(77 days)
The assay is intended for use in detecting antibodies to SSA (Ro) 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-SSA Test Kit System is an enzyme-linked immunosorbent assay (ELISA) for the detection and semi-quantitation of IgG to SSA (Ro) antigen in human serum.
Here's a breakdown of the acceptance criteria and study details based on the provided text:
Acceptance Criteria and Device Performance
The provided document describes a comparison study against a predicate device. The acceptance criteria are implicitly defined by the performance of the predicate device and the desired level of agreement, sensitivity, and specificity.
Table 1: Acceptance Criteria and Reported Device Performance (Comparison Testing)
| Metric | Acceptance Criteria (Implied by Predicate - Helix Diagnostics) | Is-anti-SSA Test System (Manual) Performance | Is-anti-SSA Test System (MAGO) Performance |
|---|---|---|---|
| Relative Sensitivity | High (e.g., in the 90s) | 93% (64/69) with 95% CI (84-98) | 93% (64/69) with 95% CI (84-98) |
| Relative Specificity | Very High (e.g., in the high 90s) | 99% (92/93) with 95% CI (94-100) | 98% (91/93) with 95% CI (92-100) |
| Agreement | Very High (e.g., in the high 90s) | 96% (156/162*) with 95% CI (92-99) | 96% (155/162*) with 95% CI (91-98) |
Note: Three borderline samples were excluded from the agreement calculation.
Additional Performance Characteristics:
- Linearity: The device demonstrated a high degree of linearity throughout the testing range, both manually (R-squared = 0.9892) and with MAGO (R-squared = 0.9795).
- Precision:
- Intra-assay CV% for Positives: Ranged from 3.1% to 6.5% (Manual) and 2.3% to 6.6% (MAGO).
- Inter-assay CV% for Positives: Ranged from 5.0% to 8.5% (Manual) and 4.4% to 10.4% (MAGO).
- Intra-assay CV% for Negatives: Ranged from 6.5% to 14.5% (Manual) and 11.1% to 16.3% (MAGO).
- Inter-assay CV% for Negatives: Ranged from 20.0% to 22.2% (Manual) and 12.5% to 13.0% (MAGO).
- Cross-reactivity: Out of 24 sera positive for other autoimmune specificities, 4 anti-SSA positive and 4 anti-SSB positive sera were correctly identified as positive for SSA. One Sm positive sample was also positive for SSA (confirmed by an alternative ELISA), and one RNP positive sample was equivocal. The remaining 14 samples with other specificities (Sm, RNP, Jo-1, Scl-70) were negative for SSA, suggesting low cross-reactivity with these specificities.
- Correlation of Manual and MAGO Results: Pearson correlation of 0.85 for 165 samples.
Study Details
-
Sample Size used for the test set and the data provenance:
- Sample Size: 165 sera (100 from normal blood donors and 65 from autoimmune patients).
- This is the total for the comparison testing. For cross-reactivity, 24 sera were used. For precision, 6 sera, the calibrator, and controls were used. For expected values, 100 normal donor sera and 65 clinically characterized sera were used.
- Data Provenance: The 100 normal donor sera were collected in South Florida. The provenance of the 65 autoimmune patient sera is not explicitly stated but implies a clinical setting. This indicates a retrospective evaluation of collected samples.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not specify the number of experts or their qualifications for establishing the ground truth. The "ground truth" for the comparison study appears to be defined by the results of the "commercially available anti-SSA ELISA test kit" (predicate device) and, in some ambiguous or discrepant cases, by a "third method" or a "referee method". For the "clinically characterized sera" used in expected values, the clinical characterization would likely have been established by medical professionals, but their specific roles, number, or qualifications are not detailed.
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Adjudication method for the test set:
- The primary method was comparison to a predicate device.
- In cases of disagreement between the predicate and the "Is-anti-SSA Test System", a "third method" or "referee method" was used for adjudication. For example, "Five sera negative by Is-anti-SSA (manual and MAGO) and positive by the comparative method were negative when tested by a third method." and "For manual testing, one serum positive by Is-anti-SSA and negative by the comparative method was negative when tested by a referee method." This suggests a form of discrepancy resolution with an additional method, but not necessarily by human experts.
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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 was not an MRMC comparative effectiveness study involving human readers and AI assistance. This device is an immunoassay (ELISA) test kit which is typically run in a lab, either manually or using an automated instrument (MAGO). The "manual" and "MAGO" refer to the method of running the test (manual pipetting and reading vs. automated instrument), not to human reader interpretation of complex images or data that AI would typically assist with.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, performance of the device "MAGO" (an automated instrument processing the immunoassay) can be considered a standalone performance, as it generates results without direct human interpretation of the assay reaction in the same way a human reader interprets an image. The manual method also provides standalone performance of the kit itself. The comparison to other tests (predicate, third method) establishes its diagnostic accuracy.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The ground truth for the comparison study was largely based on the results of a commercially available predicate anti-SSA ELISA test kit and, for discrepant cases, confirmation by a "third method" or "referee method."
- For the "Expected Values" section, 65 "clinically characterized sera" were used, implying clinical diagnosis or patient outcomes as a ground truth, but the details are sparse.
- For the cross-reactivity study, the samples were "positive for the six autoimmune specificities," suggesting pre-established diagnostic criteria or other validated assays for these specificities.
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The sample size for the training set:
- The document does not specify a separate "training set" in the context of machine learning or AI models. This device is a diagnostic test kit (ELISA), and the data provided relates to its analytical and clinical performance against reference methods and established populations.
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How the ground truth for the training set was established:
- As there's no explicit "training set" in the AI/ML sense, this question is not directly applicable. The "training" for such an immunoassay kit would involve its internal development and optimization based on known positive and negative controls and antigen/antibody interactions, which is not detailed in this 510(k) summary.
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K970218
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-SSA Test System |
|---|---|
| Common Name: | Anti-SSA EIA Test |
| Classification Name: | Extractable Antinuclear Antibody |
305-324-2585
Equivalent Device:
Helix Diagnostics Enzyme Immunoassay Anti-SS-A/Ro Antibody Test Kit
Device Description: The Is-anti-SSA Test Kit System is an enzyme-linked immunosorbent assay (ELISA) for the detection and semi-quantitation of IgG to SSA (Ro) antigen in human serum.
Intended use: The assay is intended for use in detecting antibodies to SSA (Ro) 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-SSA Test System is an enzyme-linked immunosorbent assay to detect IgG to SSA (Ro) in human serum. Purified SSA (Ro) antigen is attached to a solid phase microtiter well. Diluted test sera are added to each well. If antibodies which recognize the SSA 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-SSA Test Kit was evaluated relative to another commercially available anti-SSA ELISA test kit using 100 sera from normal blood donors and 65 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 | 64/69 | 93 | 84-98 | 64/69 | 93 | 84-98 |
| RelativeSpecificity | 92/93 | 99 | 94-100 | 91/93 | 98 | 92-100 |
| Agreement | 156/162* | 96 | 92-99 | 155-162* | 96 | 91-98 |
- Three borderline samples were excluded from the calculation.
Five sera negative by Is-anti-SSA (manual and MAGO) and positive by the comparative method were negative when tested by a third method. For manual testing, one serum positive by Is-anti-SSA and negative by the comparative method was negative when tested by a referee method. For MAGO testing, two sera were positive by Is-anti-SSA and negative by the comparative method. When tested by a third method, one was negative and one was positive.
B. Linearity
Figures 1 and 2 show typical examples of Is-anti-SSA Test Kit linearity. The figures depict the results of the Calibrator tested by Is-anti-SSA 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-SSA Test Kit throughout the testing range.
Image /page/1/Figure/9 description: The image is a plot titled "Is anti-SSA Calibrator Linearity". The plot 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 plot also shows an R-squared value of 0.9892.
Figure 1 Manual Linearity
Image /page/1/Figure/11 description: The image is a graph titled "Is anti-SSA 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 2.5. The graph shows a linear relationship between dilution and absorbance, with an R-squared value of 0.9795.
Figure 2 MAGO Linearity
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C. Precision Testing
| Table 2 | Z anti-SSA PRECISION | ||||
|---|---|---|---|---|---|
| SERUM | OverallMEANEU/ml | MANUAL | MAGO | ||
| INTRA-CV% | INTER-CV% | INTRA-CV% | INTER-CV% | ||
| 1 (NEG) | 2.0 | 14.5 | 22.2 | 16.3 | 13.0 |
| 2 (NEG) | 2.4 | 6.5 | 20.0 | 11.1 | 12.5 |
| 3 (POS) | 46.7 | 4.1 | 6.3 | 3.9 | 5.2 |
| 4 (POS) | 23.6 | 6.5 | 8.5 | 6.6 | 10.4 |
| 5 (POS) | 65.6 | 5.0 | 8.2 | 2.3 | 5.2 |
| 6 (POS) | 104.5 | 4.4 | 7.5 | 2.4 | 4.4 |
| CAL | 100.1 | 4.8 | 5.8 | 6.2 | 8.6 |
| POS CTRL | 42.6 | 3.1 | 5.0 | 5.0 | 7.4 |
| NEG CTRL | 1.5 | 9.1 | 21.4 | 24.9 | 25.0 |
The precision of the Is-anti-SSA Test Kit was determined at Diamedix by testing six different sera and kit Calibrator and controls in two runs on three different days. The intra- and interassay precision is shown in Table 2 below.
D. Crossreactivity
Twenty-four sera positive for the six autoimmune specificities were tested in Z anti-SSA Test Kit. The results are shown in Table 5. Since anti-SSB antibodies are nearly always accompanied by anti-SSA antibodies, samples 5-8 are positive in the anti-SSA test due to the additional presence of anti-SSA antibodies,
| Sample | Is-anti-SSA EU/ml | Interp | Specificity |
|---|---|---|---|
| 1 | 154.8 | POS | SSA |
| 2 | 204.0 | POS | SSA |
| 3 | 54.8 | POS | SSA |
| 4 | 203.6 | POS | SSA |
| 5 | 203.7 | POS | SSB |
| 6 | 204.7 | POS | SSB |
| 7 | 203.9 | POS | SSB |
| 8 | 203.7 | POS | SSB |
| 9 | 31.8* | POS | Sm |
| 10 | 4.4 | NEG | Sm |
| 11 | 1.8 | NEG | Sm |
| 12 | 3.6 | NEG | Sm |
| 13 | 6.0 | NEG | RNP |
| 14 | 18.2** | EQ | RNP |
| 15 | 8.0 | NEG | RNP |
| 16 | 6.8 | NEG | RNP |
| 17 | 2.5 | NEG | Jo-1 |
| 18 | 5.1 | NEG | Jo-1 |
| 19 | 4.3 | NEG | Jo-1 |
| 20 | 2.6 | NEG | Jo-1 |
| 21 | 4.1 | NEG | Scl-70 |
| 22 | 6.4 | NEG | Scl-70 |
| 23 | 2.1 | NEG | Scl-70 |
| 24 | 6.5 | NEG | Scl-70 |
*Confirmed positive for anti-SSA by an alternative ELISA method.
** Repeated equivocal in Is-anti-SSA.
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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 SSA results in the normal population performed manually and on MAGO respectively.
The distribution of EU/ml values for 65 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-SSA 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 EU/ml and a curve that starts at 0.0 and increases to approximately 26.0 at 100 Sera.
Image /page/3/Figure/4 description: The image shows a graph titled "Is anti-SSA Expected Values". The x-axis is labeled "Number of Sera" and ranges from 0 to 160. The y-axis is labeled "EU/m" and ranges from 0.0 to 240.0, with a horizontal line at approximately 20.0.
Figure 3. Manual Normals
Image /page/3/Figure/6 description: This image is a graph titled "Is anti-SSA 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 to 40.0. There is a horizontal line at 20.0 on the y-axis.
Image /page/3/Figure/7 description: The image is completely white and contains no discernible objects, shapes, or patterns. The image appears to be a blank canvas with a uniform color distribution. There are no variations in tone, texture, or shading present. It is a simple, unadorned image with no visual elements.
Figure 5. MAGO Normals
Image /page/3/Figure/8 description: The image shows the title of a figure. The title is "Figure 4. Manual Expected Values". The text is in bold font.
Image /page/3/Figure/9 description: This image is a graph titled "Is-enti-SSA 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 250.0. The graph shows a line that is relatively flat at the bottom until the number of sera reaches 100, at which point the line increases sharply.
Figure 6. MAGO Expected Values
F. Correlation of Manual and MAGO Results
Numerical comparison of EU/ml values, between manual and MAGO results for 165 samples in the Is-anti-SSA Test Kit showed a correlation of 0.85 (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).