(382 days)
Immunoassay for the in vitro quantitative determination of antibodies to thyroglobulin in human serum and plasma. The anti-Tg autoantibodies determination is used as an aid in the detection of autoimmune thyroid diseases in conjunction with other laboratory and clinical findings.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the cobas e 411 immunoassay analyzer.
The Elecsys Anti-Tg immunoassay makes use of a competitive test principle using biotinylated human antigen and monoclonal human anti-Tg antibodies labeled with a ruthenium complex. The Elecsys Anti-Tg immunoassay is intended for the quantitative determination of antibodies to thyroglobulin in human serum and plasma. It is intended for use on the cobas e immunoassay analyzers.
Results are determined via a calibration curve which is instrument-specifically generated by 2 point calibration and a master curve provided via the reagent barcode or e barcode.
The provided text describes the performance evaluation of the Elecsys Anti-Tg immunoassay, a diagnostic device, and its acceptance criteria. Here's a breakdown of the requested information based on the text:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly present a single table labeled "Acceptance Criteria" with corresponding "Reported Device Performance" in a direct side-by-side format. Instead, it describes various performance evaluations and states whether "All predefined acceptance criteria was met" for each. However, we can reconstruct a table based on the provided details for the non-clinical performance evaluation.
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Precision | All predefined acceptance criteria met (specific numerical criteria not detailed in this section for repeatability/intermediate precision and lot-to-lot reproducibility) | Repeatability (within-run precision) and Intermediate Precision (within-laboratory precision) measured according to CLSI guideline EP05-A3. Accepted for all samples. |
| Lot-to-lot Reproducibility measured according to CLSI guideline EP05-A3 using three reagent lots. Accepted. | ||
| Analytical Sensitivity | ||
| Limit of Blank (LoB) | LoB claim in labeling set to 9 IU/mL (implied acceptance) | Determined according to CLSI EP17-A2. LoB claim in labeling will be set to 9 IU/mL. |
| Limit of Detection (LoD) | LoD claim in labeling set to 10 IU/mL (implied acceptance) | Determined according to CLSI EP17-A2. LoD claim in labeling will be set to 10 IU/mL. |
| Limit of Quantitation (LoQ) | LoQ claim in labeling set to 15 IU/mL (implied acceptance) | Determined according to CLSI EP17-A2. LoQ claim in labeling will be set to 15 IU/mL. |
| Linearity | Confirmed to support the measuring range of 15 - 4000 IU/mL (implied acceptance) | Assessed according to CLSI EP06-Ed2, study design B, using weighted linear regression analysis. Linearity confirmed to support measuring range of 15 - 4000 IU/mL. |
| Endogenous Interferences | All predefined acceptance criteria met (specific numerical criteria not detailed) | Evaluated for Biotin, Lipemia, Hemoglobin, Bilirubin, Rheumatoid Factor, Tg. All predefined acceptance criteria met. Proposed labeling claims: Biotin ≤ 1200 ng/mL, Lipemia ≤ 2000 mg/dL, Hemoglobin ≤ 600 mg/dL (for conc. ≤ 115 IU/mL), Bilirubin ≤ 66 mg/dL, Rheumatoid Factor ≤ 300 IU/mL, Tg ≤ 100 ng/mL. |
| Analytical Specificity/Cross-Reactivity | No cross-reaction with Anti-TPO detected (implied acceptance) | Cross-reactivity study conducted with anti-TPO. No cross-reaction with Anti-TPO detected. |
| Exogenous Interferences | All predefined acceptance criteria met for all drugs tested (implied acceptance) | Evaluated 17 commonly and 14 specially used pharmaceutical compounds. All predefined acceptance criteria met, and no interference observed. |
| Sample Matrix Comparison | Results within specification and support use of specified matrices (implied acceptance) | Compared values from serum, K2-EDTA, and K3-EDTA plasma. Results were within specification and support the use of Serum (standard or separating gel), K2-EDTA, and K3-EDTA plasma. |
| Method Comparison to Predicate | Not explicitly stated as pass/fail; presented as regression results | Compared to predicate device (K053426) using 129 human serum samples. |
| Linear Regression: y = 0.905x + 48.0, r = 0.990 | ||
| Passing Bablok: y = 0.974x + 1.72, τ = 0.930 | ||
| Reagent Stability | ||
| Reagent On-board Stability | 42 days (6 weeks) on-board (implied acceptance) | Tested on one cobas e 411 analyzer. Stable for up to 42 days (6 weeks). |
| Reagent Stability After First Opening | 42 days (6 weeks) after first opening (implied acceptance) | Tested on one cobas e 411 analyzer. Stable for up to 42 days (6 weeks) when stored at 2-8°C. |
| Calibration Stability | ||
| Lot Calibration Stability | Calibration every 28 days (1 month) (implied acceptance) | Tested on one cobas e 411 analyzer. Recommended calibration frequency of every 28 days (1 month). |
| On-board Calibration Stability | 7 days without new calibration (implied acceptance) | Tested on one cobas e 411 analyzer. Stable for up to 7 days without a new calibration. |
2. Sample sizes used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Test Set Sample Sizes:
- Precision: Not explicitly stated, but includes "Human serum 1-5" and "PC THYRO1-2" (presumably replicates for each, as per CLSI EP05-A3 which requires sufficient replicates).
- Lot-to-lot Reproducibility: "three reagent lots" (number of samples per lot not specified).
- Analytical Sensitivity (LoB, LoD, LoQ): Not explicitly stated, determined according to CLSI EP17-A2 which has sample size recommendations.
- Linearity: "Six dilution series" using "native human serum samples and sample pools" (number of samples/pools not specified).
- Endogenous Interferences: Not explicitly stated per substance, but mentions "Six endogenous substances."
- Analytical Specificity/Cross-Reactivity: Not explicitly stated (for anti-TPO).
- Exogenous Interferences: "17 commonly and 14 specially used pharmaceutical compounds" (number of samples not stated).
- Sample Matrix Comparison: "blood from 13 donors" (tested across serum, K2-EDTA, K3-EDTA plasma, and serum separation tubes from 3 manufacturers).
- Method Comparison to Predicate: "total of 129 human serum samples."
- Data Provenance: The document does not specify the country of origin for the data or whether the studies were retrospective or prospective. It is a "510(k) Summary" for an FDA submission, reporting on laboratory performance studies. Given they are "non-clinical performance evaluation," these are typically controlled laboratory studies.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This device is an in-vitro diagnostic (IVD) immunoassay. The ground truth for such devices is established through analytical testing against reference materials, established methods, and clinical samples with known characteristics, not typically by expert consensus in the same way as an imaging AI. The "ground truth" here is the precise concentration or presence/absence of the analyte (thyroglobulin antibodies) as determined by the study's reference method or expected values for standards/controls.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable for this type of IVD analytical performance study. Adjudication methods like 2+1 or 3+1 are common in clinical trials or imaging studies where expert readers interpret results, but not for direct quantitative measurements from an immunoassay. The acceptance criteria are based on statistical analysis of quantitative results (e.g., precision, linearity, recovery, regression).
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
Not applicable. This is an immunoassay for determining antibody levels, not an imaging device or an AI intended to assist human readers. Hence, no MRMC study was performed, and human reader improvement with AI assistance is not relevant to this device's evaluation.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This entire non-clinical performance evaluation section (4. NON-CLINICAL PERFORMANCE EVALUATION) describes the standalone performance of the Elecsys Anti-Tg immunoassay (a device, not an AI algorithm). The measurements are performed by the "cobas e 411 immunoassay analyzer," which acts as the "algorithm" or automated system. There's no human "in the loop" for the direct measurement results themselves, though human operators are involved in running the tests and interpreting the results in a clinical setting.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth for the analytical performance studies (precision, linearity, sensitivity, interferences, stability) is based on:
- CLSI guidelines: The studies adhere to specific Clinical and Laboratory Standards Institute (CLSI) guidelines (e.g., EP05-A3, EP17-A2, EP06-Ed2), which define how such analytical characteristics are determined using reference materials, spiked samples, and statistical methods.
- Reference Standards/Materials: Implied in sections like "Traceability/Standardization" against the NIBSC 65/93 Standard, and the use of calibrators (Anti-Tg CalSet) and controls (PreciControl ThyroAB).
- Known Sample Characteristics: For linearity, samples with varying known concentrations are typically used. For interference studies, samples spiked with known interferents are used.
- Predicate Device Comparison: For method comparison, the predicate device's results serve as a comparative reference.
8. The sample size for the training set
Not applicable in the context of an immunoassay. This device is an in-vitro diagnostic test kit (reagents) used on an existing analyzer. It does not involve a "training set" in the machine learning sense. The "development" or "training" of such a diagnostic involves optimizing the chemical and biological components of the assay (reagents, antibodies, detection method) and calibrating the system across a range of known concentrations.
9. How the ground truth for the training set was established
As there is no "training set" in the AI/machine learning sense, this question is not applicable. The development process for an immunoassay involves extensive research and development to create reagents that accurately quantify the target analyte. Calibration is done using reference materials with assigned values, and the assay's performance characteristics (as detailed in section 4) are then rigorously validated.
§ 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).