(273 days)
The INCSTAR Rubella IgG ELISA Kit contains instructions and materials for the qualitative and/or semi-quantitative detection of IgG antibodies to rubella in human serum by indirect enzyme-linked immunosorbent assay (ELISA) - all technique. When performed according to instructions, the Rubella IgG ELISA test is of value in the determination of rubella immunological status. The evaluation of paired sera, acute and convalescent, by demonstrating seroconversion or a significant rise in antibody can aid in the diagnosis of current or recent infection with rubella.
The INCSTAR Rubella IgG ELISA test kit utilizes the ELISA technique for the detection of rubella IgG antibodies. Diluted patient serum is incubated with purified rubella antigen bound to the solid surface of a microtiter well. If IgG antibodies to rubella are present in the patient's serum, antigen-antibody complexes are formed. These complexes bind with horseradish peroxidase labeled antihuman IgG which react with the addition of chromogen, resulting in color development. The absorbance of the solution, measured at 450 nm, is directly proportional to the concentration of IgG antibodies to rubella antigen present in the reaction solution.
Here's an analysis of the provided text regarding the acceptance criteria and study for the INCSTAR Rubella IgG ELISA Kit:
It's important to note that this document is a 510(k) Summary of Safety and Effectiveness from 1996. The level of detail and specific reporting requirements for device studies have evolved significantly since then. Therefore, some of the requested information, particularly regarding ground truth establishment and MRMC studies, is not explicitly present in this summary.
Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Relative Sensitivity | The device should demonstrate comparable sensitivity to a legally marketed predicate device for the detection of Rubella IgG antibodies. | 91% to 100% (95% confidence intervals) relative to the Rubella IgG Clin-ELISA Kit (K860145). |
| Relative Specificity | The device should demonstrate comparable specificity to a legally marketed predicate device for the detection of Rubella IgG antibodies. | 97% to 100% (95% confidence intervals) relative to the Rubella IgG Clin-ELISA Kit (K860145). |
| Overall Agreement | The device should show a high degree of concordance with a legally marketed predicate device in classifying samples as positive or negative. | 96% to 99% overall agreement with the Rubella IgG Clin-ELISA Kit (K860145). |
| Substantial Equivalence | The device must be deemed substantially equivalent to a predicate device in terms of safety and effectiveness. | The document explicitly states: "The INCSTAR Rubella IgG ELISA Kit is substantially equivalent (SE) to the Rubella IgG Clin-ELISA Kit, 510(k) No. K860145, which has been cleared by the FDA and is currently in U.S. commercial distribution." This is the overarching acceptance criterion addressed by the study. |
| Discrepant Resolution | Discrepant results between the test device and the reference device should be further investigated to support the device's performance claims. | Of 5 samples positive by INCSTAR but negative by reference ELISA, 4 were positive by a commercial Rubella IgG EIA (Abbott Rubazyme EIA). |
| Of 7 samples negative by INCSTAR but positive by reference ELISA, 4 were negative by the commercial Rubella IgG EIA (Abbott Rubazyme EIA). This suggests the INCSTAR device performed favorably or similarly to the commercial EIA in resolving these discrepancies, bolstering its reliability. |
Study Details
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Sample Size Used for the Test Set and Data Provenance:
- Sample Size: 497 serum samples, representing 497 individuals.
- Data Provenance: The samples utilized represented a "mixed population of clinical patients (nonrubella disease related), newborns, employee/student screenings, and pregnant women." The country of origin is not explicitly stated, but given it's an FDA submission, it's highly probable the samples were collected in the United States. The collection method (retrospective or prospective) is not specified, but for a 510(k) submission of this era, retrospective collection of banked samples would be common.
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Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- Not explicitly stated. The "ground truth" in this context is established by comparison to a legally marketed predicate device (Rubella IgG Clin-ELISA Kit, K860145) and, for discrepant samples, a commercial Rubella IgG EIA (Abbott Rubazyme EIA, K885297). The performance of these reference devices presumes their own validation and established accuracy, but no human expert ground truth establishment is detailed for the test samples themselves.
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Adjudication Method for the Test Set:
- Not explicitly stated. The comparison is directly between the INCSTAR device and the reference ELISA kit. For discrepant samples, a third commercial EIA product (Abbott Rubazyme EIA) was used for "further resolution." This acts as a form of tie-breaking or verification for discordant results, analogous to a 2+1 adjudication if the primary two disagree, but it's not a human expert adjudication in the traditional sense.
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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 is an in vitro diagnostic (IVD) device for serological testing, not an imaging or AI-assisted diagnostic, so MRMC studies involving human readers and AI assistance are not applicable in this context.
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If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
- Yes, effectively. The study described here is a standalone performance study. The INCSTAR Rubella IgG ELISA Kit itself is an assay, and its performance (sensitivity, specificity, agreement) is evaluated independently against a comparator. While technical staff perform the ELISA, the interpretation of the results as positive/negative/semi-quantitative is based on optical density readings and predefined cutoff values, making it an "algorithm only" type of evaluation in the sense that human subjective interpretation of results is minimized after the initial lab work.
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The Type of Ground Truth Used:
- Reference standard/comparator assay. The primary "ground truth" used for evaluating the INCSTAR device was the results generated from the "Rubella IgG Clin-ELISA kit" (K860145), which is a legally marketed predicate device. For discrepant samples, a second commercial Rubella IgG EIA (Abbott Rubazyme EIA, K885297) was used as an additional reference. This is a common approach for IVD devices seeking substantial equivalence.
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The Sample Size for the Training Set:
- Not applicable/Not explicitly stated for a traditional "training set" in the context of an algorithm or AI. This is a laboratory assay. The development and internal calibration of such kits would involve various internal studies (e.g., linearity, precision, cross-reactivity) using various samples, but these are not typically referred to as a "training set" for a classical algorithm. The 497 samples were for the clinical performance evaluation/validation.
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How the Ground Truth for the Training Set Was Established:
- Not applicable, as there isn't a "training set" in the sense of predictive modeling. The development of the assay, including establishing cutoff values and calibrators, would have been based on extensive internal studies using characterized samples, likely with confirmed rubella status (positive/negative) determined by a combination of established reference methods, clinical history, and often, panels of characterized serum samples. This process is usually part of the manufacturer's R&D and internal validation, which precedes the 510(k) submission. The summary does not provide details on this internal development process.
§ 866.3510 Rubella virus serological reagents.
(a)
Identification. Rubella virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to rubella virus in serum. The identification aids in the diagnosis of rubella (German measles) or confirmation of a person's immune status from past infections or immunizations and provides epidemiological information on German measles. Newborns infected in the uterus with rubella virus may be born with multiple congenital defects (rubella syndrome).(b)
Classification. Class II. The special controls for this device are:(1) National Committee for Clinical Laboratory Standards':
(i) 1/LA6 “Detection and Quantitation of Rubella IgG Antibody: Evaluation and Performance Criteria for Multiple Component Test Products, Speciment Handling, and Use of the Test Products in the Clinical Laboratory, October 1997,”
(ii) 1/LA18 “Specifications for Immunological Testing for Infectious Diseases, December 1994,”
(iii) D13 “Agglutination Characteristics, Methodology, Limitations, and Clinical Validation, October 1993,”
(iv) EP5 “Evaluation of Precision Performance of Clinical Chemistry Devices, February 1999,” and
(v) EP10 “Preliminary Evaluation of the Linearity of Quantitive Clinical Laboratory Methods, May 1998,”
(2) Centers for Disease Control's:
(i) Low Titer Rubella Standard,
(ii) Reference Panel of Well Characterized Rubella Sera, and
(3) World Health Organization's International Rubella Standard.