(17 days)
The MESACUP TEST MPO is a semi-quantitative enzyme-linked immunosorbent assay (ELISA) for the detection of IgG anti-myeloperoxidase (MPO) antibodies in human serum. The MESACUP TEST MPO is intended for in vitro diagnostic use as an aid in the diagnosis of certain systemic vasculitides such as microscopic polyarteritis and crescentic glomerulonephritis.
The MESACUP Test MPO is an enzyme-linked immunosorbent assay (ELISA), utilizing the 96-microwell plate format, similar to the predicate device. Diluted serum samples, calibrator sera, and controls are incubated in microwells coated with myeloperoxidase antigen. Incubation allows the anti-MPO antibodies present in the samples to react with the immobilized antigen. After the removal of unbound serum proteins by washing, antibodies specific for human IgG immunoglobulins, labeled with horseradish peroxidase (HRP), are added forming complexes with the MPO bound antibodies. Following another washing step, the bound enzyme-antibody conjugate is assayed by the addition of a single solution containing tetramethlybenzidine (TMB) and hydrogen peroxide (H2O2) as the chromogenic substrate. The intensity of the color generated is proportional to the serum concentration of anti-MPO antibodies. Optical density is read spectrophotometrically at 450nm. The total incubation time (at room temperature) of the assay is 150 minutes. The assay makes use of two callbrators to measure the amount of anti-MPO antibody in patient samples.
Acceptance Criteria and Device Performance Study
The MESACUP Test MPO is an enzyme-linked immunosorbent assay (ELISA) designed for the semi-quantitative detection of IgG anti-MPO antibodies in human serum to aid in the diagnosis of certain systemic vasculitides. The device's performance was compared to a legally marketed predicate device, the Bindazyme Human Anti MPO Enzyme Immunoassay Kit (K981030).
1. Table of Acceptance Criteria and Reported Device Performance
The public summary does not explicitly state pre-defined acceptance criteria with numerical targets. Instead, it focuses on demonstrating equivalence to the predicate device. The primary performance metrics reported are clinical specificity and sensitivity.
| Metric | Acceptance Criteria (Implied) | Reported MESACUP Test MPO Performance | Reported Predicate Device Performance (Bindazyme Human Anti MPO) |
|---|---|---|---|
| Clinical Specificity | Equivalent to predicate device in healthy donor serum population | 100% | 100% |
| Clinical Sensitivity | Equivalent to predicate device in vasculitis population | 37% | 38% |
| Relative Agreement | Demonstrate high agreement with predicate device | 96% | - (Comparison metric) |
Note: The acceptance criteria are "implied" based on the phrasing "Performance indicates that MESACUP Test MPO and the Bindazyme Human Anti MPO Enzyme Immunoassay are equivalent" and the direct comparison of performance metrics.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Healthy Donor Serum Population: The specific number is not provided, but the document mentions "a healthy donor serum population."
- Vasculitis Population: The specific number is not provided, but the document mentions "a vasculitis population."
- Data Provenance: The studies were described as "In-house studies." This typically suggests that the studies were conducted by the manufacturer or a contracted research organization. There is no information regarding the country of origin or whether the data was retrospective or prospective.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This type of information is generally not applicable to an ELISA device performance study for antibody detection. The "ground truth" for ELISAs is typically established by the clinical diagnosis of the patient from whom the serum sample was taken (e.g., diagnosed with a vasculitis, or considered healthy). The diagnostic status of the patients (e.g., healthy vs. vasculitis) would have been determined by medical professionals (e.g., physicians, specialists) involved in their care, but these individuals are not functioning as "experts" establishing a ground truth for the device's output in the way a radiologist would interpret an image.
4. Adjudication Method for the Test Set
Adjudication methods (e.g., 2+1, 3+1) are typically used in studies involving subjective interpretations, such as image analysis, where multiple readers provide their opinion and discrepancies need to be resolved. This is not applicable to an objective laboratory test like an ELISA, where the result is a numerical optical density reading that is then interpreted against cutoff values.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. MRMC studies are relevant for diagnostic devices that involve human interpretation of results (e.g., imaging devices) to assess reader performance with and without AI assistance. This document describes an in vitro diagnostic (IVD) device that yields a quantitative result, not one where human readers perform a diagnostic interpretation based on the device's direct output in a way that could be "assisted" by AI.
6. Standalone (Algorithm Only) Performance
Yes, the study primarily describes the standalone performance of the MESACUP Test MPO. As an ELISA kit, it is effectively an "algorithm only" device in a laboratory setting, producing a result based on chemical reactions and optical density measurements, without requiring human "in-the-loop" interpretation beyond performing the assay and reading the result. The performance metrics (sensitivity, specificity, relative agreement) directly reflect this standalone performance.
7. Type of Ground Truth Used
The ground truth for the test samples was based on the clinical status of the patients:
- "Healthy donor serum population": These samples represent individuals without the target condition, providing the ground truth for specificity.
- "Vasculitis population": These samples presumably represent individuals clinically diagnosed with vasculitis, providing the ground truth for sensitivity.
Therefore, the ground truth is based on clinical diagnosis/patient case status, not pathology reports (though pathology may contribute to clinical diagnosis) or expert consensus on the device's output.
8. Sample Size for the Training Set
The document does not provide information on a specific "training set" or its sample size. For an ELISA device, the development process typically involves optimizing reagents and protocols, and establishing cutoff values, rather than training an algorithm in the way machine learning models are trained. The samples mentioned (healthy donor and vasculitis populations) are used for "in-house studies" to assess performance and likely to establish or validate cutoff values, which could be considered part of the development/validation process.
9. How the Ground Truth for the Training Set Was Established
As noted above, the concept of a "training set" in the context of an ELISA kit is different from that of an AI algorithm. If the "in-house studies" that defined the cutoff values are considered part of a "training" or optimization phase, the ground truth would have been established by the clinical status of the patients (healthy vs. vasculitis diagnosis), similar to the test set. However, the document does not explicitly detail a separate training phase with distinct ground truth methods.
§ 866.5660 Multiple autoantibodies immunological test system.
(a)
Identification. A multiple autoantibodies immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when the body's own tissues are injured by autoantibodies).(b)
Classification. Class II (performance standards).