(75 days)
The Varelisa TPO Antibodies EIA kit is designed for the quantitative and qualitative determination of TPO (thyroid peroxidase) antibodies in serum or plasma to aid in the diagnosis of thyroid diseases such as Autoimmune Thyroiditis and Graves' Disease.
The Varelisa TPO Antibodies assay is an indirect noncompetitive enzyme immunoassay for the quantitative and qualitative determination of TPO (thyroid peroxidase) antibodies in serum or plasma. The wells of a microplate are coated with human recombinant TPO antigen. Antibodies specific for TPO present in a patient sample bind to this antigen. In a second step an enzyme labeled second antibody (Conjugate) binds to the antigenantibody complex which leads to the formation of an enzyme labeled antigen-antibody sandwich complex. The enzyme labeled antigen-antibody complex converts the added substrate to form a colored solution. The rate of color formation from the chromogen is a function of the amount of Conjugate complexed with the bound antibody and thus is proportional to the initial concentration of the respective antibodies in the patient sample.
The provided text describes a 510(k) submission for a device modification of the Varelisa® TPO Antibodies EIA kit. The submission aims to establish substantial equivalence to a predicate device, the elias™ TM Antibodies assay.
Here's an analysis based on the provided text, addressing your specific questions:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated in numerical terms (e.g., a specific percentage of agreement or a benchmark for R-value). Instead, the substantial equivalence is demonstrated through a correlation study comparing the modified device (Varelisa® TPO Antibodies) with the predicate device (elias™ TM Antibodies).
| Acceptance Criteria Category | Specific Metric (Inferred) | Reported Device Performance |
|---|---|---|
| Overall Agreement | High degree of similarity to predicate device | "a high degree of similarity was demonstrated: comparing 183 positive and negative samples, an R-value of 0.90 (Pearson's coefficient of correlation: 0.95) was obtained." |
| Negative Samples | All defined negative samples should be found negative | "All defined negative samples were found negative in both assays." |
| Blood Donor Samples | Mean values for blood donor samples (expected to be low/negative) | "the evaluation of the results obtained for 39 blood donor samples gave mean values of 0.4 IUC" (Inferred to be a low value indicating negativity) |
| Equivocal Range Handling | Agreement when accounting for differing equivocal ranges | "Onititing 7 samples (out of 183 samples) which were found equivocal in Varelisa TPO Antibodies (for elias TM Abs no equivocal range is defined), the overall agreement was 98.9%." |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 183 positive and negative samples were used for the correlation study, plus an additional 39 blood donor samples. So, the total number of samples used in these performance evaluations is 222 (183 + 39).
- Data Provenance: The text does not specify the country of origin of the data. It is implied to be retrospective, as it involves pre-existing samples (
183 positive and negative samplesand39 blood donor samples) being compared against a predicate device.
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 text. This is a diagnostic assay, not an imaging AI device that would typically rely on human expert interpretation for ground truth. The "ground truth" for the test set is established by the results of the predicate device (elias™ TM Antibodies assay).
4. Adjudication Method for the Test Set
This information is not applicable for this type of in-vitro diagnostic device comparison. Adjudication methods like 2+1 or 3+1 are typically used in studies involving human interpretation (e.g., radiologists) where there might be disagreement in reading cases. Here, the comparison is directly between two assays, and discrepancies would be analyzed statistically, not through an adjudication process among human readers.
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
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for evaluating AI's impact on human readers, typically in image interpretation scenarios. This submission concerns an in-vitro diagnostic assay and does not involve human readers interpreting AI outputs.
6. If a Standalone (i.e. algorithm only, without human-in-the-loop performance) was done
Yes, a standalone performance evaluation was done. The study directly compares the results of the Varelisa® TPO Antibodies assay (the modified device, which functions as a standalone algorithm/assay) with the results of the elias™ TM Antibodies assay (the predicate device, also a standalone assay). The performance metrics (R-value, agreement) reflect the assay's performance without human intervention in the result generation.
7. The Type of Ground Truth Used
The "ground truth" for the performance evaluation is the results obtained from the legally marketed predicate device, the elias™ TM Antibodies assay. The underlying assumption is that the predicate device provides an accepted standard for measuring TPO antibodies, and therefore, strong correlation with it demonstrates acceptable performance of the new device. The text also mentions the standardization against the "Anti-Thyroid Microsome Serum, NIBSC Research Standard 66/387," which serves as a common reference for both assays.
8. The Sample Size for the Training Set
The provided text does not contain information about a training set. This document describes a modification to an existing device (Varelisa TPO Antibodies) and its comparison to a predicate device for regulatory approval. While such assays likely undergo development and calibration, the specific details of a "training set" in the context of an AI/machine learning model are not relevant here, as this is a chemical/biochemical assay rather than an AI or ML-driven diagnostic.
9. How the Ground Truth for the Training Set was Established
As noted in point 8, information about a "training set" and its ground truth is not provided and is likely not applicable in the context of this device's type.
§ 866.5870 Thyroid autoantibody immunological test system.
(a)
Identification. A thyroid autoantibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the thyroid autoantibodies (antibodies produced against the body's own tissues). Measurement of thyroid autoantibodies may aid in the diagnosis of certain thyroid disorders, such as Hashimoto's disease (chronic lymphocytic thyroiditis), nontoxic goiter (enlargement of thyroid gland), Grave's disease (enlargement of the thyroid gland with protrusion of the eyeballs), and cancer of the thyroid.(b)
Classification. Class II (performance standards).