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.