(74 days)
The Diastat™Anti-CCP test is a semi-quantitative/ qualitative enzyme-linked immunosorbent assay (ELISA) for the detection of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in human serum. It is intended to aid in the diagnosis of Rheumatoid Arthritis (RA) and is not definitive in isolation. Autoantibody levels represent one parameter in a multi-criterion diagnostic process, encompassing both clinical and laboratory-based assessments.
semi-quantitative/ qualitative enzyme-linked immunosorbent assay (ELISA) for the detection of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in human serum.
The provided text describes a FDA 510(k) clearance letter for the DIASTAT™ Anti-Cyclic Citrullinated Peptide (anti-CCP) ELISA device. This document is a regulatory approval, and as such, it primarily focuses on establishing substantial equivalence to a predicate device rather than detailing specific studies with acceptance criteria and performance data in the format typically used for a scientific study report.
Therefore, many of the requested details about acceptance criteria and study design are not explicitly contained within this regulatory clearance letter. However, I can infer some information from the context of a 510(k) submission for an in vitro diagnostic device.
Here's how I can address your request based on the provided text:
1. A table of acceptance criteria and the reported device performance
The provided FDA letter does not contain a table of acceptance criteria or reported device performance metrics for the DIASTAT™ Anti-CCP ELISA. This information would typically be found in the 510(k) submission itself, which is not provided here. The letter only states that the device is "substantially equivalent" to a legally marketed predicate device. For an ELISA, common performance metrics would include sensitivity, specificity, accuracy, precision (intra-assay and inter-assay variability), linearity, and range. Acceptance criteria would be thresholds for these metrics.
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
This information is not provided in the FDA clearance letter. For a 510(k) submission of an in-vitro diagnostic, a clinical study would have been performed, and details like sample size, patient population characteristics, and study design (prospective vs. retrospective) would be included in the submission.
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 information is not provided in the FDA clearance letter. For an in-vitro diagnostic device intended to aid in the diagnosis of Rheumatoid Arthritis, the "ground truth" for RA would likely rely on accepted clinical diagnostic criteria (e.g., ACR/EULAR criteria) applied by rheumatologists or other qualified clinicians. The number and qualifications of these experts would be detailed in the original 510(k) submission.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
This information is not provided in the FDA clearance letter. If multiple experts were involved in establishing ground truth, an adjudication method would be crucial, but this detail is absent from the provided document.
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
A Multi-Reader Multi-Case (MRMC) study is typically relevant for interpretative devices like medical imaging AI. The DIASTAT™ Anti-CCP ELISA is a laboratory-based immunoassay, not an imaging device or an AI assistant for human readers. Therefore, an MRMC study as described would not be applicable or performed for this type of device. The concept of "human readers improve with AI vs without AI assistance" does not directly apply to an ELISA kit.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
The DIASTAT™ Anti-CCP ELISA is a standalone in-vitro diagnostic test. It is an algorithm-only system in the sense that the test results (e.g., optical density readings) are processed according to a pre-defined algorithm (e.g., calculating a ratio or index to determine a positive/negative/equivocal result). The interpretation of these results is then used by a clinician as "one parameter in a multi-criterion diagnostic process." It is not a device that directly interacts with human interpretation in a "human-in-the-loop" fashion like an imaging CAD system.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The "Indications for Use" statement indicates the device "is intended to aid in the diagnosis of Rheumatoid Arthritis (RA) and is not definitive in isolation." It also states, "Autoantibody levels represent one parameter in a multi-criterion diagnostic process, encompassing both clinical and laboratory-based assessments."
Therefore, the ground truth for demonstrating the device's diagnostic utility would most likely be based on established clinical diagnostic criteria for Rheumatoid Arthritis, such as the American College of Rheumatology (ACR) criteria or the more recent ACR/EULAR classification criteria for RA. This would involve a combination of:
- Clinical assessments: Swollen and tender joint counts, duration of symptoms, other relevant clinical signs.
- Laboratory-based assessments: Other blood tests (e.g., rheumatoid factor, ESR, CRP).
- Potentially, imaging data: X-rays of affected joints.
This would essentially be an expert consensus based on these multi-criterion assessments by qualified rheumatologists.
8. The sample size for the training set
This information is not provided in the FDA clearance letter. While the device uses ELISA technology, which doesn't typically involve "training sets" in the machine learning sense, the assay development and optimization would involve numerous samples. However, the term "training set" as often used in AI/ML is not directly applicable here. The performance evaluation samples would be considered the test set.
9. How the ground truth for the training set was established
As noted above, the concept of a "training set" with ground truth in the AI/ML context isn't directly applicable to this traditional ELISA device. If we interpret "training set" broadly as the samples used during assay development and optimization, the "ground truth" for those samples would be established by the same clinical and laboratory criteria for RA as described in point 7.
§ 866.5775 Rheumatoid factor immunological test system.
(a)
Identification. A rheumatoid factor immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and tissues. Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis.(b)
Classification. Class II (performance standards).