(77 days)
The assay is intended for use in detecting antibodies to Jo-1 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-Jo-1 Test Kit System is an enzyme-linked immunosorbent assay (ELISA) for the detection and semi-quantitation of IgG to Jo-1 antigen in human serum.
Acceptance Criteria and Study for Diamedix Is-anti-Jo-1 Test System
1. Table of Acceptance Criteria & Reported Device Performance
The provided summary does not explicitly state pre-defined acceptance criteria with numerical targets. However, based on the Comparison Testing section, we can infer the performance metrics that were evaluated and achieved. The study demonstrates performance by comparing the device against a predicate device.
| Performance Metric | Implied Acceptance Criteria (Inferred from Predicate's Performance) | Reported Device Performance (Manual) | Reported Device Performance (MAGO) |
|---|---|---|---|
| Relative Sensitivity | High sensitivity (e.g., in the range of the predicate device, 95%) | 95% (18/19) | 95% (18/19) |
| Relative Specificity | High specificity (e.g., in the range of the predicate device, 99%) | 99% (142/144) | 99% (141/143) |
| Agreement | High agreement (e.g., in the range of the predicate device, 98%) | 98% (160/163) | 98% (159/162) |
| Linearity (R-squared) | High linearity (e.g., >0.99) | 0.9962 (Figure 1), 0.9911 (Figure 2) | Achieved (Figure 2 mentions MAGO linearity) |
| Precision (Intra-assay CV%) | Low variability (e.g., <20% for negative, <10% for positive) | Ranged from 3.1% to 18.2% | Ranged from 2.5% to 28.2% |
| Precision (Inter-assay CV%) | Low variability (e.g., <50% for negative, <15% for positive) | Ranged from 7.3% to 44.8% | Ranged from 6.2% to 31.3% |
| Cross-reactivity | No significant cross-reactivity with other autoimmune specificities | All 20 non-Jo-1 samples were negative for anti-Jo-1 | Not explicitly stated for MAGO mode, but assumed to be similar based on overall comparison. |
| Correlation (Manual vs. MAGO) | High correlation (e.g., >0.85) | Not applicable (comparison between manual and MAGO) | 0.87 (Pearson) |
2. Sample Size and Data Provenance for Test Set
- Sample Size: 163 serum samples were used for comparison testing. This consisted of 100 sera from normal blood donors and 63 sera from autoimmune patients.
- Data Provenance: The origin of the data (e.g., country) is not specified. It is likely a retrospective collection of existing serum samples. The summary states "63 sera from autoimmune patients," implying these were pre-diagnosed individuals.
3. Number of Experts and Qualifications for Ground Truth - Test Set
The document does not indicate the use of "experts" in the sense of clinicians or radiologists to establish ground truth for individual samples in the comparison testing. The autoimmune patient samples were "clinically characterized sera," implying their autoimmune status was determined through standard clinical diagnostic procedures, rather than by individual expert consensus on the specific test results within the study.
4. Adjudication Method for Test Set
The document does not describe an adjudication method for the test set. Instead, it compares the performance of the sponsor's device (Is-anti-Jo-1 Test Kit) to a predicate device (another commercially available anti-Jo-1 ELISA test kit). For discordant results, it mentions testing by a "third method," but this is not an adjudication process by experts to establish a definitive ground truth.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This device is an in-vitro diagnostic (IVD) assay, not an imaging device typically evaluated with MRMC studies comparing human readers with and without AI assistance. The "MAGO" system mentioned appears to be an automated assay platform or reading system rather than an AI in the sense of an algorithm interpreting complex data alongside a human.
6. Standalone Performance
Yes, a standalone performance of the algorithm (the Diamedix Is-anti-Jo-1 Test System) was done. The entire study describes the performance of this device in detecting and semi-quantitating anti-Jo-1 antibodies. The "Manual" results directly represent the standalone performance of the assay when manually processed.
7. Type of Ground Truth Used
The ground truth for the comparison testing was based on:
* Clinical Characterization: For the "63 sera from autoimmune patients," their status as autoimmune patients (and presumably Jo-1 positive or negative) was based on their clinical diagnosis, independent of the assay being tested.
* Normal Blood Donors: The 100 normal blood donor sera served as a negative control group, with the presumption that they are negative for anti-Jo-1 antibodies.
* Predicate Device/Third Method Comparison: The primary method of assessing sensitivity and specificity was by comparing results against a "commercially available anti-Jo-1 ELISA test kit" (the predicate device). In cases of discordance, a "third method" was used for further investigation, implying a hierarchical or confirmatory testing approach rather than a single definitive ground truth method by experts.
8. Sample Size for Training Set
The document does not explicitly mention a separate "training set" or "test set" in the context of machine learning or AI development. The samples discussed appear to be part of a single validation study for the device's performance. The device is an ELISA kit, not an AI algorithm that typically has distinct training and testing phases.
9. How Ground Truth for Training Set Was Established
As there is no explicit mention of a training set as understood in AI/machine learning contexts, this question is not directly applicable. The device's development and validation relied on established laboratory procedures and comparisons to existing methods for characterization.
{0}------------------------------------------------
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-Jo-1 Test System |
|---|---|
| Common Name: | Anti-Jo-1 EIA Test |
| Classification Name: | Extractable Antinuclear Antibody |
Equivalent Device:
Helix Diagnostics Enzyme Immunoassay Anti-Jo-1 Antibody Test Kit
Device Description: The Is-anti-Jo-1 Test Kit System is an enzyme-linked immunosorbent assay (ELISA) for the detection and semi-quantitation of IgG to Jo-1 antigen in human serum.
Intended use: The assay is intended for use in detecting antibodies to Jo-1 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-Jo-1 Test System is an enzyme-linked immunosorbent assay to detect IgG to Jo-1 in human serum. Purified Jo-1 antigen is attached to a solid phase microtiter well. Diluted test sera are added to each well. If antibodies which recognize the Jo-1 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.
{1}------------------------------------------------
Summary of Safety and Effectiveness
Performance Characteristics
A. Comparison Testing
The Diamedix Is-anti-Jo-1 Test Kit was evaluated relative to another commercially available anti-Jo-1 ELISA test kit using 100 sera from normal blood donors and 63 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 | 18/19 | 95 | 74-100 | 18/19 | 95 | 84-98 |
| RelativeSpecificity | 142/144 | 99 | 95-100 | 141/143 | 99 | 94-100 |
| Agreement | 160/163 | 98 | 95-100 | 159/162** | 98 | 92-99 |
** One equivocal sample was excluded from the calculations.
One serum negative by Is-anti-Jo-1 (manual) and positive by the comparative method was negative when tested by a third method. Of the two sera positive by Is-anti-Jo-1 (manual) and negative by the comparative method, one was positive and one was negative when tested by a third method. One serum negative by Isanti-Jo-1 (MAGO) and positive by the comparative method was negative when tested by a third method. Of the twp sera positive by Is-anti-Jo-1 (MAGO) and negative by the comparative method, one was positive and one was negative when tested by a third method. Two of the discordant sera were from patient samples.
B. Linearity
Figures 1 and 2 show typical examples of Is-anti-Jo-1 Test Kit linearity. The figures depict the results of the Calibrator tested by Is-anti-Jo-1 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-Jo-1 Test Kit throughout the testing range.
Image /page/1/Figure/9 description: The image is a graph titled "Is anti-Jo-1 Calibrator Linearity". The graph plots absorbance on the y-axis versus dilution on the x-axis. The graph shows a linear relationship between absorbance and dilution, with an R-squared value of 0.9962. The x-axis ranges from 0.0 to 1.0, while the y-axis ranges from 0.0 to 1.5.
Image /page/1/Figure/10 description: The image shows the title of a figure. The title is "Figure 1 Manual Linearity". The text is black and the background is white.
Image /page/1/Figure/11 description: The image is a graph titled "Is anti-Jo-1 Calibrator Linearity". The graph shows the relationship between absorbance and dilution. 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. The R-squared value of the graph is 0.9911.
Figure 2 MAGO Linearity
{2}------------------------------------------------
C. Precision Testing
The precision of the Is-anti-Jo-1 Test Kit was determined at Diamedix by testing six different sera and kit The problem of arrols in two runs on three different days. The intra- and interassay precision is shown in Table 2 below.
| Table 2 | anti-Jo-1 PRECISION | ||||
|---|---|---|---|---|---|
| Overall | MANUAL | MAGO | |||
| SERUM | MEAN EU/ml | INTRA-CV% | INTER-CV% | INTRA-CV % | INTER-CV % |
| 1 (NEG) | 1.8 | 9.2 | 11.1 | 13.7 | 11.1 |
| 2 (NEG) | 2.6 | 18.2 | 44.8 | 5.9 | 8.7 |
| 3 (POS) | 54.1 | 4.7 | 9.1 | 5.0 | 9.6 |
| 4 (POS) | 29.5 | 7.5 | 9.7 | 5.7 | 9.3 |
| 5 (POS) | 90.7 | 3.1 | 7.5 | 2.9 | 7.0 |
| 6 (POS) | 116.8 | 3.2 | 7.9 | 3.4 | 6.2 |
| CAL | 109.2 | 3.6 | 7.3 | 4.4 | 6.3 |
| POS CTRL | 54.5 | 3.2 | 9.2 | 2.5 | 9.7 |
| NEG CTRL | 1.5 | 12.1 | 15.4 | 28.2 | 31.3 |
D. Crossreactivity
. . . . . .
Twenty-four sera positive for the six autoimmune specificities were tested in Is- anti-Scl-70 Test Kit. The results are shown in Table 3.
| Sample | Is-anti-Jo-1 EU/ml | Interp | Specificity |
|---|---|---|---|
| 1 | 4.2 | NEG | SSA |
| 2 | 3.8 | NEG | SSA |
| 3 | 0.8 | NEG | SSA |
| 4 | 1.8 | NEG | SSA |
| 5 | 4.8 | NEG | SSB |
| 6 | 2.6 | NEG | SSB |
| 7 | 2.7 | NEG | SSB |
| 8 | 2.0 | NEG | SSB |
| 9 | 3.4 | NEG | Sm |
| 10 | 2.5 | NEG | Sm |
| 11 | 2.0 | NEG | Sm |
| 12 | 2.5 | NEG | Sm |
| 13 | 3.1 | NEG | RNP |
| 14 | 3.5 | NEG | RNP |
| 15 | 5.6 | NEG | RNP |
| 16 | 3.3 | NEG | RNP |
| 17 | 218.0 | POS | Jo-1 |
| 18 | 225.5 | POS | Jo-1 |
| 19 | 199.2 | POS | Jo-1 |
| 20 | 225.0 | POS | Jo-1 |
| 21 | 2.2 | NEG | Scl-70 |
| 22 | 3.8 | NEG | Scl-70 |
| 23 | 1.3 | NEG | Scl-70 |
| 24 | 1.5 | NEG | Scl-70 |
Table 3 Crossreactivity
{3}------------------------------------------------
E. Expected Values
The expected values in the normal population were determined by assaying 100 normal lonor serv The expected values in the normal population were decembed of Jo-1 results in the normal population performed manually and on MAGO respectively.
The distribution of EU/ml values for 63 clinically characterized sera along with the 100 normal donor sera The disulbution of EOMIN values for collection of MAGO respectively.
Image /page/3/Figure/3 description: The image is a graph titled "Is-anti-Jo-1 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 increases sharply near the end of the x-axis.
Image /page/3/Figure/4 description: The image is a graph titled "Is-anti-Jo-1 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. The graph shows a line that is relatively flat until the number of sera reaches approximately 140, at which point the line increases sharply.
Figure 3. Manual Normals
Figure 4. Manual Expected Values
Image /page/3/Figure/7 description: The image contains two plots comparing the Is-anti-Jo-1 normals and expected values. The left plot, titled "Is-anti-Jo-1 Normals," shows the distribution of values for normal samples, with the y-axis representing EU/ml and the x-axis representing the number of sera. The right plot, titled "Is-anti-Jo-1 Expected Values," shows the distribution of expected values, with a significant jump in EU/ml values after around 150 sera.
Figure 5. MAGO Normals
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-Jo-1 Test Kit showed a correlation of 0.87 (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).