(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.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
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Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JUL 2 3 2002
Ms. Eileen McCafferty Regulatory Affairs Manager Axis-Shield Diagnostics Limited Luna Place The Technology Park Dundee DD2 1XA SCOTLAND
Re: K021516
Trade/Device Name: DIASTAT™ Anti-Cyclic Citrullinated Peptide (anti-CCP) ELISA Regulation Number: 21 CFR § 866.5775 Regulation Name: Rheumatoid Factor Immunological Test system Regulatory Class: II Product Code: NHX Dated: May 8, 2002 Received: May 10, 2002
Dear Ms. McCafferty:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".
Sincerely vours.
Steven Autman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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INDICATIONS FOR USE
510(k) number if known:
Device Name: Diastat™Anti-Cyclic Citrullinated Peptide (anti-CCP) ELISA
Indications for Use: 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.
H. Reeves for S. Altaie
(Division Sign-Off) Division of Clinical Laboratory Devices
510(k) Number_________________________________________________________________________________________________________________________________________________________________
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§ 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).