(84 days)
The ADVIA Centaur® CMV IgG (CMV IgG) assay is for in vitro diagnostic use in the qualitative detection of IgG antibodies to cytomegalovirus (CMV) in human pediatric and adult serum and plasma (dipotassium EDTA, lithium heparin) using the ADVIA Centaur XP system. The assay is used to determine CMV IgG serological status and as an aid in the diagnosis of CMV infection in individuals for whom a CMV IgG test was ordered, including pregnant women. The ADVIA Centaur CMV IgG assay is not intended for blood and tissue donor screening.
The ADVIA Centaur® CMV IgG) Quality Control material is for in vitro diagnostic use for monitoring the performance of the ADVIA Centaur CMV IgG (CMV IgG) assay on ADVIA Centaur systems.
CMV IgG Assay Kit (100-Tests) consists of 1 ReadyPack containing ADVIA Centaur CMV IgG Lite Reagent and Solid Phase reagent, and 1 ReadyPack ancillary reagent pack that contains ADVIA Centaur CMV IgG Diluent, and a set of Calibrators (1 vial each of Low and High, with fill volume of 2 mL each). The reagents and calibrators are packaged together in the ADVIA Centaur CMV IgG Assay kit, while the associated ADVIA Centaur CMV IgG Quality Control is packaged separately.
The ADVIA Centaur CMV IgG assay is a fully automated, 2-step sandwich immunoassay using indirect chemiluminometric technology.
Here's a breakdown of the acceptance criteria and study information for the ADVIA Centaur CMV IgG assay, based on the provided FDA 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are generally inferred from the "Assay Cut-off" section, where the cutoff value was set to achieve a certain agreement with a comparator device. The performance is then demonstrated in the clinical studies.
| Acceptance Criteria Category | Specific Acceptance Criteria (Inferred) | Reported Device Performance (Combined Population) |
|---|---|---|
| Agreement with Comparator | ≥ 95% Positive Agreemen | 99.6% (1037/1041) |
| ≥ 95% Negative Agreemen | 96.8% (637/658) | |
| Precision (Within-Lab) | Not explicitly stated as acceptance criteria, but demonstrated by low %CV values. | Ranges from NA (for very low mean values) up to 3.9% CV for positive control. |
| Reproducibility | Not explicitly stated as acceptance criteria, but demonstrated by low %CV values across sites. | Ranges from NA (for very low mean values) up to 7.0% CV for a high positive serum pool. |
| No Interference | No change in clinical interpretation at specified interferent concentrations. | No change in clinical interpretation throughout the assay range. |
| Cross-Reactivity | Agreement with comparator assay (no significant false positives/negatives due to cross-reactants). | Generally good agreement with comparator, minimal discrepancies identified for equivocal samples. |
| Matrix Equivalence | Good correlation (high 'r' value, slope near 1, intercept near 0) for different plasma types compared to serum. | Correlation Coefficient (r) = 0.99 (Dipotassium EDTA plasma vs. Serum), 0.96 (Lithium heparin plasma vs. Serum). Slopes were 1.01. |
| CDC Panel Agreement | Not explicitly stated as acceptance criteria, but 100% agreement indicates strong performance. | 100% agreement with CDC serological status (39 positive, 41 negative). |
2. Sample Sizes Used for the Test Set and Data Provenance
- Initial Cut-off Study: 389 remnant clinical samples (negative: 196, positive: 186, equivocal: remainder - exact number not specified but implied to be few).
- Method Comparison (Primary Test Set): A total of 1842 samples
- Prospective Study: 1699 specimens
- 684 general population subjects
- 348 pregnant subjects
- 229 pediatric subjects (2-21 years old)
- 44 HIV-positive subjects
- 394 transplant-patient subjects
- Provenance: 6 collection sites in the United States.
- Retrospective Study: 143 HIV-positive specimens
- Provenance: 1 site (implied to be in the US, given the overall context of the submission).
- Prospective Study: 1699 specimens
- CDC Panel: 80 previously characterized serum samples.
- Provenance: Centers for Disease Control (CDC).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not explicitly provided in the document. The ground truth for the comparison studies was established by a "comparator CMV IgG assay" (bioMerieux VIDAS CMV IgG (CMVG) Assay, K920661). For equivocal samples, additional testing was done on "2 other CMV IgG comparator assays" to achieve a "two out of three consensus result."
There is no mention of human experts (e.g., radiologists, pathologists) establishing ground truth for the primary clinical studies. The ground truth for the CDC panel samples was "previously characterized" by the CDC, implying expert determination at some point in the past, but details are absent.
4. Adjudication Method for the Test Set
- For the primary method comparison, the comparator CMV IgG assay served as the reference.
- For samples that tested equivocal on the comparator assay, an adjudication method of "two out of three consensus result" was used, comparing the initial comparator result with results from two other CMV IgG comparator assays.
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 is not applicable. The device is an in-vitro diagnostic (IVD) assay for detecting antibodies, not an AI-assisted diagnostic imaging or pathology device that involves human readers interpreting cases. Therefore, no MRMC study or effect size for AI assistance is provided or expected.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this is a standalone device. The ADVIA Centaur CMV IgG assay is a fully automated immunoassay that generates a qualitative result (reactive or non-reactive) based on an Index value. Its performance is evaluated entirely without human interpretation of raw assay data. The results are reported directly by the system.
7. The Type of Ground Truth Used
The primary ground truth for the clinical studies was established by a comparator CMV IgG assay. This is a surrogate ground truth based on the performance of an already legally marketed and accepted diagnostic test. For equivocal samples, an expert consensus of other comparator assays (two out of three consensus) was used. For the CDC panel, the ground truth was previously characterized serological status provided by the CDC.
8. The Sample Size for the Training Set
The document does not explicitly describe a separate training set for the device in the context of machine learning or AI. The term "training set" is typically used in the development of AI algorithms. This device is an immunoassay, and its development would involve optimization and calibration rather than distinct "training" in the AI sense.
However, the "Assay Cut-off" section describes a study performed to determine the cutoff value:
- A comparison study involving 389 remnant clinical samples was used to determine the placement of the cutoff value. While not a "training set" in the AI sense, these samples were used to establish a critical decision-making parameter for the assay.
9. How the Ground Truth for the Training Set Was Established
As discussed above, there isn't a "training set" in the AI context. For the 389 samples used to establish the cut-off value:
- The ground truth for these samples was established by a comparator CMV IgG assay. The aim was to set the cutoff such that the new device's results agreed with the comparator.
§ 866.3175 Cytomegalovirus serological reagents.
(a)
Identification. Cytomegalovirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to cytomegalovirus in serum. The identification aids in the diagnosis of diseases caused by cytomegaloviruses (principally cytomegalic inclusion disease) and provides epidemiological information on these diseases. Cytomegalic inclusion disease is a generalized infection of infants and is caused by intrauterine or early postnatal infection with the virus. The disease may cause severe congenital abnormalities, such as microcephaly (abnormal smallness of the head), motor disability, and mental retardation. Cytomegalovirus infection has also been associated with acquired hemolytic anemia, acute and chronic hepatitis, and an infectious mononucleosis-like syndrome.(b)
Classification. Class II (performance standards).