(49 days)
This kit has been designed for the measurement of C-reactive protein in human serum and plasma. When used according to instructions, the kit is useful in measuring the acute phase responses in humans to infection, tissue damage and various inflammatory conditions.
An enzyme-linked immunosorbent assay (ELISA) designed for the semiquantitative detection of C-Reactive Protein (CRP) in human serum and plasma. The ELISA methodology is commonly used for serological evaluations. Antibodies to CRP have been attached to the inner surfaces of the microwell plate. During the initial incubation step, CRP in patient serum binds specifically to the immobilized antibody and remains in place after a wash step. A second antibody, which is conjugated to the enzyme horseradish peroxidase, reacts with CRP bound in the first step. In the wells where the second antibody remains bound, the enzyme catalyzes a color change in the substrate, tetramethylbenzidine (TMB). After the reaction is stopped, the color is read in an EIA plate reader.
Here's an analysis of the provided text regarding the acceptance criteria and study for the Hemagen® CRP 150 Kit:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Specific Criteria (Implicitly Derived) | Reported Device Performance |
|---|---|---|
| Correlation with WHO Standard (CRP Standards Verification) | High degree of correlation with W.H.O International Standard for Human C-Reactive Protein (1st International Standard, Code 85/506). | "high degree of correlation that exists between the Kit standards and the W.H.O. Standard." |
| Equivalence to Predicate Device (Comparison Testing) | Linear relationship with the predicate device, evidenced by a regression slope of approximately +1.0 and a correlation coefficient > 0.90 for estimated CRP concentrations. | "linear relationship with a high degree of correlation exists between the estimated CRP concentrations for assayed serum samples as evidenced by an estimated regression slope of +1.0 and a correlation coefficient of > 0.90." |
| Performance with Serum and Plasma | Provide accurate estimates of CRP concentrations in both human serum and plasma. | "it can provide accurate estimates of CRP concentrations in both human serum and plasma." |
| Interference by Lipemia, Hemolysis, Icterus | Hemoglobin concentrations of ≤ 500 mg/dL, lipid concentrations of ≤ 3,000 mg/dL, and bilirubin concentrations of 20 mg/dL should not significantly affect assay results. | "Samples with hemgall on concentrations of ≤ 500 mg/dL, lipid concentrations of ≤ 3,000 mg/dL, and bilirubin concentrations of 20 mg/dL did not significantly affect the assay results." |
| Between-run reproducibility (Inter-Assay Precision) | (Implicitly based on CVs shown) Acceptable Coefficient of Variation (CV) for various CRP concentrations. | CVs ranging from 5% to 12% for different CRP levels (Mean µg/mL 1.4-32.5). |
| Within-run reproducibility (Intra-Assay Precision) | (Implicitly based on CVs shown) Acceptable Coefficient of Variation (CV) for various CRP concentrations. | CVs ranging from 5% to 25% for different CRP levels (Mean µg/mL 1.0-31.9). |
2. Sample Size Used for the Test Set and Data Provenance
- CRP Standards Verification: Not explicitly stated, but it describes a "study...to demonstrate the high degree of correlation." Given it's a standard, it's likely a limited, controlled prospective assessment of the manufactured standards against the WHO standard.
- Comparison Testing (Predicate Device): 18 human serum samples.
- Data Provenance: Not explicitly stated, but human serum samples imply clinical origin. No country of origin is mentioned. The study is retrospective in the sense that these samples are being tested concurrently on two devices.
- (Note: The text also mentions a previous predicate device submission where EIA was compared to latex agglutination with 166 human serum samples, indicating that previous data was also retrospective.)
- Assay performance with Serum and Plasma: Two sets of plasma samples of 41 samples each (total 82 plasma samples, which were then converted to 41 serum samples).
- Data Provenance: "apparently healthy donors." No country of origin is mentioned. This is a prospective collection of samples for this specific study.
- Interfering Substances: Not explicitly stated, but "samples with hemgall on concentrations... lipid concentrations... and bilirubin concentrations" suggests a controlled study where samples were spiked or selected to have these characteristics.
- Data Provenance: Not explicitly stated. Likely prospective or controlled in vitro preparation of samples.
- Precision Studies (Inter-Assay & Intra-Assay): 8 serum samples for both.
- Data Provenance: Not explicitly stated, but "serum samples" imply clinical origin. This is a prospective study designed to assess repeatability and reproducibility.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
There is no mention of experts being used to establish ground truth for this device's performance evaluation. The ground truth is primarily based on:
- Comparison to an established international standard (WHO International Standard for Human C-Reactive Protein).
- Comparison to a legally marketed predicate device.
- The results of the test method itself, with precision and interference assessed internally.
4. Adjudication Method for the Test Set
None. Adjudication methods (like 2+1 or 3+1) are typically used when subjective expert interpretation is involved in establishing ground truth (e.g., radiology image interpretation). This device involves quantitative measurement, where ground truth is an objective value (e.g., from the WHO standard or a reference method).
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. This is not an AI-assisted diagnostic device, nor does it involve human "readers" or subjective interpretation in the way an MRMC study would apply. It's a quantitative immunoassay.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, effectively. The entire study for the Hemagen® CRP 150 Kit assesses its standalone performance (the kit itself) in measuring CRP concentrations, without human interpretation being a variable. The "human-in-the-loop" here is the lab technician performing the assay, but the output (CRP concentration) is objective, not interpretive.
7. The Type of Ground Truth Used
- CRP Standards Verification: The WHO International Standard for Human C-Reactive Protein (1st International Standard, Code 85/506) served as the ground truth/reference.
- Comparison Testing: The predicate device (Hemagen® C-Reactive Protein Kit) served as the reference/ground truth for equivalence.
- Assay performance with Serum and Plasma: The measured CRP concentrations in "apparently healthy donors" were considered the truth for assessing consistency across sample types.
- Interfering Substances: The absence of significant effect on the assay results from known concentrations of interferents (hemoglobin, lipids, bilirubin) served as the ground truth for non-interference.
- Precision Studies: The internal consistency of the device's measurements (mean, standard deviation, CV) formed the ground truth for repeatability and reproducibility.
8. The Sample Size for the Training Set
No training set is mentioned or applicable. This is a traditional immunoassay kit, not a machine learning or AI model that requires a "training set." The development of the kit (e.g., antibody selection, assay parameters) would involve internal R&D and validation, but not a formally defined "training set" in the context of AI.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no training set for this type of device.
§ 866.5270 C-reactive protein immunological test system.
(a)
Identification. A C-reactive protein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the C-reactive protein in serum and other body fluids. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues.(b)
Classification. Class II (performance standards).