(106 days)
The IMDx HSV-1/2 for Abbott m2000 assay is an in vitro diagnostic test for the direct, qualitative detection and differentiation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) DNA from male and female skin lesions from anogenital or oral sites. The test is intended for use as an aid in the diagnosis of HSV infection in symptomatic patients. The assay is intended to be run on the Abbott m2000 instrument system.
Warning: The IMDx HSV-1/2 for Abbott m2000 assay is not FDA cleared for use with cerebrospinal fluid (CSF). The assay is not intended for prenatal screening.
The IMDx FISV-1/2 for Abbott m2000 assay uses PCR to generate amplified product from HSV-1 and HSV-2 present in clinical specimens. The presence of HSV-1 and/or HSV-2 target DNA is indicated by the fluorescent signal generated through the use of fluorescently labeled oligonucleotide probes on the Abbott m2000rt instrument. The probes do not generate a signal unless they are specifically bound to the amplified product. The amplification cycle at which fluorescent signal is detected by the Abbott m2000rt is inversely proportional to the HSV-1 and/or HSV-2 DNA target concentration present in the original specimen. A plasmid containing DNA unrelated to HSV-1 and HSV-2 is introduced into each specimen during sample preparation to serve as an internal control. The internal control is amplified in the same reaction as the HSV-1 and HSV-2 DNA targets, and serves to demonstrate that the sample preparation and amplification proceeded correctly for each specimen. A preparation of intact, inactivated HSV-1 and HSV-2 virus is included as the positive control in the IMDx HSV-1/2 for Abbott m2000 assay. Run as a separate control, the positive control serves to demonstrate that the HSV-1/2 PCR reagents are functional. In addition, the positive control functions as a process control to demonstrate that sample preparation has proceeded correctly during the run. A negative control consisting of M4RT viral transport medium is included in each run to independently verify the absence of contaminating target material in assay reagents.
Acceptance Criteria and Device Performance Study for IMDx HSV-1/2 for Abbott m2000
The IMDx HSV-1/2 for Abbott m2000 assay is an in vitro diagnostic test for the direct, qualitative detection and differentiation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) DNA from male and female skin lesions from anogenital or oral sites.
The study that proves the device meets the acceptance criteria involved Prospective Clinical Performance Characteristics and Retrospective Clinical Performance Characteristics studies, as well as several analytical performance studies. The primary comparison for clinical performance was against the ELVIS® (Enzyme Linked Virus Inducible System) HSV ID and D3 Typing Test System.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of target sensitivity and specificity percentages. However, the study results, particularly from the prospective clinical performance, would implicitly represent the performance deemed acceptable for FDA clearance through substantial equivalence. If acceptance criteria were required, they would typically be set at a high level given the diagnostic nature of the device. For this summary, we will present the reported performance from the primary prospective study as the "met acceptance criteria".
| Parameter | Acceptance Criteria (Implied by Study Results) | Reported Device Performance (Prospective Study) |
|---|---|---|
| HSV-1 Anogenital | ||
| Sensitivity | High (e.g., >90%) | 99.0% (95% CI: 94.7%-99.8%) |
| Specificity | High (e.g., >85%) | 96.3% (95% CI: 94.4%-97.6%) |
| HSV-2 Anogenital | ||
| Sensitivity | High (e.g., >90%) | 97.5% (95% CI: 93.8% - 99.0%) |
| Specificity | High (e.g., >80%) | 89.5% (95% CI: 86.9% - 91.6%) |
| HSV-1 Oral | ||
| Sensitivity | High (e.g., >90%) | 100.0% (95% CI: 90.6% - 100.0%) |
| Specificity | High (e.g., >70%) | 77.8% (95% CI: 69.1% - 84.6%) |
| HSV-2 Oral | ||
| Sensitivity | (Due to low positive count, this is challenging to set a high bar, but detection is important) | 0.0% (95% CI: 0.0% - 65.8%) (Very low N, limited conclusions) |
| Specificity | High (e.g., >95%) | 98.6% (95% CI: 95.1% - 99.6%) |
Note on HSV-2 Oral Sensitivity: The reported sensitivity of 0.0% in the prospective study for oral HSV-2 is based on only 2 reference method positive cases. This low sample size limits definitive conclusions, and a contrived specimen study was performed to provide additional data for HSV-2 oral detection. This contrived study showed 100% detection of HSV-2 in spiked oral samples across various concentrations.
2. Sample Size Used for the Test Set and Data Provenance
- Prospective Studies (Clinical Performance Characteristics):
- Test Set Size: 954 prospective specimens (807 anogenital and 147 oral).
- Data Provenance: From four geographically diverse locations within the United States.
- Retrospective Studies:
- Test Set Size: 54 retrospective specimens (27 anogenital and 27 oral).
- Data Provenance: Not explicitly stated, but "historical results" for the ELVIS system suggests previously collected specimens.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
The ground truth was established by the ELVIS® (Enzyme Linked Virus Inducible System) HSV ID and D3 Typing Test System. This is a commercially available viral culture system, which is a recognized reference method for HSV detection and typing. The document does not specify the number of human experts or their qualifications involved in interpreting the ELVIS results for establishing ground truth. The ELVIS system itself is the "expert" or gold standard in this context.
4. Adjudication Method for the Test Set
The document mentions "Discordant analysis" was performed.
- For anogenital HSV-1, 20 initial IMDx positive / ELVIS negative results were analyzed; 6 were confirmed positive for HSV-1, 11 remained discordant.
- For anogenital HSV-2, 68 initial IMDx positive / ELVIS negative results were analyzed; 55 were confirmed positive for HSV-2, 7 remained discordant.
- For oral HSV-1, 24 initial IMDx positive / ELVIS negative results were analyzed; 14 were confirmed positive for HSV-1, 10 remained discordant.
- For oral HSV-2, 2 initial IMDx positive / ELVIS negative results were analyzed; both were confirmed positive for HSV-2.
The specific "adjudication method" beyond re-testing or further analysis of discordant samples with an unspecified method is not detailed (e.g., whether a third, independent gold standard was used, or if expert review of discrepant results was performed). However, the results presented in the tables incorporate the outcomes of this discordant analysis by adjusting the counts (e.g., "HSV-1 was detected in 6 of the 17 specimens" changes the true positive count for HSV-1).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic assay (a lab test), not an imaging or interpretation assistance device for human readers. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable here. The device provides a direct qualitative detection and differentiation of HSV-1/2 DNA.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, a standalone performance study was done. The entire set of clinical performance characteristics (prospective and retrospective studies) evaluates the performance of the IMDx HSV-1/2 for Abbott m2000 assay directly against the reference method (ELVIS viral culture). This is an "algorithm only" or "device only" performance without human interpretation being the primary variable. The results are based on the device's output.
7. The Type of Ground Truth Used
The primary ground truth used for clinical performance studies was the ELVIS® (Enzyme Linked Virus Inducible System) HSV ID and D3 Typing Test System. This is a viral culture-based method, which is a widely accepted laboratory gold standard for direct detection of viable virus.
8. The Sample Size for the Training Set
The document does not explicitly describe a separate "training set" for the IMDx HSV-1/2 for Abbott m2000 assay. This is a PCR-based diagnostic test, not a machine learning model that typically requires a distinct training phase with a large dataset. The assay's design and optimization (e.g., primer and probe selection, reaction conditions) would have occurred during development, likely using various characterized samples, but these are not formally presented as a "training set" in the context of this 510(k) submission. Therefore, the concept of a separate "training set" as understood in machine learning is not directly applicable or reported for this type of IVD.
9. How the Ground Truth for the Training Set Was Established
As mentioned above, no explicit "training set" is described for this PCR-based IVD. The ground truth for the analytical and clinical validation of the device relies on established laboratory culture methods (ELVIS system for clinical specimens) and characterized viral strains/isolates for analytical studies (e.g., limit of detection, analytical reactivity, cross-reactivity). These reference methods serve as the "ground truth" to evaluate the accuracy of the IMDx assay.
§ 866.3305 Herpes simplex virus serological assays.
(a)
Identification. Herpes simplex virus serological assays are devices that consist of antigens and antisera used in various serological tests to identify antibodies to herpes simplex virus in serum. Additionally, some of the assays consist of herpes simplex virus antisera conjugated with a fluorescent dye (immunofluorescent assays) used to identify herpes simplex virus directly from clinical specimens or tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by herpes simplex viruses and provides epidemiological information on these diseases. Herpes simplex viral infections range from common and mild lesions of the skin and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal herpes virus infections range from a mild infection to a severe generalized disease with a fatal outcome.(b)
Classification. Class II (special controls). The device is classified as class II (special controls). The special control for the device is FDA's revised guidance document entitled “Class II Special Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 Serological Assays.” For availability of the guidance revised document, see § 866.1(e).