(130 days)
The MarDx ENA IgG ImmunoStripe Test System is intended for use in testing human serum for the presence of human IgG to extractable nuclear antigens, as an aid in the diagnosis of autoimmune disease, such as systemic lupus erythematosus. Siogren syndrome, scieroderma, and myositis.
The MarDx ENA IgG Immunostripe Test System is an enzyme-linked immunosorbent assay (ElA) for the detection of IgG to extractable nuclear antigens in human serum.
The MarDx ENA IgG Immunostripe Test System is an enzyme-linked immunosorbent assay (EIA) for the detection of IgG to extractable nuclear antigens (SSA, SSB, Sm, RNP, Jo-1, Scl-70) in human serum. It is intended for use as an aid in diagnosing autoimmune diseases such as systemic lupus erythematosus, Sjogren's syndrome, scleroderma, and myositis.
The device's performance was evaluated by comparing it against two predicate devices: the INOVA ENA's for SSA, SSB, Sm, RNP, Jo-1, Scl-70, and the MarDx ENA EIA 6 in 1 Test System.
1. Table of Acceptance Criteria and the Reported Device Performance
Although explicit "acceptance criteria" values were not formally stated as thresholds in the provided text, the study aimed to demonstrate "substantial equivalence" to predicate devices, implying that performance metrics (sensitivity and specificity) should be comparable. Based on the study results, the implied acceptance criteria were successfully met.
| Metric (Antigen / Condition) | Implied Acceptance Criteria (via predicate equivalence) | Reported Device Performance (MarDx Immunostripe) |
|---|---|---|
| Specificity (vs INOVA EIA) | High specificity (comparable to INOVA) | 100% (40/40) |
| Specificity (vs MarDx 6-in-1 EIA) | High specificity (comparable to MarDx 6-in-1) | 100% (139/139) |
| Sensitivity (SSA vs INOVA SSA EIA) | High sensitivity (comparable to INOVA SSA) | 95% (35/37) |
| Sensitivity (SSB vs INOVA SSB EIA) | High sensitivity (comparable to INOVA SSB) | 94% (16/17) |
| Sensitivity (Sm vs INOVA Sm EIA) | High sensitivity (comparable to INOVA Sm) | 100% (20/20) |
| Sensitivity (RNP vs INOVA RNP EIA) | High sensitivity (comparable to INOVA RNP) | 89% (33/37) |
| Sensitivity (Jo-1 vs INOVA Jo-1 EIA) | High sensitivity (comparable to INOVA Jo-1) | 100% (2/2) |
| Sensitivity (Scl-70 vs INOVA Scl-70 EIA) | High sensitivity (comparable to INOVA Scl-70) | 100% (7/7) |
| Sensitivity (Combined ENA vs INOVA) | High sensitivity (comparable to combined INOVA ENA) | 94% (113/120) |
| Sensitivity (vs MarDx 6-in-1 ENA EIA) | High sensitivity (comparable to MarDx 6-in-1) | 97% (67/69) |
| Overall Combined Sensitivity | Not explicitly stated, but high | 95% |
| Overall Combined Specificity | Not explicitly stated, but high | 100% |
| Precision | High precision | 100% (within and between assays) |
| Cross-Reactivity (to dsDNA) | No cross-reactivity | 0% (7/7 negative) |
2. Sample Size Used for the Test Set and the Data Provenance
A total of 264 sera were used in the comparative study.
- 139 sera were from normal individuals.
- 125 sera were from patients "thought to have autoimmune disease and submitted as blind specimens for ENA antigen detection."
The data provenance is not explicitly stated in terms of country of origin. The study was conducted by the R&D laboratory at MarDx. The nature of the "blind specimens" suggests a prospective collection or at least blinding of historical samples for the purpose of the study. The phrasing "sera from patients thought to have autoimmune disease" indicates these were clinical samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
No experts were used to establish the ground truth in this study. The ground truth was established by the predicate devices (INOVA ELISA for ENA antibodies and MarDx 6 in 1 ENA EIA), which served as the reference standards.
4. Adjudication Method for the Test Set
No adjudication method was used for the test set. The results of the predicate devices were directly treated as the reference standard ("ground truth") against which the MarDx ENA IgG Immunostripe Test System was compared.
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
This was not a multi-reader multi-case (MRMC) comparative effectiveness study, nor did it involve AI. The device is a diagnostic assay, and its performance was evaluated against established predicate assays. Therefore, no effect size related to human reader improvement with or without AI assistance is applicable or reported.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
This study evaluates the performance of a diagnostic assay (MarDx ENA IgG Immunostripe Test System) in a standalone manner, comparing its results directly against those of predicate assays. The "human-in-the-loop" aspect for reading the strip and interpreting the results is inherently part of the assay's use, but the reported performance metrics (sensitivity, specificity, precision, cross-reactivity) refer to the device's ability to correctly identify the presence or absence of antibodies as determined by the assay itself, not an algorithm's interpretation without human oversight. The "manufacturer's package insert" states how the assays were performed, implying a standard, non-automated reading of the strip results.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The ground truth used was the results obtained from established predicate devices:
- INOVA ELISA for ENA antibodies (for SSA, SSB, Sm, RNP, Jo-1, Scl-70)
- MarDx ENA EIA 6 in 1 Test System
These predicate devices serve as the reference standard due to their prior clearance or established clinical use for detecting these specific antibodies.
8. The Sample Size for the Training Set
No explicit training set is mentioned as this is a traditional diagnostic assay validation, not a machine learning model. The assay itself (reagent formulation, stripe design) would have been developed and optimized, but the study focuses on the validation of the final product with a test set of clinical samples.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there was no explicit separate training set for a machine learning model. The development of the assay itself would have involved internal validation and optimization, likely using characterized positive and negative control samples, but this information is not detailed in the summary.
{0}------------------------------------------------
ATTACHMENT 1 - 510K Summary
APR -8 1997
510(k) Summary of Safety and Effectiveness Information MarDx ENA IgG Immunostripe Test System
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and proposed 21 CFR Part 807.92.
ldentification of Predicate Devices:
The MarDx ENA IgG Immunostripe Test System is substantially equivalent to the INOVA ENA's for SSA, SSB. Sm. RNP. Jo-1, Scl-70 and the MarDx ENA EIA 6 in 1 Test System for the detection of immunoglobulin to SSA, SSB, Sm, RNP, Jo-1, Scl-70 in human serum.
Description of New Device:
The MarDx ENA IgG Immunostripe Test System is an enzyme-linked immunosorbent assay (ElA) for the detection of IgG to extractable nuclear antigens in human serum.
Statement of Intended Use:
The MarDx ENA IgG ImmunoStripe Test System is intended for use in testing human serum for the presence of human IgG to extractable nuclear antigens, as an aid in the diagnosis of autoimmune disease, such as systemic lupus erythematosus. Siogren syndrome, scieroderma, and myositis.
Technological Characteristics of the Device:
The MarDx ENA IgG Immunostripe Test System is an enzyme linked immunosorbent assay to detect IgG, to SSA, SSB, Sm, RNP, Jo-1, Scl-70. Purfiled antigens are individually attached to specific locations on a solid phase support, nitrocellulose. Diluted test sera is added to a well containing the Immunostripe strip. If the antibodies are present that recognize an antigen, they will bind to the antigen present on the strip. After incubation the nitrocellulose strip is washed to remove unbound antibody. An enzyme labeled antihuman IgG is added to each strip. If antibody is present the conjugate will bind to the antibody attached to the specific antigens. The strip is washed to remove unbound coniugate and a substrate solution is then added. If the enzyme/antibody complex is present, the substrate will undergo a precipitation and color change. After an incubation period, the reaction is stopped and the presence of precipitated substrate is visualized at specific locations on the strip. The presence of a colored precipitation at pre-determined locations on the Immunostripe strip is an indirect measurement of specific antibody for SSA, SSB, Sm, RNP, Jo-1, Scl-70 in the patient specimen.
Description and Conclusions of the Clinical Studies.
The MarDx ENA IgG Immunostripe Test System is substantially equivalent to the INOVA ENA EIA's for SSA, SSB, Sm, RNP, Jo-1, Scl-70 and the MarDx ENA EIA 6 in 1 Test System for the detection of immunoglobulin to SSA, SSB, Sm, RNP, Jo-1, Scl-70 in human serum. Equivalence is demonstrated by the following comparative results:
{1}------------------------------------------------
Two hundred and sixty four sera were tested by EIA (INOVA ELISA for ENA antibodies), and the MarDx 6 in 1 ENA EIA, to determine the relative sensitivity and specificity of the MarDx ENA IgG Immunostripe test kit. One hundred and thirty-nine of the sera were from normal individuals which should not have antibodies to ENA antigens. One hundred and twenty five sera were from patients thought to have autoimmune disease and submitted as blind specimens for ENA antigen detection. The MarDx and INOVA assays were performed by the R&D laboratory at MarDx following manufacturer's package insert. Assay sensitivity ranged from 89 to 100%, specificity was 100%. The raw data from the study is prepared in Attachment 5. The data is summarized in Tables 1-11.
| Table 1 |
|---|
| Specificity of the MarDx ENA IgG Immunostripe Test System |
| relative to the INOVA EIA Test Systems |
| INOVA EIA | ||||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| MarDx | Positive | 0 | 0 | 0 |
| Immunostripe | Negative | 0 | 40 | 40 |
| Total | 0 | 40 | 40 |
(40/40) = 100% Specificity
| Table 2 |
|---|
| Specificity of the MarDx ENA IgG Immunostripe Test System |
| relative to the MarDx 6 in 1 ENA ElA Test System |
| MarDx 6 in 1 ENA EIA | ||||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| MarDxImmunostripe | Positive | 0 | 0 | 0 |
| Negative | 0 | 139 | 139 | |
| Total | 0 | 139 | 139 |
Specificity (139/139) = 100%
Table 3
Sensitivity of the MarDx ENA IgG Immunostripe Test System relative to the INOVA SSA EIA Test System
| Antigen: SSA | INOVA SSA EIA | |||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| MarDx | Positive | 35 | 0 | 35 |
| Immunostripe | Negative | 2 | 0 | 2 |
| Total | 37 | 0 | 37 |
SSA Sensitivity (35/37) = 95%
{2}------------------------------------------------
Table 4 Sensitivity of the MarDx ENA IgG Immunostripe Test System relative to the INOVA SSB EIA Test System
| Antigen: SSB | INOVA SSB EIA | |||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| MarDx | Positive | 16 | 0 | 16 |
| Immunostripe | ||||
| Negative | 1 | 0 | 1 | |
| Total | 17 | 0 | 17 |
SSB Sensitivity (16/17) = 94%
| Table 5 | |||
|---|---|---|---|
| Sensitivity of the MarDx ENA IgG Immunostripe Test System | |||
| relative to the INOVA Sm EIA Test System |
| Antigen: Sm | INOVA Sm EIA | |||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| MarDx | Positive | 20 | 1 | 21 |
| Immunostripe | ||||
| Negative | 0 | 0 | 0 | |
| Total | 20 | 1 | 21 |
Sm Sensitivity (20/20)= 100%
Table 6 Sensitivity of the MarDx ENA IgG Immunostripe Test System relative to the INOVA RNP EIA Test System
| Antigen: RNP | INOVA RNP EIA | |||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| MarDx | Positive | 33 | 0 | 33 |
| Immunostripe | ||||
| Negative | 4 | 0 | 4 | |
| Total | 37 | 0 | 37 |
RNP Sensitivity (33/37) = 89%
{3}------------------------------------------------
Table 7 Sensitivity of the MarDx ENA IgG Immunostripe Test System relative to the INOVA Jo-1 ElA Test System
| Antigen: Jo-1 | INOVA Jo-1 EIA | |||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| MarDxImmunostripe | Positive | 2 | 0 | 2 |
| Negative | 0 | 0 | 0 | |
| Total | 2 | 0 | 2 |
Jo-1 Sensitivity (2/2)= 100%
Table 8 Sensitivity of the MarDx ENA IgG Immunostripe Test System relative to the INOVA Scl-70 ElA Test System
| Antigen: Scl-70 | INOVA Scl-70 | |||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| MarDxImmunostripe | Positive | 7 | 0 | 7 |
| Negative | 0 | 0 | 0 | |
| Total | 7 | 0 | 7 |
Scl-70 Sensitivity (7/7)= 100%
Table 9
INOVA SUMMARY
Sensitivity of the MarDx ENA IgG Immunostripe Test System relative to the Six Combined Results from the INOVA ENA EIA Test Systems
| Combined | INOVA ENA EIA | |||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| MarDxImmunostripe | Positive | 113 | 0 | 113 |
| Negative | 7 | 0 | 7 | |
| Total | 120 | 0 | 120 |
Sensitivity (113/120) = 94%
.
. .
{4}------------------------------------------------
Table 10
| MarDx ENA EIA | ||||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| MarDxImmunostripe | Positive | 67 | 0 | 67 |
| Negative | 2 | 0 | 2 | |
| Total | 69 | 0 | 69 |
Sensitivity of the MarDx ENA IgG Immunostripe Test System relative to the MarDx 6 in 1 ENA EIA Test System
Sensitivity (67/69) = 97%
Table 11 Summary Table For All Data
| MarDx | ReferenceManufacturer | Number ofSpecimens | Reference | Sensitivity | Specificity |
|---|---|---|---|---|---|
| Immunostripe | vs INOVA | 35/37 | SSA | 95% | NA |
| Immunostripe | vs INOVA | 16/17 | SSB | 94% | NA |
| Immunostripe | vs INOVA | 20/20 | Sm | 100% | NA |
| Immunostripe | vs INOVA | 33/37 | RNP | 89% | NA |
| Immunostripe | vs INOVA | 2/2 | Jo-1 | 100% | NA |
| Immunostripe | vs INOVA | 7/7 | Scl-70 | 100% | NA |
| Immunostripe | vs INOVA | 40/40 | Normals | NA | 100% |
| Immunostripe | vs MarDx | 67/69 | 6 in 1 | 97% | NA |
| Immunostripe | vs MarDx | 139/139 | Normals | NA | 100% |
| Immunostripe | Combined Sensitivity and Specificity | 95% | 100% |
판
{5}------------------------------------------------
Precision Study
The precision data is presented in Table 10 for 7 sera (Jo-1, 3 sera) assayed 8 times each on three The precision data is presented in Table 10 for 7 Sera (60 1) 6 Series (60 million)
different assays. The data indicates that the MarDx ENA Immunostripe has a high degree of precision both within and between assays.
| Sample | Assay 1 | Assay 2 | Assay 3 | |||
|---|---|---|---|---|---|---|
| Ratio | Percent | Ratio | Percent | Ratio | Percent | |
| 1 SSA | 7/7 | 100% | 7/7 | 100% | 7/7 | 100% |
| 2 SSB | 7/7 | 100% | 7/7 | 100% | 7/7 | 100% |
| 3 Sm | 7/7 | 100% | 7/7 | 100% | 7/7 | 100% |
| 4 RNP | 7/7 | 100% | 7/7 | 100% | 7/7 | 100% |
| 5 Jo-1 | 3/3 | 100% | 3/3 | 100% | 3/3 | 100% |
| 6 Scl-70 | 7/7 | 100% | 7/7 | 100% | 7/7 | 100% |
| 7 Normal | 7/7 | 100% | 7/7 | 100% | 7/7 | 100% |
| TOTALS | 45/45 | 100% | 45/45 | 100% | 45/45 | 100% |
Table 12
Precision = 100%
Cross-Reactivity Study
The cross-reactivity data is presented in Table 11 for 7 sera containing dsDNA antibodies. The data is The cross-reactivity data is procemed in russ and cross-react with dsDNA.
| Table | 13 |
|---|---|
| ------- | ---- |
| Sample | Result |
|---|---|
| 1 | Neg |
| 2 | Neg |
| 3 | Neg |
| 4 | Neg |
| 5 | Neg |
| 6 | Neg |
| 7 | Neg |
Cross Reactivity to dsDNA = 0%
§ 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).