(77 days)
The assay is intended for use in detecting antibodies to Sm/RNP antigen in a single human serum sample. The results of the assay are to be used as an aid in the diagnosis of autoimmune disorders.
The Is-anti-Sm/RNP Test Kit System is an enzyme-linked immunosorbent assay (ELISA) for the detection and semi-quantitation of IgG to Sm/RNP antigen in human serum.
Here's a breakdown of the acceptance criteria and study information for the Diamedix Is-anti-Sm/RNP Test System based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as distinct pass/fail thresholds in the document, but rather implied by the reported performance relative to a predicate device. The comparison testing data serves as the de-facto performance standard against which the device's performance is measured.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (Manual) | Reported Device Performance (MAGO) |
|---|---|---|---|
| Relative Sensitivity | High agreement with predicate device (e.g., >85%) | 88% (46/52) | 90% (46/51) |
| Relative Specificity | High agreement with predicate device (e.g., >95%) | 100% (97/97) | 100% (97/97) |
| Overall Agreement | High agreement with predicate device (e.g., >90%) | 96% (143/149)* | 97% (143/148)** |
| Linearity | High degree of linearity throughout the testing range (R^2) | R^2 = 0.985 | R^2 = 0.9419 |
| Intra-Assay Precision (CV%) | Low variability | Ranges from 2.8% to 13.4% | Ranges from 3.7% to 34.6% |
| Inter-Assay Precision (CV%) | Low variability | Ranges from 4.5% to 20.0% | Ranges from 4.6% to 30.0% |
| Cross-reactivity | Minimal to no cross-reactivity with other autoimmune specificities | Not cross-reactive with SSA, SSB, Jo-1, Scl-70 in tested samples | Not cross-reactive with SSA, SSB, Jo-1, Scl-70 in tested samples |
| Correlation (Manual vs. MAGO) | High correlation between manual and automated methods | 0.99 (Pearson) | N/A (MAGO is compared to Manual) |
*One borderline sample excluded.
**Two samples (one equivocal, one borderline) excluded.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size:
- Comparison Testing: 150 sera (100 from normal blood donors and 50 from autoimmune patients).
- Linearity Testing: Serial two-fold dilutions of a Calibrator.
- Precision Testing: 6 different sera, a Calibrator, a Positive Control, and a Negative Control tested over different days.
- Cross-reactivity: 24 sera positive for six different autoimmune specificities.
- Expected Values: 100 normal donor sera and 50 clinically characterized sera (total 150).
- Data Provenance: Not explicitly stated as country of origin. The test was conducted by Diamedix Corporation in Miami, FL, implying the studies were conducted locally. The data is retrospective as it involves testing existing serum samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- Number of Experts: Not specified.
- Qualifications of Experts: Not specified.
- How Ground Truth was Established: For the comparison testing, the "ground truth" was established by the result of a "commercially available anti-Sm/RNP ELISA test kit" (the predicate device) and, in some cases of discordance, a "third method." For cross-reactivity, serum samples were "positive for the six autoimmune specificities," implying previous diagnostic confirmation, but the method or expertise for this confirmation is not detailed. For "clinically characterized sera" it broadly refers to diagnoses made by healthcare professionals, but specific details are absent.
4. Adjudication Method for the Test Set
- Adjudication Method: Not explicitly stated for establishing the initial "ground truth." However, for discordant results between the Diamedix device and the comparative method, a "third method" was used to resolve the discrepancy for 11 samples. This implies a form of adjudication for discordant results rather than a primary ground truth establishment method.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
- No, an MRMC comparative effectiveness study was not done. This study describes a diagnostic test kit's performance, not the comparative effectiveness of human readers with and without AI assistance. The "Manual" and "MAGO" refer to manual vs. automated processing of the test kit itself, not human interpretation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Yes, a standalone performance was done for both the "Manual" and "MAGO" (automated) versions of the device. This device is an in-vitro diagnostic (IVD) test, where the output (EU/ml values and interpretation of positive/negative) is generated by the assay itself, either through manual steps or with the aid of the MAGO instrument. While a human might interpret the final results in a clinical context, the performance metrics reported here (sensitivity, specificity, precision, linearity) relate to the device's ability to accurately measure the analyte, essentially a standalone assessment of the assay.
7. The Type of Ground Truth Used
- Predicate Device Comparison and Clinical Characterization: The primary ground truth for sensitivity and specificity was the results from a "commercially available anti-Sm/RNP ELISA test kit" (predicate device) and in some discrepant cases, a "third method." For the "autoimmune patients," their status was based on clinical characterization, implying a combination of clinical diagnoses and potentially other laboratory tests, but not explicitly stated as pathology or direct outcomes data for this specific study. For cross-reactivity, it used sera known to be positive for other autoimmune specificities.
8. The Sample Size for the Training Set
- Not Applicable / Not Mentioned. This document describes a diagnostic assay (ELISA kit), not a machine learning or AI algorithm in the context of typical training sets. There is no mention of a "training set" in the context of an algorithm or statistical model being developed. The device's parameters are likely established through a biochemical development process and validated, rather than "trained" in the AI sense.
9. How the Ground Truth for the Training Set Was Established
- Not Applicable / Not Mentioned. As there's no "training set" in the AI sense for this type of device, this question is not relevant to the provided text.
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APR - 8 1997
510(k) Summary of Safety and Effectiveness
This summary of safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is:
Applicant Information:
| Date Prepared: | January 15, 1997 |
|---|---|
| Name: | Diamedix Corporation |
| Address: | 2140 N. Miami AvenueMiami, FL 33127 |
| Contact Person: | Dr. Lynne Stirling |
|---|---|
| Phone Number: | 305-324-2354 |
| Fax Number: | 305-324-2585 |
Device Information:
| Trade Name: | Is-(immunosimplicity)-anti-Sm/RNP Test System |
|---|---|
| Common Name: | Anti-Sm/RNP EIA Test |
| Classification Name: | Extractable Antinuclear Antibody |
Equivalent Device:
Helix Diagnostics Enzyme Immunoassay Anti-Sm/RNP Antibody Test Kit
Device Description: The Is-anti-Sm/RNP Test Kit System is an enzyme-linked immunosorbent assay (ELISA) for the detection and semi-quantitation of IgG to Sm/RNP antigen in human serum.
Intended use: The assay is intended for use in detecting antibodies to Sm/RNP antigen in a single human serum sample. The results of the assay are to be used as an aid in the diagnosis of autoimmune disorders.
Comparison to Predicate Device:
The Is-anti-Sm/RNP Test System is an enzyme-linked immunosorbent assay to detect IgG to Sm/RNP in human serum. Purified Sm/RNP antigen is attached to a solid phase microtiter well. Diluted test sera are added to each well. If antibodies which recognize the Sm/RNP antigen are present in the patient sample, they will bind to the antigen in the well. After incubation, the wells are washed to remove unbound antibody. An enzyme-labeled anti-human immunoglobulin (conjugate) is added to each test well. If antibody is present the enzyme-linked antibody will bind to it. After incubation, the wells are washed to remove unbound conjugate. A substrate solution is then added to each well. If enzyme is present from the prior step, the substrate will be converted to produce a colored product. The reaction is stopped and the color intensity is measured photometrically providing an indirect measure of the specific antibody present in the patient sample.
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Summary of Safety and Effectiveness
Performance Characteristics
A. Comparison Testing
The Diamedix Is-anti-Sm/RNP Test Kit was evaluated relative to another commercially available anti-Sm/RNP ELISA test kit using 100 sera from normal blood donors and 50 sera from autoimmune patients. The results are summarized in Table 1 below.
| Table 1 | Manual | MAGO | ||||
|---|---|---|---|---|---|---|
| Number ofSera | % | 95%Confidence | Number ofSera | % | 95%Confidence | |
| RelativeSensitivity | 46/52 | 88 | 77-96 | 46/51 | 90 | 79/97 |
| RelativeSpecificity | 97/97 | 100 | 96-100 | 97/97 | 100 | 96-100 |
| Agreement | 143/149* | 96 | 91-99 | 143/148** | 97 | 91-99 |
- One borderline sample was excluded from the calculations.
** Two samples, one equivocal and one borderline, were excluded from the calculations.
Six sera negative by Is-anti-Sm/RNP (manual) and positive by the comparative method were negative when tested by a third method. Five sera negative by Is-anti-Sm/RNP (MAGO) and positive by the comparative method were negative by a third method.
B. Linearity
Figures 1 and 2 show typical examples of Is-anti-Sm/RNP Test Kit linearity. The figures depict the results of the Calibrator tested by Is-anti-Sm/RNP after serial two-fold manual dilutions in Sample Diluent. Separate dilutions were tested both manually and with MAGO. The results demonstrate a high degree of linearity for the Is-anti-Sm/RNP Test Kit throughout the testing range.
Image /page/1/Figure/10 description: The image is a graph titled "Is anti-Sm/RNP Calibrator Linearity". The x-axis is labeled "Dilution" and ranges from 0.0 to 1.0. The y-axis is labeled "Absorbance" and ranges from 0.0 to 2.0. The graph shows a linear relationship with an R-squared value of 0.985.
Figure 1 Manual Linearity
Image /page/1/Figure/12 description: The image is a graph titled "Is anti-Sm/RNP Calibrator Linearity". The graph shows the relationship between dilution and absorbance. The R-squared value is 0.9419, indicating a strong correlation. The x-axis represents dilution, ranging from 0.0 to 1.0, while the y-axis represents absorbance, ranging from 0.0 to 2.0.
Figure 2 MAGO Linearity
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C. Precision Testing
The precision of the Is-anti-Sm/RNP Test Kit was determined at Diamedix by testing six different sera and The precision of the Is-anti-Shirtin Tost Itif Frent days. The intra- and interassay precision is shown in Table 2 below.
| Table 2 | anti-Sm/RNP PRECISION | ||||
|---|---|---|---|---|---|
| Overall | MANUAL | MAGO | |||
| SERUM | MEAN EU/ml | INTRA-CV% | INTER-CV% | INTRA-CV % | INTER-CV % |
| 1 (NEG) | 1.9 | 8.8 | 13.3 | 15.4 | 13.0 |
| 2 (NEG) | 1.8 | 7.3 | 6.3 | 10.9 | 10.5 |
| 3 (POS) | 26.1 | 3.5 | 4.5 | 5.9 | 9.8 |
| 4 (POS) | 47.0 | 5.6 | 6.0 | 7.8 | 9.8 |
| 5 (POS) | 81.9 | 2.8 | 6.1 | 5.5 | 7.1 |
| 6 (POS) | 108.6 | 3.1 | 5.4 | 3.7 | 7.1 |
| CAL | 100.4 | 3.5 | 5.8 | 4.3 | 4.6 |
| POS CTRL | 46.3 | 3.3 | 6.5 | 6.6 | 8.7 |
| NEG CTRL | 1.0 | 13.4 | 20.0 | 34.6 | 30.0 |
D. Crossreactivity
Twenty-four sera positive for the six autoimmune specificities were tested in Is- anti-Sm/RNP Test Kit. The results are shown in Table 3.
| 1 |
|---|
| œ |
| Samp | Is anti-Sm/RNP | Interp | Specificity |
|---|---|---|---|
| 1 | ર્ર રે | NEG | SSA |
| 2 | 5.3 | NEG | SSA |
| 3 | 2.3 | NEG | SSA |
| 4 | 3.9 | NEG | SSA |
| 5 | 7.9 | NEG | ਟ ਡੈਡ |
| 6 | 6.2 | NEG | SSB |
| 7 | 3.9 | NEG | SBB |
| 8 | 2.0 | NEG | SSB |
| 9 | ારરી તે | POS | Sm |
| 10 | ા રહ્યા | POS | Sm |
| 11 | 129.0 | POS | Sm |
| 12 | 135.9 | POS | Sm |
| 13 | 156.2 | POS | RNP |
| 14 | 156.6 | POS | RNP |
| 15 | 156.8 | POS | RNP |
| 1 Q | 156.0 | POS | RNP |
| 17 | 2.2 | NEG | Jo- I |
| 18 | 3.4 | NEG | Jo- 1 |
| 19 | 1.9 | NEG | Jo- l |
| 20 | 2.5 | NEG | Jo-1 |
| 21 | 3.6 | NEG | Scl-70 |
| 22 | 2.0 | NEG | Scl-70 |
| 23 | 2.4 | NEG | Scl-70 |
| 24 | 1.2 | NEG | Sci-70 |
Table 3. Crossreactivity
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E. Expected Values
The expected values in the normal population were determined by assaying 100 normal donor sera The Expected values in the Renies 3 and 5 show the distribution of Sm/RNP results in the normal population performed manually and on MAGO respectively.
The distribution of EU/mI values for 50 clinically characterized sera along with the 100 normal donor sera are shown in Figures 4 and 6 performed manually and on MAGO respectively.
Image /page/3/Figure/3 description: The image is a graph titled "Is-anti-Sm/RNP Normals". The x-axis is labeled "Number of Sera" and ranges from 0 to 100. The y-axis is labeled "EU/ml" and ranges from 0.0 to 30.0. There is a horizontal line at approximately 20.0 EU/ml, and a curve that starts near 0.0 and increases to approximately 17.0 at the end of the x-axis.
Image /page/3/Figure/4 description: The image shows the title of a figure. The title is "Figure 3 Manual Normals". The text is in bold font.
Image /page/3/Figure/5 description: The image is a graph titled "ls-anti-Sm/RNP". The x-axis is labeled "Number of Sera" and ranges from 0 to 150. The y-axis is labeled "EU/ml" and ranges from 0.0 to 200.0. The graph shows a line that is relatively flat until the x value is approximately 100, then the line increases sharply until the x value is approximately 140, then the line flattens out again.
Figure 4 Manual Expected Values
Image /page/3/Figure/7 description: The image contains two line plots comparing EU/ml to the number of sera. The plot on the left is titled "Is-anti-Sm/RNP Normals", and the plot on the right is titled "Is-anti-Sm/RNP Expected Values". The left plot shows the number of sera ranging from 0 to 100, and the EU/ml ranges from 0 to 30. The right plot shows the number of sera ranging from 0 to 150, and the EU/ml ranges from 0 to 250.
Figure 5 MAGO Normals
Image /page/3/Figure/9 description: The image shows the text "Figure 6 MAGO Expected Values". The text is in bold font. The text is centered in the image.
F. Correlation of Manual and MAGO Results
Numerical comparison of EU/ml values, between manual and MAGO results for 150 samples in the Is-anti-Sm/RNP Test Kit showed a correlation of 0.99 (Pearson).
§ 866.5100 Antinuclear antibody immunological test system.
(a)
Identification. An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).(b)
Classification. Class II (performance standards).