(77 days)
The assay is intended for use in detecting antibodies to Sm 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 Test Kit System is an enzyme-linked immunosorbent assay (ELISA) for the detection and semi-quantitation of IgG to Sm antigen in human serum.
Acceptance Criteria and Device Performance Study for Diamedix Is-anti-Sm Test Kit
This document summarizes the acceptance criteria and the study conducted to demonstrate the performance of the Diamedix Is-anti-Sm Test Kit.
The Diamedix Is-anti-Sm Test Kit is an enzyme-linked immunosorbent assay (ELISA) designed for the detection and semi-quantitation of IgG to Sm antigen in human serum, intended as an aid in the diagnosis of autoimmune disorders.
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for the Is-anti-Sm Test Kit are not explicitly stated in terms of predefined thresholds. Instead, the performance is reported as a comparison to an equivalent, commercially available anti-Sm ELISA test kit. The "acceptance" is implicitly based on achieving comparable or superior performance metrics to the predicate device.
Here's a table summarizing the reported device performance against a comparative method:
| Metric | Predicate Device Performance (Implicit Acceptance Criteria) | Diamedix Is-anti-Sm Test Kit (Manual) Reported Performance | Diamedix Is-anti-Sm Test Kit (MAGO) Reported Performance |
|---|---|---|---|
| Relative Sensitivity | Not explicitly stated (comparison target) | 87% (34/39) [95% CI: 73-96] | 85% (35/41) [95% CI: 71-94] |
| Relative Specificity | Not explicitly stated (comparison target) | 100% (107/107) [95% CI: 97-100] | 100% (107/107) [95% CI: 97-100] |
| Overall Agreement | Not explicitly stated (comparison target) | 97% (141/146)* [95% CI: 92-99] | 96% (142/148)** [95% CI: 92-99] |
| Linearity (R-squared) | Not explicitly stated (comparison target) | 0.9949 | 0.9879 |
| Precision (Intra-CV%) | Not explicitly stated (comparison target) | Varies per serum (e.g., 2.8-12.1%) | Varies per serum (e.g., 2.1-47.2%) |
| Precision (Inter-CV%) | Not explicitly stated (comparison target) | Varies per serum (e.g., 3.5-25.0%) | Varies per serum (e.g., 3.4-50.0%) |
| Cross-reactivity | Absence of significant cross-reactivity | No false positives for non-Sm specificities shown | No false positives for non-Sm specificities shown |
| Correlation (Manual vs. MAGO) | Not explicitly stated (internal consistency metric) | 0.99 (Pearson) | 0.99 (Pearson) |
- Two equivocal and two borderline samples were excluded from the calculations.
** Two borderline samples were excluded from the calculations.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Comparison Testing: 150 sera (100 from normal blood donors and 50 from autoimmune patients).
- Precision Testing: 6 different sera and kit controls.
- Cross-reactivity: 24 sera positive for six different autoimmune specificities.
- Expected Values: 100 normal donor sera and 50 clinically characterized sera.
- Correlation of Manual and MAGO Results: 150 samples (presumably the same 100 normal and 50 autoimmune sera from comparison testing).
- Data Provenance: The 100 normal donor sera for expected values were collected in South Florida. The document does not specify the country of origin for the autoimmune patient sera or the sera used in comparison/precision/cross-reactivity testing, nor does it explicitly state if the data was retrospective or prospective. However, given the context of a 510(k) submission for a diagnostic device, it is typically presumed to be clinical study data, which often involves a mix of retrospective and prospective recruitment depending on the specific sample needs.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not specify the number of experts used or their qualifications for establishing the ground truth for the test set.
4. Adjudication Method for the Test Set
The document does not specify any formal adjudication method for the test set. For the "Comparison Testing," discordant results between the Is-anti-Sm kit and the comparative method were resolved by testing with "a third method," but the nature of this method or any adjudication process around it is not detailed.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
There is no indication that a multi-reader multi-case (MRMC) comparative effectiveness study was performed or that the device involves human interpretation in a manner that would be assisted by AI. The device is an ELISA test system, which generates quantitative (EU/ml) or categorical (positive/negative) results directly, rather than providing an image or data that a human "reader" would interpret in the traditional sense of an MRMC study. Therefore, there is no information on the effect size of human readers improving with AI vs. without AI assistance.
6. Standalone (Algorithm Only) Performance Study
The study implicitly represents standalone performance. The "Diamedix Is-anti-Sm Test Kit" is a laboratory diagnostic device, and its performance metrics (sensitivity, specificity, linearity, precision, cross-reactivity) are derived from the device's output, either performed manually or with the "MAGO" system. There is no human-in-the-loop component mentioned in interpreting the raw output of the ELISA.
7. Type of Ground Truth Used
The ground truth for the test set appears to be established through:
- Clinical Diagnosis: For the "autoimmune patients," the description mentions "autoimmune patients" and "clinically characterized sera," implying a diagnosis based on established clinical criteria.
- Absence of Disease: For "normal blood donors," the ground truth is the absence of the condition (i.e., not having an autoimmune disorder requiring anti-Sm antibodies).
- Reference Method/Predicate Device: For "Comparison Testing," the performance is benchmarked against "another commercially available anti-Sm ELISA test kit." For discordant results, "a third method" was used, which served as a tie-breaker or confirmatory ground truth.
- Known Specificity: For "Cross-reactivity" testing, the ground truth was the known specificity of the sera (e.g., positive for SSA, SSB, Sm, RNP, Jo-1, Scl-70).
This suggests a combination of clinical diagnoses and established reference methods rather than pathology reports or direct outcomes data.
8. Sample Size for the Training Set
The document does not provide information regarding a distinct "training set" or its sample size. For in vitro diagnostic (IVD) devices like this ELISA kit, the development process typically involves optimizing reagents and protocols, but a formal "training set" in the machine learning sense is not usually delineated as it would be for an AI/ML algorithm. The performance studies described are for the finalized device.
9. How the Ground Truth for the Training Set Was Established
As no distinct training set is mentioned in the provided text, there is no information on how its ground truth might have been established. Any internal development and optimization would have relied on similar forms of ground truth (e.g., characterized patient samples, known positive/negative controls).
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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 |
Device Information:
Fax Number:
Trade Name: Is-(immunosimplicity)-anti-Sm Test System Common Name: Anti-Sm EIA Test Classification Name: Extractable Antinuclear Antibody
305-324-2585
Equivalent Device:
Helix Diagnostics Enzyme Immunoassay Anti-Sm Antibody Test Kit
Device Description: The Is-anti-Sm Test Kit System is an enzyme-linked immunosorbent assay (ELISA) for the detection and semi-quantitation of IgG to Sm antigen in human serum.
Intended use: The assay is intended for use in detecting antibodies to Sm 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 Test System is an enzyme-linked immunosorbent assay to detect IgG to Sm antigen in human serum. Purified Sm antigen is attached to a solid phase microtiter well. Diluted test sera are added to each well. If antibodies which recognize the Sm 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 Test Kit was evaluated relative to another commercially available anti-Sm 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 | 34/39 | 87 | 73-96 | 35/41 | 85 | 71-94 |
| RelativeSpecificity | 107/107 | 100 | 97-100 | 107/107 | 100 | 97-100 |
| Agreement | 141/146* | 97 | 92-99 | 142/148** | 96 | 92-99 |
- Two equivocal and two borderline samples were excluded from the calculations.
** Two borderline samples were excluded from the calculations.
Five sera negative by Is-anti-Sm (manual) and positive by the comparative method were negative when tested by a third method. Six sera negative by Is-anti-Sm (MAGO) and positive by the comparative method were negative when tested by a third method. All discordant sera were from patient samples.
B. Linearity
Figures 1 and 2 show typical examples of Is-anti-Sm Test Kit linearity. The figures depict the results of the Calibrator tested by Is-anti-Sm 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 Is-anti-Sm Test Kit throughout the testing range.
Image /page/1/Figure/10 description: The image contains two graphs titled "Is anti-Sm Calibrator Linearity". Both graphs show the relationship between absorbance and dilution. The graph on the left is labeled "Figure 1 Manual Linearity" and has an R-squared value of 0.9949, while the graph on the right is labeled "Figure 2 MAGO Linearity" and has an R-squared value of 0.9879.
Figure 1 Manual Linearity
Image /page/1/Figure/12 description: The image shows the text "Figure 2 MAGO Linearity". The text is in black font and is centered in the image. The text is likely a title or caption for a figure in a document. The figure is likely related to the linearity of MAGO, which may be a chemical compound or a process.
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C. Precision Testing
The precision of the Is-anti-Sm Test Kit was determined at Diamedix by testing six different sera and kit The precision of the in and con-res on three different days. The intra- and interassay precision is shown in Table 2 below.
| Table 2 | Z anti-Sm PRECISION | ||||
|---|---|---|---|---|---|
| OverallMEAN EU/ml | MANUAL | MAGO | |||
| SERUM | INTRA-CV% | INTER-CV% | INTRA-CV % | INTER-CV % | |
| 1 (NEG) | 1.6 | 8.2 | 7.1 | 19.7 | 23.5 |
| 2 (NEG) | 1.6 | 9.2 | 25.0 | 10.2 | 13.3 |
| 3 (POS) | 56.0 | 3.2 | 3.5 | 3.9 | 4.5 |
| 4 (POS) | 38.4 | 5.5 | 5.7 | 3.4 | 7.9 |
| 5 (POS) | 80.7 | 3.9 | 4.6 | 2.1 | 3.4 |
| 6 (POS) | 93.9 | 2.8 | 3.6 | 2.7 | 5.3 |
| CAL | 104.3 | 2.8 | 4.2 | 3.7 | 6.7 |
| POS CTRL | 52.6 | 3.1 | 4.2 | 5.2 | 7.6 |
| NEG CTRL | 0.8 | 12.1 | 25.0 | 47.2 | 50.0 |
D. Crossreactivity
Twenty-four sera positive for the six autoimmune specificities were tested in Is- anti-Sm Test Kit. The results afe shown in Table 3.
| Sample | Is anti-Sm | Interp | Specificity |
|---|---|---|---|
| 1 | 2.2 | NEG | SSA |
| 2 | 2.6 | NEG | SSA |
| 3 | 1.4 | NEG | SSA |
| 4 | 1.3 | NEG | SSA |
| 5 | 2.0 | NEG | SSB |
| 6 | 2.2 | NEG | SSB |
| 7 | 2.1 | NEG | SSB |
| 8 | 1.5 | NEG | SSB |
| 9 | 78.2 | POS | Sm |
| 10 | 66.4 | POS | Sm |
| 11 | 103.6 | POS | Sm |
| 12 | 103.1 | POS | Sm |
| 13 | 7.1 | NEG | RNP |
| 14 | 3.8 | NEG | RNP |
| 15 | 10.2 | NEG | RNP |
| 16 | 2.1 | NEG | RNP |
| 17 | 2.8 | NEG | Jo-1 |
| 18 | 4.0 | NEG | Jo-1 |
| 19 | 3.4 | NEG | Jo-1 |
| 20 | 2.6 | NEG | Jo-1 |
| 21 | 1.6 | NEG | Scl-70 |
| 22 | 2.0 | NEG | Scl-70 |
| 23 | 2.3 | NEG | Scl-70 |
| 24 | 1.9 | NEG | Scl-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 collected in South Florida. Figures 3 and 5 show the distribution of Sm results in the normal population performed manually and on MAGO respectively.
The distribution of EU/ml 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 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 20.0 and a curve that starts near 0.0 and increases to approximately 14.0 at the end of the graph.
Image /page/3/Figure/4 description: The image is a graph titled "Is-anti-Sm Expected Values". 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 around 100, then it increases sharply.
Figure 3 Manual Normals
Image /page/3/Figure/6 description: The image is a graph titled "Is-anti-Sm 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 gradually increases to approximately 5.0 at the end of the x-axis.
Figure 5 MAGO Normals
Figure 4 Manual Expected Values
Image /page/3/Figure/9 description: This image is a graph titled "Is-anti-Sm Expected Values". 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 180.0. There is a horizontal line at approximately 20.0 on the y-axis, and a curve that starts near 0 and increases sharply after 100 on the x-axis.
Figure 6 MAGO Expected Values
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 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).