(86 days)
IMMULITE® 2000 CMV IgM is for in vitro diagnostic use with IMMULITE® 2000 Systems analyzers for the qualitative detection of IgM antibodies to cytomegalovirus (CMV) in human serum or plasma (EDTA or heparinized), as an aid in the diagnosis of current and recent CMV infection in individuals with signs and symptoms of CMV infection or clinical suspicion of CMV infection. This assay is not FDA cleared or approved for use in testing (screening) blood or plasma donors, neonatal screening, or for use at point-of-care facilities.
Performance characteristics for this assay have not been established in immunocompromised, immunosuppressed or organ transplant individuals.
CMV IgM Controls are assayed, bi-level controls intended for use with the IMMULITE 2000 CMV IgM assay. They are intended as an aid in monitoring day-today assay performance.
IMMULITE 2000 CMV IgM is a solid-phase, enzyme labeled chemiluminescent three-step immunoassay. The solid phase (bead) is coated with inactivated, purified CMV antigen (strain AD-169 from infected cell lysates). The liquid phase consists of two reagents: 1) polyclonal goat anti-human IgG antibody in buffer, and 2) alkaline phosphatase (bovine calf intestine) conjugated to polyclonal goat anti-human IgM antibody in buffer.
In the first cycle, the patient sample and polyclonal goat anti-human IgG antibody are incubated together without the bead for 30 minutes. During this time, anti-IgG antibodies block IgG present in the patient's sample.
In the second cycle, the pretreated sample and polyclonal goat anti-human IgG antibody are transferred to the second reaction tube. Anti-IgG antibodies block the remaining IgG from the patient's sample from binding to the CMV antigen on the bead. During this time, CMV IgM in the patient sample binds to CMV antigen on the bead. Unbound sample and reagent are then removed by centrifugal washes.
In the third cycle, the enzyme conjugated polyclonal goat anti-human IgM antibody is added to the second reaction tube. The enzyme conjugate binds to immobilized IgM to form the antibody sandwich complex. The unbound enzyme conjugate is removed by centrifugal washes. Finally, chemiluminescent substrate is added to the reaction tube and the signal is generated in proportion to the bound enzyme.
Here's an analysis of the provided text, focusing on the acceptance criteria and study details for the IMMULITE® 2000 CMV IgM device:
Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of specific percentages for "Positive Agreement" and "Negative Agreement." Instead, it presents the results of a comparison study against a predicate device (Kit A, which is the bioMerieux Vitek VIDAS CMV IgM assay). The "acceptance criteria" are implied by the demonstration of substantial equivalence to the predicate device. The performance is reported as "Positive Agreement" and "Negative Agreement" with the predicate device.
Table 1: Acceptance Criteria (Implied) and Reported Device Performance
| Performance Metric | Implied Acceptance Criteria (Substantial Equivalence) | Reported Device Performance (IMMULITE® 2000 CMV IgM vs. Kit A) |
|---|---|---|
| Prospective Subjects | Achieve substantial equivalence to predicate device | Positive Agreement: 47.1% (95% CI: 23.0% - 72.2%) |
| Negative Agreement: 97.2% (95% CI: 95.4% - 98.5%) | ||
| Retrospective Subjects | Achieve substantial equivalence to predicate device | Positive Agreement: 97.8% (95% CI: 92.4% - 99.7%) |
| Negative Agreement: 56.3% (95% CI: 29.9% - 80.2%) | ||
| Precision | Comparable to predicate device (4.0% to 6.5% CV) | Total CV ranged from 5.1% to 21.4% |
Note on "Acceptance Criteria": The document's primary goal is to demonstrate "substantial equivalence" to a legally marketed predicate device (VIDAS® CMV IgM). This regulatory pathway often relies on showing comparable performance rather than meeting strict pre-defined numerical thresholds for a new device's absolute performance. The provided "Positive Agreement" and "Negative Agreement" with the predicate device are key metrics used to support this claim of equivalence.
Study Details
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Sample Size used for the test set and the data provenance:
- Total Samples: 636 serum samples.
- Prospective Samples: 527 samples from "target enrollment groups" collected prospectively.
- Retrospective Samples: 109 samples where the CMV IgM+ status was known.
- Data Provenance: Samples were collected at four U.S. sites and three commercial suppliers. The testing was performed at three U.S. sites. It is a multi-site, mixed retrospective and prospective study conducted within the U.S.
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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 ground truth. The "ground truth" for comparison is primarily defined by the results of a "commercially available CMV IgM assay (Kit A)" which is identified as the VIDAS® CMV IgM assay. For the 109 retrospective samples, it states "where the CMV IgM + status was known," implying a prior determination, but details on how that status was established are not provided. -
Adjudication method for the test set:
The document does not describe any adjudication method. The results are directly compared between the IMMULITE® 2000 CMV IgM assay and the predicate device (Kit A). -
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 not an MRMC comparative effectiveness study involving human readers and AI. This is a study comparing the performance of two in vitro diagnostic assays (IMMULITE® 2000 CMV IgM vs. VIDAS® CMV IgM). AI assistance for human readers is not relevant to this type of device and study. -
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
Yes, this is a standalone performance study of an in vitro diagnostic assay. There is no human-in-the-loop component described for the interpretation or operation of the device during the performance evaluation, beyond routine laboratory procedures. The output of the device is a qualitative result (Reactive, Indeterminate, Nonreactive). -
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The primary "ground truth" or reference standard used for comparison is the result obtained from a commercially available, legally marketed predicate device (VIDAS® CMV IgM assay). For the retrospective samples, "CMV IgM + status was known," implying prior clinical or laboratory determination. It is not expert consensus, pathology, or outcomes data, but rather a comparison to an established diagnostic test. -
The sample size for the training set:
The document does not provide information on a specific "training set" sample size. This is likely because the document describes a regulatory submission for device performance evaluation and equivalence demonstration, not the development process of a novel algorithm that typically involves distinct training, validation, and test sets. For an immunoassay like this, the 'training' would typically refer to the assay's development and optimization process, not a dedicated data set in the same way as machine learning models. -
How the ground truth for the training set was established:
As no explicit "training set" is mentioned in the context of ground truth establishment for an algorithm, this information is not applicable/not provided in the document. The focus is on the performance evaluation against a predicate device.
§ 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).